Mismanagement of healthcare waste (HCW) during the COVID-19 pandemic can facilitate the transmission of coronavirus. Regarding this problem, there is gap of evidence in Ethiopia, and this study aimed to assess the HCW generation rate and management in Tepi General Hospital, southwest Ethiopia. r) was used to assess the correlation between the total numbers of patients and the total amount of HCW generated. Qualitative data were transcribed verbatim, translated to English, and analyzed with Open Code version 4.02 software, and content analysis was followed.  Institution-based cross-sectional and case studies were conducted. The total amount of waste generated and its type among various case teams were compared using the Kruskal–Wallis test. Spearman's rank correlation coefficient  difference in daily HCW generation rate among different case teams. Similarly, the hospital waste generation amount and total patient flow had a strong positive linear relationship . COVID-19-related medical wastes were not properly handled, segregated, stored, and disposed. There was a scarcity of resources needed to manage HCW, and available resources were utilized poorly. Overall, healthcare wastes were managed as usual (pre-COVID-19).  The total mean weight (±SD) of waste generation rate in all service units of the hospital was 492.5 ± 11.5 kg/day. The higher proportion (61.9%) of the total HCW produced was general waste and the remaining (38.1%) was hazardous waste. There was a statistically significant ( The mean HCW generation rate in Tepi General Hospital was high. Overall, wastes were mismanaged, and COVID-19-related HCWs have been managed as usual. Availing of important resources and training the concerned bodies should be considered during the crisis of COVID-19. Healthcare waste (HCW) is a collection of waste generated by healthcare establishments, research facilities, laboratories, and home-based healthcare such as dialysis and insulin injection. Broadly, HCW can be classified as hazardous  and nonhazardous  waste. Nonhazardous waste does not pose any specific biological, chemical, radioactive, or physical hazard, whereas hazardous waste can pose several health and environmental risks , 2.Hazardous HCW contains potentially harmful microorganisms that can infect hospital communities and the general public. It may also be a source for drug-resistant microorganisms that spread from health facilities into the environment. In general, health risks associated with HCW and by-products include sharps-inflicted injuries, toxic exposure to pharmaceutical products, chemical burns, air pollution, thermal injuries, and radiation burns . In low-Hospitals produce more waste than usual during COVID-19. The diagnosis and treatment of COVID-19 produce wastes that include masks, gloves, gowns, and other protective equipment that could be infected with the virus. The amount of single-use plastics being produced is also greatly increased –7. InappThe World Health Organization (WHO) recommends that all HCWs produced during the care of COVID-19 patients should be collected safely in designated containers and bags, treated, and then safely disposed of or treated, or both, preferably on-site. Furthermore, if waste is moved off-site, it is critical to understand where and how it will be treated and destroyed. All who handle HCW should wear appropriate personal protective equipment (PPE) and perform hand hygiene after removing it . SimilarEthiopia is already stressed with hospital waste before the COVID-19 pandemic, and currently, there is an unpredicted increase in the volume of medical waste . ConfirmInstitution-based cross-sectional and case studies were conducted in Tepi General Hospital from July 1 to 30, 2020. The hospital is found in Southern Nations, Nationalities, and People's Region State, and it is one of the newly constructed hospitals in Southern Ethiopia. It was established in 2014 and providing healthcare services for more than six hundred thousand populations. Currently, it is serving as COVID-19 isolation and treatment center for people of the Sheka zone and partly for those from the other three zones of Southwest Ethiopia. The facility had 188 beds in four wards which include surgical, medical, pediatric, and gynecology/obstetrics. Outpatient departments (OPD) include adult OPD, pediatrics OPD, maternal and child health clinic, antiretroviral clinic, tuberculosis clinic, emergency case team, follow-up clinic, and others. Moreover, the hospital had a pharmacy, laboratory, and imaging (radiology) case teams. In the first quarter of 2020, the average monthly inpatient and outpatient visits of the hospital were 228 and 3562, respectively.All service units (case teams) in the hospital  were considered as a source of HCW generation. A purposively selected 42 workers of the hospital have participated in in-depth interviews.The waste generation data were collected by using observational checklists and measurement apparatus. The observational checklists were prepared to observe and evaluate how the hospital segregate, collect, transport, treat, and dispose wastes. A standard weighing scale was used to quantify the generation rate of HCW. HCWs were collected and measured daily for seven consecutive days. Empty plastic buckets of standard colors  were distributed daily to different sections of the hospital. Plastic bags with different colors were kept inside the respective buckets. The buckets and plastic bags were labeled to indicate the different categories of the HCWs, the place of generation, date of collection, and sample number. Waste weighing and recording station was arranged in a convenient site within the vicinity of the hospital. Then, the collected wastes in plastic bags were removed every morning, and the weight was measured at 8:00 AM using a weighing scale, capacity range from 15 kg to 25 kg. The measurement was taken three times, and the mean of three measurements was used as the final weight of wastes.Seven BSc nurses (data collectors) and two public health officers (supervisors) were recruited and trained for data collection. Before data collection, two-day training was given on the purpose of the study, data quality, type of HCWs, the use and calibration of a weighing scale, infection prevention, and control techniques including proper use of PPE. Data collection guideline was developed and used to facilitate the training. Data were recorded daily in a suitable datasheet. Weight scales were arranged and then calibrated every morning. Moreover, daily on-site supervision was made by investigators and supervisors. The pretest was performed before the actual data collection begins, and the daily meeting was arranged to improve data quality. Accordingly, the amendment was made based on the result of the pretest.To get details of the current status of waste management systems of the hospital, additional qualitative data were collected from workers who have direct and major contact with waste management through in-depth interviews. Workers include waste handlers and team leaders, nurses, midwives, laboratory technicians, medical doctors, hospital manager, and others. An interview tool (guide) was used for conducting a face-to-face interview. The interview tool guides the participants to discuss on the waste segregation practice of the hospital, how the hospital collects and transports waste, how the hospital finally disposes the waste, and overall, how the waste is managed during COVID-19. All interviews were audio-recorded and field notes were taken. Meanwhile, an on-site observation was made to observe the status of the current waste management systems of the hospital. The number of outpatients and inpatient flow data for the study period was taken from the patient registration office. The number of inpatients and outpatients was used to calculate the daily waste generation of the hospital.rs) was used for testing the existence of any bivariate correlation between the total numbers of patients and the total amount of healthcare waste generated. In addition, daily and annual waste generation rates were described and presented using tables. The annual healthcare waste generation rate was estimated by multiplying the mean healthcare waste generation rate in kg per day by 365 days . Qualitative data were transcribed verbatim, translated to English, and analyzed with Open Code version 4.02 software, and content analysis was followed. Codes and categories were developed, and findings were summarized by supporting with quotes from respective study participants.The data collected through measurement and observation checklist were entered and compiled by using SPSS version 22 computer software packages. The total amount of waste generated and its type among various case teams were compared using the Kruskal–Wallis test as the data distribution was not homogeneous  even when transformed. Spearman's rank correlation coefficient  in all health service delivery units. Of these, 212 (28.2%) patients were admitted to the inpatient department and 540 (71.8%) were seen at OPDs. The higher proportion (61.9%) of the total HCW produced was general waste and the remaining 38.1% was hazardous or risk waste. The types of hazardous wastes generated in Tepi General Hospital were sharps, infectious, pharmaceutical, and pathological (placenta and blood) wastes. The mean (±SD) generation rate of sharps, infectious, pharmaceutical, and pathological wastes in the studied hospital was 7.2 ± 0.9 (1.5%), 158.7 ± 0.4 (32.2%), 19.2 ± 0.5 (3.9%), and 2.3 ± 0.2 (0.5%) kg/day, respectively. More than a half (0.6) kg of waste was produced by one patient daily. Totally, an estimated yearly waste generation rate of the hospital was 179,762.5 kg/year .The sharp, infectious, and pharmaceutical hazardous wastes were mainly generated from wards. However, the highest share of the pathological waste was from the gynecology unit. There was no hazardous waste generated from the kitchen. Generally, the maximum and minimum amounts of hazardous wastes were generated from wards and radiology room, respectively .The estimated annual total waste generation rate was 179,762.5 kg/year or 956.2 kg/bed/year. The estimated annual healthcare waste generation rate in kg/bed/year for infectious, pathological, pharmaceutical, sharp, and general wastes was 308.1, 4.5, 37.3, 14, and 592.3, respectively.X2 = 82.1, p < 0.001) difference in daily healthcare waste generation rate among different case teams. This implies that the type or specialty of case teams was a factor for the generation rate of HCWs. Spearman's rank correlation coefficient (rs) estimation showed a strong positive linear relationship between the amount of hospital waste generation and the total patient flow  (The highest amount ((48.2%) 237.3 kg/day) of the hospital waste was generated from the kitchen room, whereas that of the lowest amount ((0.9%) 4.3 kg/day) was generated in the radiology room. The Kruskal–Wallis test indicated a statistically significant (p=0.032) .A total of 42 health workers have participated in an in-depth interview  and discThere are mixed wastes on the color-coded bins which are due to inappropriate waste segregation practice by concerned bodies of the hospital. (a nurse study participant)As we have observed and study participants reported, hospital wastes were temporarily stored using plastic buckets with cover for nonsharp wastes. Safety boxes were used for sharp waste in the emergency room and surgical and gynecological wards. It was also reported that the segregation of HCW by its type at the point of generation and pretreatment of infectious wastes were poorly practiced in the hospital. Majorities of study participants have pointed out that color-coded waste segregation materials were not adequately available in each unit, and front-line health service workers did not segregate those wastes as hazardous and nonhazardous. One of the study participants explained the issue as follows.Of course we have gloves but we usually miss to use it. On the other hand, although we need a face mask we could not have that and again we have also a shoe problem, we use our own shoes during cleaning the working area, no boot at all. (a waste handler study participant)Almost all study participants have discussed that, though waste from the outpatient department is collected within 24 hours' intervals, the hospital has no fixed time to transport wastes into the designated area. All waste handlers have reported that they have duty gloves but they do not use during waste collection and transportation. However, they have revealed that they lack safety boots and face masks, and for that reason, they are obliged to wear their habitual personal shoes during their routine working time. One of them depicted the concern as follows.We give attention to sharp materials and for that, we regularly collect it under separate safety boxes and dispose properly. Sometimes other wastes may be collected together without segregating based on their types. (a nurse study participant)It was observed and study participants reported that the infectious medical HCWs including face masks and nonrisk HCWs are not collected on separate plastic barrel containers; rather, infectious and noninfectious wastes are usually mixed and transported into an incinerator room. However, sharp materials are usually separated and transported with a safety box, while plastics, paper towels, and face masks were transported with large bins made up of plastic material. The following statement from one of the study participants agrees with this.Even during COVID-19, the waste handling and disposal habit is not improved and there are many things which need a rapid solution. (a laboratory technician study participant)Actually we have an incinerator and other waste management systems but I can't say we are fully practicing as recommended and expected of us. We are working for improvements to make our working environment safe. We found that the waste disposal methods employed by Tepi General Hospital were incineration and the open container that was picked by waste collector firms and plastic bottle houses and end up in the open dumpsite. Study participants have reported that the waste incinerator is used for disposal of all medical infectious wastes such as sharp materials , anatomical wastes, used face masks, and paper towels. On the other hand, the majority of study participants discussed that wastes including used batteries, broken thermometers, radioactive waste, and PVC plastic-like IV bags were not separated and disposed properly in the vicinity. Again, silver and X-ray films from radiotherapy were not managed and recycled properly. The following are part of the responses from study participants.Most study participants have pointed out that COVID-19-related healthcare waste disposal was not arranged by specifically trained staff and special vehicles or supporting materials. They have also mentioned that all healthcare workers and waste handlers did not take training on medical waste management, especially on waste segregation at the time of the COVID-19 pandemic. Standard operating procedures were not established, and the hospital did not have a healthcare waste management committee too.Medical activities generate waste that should always be discarded at the point of use by the person who used the item. The quantity of HCW generated should always be minimized, and precautions must be taken during their handling particularly in the time of COVID-19 , 13. TheThe hazardous HCW is associated with a risk of infecting workers handling HCW and others. Consequently, it requires careful waste management compared to general waste. This study revealed that 32.37% of HCWs in Tepi General Hospital were hazardous. This is lowest compared to other findings from studies conducted in Ethiopian hospitals , 17. TheThe higher proportion of hazardous waste generation may be attributable to poor segregation practice in the studied hospital. As it was noted from this study, the resources required to segregate wastes were inadequate, and the front-line health service workers did not segregate wastes using available materials. During the pandemic of COVID-19, the priority attention was given mainly to sharp materials by ignoring different infectious wastes such as facemasks. However, facemasks might be the source of infection for coronavirus. As a result, hazardous wastes should be segregated properly. Proper segregation of waste can reduce the treatment and disposal costs and the risks of infecting workers handling HCW. Moreover, the part of the HCW that is hazardous and requires special treatment could be reduced to some 2–5% if the hazardous part was immediately separated from the other wastes . TherefoThe waste collection, transport, treatment, and disposal practices of the Tepi General Hospital were substandard. In this crisis time, all people in the country are recommended to protect themselves from COVID-19 by using different PPE. Surprisingly, the waste handlers, the priority groups to use PPE, in Tepi General Hospital were facing the scarcity of the PPE such as safety boots and facemasks. They were not using their duty gloves, and this might be due to the lack of awareness creation strategies such as training since they were also reporting that they did not take any training which guides them on how to handle wastes during COVID-19. Wastes were also collected with an open container, and some of the wastes were ended up with open dumping. Furthermore, the absence of standard operating procedures and the healthcare waste management committee was an important finding in the hospital. This is in contrary to the national and international (WHO) recommendations of proper waste management during COVID-19 and the experiences of other countries , 18–21.The mean HCW generation rate in Tepi General Hospital was high, and overall wastes were mismanaged. Although available resources were poorly utilized, the scarcity of vital inputs for proper waste management was one of the important findings. Moreover, COVID-19-related HCW was being managed as usual, and no different waste management method was employed so far. Availing important resources and training the concerned bodies should be considered during the crisis of COVID-19.Due to the lack of comparable studies conducted during COVID-19, the comparison was performed with studies that were performed before the pandemic. Moreover, our study was conducted in single site and it could not be generalizable to other settings. Thus, large-scale studies which can also identify the potential determinants of COVID-19-related waste generation and management practices are recommended.


Introduction: Traditional classification that divided gliomas into glioblastoma multiformes (GBM) and lower grade gliomas (LGG) based on pathological morphology has been challenged over the past decade by improvements in molecular stratification, however, the reproducibility and diagnostic accuracy of glioma classification still remains poor. This study aimed to establish and validate a novel nomogram for the preoperative diagnosis of GBM by using integrated data combined with feasible baseline characteristics and preoperative tests.Material and method: The models were established in a primary cohort that included 259 glioma patients who had undergone surgical resection and were pathologically diagnosed from March 2014 to May 2016 in the First Affiliated Hospital of Xi'an Jiaotong University. The preoperative data were used to construct three models by the best subset regression, the forward stepwise regression, and the least absolute shrinkage and selection operator, and to furthermore establish the nomogram among those models. The assessment of nomogram was carried out by the discrimination and calibration in internal cohorts and external cohorts.Results and discussion: Out of all three models, model 2 contained eight clinical-related variables, which exhibited the minimum Akaike Information Criterion (173.71) and maximum concordance index (0.894). Compared with the other two models, the integrated discrimination index for model 2 was significantly improved, indicating that the nomogram obtained from model 2 was the most appropriate model. Likewise, the nomogram showed great calibration and significant clinical benefit according to calibration curves and the decision curve analysis.Conclusion: In conclusion, our study showed a novel preoperative model that incorporated clinically relevant variables and imaging features with laboratory data that could be used for preoperative prediction in glioma patients, thus providing more reliable evidence for surgical decision-making. Gliomas are the most common type of neuroepithelial neoplasm in the central nervous system (CNS) and account for ~3% of all systemic malignant tumors –3. Gliom+ suppressor T cells and CD4+CD25+FoxP3+Treg cells, which have been reported to play a crucial role in cancer immune surveillance and defense by inducing cytotoxic cell death and inhibiting glioma cell proliferation and migration of glioma , tumor grade, the preoperative epilepsy occurrence (pEO), and preoperative blood routine tests including neutrophil, monocyte, and lymphocyte counts, were obtained from medical records. Features of MRI, comprising of tumor volume, location, multifocality, annular enhancement, necrosis volume, and peritumoral edema volume (PTE), were also involved in our analysis.2. The threshold value for pKPS was <70 and ≥70 on the basis of WHO's standards (*M/L (Body mass index (BMI) was defined as: BMI = height/body weighttandards . The SIRds  .GBM-related predictive models were established in the primary cohort based on the selected variables by adopting binary logistic regression. Eventually, we developed three models as described below: (a) model 1 consisted of seven variables based on the BSR, (b) model 2 included SIRI besides the above seven variables according to the LASSO, and (c) model 3 also consisted of seven variables except for pEO according to the FSR.The final model was determined by the Akaike Information Criterion (AIC) , the ROCSimilarly, these methods were also used to assess the performance of prediction models. Herein, the discrimination of the model was evaluated by the C-index among three cohorts, and the IDI was used to estimate whether the model's predictive ability could become better by adding one variable in model 1 or model 3. Conclusively, the nomogram was derived from the final model.The performance of the nomogram was also demonstrated by the calibration curve among three cohorts, except for the ability of discrimination. Meanwhile, the appropriateness of the current predictors involved in nomogram was tested. As a result, the Hosmer–Lemeshow test, the studentized residuals, the variance inflation factor (VIF), the Cook's distance, the hat value, and the Box-Tidwell test were performed to evaluate model fitting, outliers, collinearity, influential observations, high leverage cases of data, and the linear relationship between continuous independent variables and the logit transformation value of the dependent variable, respectively.The decision curve analysis (DCA) was performed to assess the clinical usage of nomogram and a net benefit for diverse prediction models at different threshold probabilities by adding the benefits and minimizing the harms .http://www.r-project.org). The packages in R which we used in this study were shown as follows: “glment,” “rms,” “proc,” “PredictABEL,” “rmda,” “car,” “leaps,” and “regplot.” Statistical significance levels were determined by two-sided tests and P < 0.05 was defined as statistically significant. The Mann–Whitney U-test was used for comparing two groups of continuous variables analysis, the Kruskal–Wallis H-test was used for three groups' continuous variables analysis, and the χ2 test for categorical variables analysis. The BSR, the LASSO, and the FSR were used to select variables. The binary logistic regression was performed for model construction.All the statistical analyses were performed with the SPSS software  and R software . The proportion of GBM was 55.2, 54.7, and 50.9% among the three cohorts, respectively. Also, the baseline clinical parameters, laboratory tests, and MRI factors showed no significant differences and were comparable among the three cohorts. Additionally, the clinical information after subgroup stratification based on pathological grade in all cohorts also showed none statistical significance . Similarly, the discrimination of model 2 was also maximum in internal validation cohort with the C-index was 0.899  and external validation cohort with C-index was 0.915 . The sensitivity and specificity of model 2 were 82.8 and 79.6% in the primary cohort, 82.1 and 86.2% in the internal validation cohort, and 84.3 and 82.1% in the external validation cohort, respectively, which were more appropriate than the other models. After adding one variable to the prediction model, the IDI was significantly improved . Moreover, the random forest was used to screen out candidate variables and the ROC analysis presented that the Lasso was 0.893, which preceded the random forest combination based on increase in node purity method  among the three regression models. The discrimination of model 2 was maximum in primary cohort with the C-index 0.894 . There were no outliers for data with the P < 0.05. All predictors had no multicollinearity because the VIF in all them was <1.5. The Box-Tidwell test showed a linear relationship between all continuous independent variables and the logit transformation value of the dependent variable , and there were also no strong influential observations and high leverage cases as all of the Cook's distances were no more than 0.02 and all hat values were no more than 0.069  and a comprehensive nomogram which had favorable discrimination and calibration for prediction of PFS was established; moreover, researchers considered that increased risk score of nomogram implied malignancy of glioma. Meanwhile, Muccio et al. . The diagnostic value of hematological markers in predicting glioma grade combined with age and PNI showed fantastic discrimination with AUC of 0.750. Furthermore, Geng et al. (P < 0.01, Tumor-related inflammation has long been considered as an important hallmark of cancer . Accumulg et al.  found thAlthough our nomogram showed encouraging discrimination and calibration among the three cohorts, there were still some limitations. Since a retrospective method was used in this study, inherent deviations such as selection deviation and detection deviation were inevitably generated. Also, continuous monitoring for the variation of some parameters cannot be achieved. Further, molecular mechanism studies and large-scale and multi-center clinical trials needed to be performed to modify the model.In conclusion, our study showed a novel preoperative model incorporated clinically relevant variables and imaging features with laboratory data that could be used for preoperative prediction in glioma patients, thus providing more reliable evidence for surgical decision-making.The data generated during this study are included in this article. Raw data are available upon reasonable request.This study was approved by the Ethics Committee, the First Affiliated Hospital of Xi'an Jiaotong University. This is a retrospective study, for which formal consent is not required.WW: collection and/or assembly of data, data analysis and interpretation, manuscript writing, methodology, and software. ZD: collection and/or assembly of data, data analysis and interpretation, manuscript writing, and editing. WA: data analysis, manuscript writing, and interpretation. YW: manuscript writing and project administration. JX: manuscript writing and project administration. LZ: manuscript writing. BL: conception/design. MW: conception/design, supervision, and editing. JW: conception/design, supervision, and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Patients with comparable degree of neuropathology could show different cognitive impairments. This could be explained with the concept of cognitive reserve (CR), which includes a passive and an active component. In particular, CR is used to explain the gap between tissue damage and clinical symptoms that has been observed in dementia and, in particular, in patients affected by Alzheimer disease (AD). Different studies confirm brain neuroplasticity. Our preliminary study demonstrated that AD patients with high education showed a CR inversely associated with glucose uptake measured in fluorodeoxyglucose positron emission tomography (FDG-PET), whereas the inverse correlation was observed in AD patients with low education. In other words, our findings suggest that CR compensates the neurodegeneration and allows the maintenance of patients’ cognitive performance. Best understanding of the concept of CR could lead to interventions to slow cognitive aging or reduce the risk of dementia.  Several studies have validated the use of low levels of CSF Aβ1-42 as a marker for AD, although there is variability in the establishment of cutoff values for normality [Alzheimer disease (AD) is a neurodegenerative disorder due to pathological accumulation of β-amyloid. Clinically it is characterized by impaired short-term memory and a progressive decrease in cognitive abilities . From thormality ,11. 42 [42 and p-tau, respectively, as A and T biomarkers and MRI as N biomarker. Revised NINCDS-ADRDA diagnostic revised criteria have highlighted a common framework regarding AD definition and its staging ,13. This42 ,18. Biom42 . Biomark42 , FDG-PET42 . The sui(1)Individuals with normal AD biomarkers.(2)Those in the continuum of AD .(3)Those with a normal amyloid biomarker but with abnormal T, N, or both. This latter biomarker profile implies evidence of one or more neuropathological processes other than AD and has been labeled as “suspected non-Alzheimer pathophysiology”(SNAP) .Each group of ATN biomarkers results in eight different ATN “biomarker profiles”: A + TN-, A + T + N +, etc., based on definitions. The ATN biomarker system assigns a subject to each of the three "biomarker categories": 42 or low ratio 42/40) with a normal tau biomarker would be associated to the “Alzheimer pathological change” label. The term “AD” will be applied if biomarker evidence of both Aβ and pathological tau are present. “Alzheimer pathological change” and “AD” are not considered separate entities but as the earlier and later stages of the “Alzheimer continuum” . An individual with biomarker evidence of Aβ deposition alone , related to senile plaques. Liquor levels of T-tau are 300% higher in patients with AD than in controls [It is established that the pathological process in the brain of AD patients begins more than a decade before the first symptoms . Thanks controls . This macontrols . Other t42, P-tau, and T-tau has also been developed. Specifically, biomarkers’ values can be organized in a two-dimensional graph, with P-tau levels on the x-axis and the IATI index (INNOTEST Amyloid Tau Index) on the ordinate axis, which allows combining, for its turn, the values of Aβ1-42 and P-tau with the formula of Hulsteart [1-42/(240 + 1.18 tau)). The multicenter study conducted by Hulsteart et al. established cutoff values of 1 for IATI  and 61 ρg/mL for p-tau. Several authors then used these parameters in their studies, finding sensitivity values up to 94% in the diagnosis of AD; the lowest levels of specificity were found, however, in the diagnosis of VaD (48%) [The tau protein exists in several isoforms and can be phosphorylated on different residues. The most common ELISA test for T-tau identifies all the isoforms, regardless of their phosphorylation status. The most widespread ELISA tests for P-tau measure phosphorylated tau at residues 181 or 231 and the diagnostic performance between the different methods is similar. A multiparameter method for the simultaneous measurement of Aβulsteart  (IATI = aD (48%) . Within aD (48%) , in whicDespite better knowledge on the anatomopathological substrate of Alzheimer disease, the relationship between pathology and cognitive ability has always been recognized as complex and nonlinear. The concept of cognitive reserve (CR) was introduced to explain the gap between the extent of brain tissue damage and clinical symptoms observed on an individual level . AccordiCerebral aging is characterized by important inter-individual differences . These dThe concept of brain reserve was initially introduced in the scientific literature to explain how brain injuries typical of degenerative diseases can be diagnosed before the symptoms appear. The first study in which the term “reserve” was used dates back to Katzman . The aut, and individual differences in the processing of information in the absence of brain injuries [Mortimer, Borenstein, Gosche, and Snowdon highlighted how, when the clinical signs of Alzheimer dementia become visible, brain damage can be relatively extensive in individuals with greater brain reserves than individuals with lower brain reserves . In addiinjuries ,48.In its initial formulation, Stern distinguished two types of reserve: The CR and the compensation . While cNeural reserve refers to individual differences, probably in the form of efficiency, capacity, or differential flexibility, in the use of networks of functional connections and cognitive processes in healthy subjects. An individual whose connection networks are more efficient or more flexible has a greater ability to use these networks and may be able to react if brain damage occurs.Neural compensation refers, however, to individual differences in the use of functional connection networks and alternative cognitive processes as they are not used by healthy subjects. Neuronal compensation, understood as the ability to compensate connection networks and damaged processes, would, therefore, help to maintain or improve behavioral performance. On an empirical level, CR is currently operationalized through the use of brain visualization studies in which the similarities and differences in regional brain activation patterns and, above all, in connectivity patterns between brain regions associated with the realization of a task are examined. The peculiarity of the studies with brain visualization techniques conducted on the reserve, compared to those on cognition in aging, lies in the interest on the individual differences in the connectivity patterns between the different regions and how these differences are associated with indicators of CR. In other words, the hypothesis would be that the CR is related to a generic functional connection network that is not specific to the task performed and that it can be solicited in various tasks. For example, in 2005, Stern and collaborators examined, in a PET study, the relationships between cognitive reserve and brain activation level during a recognition task in a low memory load and a high condition memory load ,57. In tAlthough cerebral reserve and CR have been examined as two independent models, various evidences indicate that the two models are interdependent and connected to each other. Both types of reserve share the implicit postulate according to which the resources accumulated during life allow the individual to maintain adequate behavior from a functional point of view. These resources are the result of the brain’s ability to change, develop, and adapt, structurally and functionally, thanks to a dynamic and continuous interaction between biological and environmental influences.Among the factors that favor reserve accumulation as a factor of resilience to biological processes related to aging, postponing the clinical manifestations of pathologies, such as dementia, there is high schooling  or a higIndeed, how to quantify the concept of CR in patients with dementia is a problem in clinical practice . It is sThere is no validated test or questionnaire for AD patients to quantify CR in all these aspects, above all for difficulty of administration, especially in the most advanced stages of the disease. Indeed, the caregiver does not always know how to provide detailed information referring to the past of the patient.Several studies hypothesize pathophysiological mechanism underlying the concept of CR, focusing attention on three concepts: Neuroplasticity, neurogenesis, and locus coeruleus/noradrenergic system .The concept of neuroplasticity refers to modifications in the neuronal and synaptic pathways in the central nervous system. In particular, the hippocampus and entorhinal cortex seem to have a period of greatest increase in AD patients with greater cognitive reserve .The neurogenesis is a concept born in 1962 and defined as the ability to produce new neurons, especially in hippocampal dentate gyrus in adults. The damage of the neurogenesis can be highlighted in the early stages of Alzheimer disease and, therefore, could be studied as new disease markers ,65.Finally, several studies have attempted to study the relationship between AD and the locus coeruleus/noradrenergic system. A positive association between neuronal loss in locus coeruleus and the age at onset of the disease seems to be. The noradrenergic system also appears to have a neuroprotective effect, thanks to anti-inflammatory mechanism ,67.71. Resistance would represent the ability to oppose AD pathology, while resilience would represent the ability to compensate for pathological damage [However, in several recent works the concept of CR has been better investigated ,69, withl damage . In partl damage . In addition to the concepts of resistance and resilience, the concept of compensation was born. This term indicates neural recruitment that enhances cognitive performance. It is necessary to distinguish the different mechanisms of compensation: Upregulation, selection, and recruitment of additional processes . Compens1-42 and brain metabolism). In our previous study , we examTwenty-seven patients with probable AD, according to the National Institute of Neurological and Communicative Disorders and Stroke and by AD and Related Disorders Association diagnostic criteria, were consecutively recruited from the Clinic of Nervous System Diseases of OORR Foggia  between September 2012 and June 2013 see .We divided them according to years of formal education into two groups: High Education AD (HE-AD) patients (if median ≥ 5) versus Less Education AD (LE-AD) patients (if median < 5). HE-AD and LE-AD patients were similar for demographic and clinical characteristics and years of disease onset. In all patients, alternative neurological and psychiatric diagnoses were excluded, based on blood tests  and conventional MRI  images, diffusion-weighted images). After recruitment, patients underwent a detailed neuropsychological evaluation, lumbar puncture, and brain 18FDG-PET.1-42, 181p-tau, and Tau concentrations . PET images were reconstructed in repetitive Recon or Osem mode, processed with a statistical software 3DSSP, and evaluated by two independent nuclear specialists.CSF was aliquoted in polypropylene tubes and temporarily stored at −22 °C to quantify, within one month after collection, Aβt test design in SPM8, in order to evaluate the interaction between education levels and brain metabolism. Statistical tests were all performed considering the whole brain, and results were considered as statistically significant for p values < 0.05. Differences in regional glucose uptake were investigated in the two groups using a two-sample 1-42 and PET glucose metabolism, allowed us to consider both the active and the passive component of the CR concept. The main finding of the current study was the interaction between patients’ CR and β-amyloid deposition on metabolism in the medial temporal lobes, which have been previously shown as particularly sensitive to Aβ1-42 level [The interaction between CR and CSF biomarkers on FDG-PET metabolism showed significant results when considering β-amyloid levels only. Selective modulation of CR on brain metabolism was found in the inferior and medial temporal gyrus bilaterally . Such in42 level ,74. In HOur findings suggest that, at least in early/moderate stages of AD, CR compensates neurodegeneration and allows the maintenance of patients’ cognitive performance, as previously reported by other authors ,76,77,78


These results suggest that the relationship between psychological cognitive processes, fibromyalgia symptomatology, and functional limitations is complex and support the need for comprehensive models such as the present. The findings are discussed in the context of personalized psychological treatments .Differences in fibromyalgia impact on functioning exist and appear to be influenced by numerous factors, including symptomatology severity, as well as the cognitive profile of the individual. The contribution of these elements, however, tends to be explored in a fragmented manner. To address this issue, we tested a comprehensive structural equation model in which associations of cognitive fusion and pain catastrophizing with function limitations are investigated through fibromyalgia symptomatology  in 231 women with fibromyalgia. In the model, cognitive fusion and two catastrophizing components (magnification and helplessness) were associated with poorer functioning indirectly through fibromyalgia symptomatology. Only the rumination component of catastrophizing had a direct association with functional limitations. All fibromyalgia symptoms were linked to increased functional limitations. A parsimonious model with significant associations only obtained an excellent fit (S-B  Functioning is significantly impaired in people with fibromyalgia (FM). It is widely accepted that a moderate-to-strong association exists between functional limitation and pain severity ,2,3. HowWhile acknowledging the important role of FM symptomatology  in daily functioning, in the past years, researchers have been encouraged to investigate the mechanisms that explain individual differences in this symptomatology and, ultimately, in overall functioning , as these would be the actual targets during interventions . In thisAnother well-established model of pain that has contributed to the understanding of functioning in people with chronic pain is the psychological flexibility model. Different to the fear-avoidance model, the psychological flexibility model of pain shifts the emphasis from thought-content restructuring to changing the functional relationship with thoughts without challenging their content . In thisIn sum, the reviewed literature suggests that FM symptomatology  is closely interrelated and associated with functionality. Additionally, individual differences in symptomatology and functionality are influenced by other biopsychosocial components, such as cognitive factors. Several models of pain have been proposed to explain such complex associations between variables. However, to the best of our knowledge a comprehensive model that includes both the fear-avoidance and the psychological flexibility model and the combination of symptoms and functioning in a structural equation model is missing. This is important to investigate the complex associations between involved factors hypothesized in the literature.In the light of the previous literature ,8,13,17,The sample comprised 231 women with FM . Their sociodemographic characteristics are shown in The study followed the ethical principles for research with human participants (Helsinki Declaration) and was approved by the University Ethics Committee (Ref. PI17/00858).The Spanish version of the Pain Catastrophizing Scale was used to evaluate the three components of pain catastrophizing, understood as an exaggerated negative orientation towards actual or anticipated pain experiences, namely rumination, magnification, and helplessness ,21. RumiThe Spanish version of the Cognitive Fusion Questionnaire was used to assess cognitive fusion, which is conceived as the degree to which a person is psychologically tangled with and dominated by the form or content of its thoughts ,23. HighTo assess pain severity, we used the mean score of the four pain severity items from the Brief Pain Inventory : maximumThe Depression subscale of the Spanish version of the Hospital Anxiety and Depression Scale (HADS) was used to evaluate the severity and presence of depressive symptoms over the preceding week . The HADThe Physical Fatigue dimension of the Spanish version of the Multidimensional Fatigue Inventory (MFI) was used . This quWe used the “overall impact” dimension of the Spanish adaptation of the Revised Fibromyalgia Impact Questionnaire (FIQ-R) to evaluate the impact of FM on functioning ,32. In tThe Statistical Package for Social Sciences IBM SPSS for Windows, version 22.0   was usedn = 234), so data missingness did not compromise the reliability of scores [χ2 = 274.01, df = 257, p = 0.22), missing data appeared to be missing completely at random (MCAR). Because all missing data provided from 3 participants only, we eliminated them from the analyses (listwise deletion), as recommended in the literature [Preliminarily, both an analysis of missing values and an evaluation of data normality were performed. The variables of interest contained some missing values (range 0.4% to 1.7%) that did not exceed 5% of the initial sample  and composite reliability (CR), respectively. AVE over 0.50 and CR scores over 0.70 are considered good , while Aχ2 statistic (S-B χ2), its degrees of freedom (df), and p values; (2) the Comparative Fix Index (CFI), as an incremental fit index; (3) the Root Mean Square Error of Approximation (RMSEA) with its 90% confidence interval (CI); and (4) the Consistent Akaike Information Criterion (CAIC), as a parsimony index to compare non-nested models. Considering the sample size and the number of observed variables, adequate model fit was determined using the following cutoffs: CFI > 0.92, RMSEA < 0.08, and CAIC of less magnitude indicating greater parsimony [χ2, although non-significant p values indicate good fit, with complex models such as the current one, a model can be considered adequate if the rest of the fit indices reach the cut-off values [A model development strategy was followed in this study, using the robust maximum likelihood estimation method. The goodness of fit of the model was assessed by: (1) the Satorra–Bentler scaled arsimony ,38. Regaf values . Finallyf values  was emplThis was a cross-sectional survey performed in people with FM belonging to patients’ associations. Of them, 268 agreed to participate in the study and met our inclusion criteria. Finally, a total of 231 patients constituted the final sample .χ2 = 764.331, df = 532, p < 0.001; CFI = 0.942; RMSEA = 0.044 (90% CI from 0.036 to 0.050)).Regarding the measurement model, all items were included as observed variables. However, two of them  yielded reduced factor loadings and were eliminated. The measurement model consisted of 35 observed variables grouped into eight latent variables or latent factors. In all cases, we obtained adequate scores both in the factor loadings of the observed variables and in the AVE and the CR of the factors see . Finallyχ2 = 772.023, df = 533, p < 0.001; CFI = 0.940; RMSEA = 0.044 (90% CI from 0.037 to 0.051); CAIC = −2661.786) and accounted for 50% of the impact of FM. However, this first model could not confirm many of the initially hypothesized relationships between variables  obtained an adequate fit ; CAIC = −2724.04). Different to the first model, all the relationships in this second model were significant (see The hypothesized model was thus re-specified removing the non-significant pathways to test the adequacy of this modified and arguably more parsimonious model (M2). cant see , and theχ2 = 2289.813, df = 560, p < 0.001; CFI = 0.571; RMSEA = 0.116 (90% CI from 0.111 to 0.121)) revealed that a single factor could not account for the variance in the present data, implying that common method variance bias was not a critical problem in this study.To conclude, the results provided by the Harman’s single-factor test  and psychological mechanisms . Research, however, tends to explore the relationship between the aforementioned variables in a fragmented way . The present study contributes to the existing literature by proposing a more comprehensive model of functional limitations in FM patients that includes a set of important symptoms and psychological mechanisms from different psychological perspectives. Overall, our model was satisfactory in terms of explained variance (50%). Another important finding was that a large number of significant bivariate associations became non-significant when explored in a complex multivariate model. This supports the utility of such complex models that account for shared variance.Regarding the relationship between FM symptoms and functioning, our structural equations model evidenced an association of symptoms  with functional limitation, supporting the extensive research in this regard ,43. New Additionally, our findings evidenced that, while important psychological factors like catastrophizing and cognitive fusion might indeed impact on functioning, symptoms might as well uniquely contribute to functioning even after controlling for these cognitive factors. Indeed and as noted in past research, pain and other symptoms appear to have a relatively inescapable limiting nature when there are very intense, even in the presence of adaptive psychological thinking . While aThe present study has some limitations. First, the data is based on a cross-sectional design, so it is not possible to establish cause-and-effect inferences. Second, while FM patients were recruited from different associations in Spain, the sample is not representative of the whole population of FM patients in this country. Moreover, we did not include males because of the very small prevalence of this disease in this population, so the results might not be generalizable to males. Similarly, the model was tested with patients reporting very different pain durations. Therefore, the extent to which the relationship between factors differs as a function of pain duration or any other covariate  is unclear. Additionally, while we included important psychological mechanisms in pain research, the list is not complete. We expect that the present study will inspire future similar investigations including these and other important psychological processes, such as neuroticism, self-efficacy, coping, and acceptance, to name some examples. Note that future investigations should have a more confirmatory nature if attempting to replicate the present study findings, so paths should be constrained to the ones indicated in the present investigation, and alpha levels should be corrected for multiple testing. Another aspect that could be considered as a limitation refers to the utilization of the outcome variable “overall impact” as opposed to the total FIQ-R score. Note that the FIQ-R is composed by three dimensions, namely, overall functioning, a physical functioning scale that mainly focuses on household chorus, and a measure of symptom severity that includes pain severity and depression. The preference for the “overall impact” dimension was motivated by the study focus on overall functioning as opposed to functioning in specific situations . Additionally, as indicated in past similar research , the incWhile acknowledging the aforementioned shortcomings, the present study results might as well have a number of clinical implications. In particular, our findings support the idea that psychological cognitive processes  are associated with poor outcomes in FM patients, which justifies their inclusion in interdisciplinary treatment programs for FM . Similar


There is limited evidence on the use of antipsychotics in patients with early-onset schizophrenia, which lags significantly behind the studies on adult patients’ medication and has a large disparity from actual clinical needs. Hence, this study aims to analyse the status of the drug use and its changes for patients with early-onset schizophrenia in our ward and to provide references on clinical medications for children and adolescents with schizophrenia.χ2 tests were carried out.The distribution of antipsychotics on the day of discharge and their changes over time were retrospectively analysed in our inpatient department from March 2012 to July 2019. Descriptive statistical methods and P < 0.01), whereas aripiprazole was used less frequently (P < 0.01). Olanzapine and paliperidone were used more frequently in patients with adolescent-onset schizophrenia (AOS) (P < 0.05), and risperidone was used more frequently in patients with child-onset schizophrenia (COS) (P < 0.01). Multiple antipsychotics during hospitalization were prescribed in 23.1% of patients. The combination of aripiprazole and olanzapine was the most common in the AOS group, and the combination of risperidone and clozapine was the most common in the COS group. Before and after approval by the competent Chinese authorities, the use of paliperidone and aripiprazole tended to be stable.A total of 746 inpatients with early-onset schizophrenia were included. Among them, 99.3% of patients were prescribed atypical antipsychotic drugs, with 5.5% of patients prescribed typical antipsychotic drugs. The top five most commonly used antipsychotics were aripiprazole, olanzapine, risperidone, paliperidone and clozapine. Olanzapine and risperidone were used more frequently in men (Atypical antipsychotics have been increasingly valued and used clinically. The consideration of medications for patients with early-onset schizophrenia needs to include factors such as age, sex, and severity of illness, metabolism and cognitive function at baseline. Although early-onset schizophrenia has similar schizophrenic symptoms as adult-onset schizophrenia in terms of cognition, emotion, and perception, it also has own characteristics. Although the incidence of early-onset schizophrenia is low , hundredAntipsychotic medication remains the first-line treatment for schizophrenia. However, children and adolescents are in a special stage of growth and development, and many factors, such as efficacy, safety and acceptability, need to be considered during drug treatment. Atypical antipsychotics have proven to be safer and more effective, so they gradually have become the first-line drugs in the treatment of schizophrenia in children and adolescents , 5. For At present, little solid evidence exists regarding the use of antipsychotics in patients with early-onset schizophrenia, which lags significantly behind studies on adult patients’ medication and reflects a large disparity from actual clinical needs. Thus, exploring the current status of drug treatment for early-onset schizophrenia may be helpful in choosing reasonable medications in clinical practice. Hence, this study aims to provide references on clinical medication for children and adolescents by conducting a retrospective analysis of the drug regimens of 746 inpatients with early-onset schizophrenia to analyse the status of drug use and its changes.Data were collected from hospitalization medical records in the Child Mental Health Research Center of the Affiliated Brain Hospital of Nanjing Medical University from March 2012 to July 2019. Inclusion criteria were as follows: 1) meeting the diagnostic criteria for schizophrenia per the International Classification of Diseases, 10th Edition (ICD-10), 2) age ≤ 18, and 3) hospital stay longer than 7 days. During hospitalization, three-level rounds were strictly performed to make a definitive diagnosis and establish treatment plans.The patients’ medical history data were collected via the electronic medical record system, and the patients’ age, sex, diagnosis, days of hospitalization, family history of mental illness, drug prescription on the day of discharge, age of onset, duration of illness, PANSS total, positive and negative scores at admission, and other information were collected. All patients were clinically assessed within the first 24 h after their admission to the unit and on the day of discharge, by the staff, who had received training in the use of the PANSS. The efficacy outcome was assessed by the Clinical Global Impression-Global Improvement (CGI-I) scale  on the dχ2 tests. P < 0.05 (two-tailed) was used to define differences that were statistically significant.The statistical analyses were carried out using SPSS Statistics (v22.0 software). The measurement data were expressed by means ± standard deviations or medians, and the differences among groups were analysed by the A total of 746 inpatients were included in the analysis. The basic demographic information and clinical characteristics of the patients are shown in Table On the day of discharge, 744 (99.7%) of the 746 patients were prescribed psychotropic drugs. Among all patients, 315 (42.2%) patients used anti-tremor paralysis drugs such as trihexyphenidyl, 66 (8.8%) used liver-protecting drugs such as polyene phosphatidylcholine capsules and silibinin, and 79 (10.6%) used heart-protecting drugs.Seven hundred and forty-three (99.6%) patients were prescribed antipsychotics, involving 12 different types. Among them, 741 patients (99.3%) were prescribed atypical antipsychotics, and 41 patients (5.5%) were prescribed typical antipsychotics. The top five most frequently used antipsychotics were aripiprazole, olanzapine, risperidone, paliperidone and clozapine. An analysis of the frequency of use and the dosage of common antipsychotic drugs is shown in Table A total of 172 patients 23.1%) received a combination of antipsychotics, all of which were a combination of two types of antipsychotics. The common combinations of antipsychotics are shown in Table .1% receiOlanzapine and risperidone were used more frequently in men than in women, whereas aripiprazole was used less frequently in men. Olanzapine and paliperidone were used more frequently in AOS patients, and risperidone was used more frequently in COS patients Table .Table 4In the past 7 years, the frequency of use of clozapine has been on the rise. The frequency of use of olanzapine has been less than in previous years. The use of aripiprazole, risperidone, and paliperidone has fluctuated Fig. .. PalipeIn this study, almost all inpatients were prescribed atypical antipsychotics, and the top five most commonly used antipsychotics were aripiprazole, olanzapine, risperidone, paliperidone and clozapine. A combination of antipsychotics was prescribed in 23.1% of patients. The combination of aripiprazole and olanzapine was that most commonly seen in the AOS group, and the combination of risperidone and clozapine was that most commonly used in the COS group. Olanzapine and risperidone were used more frequently in men, whereas aripiprazole was used less frequently. Olanzapine and paliperidone were used more frequently in AOS patients, and risperidone was used more frequently in COS patients.In this study, female patients accounted for 59.9% of patients, which seems to be unusual. The reason may be that the older male patients with obvious impulsive and aggressive behaviours may have been admitted to the adult ward in our hospital. The mean age of onset was 12.94 ± 2.28 years, and patients with COS accounted for 33.9% of the sample. The younger the age of onset is, the more difficult the treatment is . ChildreThis study found that almost all patients were prescribed second-generation antipsychotics (SGAs), with only 5.5% of patients prescribed with first-generation antipsychotics (FGAs). The use of antipsychotics (APs), especially SGAs, is on the rise in the paediatric population worldwide , 15. ThiThe second challenge is a lack of evidence that antipsychotics improve cognitive function. Cognitive dysfunction is the core symptom of schizophrenia . StudiesThe third challenge is that most available antipsychotics have limited effects on negative symptoms and are studied almost exclusively in adults. Negative symptoms are associated with long-term poor prognosis . Some stIn this study, the antipsychotics selected for AOS and COS patients were different. For example, olanzapine and paliperidone were used more frequently in AOS patients than COS patients. The possible reasons could be the short onset time and stronger sedative effect of olanzapine, which makes it more conducive to controlling impulsive behaviours and positive symptoms of schizophrenia. In addition, olanzapine can relieve symptoms quickly in the acute phase of psychosis . PaliperIn this study, 23.1% of patients were prescribed multiple antipsychotics during hospitalization, of which aripiprazole and olanzapine were the most commonly used combination in the AOS group and risperidone and clozapine were the most commonly used in the COS group. In clinical practice, it is common to use multiple antipsychotic drugs during the treatment of EOS, although this is not recommended by guidelines. In this study, refractory cases accounted for approximately 30%. It has been found in clinical practice that treatment for refractory schizophrenia often requires combination treatment. Clozapine is often used jointly with other drugs, in which the dose of clozapine could be appropriately lowered to reduce the rate of adverse clozapine reactions and increase the patient’s compliance with treatment . TiihoneIn psychiatric prescriptions for children and adolescents, off-label use is a common and important problem due to the small variety of drugs available. Most antipsychotic drugs are developed by foreign manufacturers and have been approved by the FDA before they are marketed in China. Therefore, clinicians in China are likely to refer to foreign guidelines and medication instructions when using these drugs in clinical diagnosis and treatment before they are approved by CFDA . In thisThere were several limitations to this study. First, the results of the present study are limited by its retrospective design rather than longitudinal study and this may be the case in most of previous studies concerned with retrospective data. Furthermore, the results of this study may be limited in Chinese population.In summary, the present study retrospectively analysed the clinical drug use of patients with early-onset schizophrenia in our ward over the past 7 years, indicating that atypical antipsychotics have been increasingly valued and used clinically. Clinicians should select the appropriate medication regimens based on the age, sex, metabolism and cognitive function at baseline of patients with early-onset schizophrenia. Although the guidelines emphasize a single medication, the combination of several antipsychotics is clinically meaningful in the treatment of refractory patients. Only with reasonable and scientific consideration of the medication regimens can children and adolescents with schizophrenia recover fully and quickly.


Background. Diabetes mellitus (DM) is a non-infectious pandemic of the modern world; it is estimated that in 2045 it will affect 10% of the world’s population. As the prevalence of diabetes increases, the problem of its complications, including diabetic retinopathy (DR), grows. DR is a highly specific neurovascular complication of diabetes that occurs in more than one third of DM patients and accounts for 80% of complete vision loss cases in the diabetic population. We are currently witnessing many groundbreaking studies on new pharmacological and surgical methods of treating diabetes. Aim. The aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR. Material and methods. An analysis of the data on diabetes treatment methods currently available in the world literature and their impact on the occurrence and progression of DR. Results. A rapid decrease in glycaemia leads to an increased occurrence and progression of DR. Its greatest risk accompanies insulin therapy and sulfonylurea therapy. The lowest risk of DR occurs with the use of SGLT2 inhibitors; the use of DPP-4 inhibitors and GLP-1 analogues is also safe. Patients undergoing pancreatic islet transplants or bariatric surgeries require intensive monitoring of the state of the eye, both in the perioperative and postoperative period. Conclusions. It is of utmost importance to individualize therapy in diabetic patients, in order to gradually achieve treatment goals with the use of safe methods and minimize the risk of development and progression of DR. According to the current World Health Organization (WHO) definition, diabetes mellitus (DM) is a group of metabolic disorders characterized by the presence of hyperglycaemia caused by impaired release or function of insulin. Chronic hyperglycaemia in DM leads to damage, impairment of functioning, and insufficiency of various body organs, especially eyes, kidneys, nerves, the heart, and blood vessels . At presThe aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR.The study presents an analysis of data currently available in the literature that concern treatment methods of DM and their effect on the occurrence and progression of DR. The methods have been divided into pharmacological (including new antihyperglycaemic agents), surgical, and modification of lifestyle. Moreover, the study contains a brief presentation of new theories concerning the development of DR.The phenomenon of early worsening of diabetic retinopathy (EWDR) is a specific paradox that can occur in successful treatment of diabetes, which is characterized by deterioration of the eye condition in response to a rapid improvement in metabolic control. Both the appearance of soft exudates, haemorrhages, intraretinal microvascular abnormalities (IRMA), or microaneurysms at the fundus, as well as progression of the existing DR are characterized for EWDR ,8,9. TheBelow, we present an original acronym that corresponds to modifiable risk factors for the development of EWDR, which should be taken into account in everyday clinical practice .Prevention of EWDR comprises patient education and step-by-step implementation of metabolic goals in diabetes treatment, which are related to glycemia, lipids, or blood pressure. When diabetes treatment is intensified, more frequent visual assessment is recommended—every 3–6 months, depending on the baseline fundus condition. Feldman-Billard et al. proposed a practical management algorithm in the period of intensified diabetes treatment , Figure .Before analyzing particular pharmacological and surgical methods of treating DM, it can be asked in which pathophysiological mechanisms DR occurs and develops. There are a number of theories concerning this issue; however, the EWDR pathomechanism has not been fully comprehended as of yet.The osmotic force theory assumes that glucose is an osmotically active molecule. A change in the glucose concentration alters the osmotic pressure and water retention. Hyperglycaemia lowers the intra-vascular osmotic pressure, and the change in the osmotic gradient inside the cell compared to that inside the vessel results in fluid displacement, excessive stretching of the vessels, and the formation of microaneurysms. It is a disadvantage of this theory that it does not rationally account for a higher frequency of DR in patients treated with insulin compared to those on oral antidiabetic agents (OADAs) and the fact that it does not explain increased angiogenesis and neovascularization ,26,27,28Another theory concerns the effect of insulin on retinal haemorrhages. An in vivo study scrutinized the effect of insulin on the development of oxygen-induced retinopathy in seven-day-old rats in a 55% oxygen environment for day days. Normal saline or human insulin was administered subcutaneously with or without riluzole  at normal oxygen levels. The insulin group was found to exhibit higher levels of vascular endothelial growth factor (VEGF), vascular carcinogenesis, greater activity of matrix metalloproteinases, and a greater area of retinal haemorrhages. Riluzole significantly reduced all the insulin-induced changes .In contrast, the synergistic theory is based on the fact that insulin is an anabolic hormone. Under conditions of rapid glycaemic reduction, high doses of exogenous insulin may affect retinal hypoxia synergistically with VEGF, causing vascular proliferation and progression of retinopathy . Insulinp < 0.001) [The role of growth hormone (GH), insulin-like growth factor (IGF-1), and insulin-like growth factor-binding protein (IGFBP) is also discussed in DR pathogenesis. Both insulin and IGF-1 have an impact on retinal neovascularization by modulating the expression of various vascular mediators ,35. Stud< 0.001) . However< 0.001) . The GH/< 0.001) .Other experimental and clinical observations reported metabolic memory in DM patients, which is based on cells, mainly the endothelium, early exposure to a hyperglycaemic environment, and which may be the cause of vascular complications in DM, when glycaemic control has not been achieved very early ,41,42. TEpigenetic drugs are small molecules with epigenetic and anti-diabetic activity. Intense research is undertaken to investigate the enzymes responsible for epigenetic modifications. The enzymes modify chromatin: histone acetyltransferase inhibitors (HATi), histone deacetylase inhibitors (HDACi), HDAC activators, and miRNA inhibitors. Interference with RNA-based mechanisms is also used . Among eNovel therapies based on epigenetic modulators, emerging from innovative technologies, might help reduce the global burden of DM and it complications. Mechanisms involved in reversible epigenetic changes increased the possibility of developing new therapeutic strategies and might represent an additional opportunity in combination with standard anti-diabetic treatments. Summarizing the above chapter, we present potential mechanisms of EWDR development .p < 0.001). The risk factors for DR worsening in this trial were the presence of previous eye fundus lesions ), a high HbA1c level at the screening visit, and high HbA1c reduction within 0–6 months. However, in a 10-year follow-up, the risk of DR progression was significantly lower in the FIT group [In 2021, the 100th anniversary of the discovery of insulin will be celebrated. On 23 January 1922, insulin saved a patient’s life for the first time, the lucky one being Leonard T. Since then, insulin has been modified many times through genetic engineering to improve the length and quality of life . HoweverIT group . The preIT group . In a prIT group . InsulinIT group ,65,66,67IT group . InsulinIn accordance with the current guidelines of diabetes societies, metformin is still the drug of first choice in the treatment of DM2 ,70. NumeSulfonylurea (SU) derivatives were discovered in 1942 by Janbon and his team, who observed their hypoglycaemic effect in animal models , yet thep = 0.0091) and was not associated with an increased risk of DMO [Thiazolidinediones (TZDs) are agonists of peroxisome proliferator-activated receptor (PPARγ) found in adipose tissue as well as macrophage cells, endothelium, beta-cells of the pancreas, liver, heart, lungs, and skeletal muscles. TZDs were introduced into the treatment of diabetes in 1997, and thanks to their strong effect on reducing insulin resistance, they were initially believed to be drugs that could cure DM2 patients. However, currently they are used only in a few groups of patients due to their serious side effects ,87. Trogk of DMO . FindingIn 1964, in London and Denver, the glucose-dependent incretin effect was demonstrated, which gave rise to new research and contributed to the discovery of new drugs to administer in the treatment of DM2 patients . Sitaglip = 0.33) [p = 0.02) [p = 0.49), and their use was associated with a lower risk of DR than therapy with SU derivatives [A glucagon-like peptide 1 (GLP-1) molecule was discovered in 1983, but the first drug in this group—exenatide—appeared on the American market only in April 2005 ,106. A b = 0.33) . Another = 0.02) . The ris = 0.02) . At the  = 0.02) . In othe = 0.02) . In the  = 0.02) . In turn = 0.02) . The abo = 0.02) ,114. In ivatives . Similarivatives . In 2019ivatives .p = 0.1732) [Flozin was isolated from the bark of apple tree roots as early as 1835, but it was not until 2012 that dapagliflozin had become the first representative of this group of drugs to be approved for the treatment of DM2 in the EU . Recomme 0.1732) . On the  0.1732) . Followi 0.1732) ,128. SumAmong methods of treating diabetes, apart from the pharmacological approach, pancreas transplantation and pancreatic islet transplantation (PIT) are becoming more and more common. Since the first PIT in 1974 performed by Najarian and Sutherland, the number of such transplants has been steadily increasing. Data on such procedures are collected in the CITR (Collaborative Islet Transplant Registry), which includes data from North America and partially from centers in Europe and Australia. The 10th CITR Report of 2017 shows the number of transplant recipients from 1999–2015, which is 1086 people. Ocular side effects such as eye disorder, ocular surface disease, retinal detachment, retinal haemorrhage, uveitis, and vitreous haemorrhage were reported in 21 patients out of 877 after an ITA (Inslet Transplant Alone) surgery, in two out of 24 after SIK (Simultaneous Islet Kidney), and in six out of 183 after IAK (Islet After Kidney). The registry does not contain data on the condition of transplant recipients’ retinas before transplantation . In 20052), with metabolically decompensated diabetes (HbA1c 8.4 ± 3.2%) and mean values of systolic BP 140.2 ± 7.91mmHg, and diastolic BP 85.7 ± 5.57 mmHg. Following the postoperative analysis of patients, the BMI (34.4 ± 5.08), HbA1c (7.0 ± 3.1%), and blood pressure  all improved, but there was no statistically significant correlation between these parameters and the frequency or progression of DR [Currently, we witness great progress in bariatric treatment, i.e., obesity surgery, also referred to as metabolic surgery. The most common procedures are: gastric banding (GB), sleeve gastrectomy (SG), and a surgery to bypass (reduce) the stomach according to Mason—Roux-en-Y Gastric Bypass (RYGB) ,135. In on of DR . PatientA fundamental element of treating patients with diabetes is them changing their current lifestyle, which is understood as the use of nutritional treatment, regular physical activity, and stimulant use cessation. A post hoc analysis of the DCCT showed that a high-calorie diet, especially rich in fatty acids, as well as smoking are statistically significantly correlated with a higher risk of DR progression . InteresWe live in a period of the COVID-19 pandemic caused by the SARS-CoV-2 virus, but in these difficult times it is crucial not to forget about diabetes, which has been recognized by the WHO as the first non-infectious pandemic of the modern world. Modern individualized treatment of a patient with diabetes requires not only achieving glycaemic goals but, above all, reducing mortality and improving the quality of patients’ lives. These goals can be achieved by counteracting the occurrence and progression of macro- and microvascular complications of diabetes, including DR. The safety of the administered therapy should be doctors’ priority, and information about its benefits and risks should be included in each of the modern diabetes treatment algorithms proposed by global diabetes societies.


Although RNA-binding proteins play an essential role in a variety of different tumours, there are still limited efforts made to systematically analyse the role of RNA-binding proteins (RBPs) in the survival of colorectal cancer (CRC) patients.Analysis of CRC transcriptome data collected from the TCGA database was conducted, and RBPs were extracted from CRC. R software was applied to analyse the differentially expressed genes (DEGs) of RBPs. To identify related pathways and perform functional annotation of RBP DEGs, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the database for annotation, visualization and integrated discovery. Protein-protein interactions (PPIs) of these DEGs were analysed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Based on the Cox regression analysis of the prognostic value of RBPs (from the PPI network) with survival time, the RBPs related to survival were identified, and a prognostic model was constructed. To verify the model, the data stored in the TCGA database were designated as the training set, while the chip data obtained from the GEO database were treated as the test set. Then, both survival analysis and ROC curve verification were conducted. Finally, the risk curves and nomograms of the two groups were generated to predict the survival period.Among RBP DEGs, 314 genes were upregulated while 155 were downregulated, of which twelve RBPs  with prognostic value were obtained.The twelve identified genes may be promising predictors of CRC and play an essential role in the pathogenesis of CRC. However, further investigation of the underlying mechanism is needed. As a significant class of cellular proteins, RNA-binding proteins (RBPs) can interact with RNA by recognizing special RNA-binding domains and are widely involved in multiple posttranscriptional regulatory processes, such as RNA shearing, transport, sequence editing, intracellular localization and translation control . It is eColorectal cancer (CRC), which includes colon and rectal cancer, is a common digestive tract tumour. The molecular pathogenesis of CRC is a complex multistep process involving multiple acquired genetic and epigenetic abnormalities . Some RBIn this study, an analysis was conducted of RBP-related genes in CRC patients through differential gene expression and protein molecule interactions. In addition, a prognostic model was adopted to identify twelve genes associated with the survival of CRC patients. We verified the model and performed survival analysis and risk assessment. These results will help elucidate the underlying mechanism related to the survival of CRC at the molecular level, thus providing a new direction for the prognosis of CRC and clinical treatment.https://portal.gdc.cancer.gov/). The total number of samples is 521, of which there are 479 samples in the tumour group and 42 samples in the normal group. Then, the RBP gene was obtained from the GOA database website (https://www.ebi.ac.uk/GOA/). Combined with the CRC transcriptome sequencing map, CRC RBPs were obtained. The data on gene expression (GSE17536) in colorectal patients were obtained from the GEO database website (https://www.ncbi.nlm.nih.gov/geo/), involving a total of 177 cases. All the data were publicly available online. This study requires no experiments to be conducted by any author on humans or animals. The flowchart of it is shown in Fig. The FPKM transcriptome data of CRC were obtained from the TCGA database website .GO analysis represents a common method applied to conduct large-scale functional enrichment study. Gene functions can be categorized into biological processes (BP), molecular functions (MF) and cellular components (CC). KEGG is known as a commonly used database where a large amount of data on genomes, biological pathways, diseases, chemicals and drugs is stored. Through GO and KEGG analysis of DEGs, barplot and bubble were drawn respectively. All of the GO and pathway terms were ranked by their −log10 (https://string-db.org/) is designed to analyse the PPI information. DEGs were input into the STRING database to obtain PPI information. Subsequently, the Cytoscape software was applied to visualize the PPI network, the Cytoscape plug-in MCODE was used to obtain the most relevant sub-network module and then the hub genes of the four modules were enriched for GO and KEGG analysis.The Search Tool for the Retrieval of Interacting Genes (STRING) database  with survival time, the RBPs related to survival were identified and a forest map was generated. Then, the samples of the TCGA database were designated as the training set, and the samples of the GEO database were treated as the test set to construct the best prognostic model based on the training set. Twelve survival-related genes were identified by the model, based on which the correlation coefficient of each gene was obtained. Then, the risk score of each patient in the training set and test set was calculated according to gene expression. In addition, the patients were classified into high-risk and low-risk groups by the median value of the risk score. The patients in the training set and the test set were categorized into either the high-risk group or low-risk group. A survival analysis was conducted, an ROC curve was generated and then the risk curves were constructed for the training and test sets. Furthermore, with univariate and multivariate analyses, nomograms based on the genes obtained from the prognostic model were generated to predict the length of survival for the patients.Transcriptome sequencing data of 1493 RBPs of CRC was obtained from the TCGA database. The differential expression analysis was conducted to find out that there were 314 upregulated genes and 155 downregulated genes, based on which volcano and heat maps were drawn as shown in Fig. The up- and downregulated genes of DEGS were analysed for GO function and KEGG pathway enrichment, while both barplot and bubble were plotted. The enriched GO terms were divided into CC, BP and MF ontologies. The top 10 most relevant items were selected, as shown in Fig. The protein interactions among the DEGs were predicted using STRING tools. A total of 442 nodes and 6233 edges in the PPI network were obtained, as shown in Fig. Cox regression analysis was carried out of the prognostic value of 442 RBPs interacting with survival time, 19 RBPs related to survival were screened and a forest map was drawn as shown in Fig. p < 0.05). In the multivariate independent prognostic analysis, age and stage can be taken as independent prognostic factor for CRC in the test set (p < 0.05). For the training set, however, only stage can be taken as independent prognostic factors for CRC (p < 0.01), not age (p = 0.492).Then, independent prognostic analysis was conducted of univariate and multivariate for the training and test sets, as shown in Fig. Finally, nomograms were plotted for these 12 RBP prognostic genes in the training set to predict the survival time of the patients, as shown in Fig. As one of the most common malignant tumours, CRC is characterized by a high recurrence rate and poor prognosis, especially in developed countries. It is the third most common cancer among males and ranks second among females , 10. To Tudor domain-containing (TDRD) refers to a family of evolutionarily conserved proteins. In general, PIWI and TDRD proteins are recognized as the major influencing factors in piRNA biogenesis and the development of germ cells . In a prPOP1 is a component of ribonuclease P, which is a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5′ end s, 25. In PPARGC1A, also known as PGC1α, is a transcriptional coactivator of genes encoding proteins responsible for the regulation of mitochondrial biogenesis and function . D’ErricIt is thought that LRRFIP2 functions as an activator of the canonical Wnt signalling pathway, which is associated with DVL3, a factor upstream of CTNNB1/beta-catenin. It positively regulates Toll-like receptor (TLR) signalling in response to agonists, probably by competing with the negative FLII regulator for MYD88 binding, which plays a crucial role in the progression of colon cancer , 36. In CELF4 is responsible for encoding a protein with three domains that bind an RNA recognition motif and regulate pre-mRNA alternative splicing. Some studies showed that CELF4 was hypermethylated in endometrial cancer. Methylated CELF4 may be suitable for endometrial cancer screening of cervical smears . FurtherDrosophila melanogaster RNA-binding proteins. It has been identified as a critical regulator of haematopoietic stem cell (HSC) self-renewal and fate determination [As a member of the Musashi family, MSI2 belongs to the family of mination , 42. In mination . MSI2 ismination , 45. Recmination . The expmination . In othemination . High exmination . Furthermination , bladdermination  and oesomination . It was LIN28, an oncofoetal RNA-binding protein, modulates stem cell maintenance, somatic reprogramming, metabolism, organismal growth, tissue development and tumourigenesis . Two parNOP14 is a stress-responsive gene required for 18S rRNA maturation and 40S ribosome production . As indiThe MRPS23 gene, which is responsible for encoding a 28S subunit protein, has been found to be overexpressed in breast cancer , uterineMAK16 encodes a ribosomal protein and plays an important role in ribosome biogenesis throughout the cell cycle . In thisIn this paper, a discussion was conducted about the role of the 12 identified genes in tumours. Although some genes were found irrelevant to the pathogenesis of CRC, their biological functions and changes in their expression in CRC suggest that they may play a role in CRC to some extent, and further experiments need to be conducted for verification. This is also a limitation of our study. More research is needed to explore the pathogenesis of CRC.The above genes are related to the prognosis of CRC. More research, especially experimental studies, is needed to verify the specific function of each gene. Our findings may improve the understanding of the incidence and prognosis of CRC, thus providing a reference for further improvement of the diagnosis and treatment of CRC.In summary, 12 prognostic RBPs were obtained through TCGA database analysis, including NOP14, MRPS23, MAK16, TDRD6, POP1, TDRD5, TDRD7, PPARGC1A, LIN28B, CELF4, LRRFIP2 and MSI2, which were then verified through the sample data obtained from the GEO database. In CRC, NOP14, MRPS23, MAK16, TDRD6, POP1, TDRD5, LIN28B and MSI2 were upregulated, while TDRD7, PPARGC1A, CELF4 and LRRFIP2 were downregulated. These genes are related to the prognosis of CRC. More research is deemed necessary to verify the specific function of each gene, especially experimental studies. Our findings may improve the understanding of the incidence and prognosis of CRC, thus providing reference for the further exploration of the diagnosis and treatment of CRC.


Background: Anemia has been one of the main nutritional challenges around the world. Not enough attention has been paid to this issue in children and adolescents in China. In this study, we aimed to estimate the prevalence of anemia among 9-, 12-, and 14-year old Chinese children and investigate the associated factors of anemia. Methods: Data come from a cross-sectional survey conducted in 26 provinces and 4 municipalities in mainland China. A total of 48,537 children aged 9, 12, and 14 years old were included in data analyses. Anthropometric measurements were conducted to obtain information about height and weight. Capillary blood was collected from the fingertip, and hemoglobin concentration was tested by HemoCue201+. Information about sleep duration, daily consumption of eggs, milk, and breakfast were obtained from a self-administrated questionnaire. The mixed-effects logistic regression model was applied to estimate the association between selected variables and risk of anemia. Results: A total of 8.4% of participants were identified as being anemic; and the prevalence was higher in girls and rural children. Mixed-effects logistic regression analysis showed that children who were overweight, obese, and consumed eggs and milk every day had a lower risk of anemia. Spermarche, overweight/obesity, and having milk every day were associated with lower risk of anemia in boys, while menarche was found to be a risk factor and eating eggs every day to be a protective factor of anemia in girls. Conclusions: Anemia among 9-, 12-, and 14-year-old children is still high. Intervention programs of adding egg and milk into school daily diet might contribute to reducing anemia in Chinese school aged children, especially for those living in rural areas or girls with menarche. Anemia is regarded as the most common micronutrient deficiency disorder around the world , which aThe pathophysiology of anemia is diverse and often multifactorial, and possible causes include genetic mutations in hemoglobin genes, acute and chronic blood loss, inadequate nutrients intake, and infectious processes. Of them, iron deficiency is assumed to be the major one ,8. PreviAlthough people at any time and at all stages of life may face the problem of anemia, children and pregnant women are deemed to be at greater risk than the standard population . Over thThis study uses data from the Chinese National Surveys on Students Constitution and Health (CNSCCH) in 2014, which is, so far, the largest nationally representative sample of school aged children. The objectives of our study were: (1) to estimate the concentration of hemoglobin and prevalence of anemia in Chinese 9-, 12-, and 14-year-old children and compare the differences between sex, residence area, and age; and (2) to explore the potential associated factors with anemia.Data was obtained from the 2014 cycle of the Chinese National Survey on Students Constitution and Health (CNSSCH), which is a joint nationwide investigation conducted every five years by the Ministries of Education, Health, Science, and Technology, the State Ethnic Affairs Commission, and the State Sports General Administration of China since 1985. Subjects were Han students from 26 mainland provinces and 4 municipalities, excluding Tibet (where the Han ethnicity is a minority), and a more detailed description of the study design and conduct can be assessed elsewhere . Briefly2), and nutritional status was divided into thinness, normal BMI, overweight, and obese according to the gender- and age-specific Z-score for 7- to 18-year-old children developed by the WHO [All measurements were conducted by trained investigators according to the standard protocol at all survey sites. During the anthropometric measurement process, subjects were asked to take off their coat, shoes, and wear only light clothing. Height was measured to the nearest 0.1 cm using a stadiometer , and weight was recorded to the nearest 0.1 kg with a scale . A 5% sample measured height and weight twice every day for quality control. If any part of readings exceeded the maximum acceptable difference for a given variable , both records were measured once again independently and a second and, if necessary, third set of measurements were recorded. The final record was calculated by an average of the readings, both the stadiometer and scale were calibrated before use, and similar instruments were used in measurement at all survey sites. BMI was calculated as the weight (kg) divided by the square of the height , and data collection was supervised daily by trained field supervisors. Anemia was diagnosed as <115 g/L for 9-year-old children and <120 g/L for 12- and 14-year-old children after corrected by altitude as proposed by the WHO criteria [Self-administrated structured questionnaires were applied in children to obtain information about age, spermarche (in boys)/menarche (in girls), sleep duration, and dietary behaviors, such as eating eggs, drinking milk, and having breakfast. Subjects were asked to report the average sleep duration over the past year by selecting from 6 options: (1) < 6 h; (2) 6 ~7 h; (3) 7~8 h; (4) 8~9 h; (5) 9~10 h and ≥10 h. Enough sleep duration was defined as ≥9 h for 9- and 12-year-old and ≥ 8 h for 14-year-old students according to recommendation of the American Academy of Sleep Medicine . Childret-test was used to compare the difference of hemoglobin concentration between sex and residence subgroup participants, and Chi-square test was used to compare the prevalence of anemia among children with different ages and residence areas. Considering that the multistage sampling method was used in this study and children from the same region and same school were more likely to have similar characteristics, the mixed-effects logistic regression model was used to examine the relationship between anemia and covariates by controlling the cluster effects. All analyses were conducted with univariable and multivariable models, respectively. Continuous variables were characterized as mean ± standard deviation, and categorical variables were characterized by frequencies and percentages. One-way ANOVA was used to compare the distribution of nutritional status between boys and girls, independent sample Student’s P value of < 0.05 was considered statistically significant.At first, we use a bivariate model to assess association between anemia and selected variables, including nutritional status, sleep duration, eating eggs, drinking milk, having breakfast, and spermarche/menarche. Second, variables that were found significant in the bivariate regression models were then included in the mixed-effects multivariate logistic regression analyses to yield the final model. All analyses were performed using R software (version 3.4.0) and related packages “lme4” , and a tp < 0.001). The descriptive characteristics of the analyzed population are presented in p < 0.001). The prevalence of anemia was 8.4% in all participants (p < 0.001). In addition, the prevalence of anemia was higher in rural children (8.9%) than urban children (8.0%) (p < 0.001); however, when analyzed stratified by sex and age, the difference was still significant only in 12- and 14-year-old girls.icipants , and thePotential associated factors were analyzed in a mixed-effects model. Univariate models  showed tAnemia is one of the most common nutritional problems affecting adolescents from both developing and developed countries. In this study, we observed a prevalence of 8.4% for anemia in Chinese 9-, 12-, and 14-year-old children, and a higher prevalence was observed in girls and rural children. We also found that eating eggs every day and having milk every day were associated with lower risk of anemia.As expected, anemia in Chinese 9-, 12-, and 14-year-old children and adolescents represented a mild public health problem according to the WHO criteria . The preIn the present study, we found that girls and rural children had lower hemoglobin concentration and a higher prevalence of anemia, which was consistent with a study conducted in India . One posUnderstanding factors correlated with anemia can provide more insight to the measures that can be applied to combat anemia. In the present study, we found that overweight and obese children were less likely to have anemia, which was consistent with a study conducted by Hoang , althougAlthough egg and milk are considered to be low cost but high benefit foods, they are not widely consumed among Chinese people, and according to estimates, mean national milk intake in China was 23.4 g/day in 2015 , which wThe major limitation of this study was cross-sectional design, which weakened the capacity in revealing the temporal sequence between the factors and anemia. Furthermore, information about sleep duration and eating habits were obtained from self-administrated questionnaires rather than a validated scale, which may lead to poor precision and incomprehensive measurements, and we also did not collect information about household composition, social economic status, and detailed dietary intake, which were regarded as potential confounding factors of anemia. Moreover, participants of this study included only 9-, 12-, and 14-year-old children, who cannot represent the whole adolescent population. Further studies with reasonable and scientific design are needed to prove the results in the present study.Overall, anemia prevalence was still relatively high among Chinese 9-, 12-, and 14-year-old children, even though it has been improved over the past years. Gender and urban–rural disparities exist, e.g., girls and rural children were more likely to suffer from anemia. Children with overweight/obesity status, spermarche, eating eggs every day, and having milk every day were associated with a lower risk of anemia, and menarche in girls was a risk factor for anemia. Intervention programs of adding egg and milk into school daily diet might contribute to reducing anemia in Chinese school aged children, especially for those living in rural areas or girls with menarche.