Thirty samples of surface sediments (0–5 cm) from the northern Beibu Gulf were analyzed to determine the spatial distribution, potential risks and sources of six heavy metals . The concentrations  of Cr, Cu, Zn, As, Cd and Pb were 15.38 ± 6.06, 6.54 ± 3.23, 41.86 ± 17.03, 6.92 ± 2.75, 0.04 ± 0.02 and 17.13 ± 6.38, respectively. Higher levels of Cr, Cu, Cd and Zn were observed in the western part of the study area. According to the potential ecological risk indexes and sediment quality guidelines, the measured metals were assessed at low contamination levels, with Pb posing the largest ecological risks. The results of positive matrix factorization (PMF) indicated that Cr and Zn mainly originated from natural geological background sources, while Cu, As, Cd and Pb were influenced by anthropogenic sources such as atmospheric deposition and anthropogenic activities. These three sources contributed 60.4%, 28.1% and 11.5% of the heavy metals, respectively. In addition, further research should be conducted focusing on the general relationships between As and various controls in sediments of the northern Beibu Gulf. Heavy metals are pollutants of particular concern due to their bio-toxicity, bioaccumulation, persistence, abundance, and ubiquity in the environment, and subsequent impact on both biotic and abiotic aquatic ecosystems in different ways ,2. Heavy2, with plenty of seafood and fishery resources. It lies in the northwestern part of South China Sea and is surrounded by Hainan Island, Leizhou Peninsula, Guangxi Province and northern Vietnam [7 ton sediment load per year [The Beibu Gulf is a semi-enclosed bay covering a sea area of 128,000 km Vietnam . Many riper year ,11. Thesper year ,10,11,12per year , who onlgeoI), potential ecological risk index (RI), contamination factor (CF) and sediment quality guideline method (SQGs) have been successfully applied for evaluation of the sediment quality [Appropriate geochemical approaches, such as geoaccumulation index . The treated samples were diluted to a specified volume after adding 5% HNO3. Then, the concentrations of five heavy metals  were determined using an inductively coupled plasma mass spectrometer (ICP-MS) , while concentrations of As were examined using the method of atomic fluorescence spectrometry (AFS). Contents of total organic carbon (TOC) were analyzed using the potassium dichromate oxidation-colorimetric method. All of the concentration values in the present study were presented in mg/kg dry weight.All the sediment samples were freeze-dried, ground, and then sieved through a 0.5 mm nylon mesh to remove large debris. Approximately 0.15 g samples were microwave-digested in acid-washed Teflon digestion vessels. Samples were treated with a mixed solution of 2 mL HNO3 and Milli-Q water to eliminate possible contamination.For strict quality assurance and quality control, reagent blank, procedural blank samples, and Chinese National Reference Materials ERM-S-510204 were applied throughout the study. Duplicate samples were examined three times and the relative deviations were below 7%. The results of reference materials were consistent with the certified values, being 108%, 115%, 96%, 109%, 91% and 93% for Cr, Cu, Zn, Cd, Pb and As, respectively. All reagents were prepared with 10% HNOSpatial analyzing methods based on geographic information system have been commonly used to map and investigate environmental contamination ,19,20. ITEL) and effect range median (ERM), were selected to classify the pollution degree in this method. The corresponding TEL and ERM values are listed in iC is the concentration of metal i in sediment, iERM is the ERM value for the selected metal i and n is the number of measured metals. Generally, the SQGs can be categorized into seven classes [In natural environments, human activities may affect multiple contaminations, and sediment quality guidelines (SQGs) were used to determine the potential harmful effects on aquatic environments. Two metrics, threshold effect level  has been frequently used to assess the contamination degree of heavy metals by reducing the impact of geological contributions [iC is the metal concentration in sediment and iB is the geochemical background value of metal i. In this study, we use the background values according to Zhang and Du (2005) [geoI are divided into seven classes  . A facto classes .RI) was a useful approach for determining the unique and combined contamination risks caused by heavy metals. In this approach, not only the contamination level of each metal element can be evaluated, but also the ecological and environmental factors combined with toxicological risks are taken into consideration [RI can be calculated with the equation:riE is the potential ecological risk index of heavy metal i, sCi is the content of element i in sediment sample, nCi is the background value of element i, Tri is the toxic and biological response factor of metal i. The Tri values for Cr, Cu, Zn, Cd, Pb and As are 2, 5, 1, 30, 5 and 5, respectively [riE and RI values are then categorized into five and four grades, respectively, which are given in Firstly proposed by Hakanson (1980) , the potderation ,27. RI cectively . The calThe PMF method was firstly proposed by Paatero and Tapper (1994)  and has ijX can be viewed as an ambient data set in which i and j represent the number of samples and the number of metal species, respectively. The multivariate receptor modeling has three goals: (1) to identify a number of metal sources (p), (2) to distinguish the species profile (f) of each source, (3) to assess the amount of mass (g) contributed by each source species to each sediment sample as well as the related residual (ije). ijX can be expressed using the following relationship:ije represents the related residual of each sediment sample or source species.The matrix In the PMF model, the different number of sources was tested to find out the optimal value corresponding to the most reasonable results. The properly estimated source number indicated the theoretical Q value was approximately the number of degrees of freedom or the total number of data points. Based on the uncertainties (u), the PMF solution minimizes the objective function Q as the following relationship:Two data files including metal concentrations and uncertainty data were input to run the PMF model. According to Zhang et al. (2014) , 15% of In the present study, the data normality was evaluated using the Kolmogorov–Smirnov test, and all the data showed normal distribution. Pearson correlation analysis (PCA) and Pearson Correlation Matrix (PCM) were applied to determine the relationships among heavy metals in the surface sediments. The statistical analysis was performed with the statistical package SPSS 19.0 . Hierarchical clustering analyses (HCAs) of heavy metals and sampling stations were conducted using the Gplot package in R software .The concentrations and distribution patterns of six heavy metals  in sediments from Northern Beibu Gulf are summarized in In the present study, some metals like Cr, Cu, Cd and Zn in the western stations were relatively higher than those in the eastern stations . This spCompared with the standard values for the marine sediment quality (GB 18668-2002) of China, the examined heavy metal concentrations of the analyzed elements were all within the range of Grade I (MSQ-1) criteria, indicating good sediment quality in the northern Beibu Gulf. Our results were different from those previously reported by Dou et al. (2013) , who fouTEL and ERM SQGs. The average concentrations of all the six examined metals in sediments of the study region were lower than their corresponding TEL values, suggesting no adverse biological effects to the local benthic organisms. Generally, As concentrations in nine sediment samples (30%) exceeded the TEL reference values but were lower than the ERM reference values, which indicates occasional occurrence of adverse biological effects. However, As is reputed to be a redox-sensitive element and can respond to redox variation under some conditions due to its nature; thus, its enrichment is often overestimated [The potential ecological effects caused by heavy metals in the sediments were evaluated by stimated . TherefoThe spatial distribution of m-ERM-Q values for all sampling stations was illustrated in geoI) indexes of the six measured heavy metals were calculated based on the Earth’s crust and their values were presented in geoI values for Cr, Cu, Zn, Cd and As, and were characterized as “Uncontaminated”. The means geoI values ranked in the following order: Pb > Cu > Zn > As > Cr > Cd, ranging from −2.95 to −0.58. The geoI values for the majority of metals except Pb in three stations were lower than 0, indicating that most of the measured elements pose negligible contamination risk in the coastal northern Beibu Gulf. The highest geoI values for Pb appeared in the station S23, which is located in the northeastern part of the Weizhou oil fields. The long-term and large-scale exploration of petroleum were considered to increase the pollution risk of heavy metals such as As and Pb, and likely pose adverse impacts on the seafloor environment [The geoaccumulation  > Cr (0.78) > As (3.56) > Cu (4.40) > Pb (5.49) > Cd (6.56), suggesting that the ecological risks were considered to be low. In addition, the RI values were lower than the first threshold (150) in all samples of northern Beibu Gulf, again indicating low ecological risks from these heavy metals. Overall, the values of riE and RI showed a similar distribution pattern, and were primarily affected by anthropogenic activities and hydrodynamic conditions [In order to assess the potential ecological risks, nditions ,54.In the present study, three main sources of heavy metals were identified using the PMF model and related results are exhibited in p < 0.01)  . Concentp < 0.01)  C. ConcenThe profile of the third source was dominated by As D, and itHierarchical clustering analysis results were in consonance with the above findings of PMF analyses . The clugeoI, riE and RI values indicated that the measured elements posed low ecological risks to the seafloor environment. Moreover, our findings suggest that Cr and Zn mainly originated from natural geological background sources, while Cu, As, Cd and Pb were influenced by anthropogenic sources such as industrial discharges, leaded gasoline, atmospheric deposition and agricultural activities.In the present study, six heavy metals in the surface sediments of northern Beibu Gulf were measured to investigate their distribution, sources and contamination levels. The measured concentrations were all within the range of Grade I (MSQ-1) criteria according to the marine sediment quality (GB 18668-2002) of China. In comparison with historical data, the metal concentrations were found to be at relatively low levels. The overall spatial distribution pattern was characterized by relatively higher metal levels in the western region. The calculated values of m-ERM-Q showed that Pb and As exhibited higher negative biological effects than the remaining four metals, with the toxic probability occurrence amounting to 21%.


Subsequently, we validate our model in the validation cohort. Finally, clinical factors are incorporated into the model. The final model includes four SNPs  as well as two clinical factors that contributed to the efficacy of platinum chemotherapy in NSCLC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.726.Platinum drugs combined with other agents have been the first-line treatment for non-small cell lung cancer (NSCLC) in the past decades. To better evaluate the efficacy of platinum–based chemotherapy in NSCLC, we establish a platinum chemotherapy response prediction model. Here, a total of 217 samples from Xiangya Hospital of Central South University were selected as the discovery cohort for a genome-wide association analysis (GWAS) to select SNPs. Another 216 samples were genotyped as a validation cohort. In the discovery cohort, using linkage disequilibrium (LD) pruning, we extract a subset that does not contain correlated SNPs. The SNPs with  Platinum is one of the most promising and widely used drugs for the treatment of various cancers. Cisplatin and other platinum–derivative drugs exert anticancer activity mainly by binding to DNA and forming adducts that affect DNA transcription and replication . HoweverNon-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and is the major subtype of lung cancer . PlatinuIn one of our previous studies, a predictive model was established for platinum–based chemotherapy response, with a sensitivity of 0.90, specificity of 0.47, and area under the receiver operating characteristic (ROC) curve (AU-ROC) of 0.80 [This study intends to improve on previous studies by adopting GWAS to find more genetic factors affecting the efficacy of NSCLC platinum chemotherapy. BayesNet, NaiveBayes, Random Forest (RF), Logistic, support vector machine (SVM), Bagging, Decision Tree (DT), K-Nearest-Neighbors (KNN), Random Tree (RT), AdaBoost, and Polygenic risk score (PRS), will be used to establish the new model. After that, the previous model will be validated in another cohort, and finally, clinical factors will be incorporated to optimize the model.2) or carboplatin (AUC 5) on day 1, in combination with pemetrexed (500 mg/m2) on day 1, gemcitabine (1250 mg/m2) on days 1 and 8, paclitaxel (175 mg/m2) on day 1, or docetaxel (75 mg/m2) on day 1. No other antitumor treatments, such as surgery, targeted drugs, or radiotherapy were received before the chemotherapy.The patients in this study were recruited from Xiangya Hospital of Central South University and Hunan Cancer Hospital , from 2012 to 2019, and were diagnosed with NSCLC by histopathological examination. The patients received platinum–based chemotherapy regimens for at least 2 cycles: one course of treatment lasts for three weeks. The platinum–based drugs used were cisplatin  version 1.1 , and patn = 15), failed DNA quality control (n = 9), and failed call rate < 90% (n = 1). In the validation cohort, 216 patients were enrolled; and excluded patients without an efficacy assessment (n = 14), failed DNA quality control (n = 7), and failed call rate < 90% (n = 3).As shown in ® Genomic DNA Purification Kit  according to the instructions.Whole blood samples were collected from patients, and blood samples were preserved with EDTA disodium salt (EDTA-2NA). Genomic DNA was extracted from peripheral blood using the Wizardn = 227) from the discovery cohort were genotyped using Illumina BeadChip Array Global Screening Array-24+ V1.0 . Quality control was performed on the original genotyping data by PLINK (v1.90b6.24) to filter unqualified samples and SNPs [−5; (3) minor allele frequency (MAF) ≥ 0.01; (4) mapped on autosomal chromosomes. Sample quality control included (1) sample call rates ≥ 90%; (2) heterozygosity check; (3) sex check; (4) sample relatedness check; (5) PCA analysis. Principal component analysis (PCA) was performed using the PLINK package. PLINK calculated the PC values from the SNP information of the samples, determined the location of the samples based on the PC1 and PC2 of each sample, and presented these in a scatter plot  sample call rate ≥ 90%; (5) sample relatedness check; (6) heterozygosity checks; (7) sex check. After quality control, there were 217 samples in our discovery cohort; a total of 104 in the sensitive group and 113 in the resistant group. The Hardy–Weinberg equilibrium test was failed by 2035 SNPs, and 151,215 SNPs were filtered out due to minor allele frequencies < 1%; a total of 629,4406 SNPs were included in the analysis.DNA samples  according to the manufacturer’s instructions. The quality control criteria included (1) sample call rates ≥ 90%; (2) SNP call rate ≥ 90%; (3) MAF ≥ 0.01; (4) HWE ≥ 0.05; (5) sample relatedness check; (6) heterozygosity check; (7) sex check. The overall methodological flow is shown in Multivariate logistic regression analysis was used, adjusting for pathology type, disease stage, age, smoking history, chemotherapy regimen, and sex as covariates, and performed genome–wide association analysis under an additive model. LD pruning was carried out for all SNPs, with a window size of 500 KB, a step size of 50ct, and the r2 threshold for determining association set to 0.2.p-value intercepts were selected after association analysis using multivariate logistic regression in PLINK. In choosing these SNPs, the PLINK package was used to calculate all the odds ratio (OR) values of the SNPs. Models were built using different algorithms: PRS, BN, NB, RF, LR, SVM, Bagging, KNN, and RT. The PRS score was calculated by the PRSice software  [SNPs with specific  V2.3.5) . After o V2.3.5) . AU-ROC,Then, the SNPs selected from the discovery cohort were genotyped in the validation cohort to verify the model. Finally, clinical factors were integrated into the model to observe whether we can have a better prediction effect.p ≥ 0.05). In addition, the proportion of each clinical phenotype subtype is consistent between the discovery and validation cohorts.The study was divided into two cohorts: the discovery cohort and the validation cohort. The discovery cohort was used to select SNPs to build the model, and the validation cohort was used to verify the contribution of the selected SNPs to the phenotype in another independent cohort. The sample numbers of the case group and the control group were roughly the same. There were 217 patients in the discovery cohort, 104 (47.93%) were evaluated as sensitive and 113 (52.07%) as resistant to platinum chemotherapy; and 216 patients in the validation cohort, 102 (47.22%) were evaluated as sensitive, and 114 (52.78%) as resistant. The pathology type, disease stage, age, smoking history, chemotherapy regimen, and gender of the patients were collected. p-value after association analysis. The Manhattan plot  were included in the analysis, a total of 6,294,406 SNPs were included in the analysis, and 6,278,311 SNPs obtained the determined tan plot  shows thp values < 10−3 were analyzed. LD exists when alleles from two adjacent genetic variants co-occur in a non-random, linkage manner. To eliminate the false positives caused by the inclusion of SNPs with LD, we conducted linkage imbalance pruning for SNPs after a logistic multiple Correction Association analysis. p < 10−3 after the logistic multiple correction association analysis and LD pruning, as well as the genes and mutation types of SNPs. There were 57 SNPs with p < 10−3, of which 59.65% of the SNPs were located on genes and 40.35% on gene deserts, and most of the SNPs on genes were introns. Considering that there were still many SNPs, the SNPs with p < 10−4 were selected. There were four SNPs with p < 10−4: rs7463048 , rs17176196 , rs527646 , and rs11134542 ; all four of these SNPs are located on genes. rs7463048 is an intron of LOC105375676, rs17176196 is an intron of the read–through gene ANKRD34C antisense RNA 1 (ANKRD34C-AS1), rs527646 is an intron of opioid binding protein/cell adhesion molecule like (OPCML), and rs11134542 is an intron of slit guidance ligand 3 (SLIT3) or a non-coding mutation of LOC105377713.The SNPs with significant phenotypic contributions were selected to establish the prediction models. At first, the SNPs with At the same time, to compare our new model with the previous model, 20 SNPs from the previous model were analyzed. Of these, two SNPs were not among the SNPs we analyzed, and five SNPs failed to pass the quality control. Thirteen SNPs remained after LD pruning.p < 10−3; (2) SNPs with p < 10−4; (3) SNPs that were selected by the candidate gene method in the previous model.In general, different numbers of SNPs were selected to build the models. The SNPs used for modeling were divided into three groups: (1) SNPs with p < 10−3); (2) high correlation model (SNPs with p < 10−4); (3) the prior model (SNPs selected by the candidate gene method in the previous model). To obtain the best prediction model, multiple algorithms were used to build the models. Eleven algorithms including PRS, BayesNet, NaiveBayes, RF, LR, SVM, Bagging, KNN, RT, DT, and AdaBoost were used. The sensitivity, specificity, accuracy, and the AU-ROC of each model were analyzed, as shown in After selecting these three groups of SNPs, the SNPs were used to build the prediction models. The models established by these SNPs were named as, (1) medium correlation model . In the high correlation models, PRS is also the best method . In the prior models, the effect of PRS is much better than other algorithms. Only the model built using PRS obtained an accuracy above 0.6 .The results show that the medium correlation models with the PRS algorithm have the best performance. Among all of the model indicators, AU-ROC is one of the most commonly used indicators in evaluating binary classifiers, and shows the true positive rate relative to the false positive rate. Therefore, finally, AU-ROC was used to evaluate the performances of the models. Because in the discovery cohort, the medium correlation models and the high correlation models have a higher AUC than the prior models, therefore, only the groups of SNPs selected using GWAS were verified in another independent cohort. Again, since the models built using PRS have the highest accuracy among all the models, only PRS was used for modeling in the validation cohort. After quality control, 216 samples were included in our validation cohort. p < 10−4 and adopted the PRS algorithm. By calculating the ORs and genotypes of the SNPs included in the analysis, PRS gives each sample a score; based on the scores, the samples were divided into three groups: low, medium, and high. Therefore, our model considered including four SNPs with To further improve the model performance, clinical factors were included in the model ,14,15. Tp < 10−4 as well as the two clinical factors, pathology and chemotherapy regimen. By combining the discovery and validation cohorts to build this prediction model, the model had a sensitivity of 0.705, a specificity of 0.670, and an accuracy of 0.689, with an AUC of 0.726. After selecting SNPs to build the model and verify it, our model finally adopted PRS and included the four SNPs with OPCML), and rs11134542 is an intron mutation of SLIT3. The four SNPs were included in the model along with two clinical factors, pathology and chemotherapy regimen, modeled with PRS, and the AUC of the NSCLC platinum drugs response prediction model was 0.726.In our study, four SNPs were identified that influence the response to platinum–based chemotherapy in NSCLC: rs7463048, rs17176196, rs527646, and rs11134542. rs527646 is an intron mutation of Opioid-binding Protein/Cell-adhesion Molecule-Like  group. OPCML functions as a tumor suppressor and is silenced in over 80% of ovarian cancers by loss of heterozygosity and by epigenetic mechanisms. In addition to ovarian cancer, OPCML is also hypermethylated in other solid tumors such as cervical cancer, lung, brain, live, bladder, prostate cancer, colorectal and gastric cancer, and lymphoma. OPCML exerts its tumor suppressor effect by inhibiting several cancer hallmark phenotypes in vitro, and abrogating tumorigenesis in vivo, by downregulating/inactivating a specific spectrum of Receptor Tyrosine Kinases (RTKs), including EphA2, FGFR1, FGFR3, HER2, HER4, and AXL [ and AXL ,21,22,23SLIT3 is also associated with tumor proliferation, migration, and invasion. The Slit/Robo signaling pathway is reportedly involved in breast cancer development and metastasis. Overexpression of Slit/Robo induces its tumor suppressive effects possibly by altering β-catenin/E-cadherin-mediated cell-cell adhesion in breast cancer cells [er cells ,25.Our study suggests that, when discussing complex phenotypes with many influencing factors, the contribution of a single SNP is limited, and the predictive effect could be better if multiple SNPs with higher contributions were included in the model . ThroughWe also suggest that PRS is better than other algorithms at building predictive models. PRS is the mainstream method to discuss the influence of genetic factors on phenotypes in recent years, and has become the standard to quantify the genetic role in disease risk prediction, such as the prediction of the risk of inflammatory bowel disease (IBD), thyroid cancer, lung cancer, fatal prostate cancer, colorectal cancer, and type 2 diabetes ,30,31,32Our team has been focused on the pharmacogenomics of platinum responses for over a decade. A number of genes and mutations were observed that affect the efficacy of platinums. For example, our study found that rs2280496 and rs189178649 in the ADCY1 gene were associated with the sensitivity of platinum–based chemotherapy in NSCLC patients . It was When discussing clinical factors, we suggest that most of the clinical factors had no significant effect on the model’s performance , and the improvement of the model’s performance when only considering pathology and chemotherapy regimen was similar to that when considering all clinical factors.Therefore, SNPs were selected for the first time by the GWAS method to build a predictive model for platinum drug efficacy in NSCLC, modelled by the PRS method, and two clinical factors with significant effects on phenotype were incorporated into the model, ultimately perfecting the previous predictive model for platinum drug efficacy in NSCLC.Many studies have attempted to integrate genetic factors with clinical characteristics to develop models for predicting responses to drug therapies. Most of these models have an AUC above 0.7. Meenal Gupta et al. identified a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients, their model had an AUC of 0.733 . Kimi DrIn conclusion, by GWAS, we identified four genetic susceptibility SNPs and two clinical factors affecting platinum–based chemosensitivity in NSCLC, and constructed a new predictive model.


The efficacy and safety of integrated Chinese and western medicine in the treatment of Systemic Lupus Erythematosus (SLE) have not been systematically evaluated.This systematic review and meta-analysis will be performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will search PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP, and China National Knowledge Infrastructure (CNKI) for potentially eligible studies from their inception to Dec. 2020, and we will select all the eligible randomized controlled trials (RCTs) of the integrated Chinese and western medicine for Systemic Lupus Erythematosus. All the studies will be screened according to the inclusion and exclusion criteria and meta-analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. The primary endpoint was the clinical efficacy rate, the secondary outcomes were SLEDAI score, adverse reaction rate, and laboratory test parameters .The results of this study will systematically evaluate the effectiveness and safety of the integrated Chinese and western medicine in the treatment of primary dysmenorrhea.The efficacy and safety of integrated Chinese and western medicine will be systematically evaluated in this paper, thus providing evidence for the clinical application of this therapy.This study is a systematic review, which is based on the published studies, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.https://osf.io/mabxh. In this paper, we will include relevant studies on the clinical efficacy of combination of Chinese traditional and Western medicine in the SLE treatment, and conduct a meta-analysis of the studies meeting the inclusion criteria, hoping to evaluate the clinical efficacy and safety of combination of Chinese traditional and Western medicine in the SLE treatment. The details are as follows.Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multisystem damage, and its serum has a variety of antinuclear antibodies.22.1https://osf.io/mabxh. This systematic review protocol will be conducted and reported strictly according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, and the important protocol amendments will be documented in the full review.The protocol of the systematic review has been registered. Registration: OSF Preregisration. November 3, 2020. 2.22.2.11.The studies included are published randomized controlled trial.2.All the patients were clinically diagnosed as SLE. The treatment group was treated with conventional western medicine  combined with decoction of traditional Chinese medicine, with the general course of treatment of 1 to 12 months.2.2.2Following studies will be excluded:(1)Observational study;(2)Basic study type;(3)Repeated reports;(4)Literatures with insufficient data;(5)Unpublished medical study;(6)Clinical study with sample size less than 15;(7)Literatures with insufficient text.2.3All included patients were diagnosed with SLE.2.4The patients in the experimental group were treated with Chinese medicine in addition to routine western medicine (glucocorticoid). The patients in the control group were treated with glucocorticoid.2.5The primary endpoint is the clinical efficacy rate, the secondary outcomes are SLEDAI score, adverse reaction rate, and laboratory test parameters .2.62.6.1 Chinese words “integrated Chinese and western medicine ” and “Systemic Lupus Erythematosus” will be used as the key words , VIP, Wanfang, and CBM,rds Fig. , and in rds Fig. .2.72.7.1Two independent researchers (XL and ZH) will screen all candidate articles based on titles and abstracts according to the inclusion/exclusion criteria, and then retrieve the full text of each potentially relevant trial for further evaluation. Differences of opinion will be resolved by a third independent critic (QB).2.7.2Two researchers (XL and ZH) will read all the included text in full, and independently extract the following information:(1)General information, including trial name and registration information;(2)Trial characteristic, including trial design, location, setting, and inclusion/exclusion criteria;(3)The characteristics of the participants, including age, race/ethnicity, course of illness, etc;(4)Details of intervention, including time of intervention, course of treatment, time of single treatment, etc;(5)Details of comparison interventions;(6)Outcomes as described in Section 2.5. If we can not reach an agreement, a third researcher (QB) will make the final decision.2.7.3The risk of bias in the included RCTs will be independently appraised by 2 researchers (XL and ZH) using the “risk of bias” tool of the Cochrane Collaboration and each included study will be evaluated for quality and risk of bias in accordance with Cochrane manual 5.1.0. In case of any disagreement, a third researcher (QB) will extract the data and results will be attained by consensus. The following criteria will be assessed: random sequence generation; allocation concealment; blinding; incomplete data; selected reporting the results; and other bias. The risk of bias will be classified as “high,” “unclear,” or “low.”2.7.4Review Manager 5.3  and Comprehensive Meta-Analysis (CMA) 2.0 will be used to combine trials. Continuous outcomes will be expressed as weighted mean difference (WMD) and dichotomous data as risk ratio (RR), with their 95% confidence intervals (CIs). RR is the ratio of the probability of an event occurring in the treatment group to the probability of the event occurring in a control group.I2 statistic will be used to measure statistical heterogeneity. When P < .05 or I2 > 50%, substantial heterogeneity will be considered to exist, and the random effects model will be applied to estimate the summary RR , WMD and 95% CI, otherwise a fixed effects model will be applied. At the same time sensitivity analysis is adopted to determine the robustness of the results.Besides RR, meta-analysis will be also conducted using odds ratio (OR) and risk difference (RD) statistical methods, respectively. Chi-square test and 2.7.5This is a meta-analysis study based on previously published data, so patient and public involvement will not be included in this study.2.7.6Ethical approval will not be required as this is a protocol for systematic review and meta-analysis. The findings of this study will be disseminated to a peer-reviewed journal and presented at a relevant conference.2.7.7 To achieve transparency and simplification, the quality of evidence is divided into 4 levels in GRADE system: high, medium, low, and very low. We will employ GRADE profiler 3.2 for analysis.The quality of evidence for this study will be assessed by “Grades of Recommendations Assessment, Development, and Evaluation (GRADE)” standard.3Glucocorticoids are currently the most common drugs for SLE patients, which can better control the disease activity, and reduce the outbreak of SLE and improve the symptoms of SLE. Although western medicine has a good treatment effect, especially glucocorticoids and immunosuppressants have a positive effect on preventing the pathological lesion of lupus nephritis, there are still serious adverse drug reactions, which have become one of the causes of death of late SLE.At the present stage, SLE is clinically treated with western medicine, such as glucocorticoid, immunosuppressants, etc, which cannot achieve the ideal treatment effect, even leads to secondary infection, increases the damage to kidney organs, and even cause death of patients.This study shows that the effect of combination of Chinese traditional and western medicine in the SLE treatment is better than that of the single use of glucocorticoids, and the study results have statistical significance. The modern pharmacological study has also proved that traditional Chinese medicine has immune-regulating properties and less side effects. Therefore, The integrated Chinese and western medicine can achive better clinical efficacy in the SLE treatment, provide better treatment for patients, and reduce the side effects, the recurrence rate, and the rebound in the use process of glucocorticoids.The efficacy and safety of integrated Chinese and western medicine will be systematically evaluated in this study, thus providing evidence for the clinical application of this therapy for SLE.Conceptualization: Xueli Cheng, Zhenghong Zhong, Jing Liu.Data curation: Donghan Xu.Formal analysis: Xueli Cheng, Zhenghong Zhong.Funding acquisition: Jing Liu, Qibiao Wu.Investigation: Xushan Cha, Jing Liu.Methodology: Xueli Cheng, Zhenghong Zhong, Jing Liu.Project administration: Qibiao Wu.Resources: Xueli Cheng, Zhenghong Zhong, Donghan Xu.Software: Xueli Cheng, Zhenghong Zhong.Supervision: Qibiao Wu, Jing Liu.Validation: Xushan Cha.Visualization: Qibiao Wu.Writing – Original Draft: Xueli Cheng.Writing – Review and editing: Xueli Cheng, Qibiao Wu.


To study the clinical application value of Modified Buzhong Yiqi Decoction in the treatment of female stress urinary incontinence (SUI).A total of 103 female patients with SUI were included in this study, 13 were lost to follow-up, and the final number of studies was 90. General information about the patients, including age, years of menopause, body mass index (BMI), reproductive history, chronic respiratory disease, hypertension, and diabetes, were recorded. All the patients were treated with Modified Buzhong Yiqi Decoction alone for 4 weeks. The Patient Global Impression of Improvement (PGI-I), the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICI-QSF) and 72-h voiding diary were used to evaluate the patients' subjective symptoms and urinary incontinence degree before treatment, 1 month after treatment and 1 year after treatment, the efficacy and efficacy-related factors of Modified Buzhong Yiqi Decoction in the treatment of female SUI were analyzed.P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); One year after treatment compared with before treatment, the PGI-I questionnaire was very much better (40.00%), much better (17.78%), a little better (12.22%), no change (30.00%), the ICI-QSF score decreased (P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); and 1 year after treatment compared with 1 month after treatment, the ratio of very much better at 1 year after treatment was significantly decreased (P < 0.05), the score of the ICI-QSF was significantly increased (P < 0.05), and 72-h urine leakage frequency was significantly increased (P < 0.05). The correlation analysis showed that the efficacy at 1 month after treatment was negatively correlated with the severity of SUI and chronic respiratory diseases, but was not significantly correlated with age, menopause status, BMI, number of pregnancies, and number of births. The efficacy at 1 year after treatment was negatively correlated with the severity of SUI, chronic respiratory disease, age, and number of births and was positively correlated with BMI, but not significantly correlated with menopause status and number of pregnancies.One month after Modified Buzhong Yiqi Decoction treatment, compared with before treatment, the PGI-I questionnaire was very much better (68.89%), much better (8.89%), a little better (12.33%), no change (8.89%), the ICI-QSF score decreased (Modified Buzhong Yiqi Decoction can effectively treat SUI in women. The efficacy is related to the severity of SUI and chronic abdominal hypertension, but the long-term efficacy decreases. Stress urinary incontinence (SUI) is a disorder of voiding dysfunction due to anatomical defects in the supporting tissues of the urethra . Its cliAt present, the study on the treatment of female SUI by traditional Chinese medicine (TCM) is limited to short-term clinical efficacy reports. So far, there is no clinical short-term and long-term efficacy observation and related drug pharmacological mechanism study. Chinese medicine believes that the operation of the spleen is mainly based on the rise and the rise is to maintain the normal position of the body's internal organs. “Su Wen Linglan Secret Canon” says: “The bladder is the official of the state capital, the body fluid is stored, and after the body fluid is vaporized by the yang of the lower coke, it can go out through the waterway.” The Kidney Qi controls stool and urination. If the Kidney Qi is insufficient and the Kidney Yang is deficient, the transformation of the Qi of the bladder is not smooth and symptoms such as clear and long urination last drops and urinary incontinence will be seen. Therefore, the clinical differentiation of SUI is not simply based on spleen deficiency, but mainly based on spleen and kidney deficiency and the principle of treatment is to invigorate the middle and ascend the sag and invigorate the kidney and solidify the astringency. In this study, the modified formula was prepared on the basis of Buzhong Yiqi Decoction and the Patient Global Impression of Improvement (PGI-I), the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICI-QSF), and 72-h urination diary were used. The short-term therapeutic effect of 1 month after treatment of Modified Buzhong Yiqi Decoction and the long-term therapeutic effect of 1 year after treatment were observed, to evaluate the feasibility and influencing factors of clinical application of this prescription in the treatment of female SUI. The report is as follows.This study was a prospective self-controlled study. A total of 103 female patients with SUI who were treated with Modified Buzhong Yiqi Decoction in the Pelvic Floor Disease Diagnosis and Treatment Center of the Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine from January 2012 to January 2015 were included.It met the diagnostic criteria of the International Urogynecological Association (IUGA) for SUI in women . It is mAccording to the theory of traditional Chinese medicine and related literatures, this study divided SUI into three syndrome types: Spleen-deficiency and Qi-trapping type, Kidney-Qi deficiency type, and Spleen-Kidney Yang deficiency type.All the patients were graded according to the Ingelman–Sundberg scale : Mild: UIt meets the diagnostic criteria for SUI. Be 18 years of age or older. Patients voluntarily accepted the treatment with Modified Buzhong Yiqi Decoction and subsequent clinical observation and signed the informed consent form. The patient was never referred for this. Urinary incontinence medication should be discontinued for more than 3 months.It includes residual urine > 30 ml and maximum urinary flow rate <20 ml/s. Other types of urinary incontinence, such as neurogenic bladder, psychogenic incontinence, and impulsive incontinence, are also present. Urethral sphincter atresia insufficiency, ectopic ureter, etc., requiring surgical treatment. Patients with urinary stones, infections, lower urinary tract obstruction, and renal disease. Patients with history of surgical treatment for urinary incontinence or history of pelvic floor surgery. Genital prolapse ≥ 2°. Combined with serious medical diseases such as cardiovascular and cerebrovascular, hematopoietic system, liver, and kidney. Reluctance to accept clinical observers. Those who did not adhere to the medication as prescribed and could not judge the curative effect. Those who could not meet the follow-up conditions.Astragalus, 15 g of fried Atractylodes, 6 g of tangerine peel, 6 g of Cimicifuga, 9 g of Bupleurum, 15 g of ginseng, 3 g of Licorice, 12 g of Angelica, 15 g of Alpiniae Oxyphyllae Fructus, 9 g of Mantidis ootheca, 15 g of Cortex Eucommiae, 6 g of Lindera aggregata, and 15 g of Rosa laevigata Michx. There were slight additions and subtractions through dialectics. Oral, 1 dose per day, warmly divided into two decoctions, each decoction was about 200 ml. Decoction in the morning and evening, 4 weeks as a course of treatment. The medicines were provided by the Chinese Medicine Pharmacy of the Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine, China, and each patient was treated for one course of treatment.All the patients were treated with Modified Buzhong Yiqi Decoction orally. The main ingredients of Modified Buzhong Yiqi Decoction: 15 g of In this study, a special person was responsible for recording the general conditions of the patients, including age, menopause, year of menopause, body mass index, reproductive history, whether there was a history of chronic increased abdominal pressure such as chronic respiratory disease, whether there was a history of common medical diseases in the elderly such as hypertension and diabetes mellitus; and follow-up was performed during and after taking the medicine for up to 1 year. Before treatment, 1 month after treatment and 1 year after treatment, the PGI-I was used to evaluate the patients' subjective symptoms and the ICI-QSF and 72-h urination diary were used to evaluate the degree of urinary incontinence. The ICI-QSF questionnaire included a total of 7 questions and each question had a score of 0 to 3. The higher the score, the greater the impact of urinary incontinence on the quality of life. The urination diary was used to continuously record urination for 72 h, including each urination time, urine volume, water drinking time, water consumption, accompanying symptoms, and urinary incontinence time, etc. In this study, a total of 103 female patients with SUI were treated with Modified Buzhong Yiqi Decoction, 13 patients with SUI were lost to follow-up, and 90 patients with SUI were finally studied.t-test and the correlation between the treatment effect and various clinical characteristics was analyzed by bivariate correlation. A two-sided test with P < 0.05 was considered as statistically significant.Measurement data were described by mean ± SD, including age, height, weight, BMI, frequency of urinary leakage, and the ICI-QSF. The enumeration data were described by percentage, including age composition ratio, menopause or not and its years, reproductive history, chronic respiratory diseases, hypertension, and diabetes. Data analysis was performed using the statistical software SPSS version 11.0 . The ICI-QSF questionnaire score results and the number of urine leakage before and after treatment were analyzed by the 2) were also included. The basic information of 90 patients with SUI was shown in All the 103 patients with SUI completed 28-day treatment as required, of which 13 patients with SUI were lost to follow-up within 1 year after treatment, with a loss-to-follow-up rate of 12.62%. Lost telephone contact was the reason for the loss to follow-up. Data were analyzed using per-protocol (PP) analysis and those who were lost to follow-up were not included in the analysis. Among 90 patients who were followed-up to 1 year after treatment, age 50.04 ± 13.58 (years old), height 1.60 ± 0.05 (m), weight 60.25 ± 11.83 (kg), and BMI 23.46 ± 4.52 (kg/mP < 0.05); Compared to 1 month after treatment, there was a tendency for subjective symptoms of urinary incontinence to return 1 year after treatment: The self-reported no change and very much better 1 month after treatment were 8.89 and 68.89%, respectively, and the self-reported no change and very much better 1 year after treatment were 30.00 and 40.00%, respectively, and there was a statistical difference between the two (P < 0.05).According to the PGI-I questionnaire, P < 0.05), but the ICI-QSF score at 1 year after treatment was significantly higher than that at 1 month after treatment (P < 0.05). P < 0.05), and 72-h urine leakage frequency at 1 year after treatment was significantly higher than that at 1 month after treatment (P < 0.05).P < 0.05), but had no significant correlation with age, menopause situation, BMI, number of pregnancies, and number of births (P > 0.05). 1 year after treatment, the curative effect was negatively correlated with SUI severity, chronic respiratory disease, age, and number of births (P < 0.05) and was positively correlated with BMI (P < 0.05), but had no significant correlation with menopause situation and number of pregnancies (P > 0.05).Using the PGI-I to evaluate the treatment effect, after statistical analysis of correlation, There were no adverse reactions during and 1 year after taking the drug, including 19 elderly patients > 60 years old and 16 patients with hypertension or diabetes and no aggravation of primary underlying diseases such as hypertension and diabetes was found.Urinary incontinence can lead to inconvenience in movement, inability to perform housework, affect normal social and sexual life, etc., resulting in the isolation of patients from society and family and a series of depression or psychological disorders . AccordiThe understanding of urinary incontinence in Chinese medicine has a long history; water and fluid are controlled in the spleen; if the Spleen Qi does not rise, urinary incontinence is seen; however, its origin is in the kidney. If the Kidney Qi is insufficient and the Kidney Yang is deficient, urinary incontinence can also be seen. Therefore, to identify its etiology and pathogenesis, it must be that the Spleen Qi does not rise, the Qi transformation has no power, the Kidney Qi is insufficient, the bladder is out of restraint, and the opening and closing are abnormal. Urinary incontinence mostly occurs in elderly patients. Traditional Chinese medicine believes that when a person reaches the age of 49 years, the Ren pulse is deficient, the Taichong pulse is less weak, and the Kidney Qi is weak. Simple application of Buzhong Yiqi Decoction cannot improve the symptoms of urinary incontinence caused by kidney deficiency. Therefore, in this study, on the basis of Buzhong Yiqi Decoction, the medicine for nourishing Kidney Qi is added, the treatment is to nourish the middle and ascend the sag, invigorate the kidney, solidify astringency, and after a 1-year follow-up study, in order to evaluate the clinical application value of Modified Buzhong Yiqi Decoction in the treatment of female SUI.P < 0.05), the ICI-QSF score was decreased (P < 0.05), and 72-h urine leakage frequency was decreased (P < 0.05). It is indicated that by invigorating the middle and ascending the sag and invigorating the kidney and solidifying the astringency, the Modified Buzhong Yiqi decoction can effectively improve the symptoms of female SUI. One year after treatment, compared with before treatment, there were still significant differences in patients; subjective symptoms (P < 0.05), the ICI-QSF score still decreased (P < 0.05), and 72-h urine leakage frequency still decreased (P < 0.05). It shows that Modified Buzhong Yiqi Decoction is still effective for female SUI 1 year after treatment compared with before treatment. However, 1 year after treatment compared with 1 month after treatment, the rate of very much better at 1 year after treatment was significantly lower (P < 0.05), the ICI-QSF score was significantly higher (P < 0.05), and 72-h urine leakage frequency was significantly increased (P < 0.05). It shows that the improvement of SUI symptoms and quality of life with Modified Buzhong Yiqi Decoction cannot be permanent and the efficacy decreases with time. In addition, we found that the short-term (1 month) and long-term (1 year) efficacy of Modified Buzhong Yiqi Decoction for severe SUI were relatively poor. Based on this, we speculate that Modified Buzhong Yiqi Decoction is suitable for mild-to-moderate female SUI and patients with recurrent disease need to increase the course of treatment to consolidate the curative effect. Among the cases, 2 patients had SUI symptoms after repregnancy and the statistics were judged as no change, but they were still cured after using Modified Buzhong Yiqi Decoction again.Compared with before treatment, 1 month after treatment with Modified Buzhong Yiqi Decoction, the subjective symptoms of the patients were significantly different  and the Zhejiang Provincial Department of Education (Y202146113).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Poor nations are already facing the heat of double burden of communicable and non-communicable diseases (NCDs), often known as chronic illnesses, which are characterized by a protracted course and are multifactorial in causation. In addition to this, neglected non-communicable diseases (NNCD) in the form of gout, sickle cell disease, accidents and many more are likely to be one of the biggest public health challenges soon. Nearly three-quarters (31.4 million) of all NCD-related fatalities occur in developing nations. In terms of morbidity and mortality, the “BIG FOUR” NCDs—diabetes, cancer, chronic respiratory diseases, and cardiovascular diseases—are widely acknowledged as the main contributors to global health loss. However, other NCDs account for 55% of the global burden of NCDs and are frequently neglected in terms of premature death, increased Disability Adjusted Life Years (DALY), and decreased Quality-Adjusted Life Year (QALY). We have briefly discussed the disease burden of a few significant, yet neglected NCDs in this paper. Non-communicable diseases (NCDs), usually referred to as chronic diseases, are brought on by a confluence of physiological, behavioral, physiological, environmental, and environmental factors. Annually, they claim the lives of 41 million people, or 71% of all fatalities globally. The NCDs claim more than 15 million lives each year in people between the ages of 30 and 69 with low- and middle-income countries account for 85% of these “premature” deaths. Low- and middle-income nations represent 77% of all deaths from NCDs . Global In India, the burden of non-communicable diseases has increased over the past 20 years, replacing infectious diseases, under nutrition, maternal disorders, and pediatric illnesses (NCDs). In 2019, NCDs were responsible for 65% of all fatalities in the nation . The IndNon-communicable diseases (NCDs) have a significant economic impact on populations in addition to causing morbidity and mortality. The expansion of the national economy as well as personal financial security is negatively impacted by non-communicable diseases (NCDs). In low- and middle-income countries, NCDs frequently have an impact on a person's most productive years of life. People with NCDs must pay high healthcare costs and have few job possibilities, which put households at greater risk financially. Increase in healthcare expenditure, and decrease in productivity put strain on the economy of developing countries and impedes social and economic advancement. It is crucial to discuss the social and economic repercussions of the “chronic emergency” of NCDs in India because India contributes significantly to global mortality and lost disability adjusted life years (DALYs) .With high rates of NCD morbidity and mortality at a time when communicable diseases are not yet under control, India is one of the developing countries that has gone through a “double burden” epidemiological transition. At a time when communicable diseases had fallen to noticeably lower levels, chronic conditions have seen a rise in most developed countries. Secondly, different states in India are at various stages of the transition. This epidemiological transition is being driven by a change in demographics. In 2025, there will be 7.6 percent more people 65 who are 65 years and above than there were in 2000 .While diabetes, chronic obstructive pulmonary disease (COPD), cancer, and cardiovascular diseases all contribute significantly to global health loss, other NCDs account for a greater portion (55%) of the global NCD burden. Musculoskeletal conditions, particularly low back and neck pain, depression, substance abuse disorders, liver cirrhosis, chronic kidney disease, asthma, various digestive conditions  are a few of the more serious ones. Contrary to the “big four” NCDs, many of these illnesses result in chronic disability rather than early mortality, which suggests that preventing chronic disability should be a top priority for any health system  9). The. The9). MEDLINE, PsycINFO, Scopus, Web of Science, and Google scholar” using the following terms: (“diabetes”) and (“diabetes mellitus”), (“type 1 diabetes”), ,  (“juvenile diabetes in India”), NCDs, NNCDs, hypertension, diabetes, cancer, gout, sickle cell disease, etc. This review includes all pertinent publications and policy papers  available in the public domain from 2005 to support its claim. All relevant articles were included and a total of 890 articles were extracted after database searching. Initially, 250 duplicated information articles and 240 records were removed. By screening the article's titles and abstracts, 190 irrelevant articles were removed, and 10 reports were not retrieved, 135 articles were excluded after reviewing the full-text articles due to not fulfilling the research question and the review inclusion criteria. Finally, 35 studies and 30 reports met the inclusion criteria and entered the research process of the review.We searched the databases “The neglected non-communicable diseases include gout, sickle cell disease, asthma, chronic kidney disease, liver cirrhosis, alzheimer's disease and many more which are not even recognized.Gout, the most common kind of inflammatory arthritis, is caused by an accumulation of uric acid crystals in and around the joints as a result of hyperuricemia. The range of gout prevalence and incidence vary differently from 1 to 6.8% and 0.58 to 2.89 per 1,000 person-years, respectively. It affects more men than women as they become older and in specific ethnic communities. Obesity, nutritional variables, and other conditions are only a few of the many risk factors for gout. It has been observed that gout has connections with concomitant conditions such sexual dysfunction, tachycardia, obstructive sleep apnea, and osteoporosis, and deep vein thrombosis. In people with gout, specific patterns of comorbidity clustering  have been identified .The prevalence of gout in India is unclear. According to a study conducted by the Community Oriented Program for Control of Rheumatic Diseases (ILAR COPCORD) in the Indian village of Bhigwan, the prevalence of gout is 0.12% . AccordiSickle Cell Disease (SCD) has been recognized as a global issue of public health concern . Excess mortality in children under five is a result of the high frequency of untreated non-communicable illnesses, particularly SCD.In Nigeria, India, and the Democratic Republic of the Congo, where the disease affects up to 2% of the population and the transmission prevalence rate (sickle cell trait) is as high as 10% to 30% . At leasChronic kidney diseases (CKD) are commonly found among the individuals having diabetes and high blood pressure . The gloThe reported prevalence of CKD varies by area and ranges from 1 to 13%; most recently, statistics from the Kidney Disease Data Center Study of the International Society of Nephrology revealed a prevalence of 17% . There a2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively  had bronchial asthma, of which 10.3% experienced attacks within the previous year. Males (8.77%) had a greater prevalence rate than females (4.33%)  . As per  (4.33%) . The mos (4.33%) .India has lower rates of asthma prevalence (5–15%) than do European nations (>20%), but the condition is more severe (>40% of cases), less frequently diagnosed, and undertreated. India's rural areas have 3.6 lakh more severe asthmatics than its metropolitan areas (1.6 lakh) .According to the most recent estimates, 13% of all drug users, or 36.3 million people, take illicit drugs. 5.5% of persons worldwide between the ages of 15 and 64 had taken drugs at least once in the previous year. Alcohol abuse causes 3 million deaths worldwide each year. This contributed to 5.3% of all fatalities. Alcohol provides roughly 5.1% of the global burden of disease and injury, measured in Disability Adjusted Life Years (DALYs) . As per According to estimates, 236,000 individuals globally perished from drowning in 2019, making it a serious public health issue. In 2019, injuries made up nearly 8% of all fatalities worldwide. Seven percent of all injury-related deaths are caused by drowning. A 2019 Lancet analysis on estimates of “healthy life” lost in India projected that there were ~62,000 drowning deaths in 2017 .As per ILO estimates, around 2.3 million men and women die each year from occupational injuries or accidents, or more than 6,000 people per day. Every year, nearly 160 million cases of occupational injuries and 340 million workplace accidents occur worldwide . ReferriNCDs are complex, diverse, and significantly influence the health of people in varied ways. There is a need for more comprehensive, holistic and strategic approach for mitigating the impact of non-communicable diseases. We have to think beyond what is being practiced for the past half century pertaining to NCD research, treatment and prevention. Rather than treating the non-communicable diseases, more emphasis should be given to improve the conditions or determinants which lead to the emergence of non-communicable diseases, which hitherto have been largely ignored as global health priorities . BesidesSome of the common neglected NCDs include gout, asthma, chronic kidney disease, alzheimer's and dementia, sickle cell anemia, alcohol and substance abuse, road accidents, drowning, etc. NNCDs are very important which need urgent addressal. These are not included in NPCDCS and other health programs. Proposed solution for tackling NNCDs through lifecycle approach is given in There is very limited evidence available for Gout in India. General practitioners typically treat gout, and only a small percentage of patients may see rheumatologists. Therefore, along with patient education and training, the urgent need of the hour is for the training of physicians, orthopedic, and physiatrists. Chronic liver disorders (CLDs) are common in India somewhat presented late in the clinical course, most frequently after decompensation has begun. This poses a challenge for early treatment and overburden healthcare resources.These neglected NCDs may be integrated within the ongoing/existing national health programs being implemented at the state and district level. There is a need for coordination, integration, and convergence of efforts in dealing with the above mentioned neglected NCDs. The NHM's primary tactics were applied in the development of the health promotion model in two districts of Punjab and Haryana, with an emphasis on integration, convergence, and the best use of available human and financial resources .The Ministry of Health &Family Welfare, Government of India has been advocating for joint collaboration between various initiatives wherein activities can be planned and carried out, within the framework of the existing health system. For example, the National TB/HIV framework (2013), Pilot project on “Integration of AYUSH with NPCDCS” (2016), National Framework for Joint TB-Tobacco Collaborative Activities (2017), National framework for joint TB-Diabetes collaborative activities (2017), Tribal TB initiative (2021) . BesidesThe results from various studies conducted have displayed that such integrative strategies have shown advantage in terms of better cross-referral, improved retention of patients, timely initiation of treatment, and improved survival . In receThe screening and prevention of neglected non-communicable diseases need to be strengthened. Experts from public health must reconsider these “forgotten NCDs” on a global and national level. We must investigate the clinical effects of these conditions as well as the consequences of ignoring their medical importance and economic burden on the nations (direct and indirect). With an objective to tackle these neglected non-communicable illnesses within a global NCD program, we need to advise on how they should be prioritized within the global disease burden hierarchy. This will enable us to reduce the global disease burden, minimize DALY, and improve QALY.All authors listed have contributed to the article equally and approved it for publication.


The COVID-19 pandemic has placed an unprecedented physical and mental burden on healthcare workers who are frequently at high risk of infection, particularly in low-income countries. This study aimed to assess the prevalence and associated factors of anxiety, depression, and stress, as well as changes in daily and occupational activities among healthcare professionals due to the COVID-19 pandemic in Colombia.An observational, cross-sectional study was conducted between February and June 2021. The survey incorporated validated mental health tools such as the Generalized Anxiety Disorder–7, the Patient Health Questionnaire-9, and the Perceived Stress Scale-10. Multivariable ordinal logistic regression analysis was performed to determine the factors associated with severe mental health outcomes.Among 1345 healthcare workers the prevalence of anxiety, depression, and stress were 75.61, 59.18, and 53.09%, respectively. Anxiety , depression , and stress  were more frequent in women, and individuals who expressed fear of a negative outcome  ,  and  respectively. Age was negatively associated with anxiety , stress , and depression . Reduction in consultations and surgeries  was positively associated with anxiety. Due to the pandemic, most specialists expected to incorporate drastic long-term (> 1 year) changes in their clinical setting and daily activities.The prevalence of anxiety, depression, and stress is higher among Colombian healthcare workers compared to previous reports. Further research regarding these psychological outcomes is needed to achieve early mental health intervention strategies.Hospital Universitario Fundación Santa Fe, Ethical Committee Registration ID: CCEI-12992-2021. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of COVID-19 has rapidly spread worldwide, drastically disrupting healthcare systems and placing an unprecedented burden on healthcare professionals. By December 2021, the World Health Organization (WHO) has reported over 240 million confirmed cases and nearly 5 million deaths throughout the different waves of the disease, multiple mutations of the virus, and significant differences in clinical patterns and outcomes , 4.Since the spread of COVID-19, Vizheh et al. stated that healthcare specialists reported higher occupational stress levels and higher rates of psychological symptoms . These oThese studies highlight the importance of mental wellness in physicians during times of crisis, yet further studies are needed to capture a broader picture of the situation to efficiently manage future sanitary emergencies and thus prevent long-term impact on front-line staff. To date, very few studies have been published in English regarding these psychological outcomes in Latin America. Regarding the Colombian population, one study reported the effects of the pandemic on the mental health, daily and occupational activities of otolaryngologists, and allergists . A crossAn observational, cross-sectional study was conducted to determine the prevalence and associated factors of anxiety, depression, and stress levels in a group of healthcare professionals during the second wave of the COVID-19 pandemic in Colombia. The study was based on a non-probabilistic, consecutive sampling, using self-administered, anonymous online surveys to collect sociodemographic and mental health data from February 05, 2021, to June 30, 2021. Internationally validated questionnaires such as the Generalized Anxiety Disorder-7 (GAD7), the Patient Health Questionnaire-9 (PHQ9), and the Perceived Stress Scale-10 (PSS10) were used to determine the frequency of anxiety, depression, and stress, respectively. A sociodemographic questionnaire was also applied and assessed information about age, marital status, family income, working status, workload, work income before and after the pandemic, personal protective equipment, and geographic location. Data collection was performed online, and participants were invited to fill out the survey at any time. Ethics Committee of the Hospital Universitario Fundación Santa Fe de Bogotá approved this study (CCEI-12992-2021) according to the Helsinki Declaration, and all methods were performed in accordance with the relevant guidelines and ethic regulations. Moreover, this study was approved and involved the participation of the National Academy of Medicine from Colombia in the dissemination plans of this research. Informed Consent was obtained from all participants. No incentives were offered for study participation.In terms of the eligibility criteria, healthcare workers registered in the National Unified Registry of Human Resources in Health from Colombia and conducted in-person consultations and/or telemedicine were included. Exclusion criteria were specialists who reported a prior diagnosis of mental health disorders confirmed by a psychiatrist or mental health professional, and those who reported any acute/chronic condition that could limit their ability to answer the questionnaires. The sample size was estimated based on a meta-analysis by Pappa et al. that assessed the prevalence of mental health disorders among 33,062 healthcare workers due to the COVID-19 pandemic . A minimA 5% significance and precision level were applied, as well as a 5% adjustment for probable losses. Regarding the sample selection method, a non-probabilistic, consecutive sampling was conducted. Despite the participants registered to do the survey, only the population who completed all the questionnaires was included in the analysis.Symptoms of anxiety, depression, and stress were assessed using validated Spanish versions of the following measurement tools: GAD-7 , PHQ-9 , and PSSA “Fear score of COVID-19” developed by the researchers of this study was applied using a scale of 1 to 5 to assess fear of contagion, fear of the possibility of a negative outcome , and fear of infecting a family member and/or friends. Moreover, a questionnaire regarding the opinion on when  healthcare workers would expect to engage again in regular daily and leisure activities was applied. This questionnaire was developed by “The New York Times” and previously applied to 511 epidemiologists . We highp-value ≤0.2 were included in the multivariate analysis. The full, crude, and adjusted models are reported to compare the strength of the associations with depression and to assess the presence of confounding variables in the analysis. Percentage decrease in monthly income was calculated comparing income before the pandemic and during the fieldwork (October–November 2020). Finally, the goodness of fit of the model was assessed and assumptions were verified through a linearity test, proportional odds, and through the estimation of deviance residuals and leverage values. Statistical significance for the multivariate models was established at p < 0.05. Statistical analysis was performed using Stata 16MP software. A 5% significance level for the comparisons was established before data collection.Frequencies and percentages were calculated for the quantitative variables. Central tendency, and dispersion measures for the quantitative variables were estimated. The prevalence of symptoms of anxiety, depression, and stress was calculated along with its 95% confidence interval. Bivariate and multivariate analyses were carried out to explore the associations between the levels of anxiety, depression and stress and the sociodemographic and occupational covariates due to the COVID-19 pandemic. These analyses were based on an ordinal logistic regression analysis. The predictors of the model were selected considering the biological plausibility reported by prior studies as primary criteria, and the possible statistical association within the variables. Variables with clinical relevance first, or those with a Fisher or Kruskall Wallis test with a n = 840) were women, and 46.10% (n = 620) were specialist doctors. The baseline demographic characteristics of the study population are described in Table n = 663), Antioquia (n = 118), 66% of the participants were women, and nearly 40% were over the age of 50. Near half of the study population  performed face-to-face consultation, while 25.58% worked as telemedicine practitioners. Overall, 19.03% (n = 256) of the study population considered that the personal protection elements provided by their employer were not enough to prevent COVID-19 infection. The most frequently used biosafety elements in their practice were surgical masks with 32.94% (n = 443), and N95 respirators with 27.43% (n = 369).A total of 1345 individuals were included in this study, of which 39.26% were over the age of 50, 66.17% . Likewise, no extreme or influential values were found for the residuals and leverage values.No collinearity problems were found through the linearity and the goodness-of-fit tests, both tests showed good models ‘specification. In addition, the proportional odds assumption was not rejected for all models (n = 281) of the participants tested positive for SARS-Cov-2 and 41.93% (n = 564) had been isolated on suspicion of infection, in contrast, 84.76% (n = 1140) had been vaccinated for Covid-19. Around 87.96% (n = 1183) reported fear of contagion by SARS-CoV-2, and 85.50% (n = 1150) were afraid of the possibility of a negative outcome as death or negative sequelae due to Covid-19 infection. Finally, up to 92.71% (n = 1247) reported being afraid of the possibility of infecting their family and friends with Covid-19. These results are shown in Table At the time of the study, 20.89%  due to COVID-19. The reduction in the number of consultations and surgery was also associated positively with anxiety severity, while the reduction in income during the pandemic was positively associated with higher levels of stress. Research on these psychological outcomes is needed in Latin America to achieve early mental health prevention approaches, as well as therapeutic interventions in this population. Psychological and/or psychiatric support without occupational stigmatization should be granted by the institutions.