This study aimed to explore the risk factors for severity of white matter lesions and its correlation with in the elderly with lacunar infarction.Patients  with lacunar infarction treated in a hospital in China from 2016 to 2017were enrolled. Fazekas rating scale (0–6 points) was used to assess severity of white matter lesions. Risk factors for the severity of white matter lesions and correlation between cerebral microbleeds and white matter lesions in the elderly with lacunar infarction were studied.P = .018; 76∼80 years’ old, OR: 3.113, 95% CI: 1.723–5.625, P = .043), carotid atherosclerosis , history of hypertension  were risk factors for the severity of white matter lesions. The white matter lesions score increased corresponding to increase in the cerebral microbleeds grade (P < .001). The white matter lesions score was higher in the cerebral microbleeds combined with the white matter lesions group than in the white matter lesions group (P < .01). After correcting the effects of age, there was a correlation between white matter lesions and cerebral microbleeds (P < .001). Logistic analysis revealed that the patients’ age , history of hypertension , systolic blood pressure , high-sensitivity C-reactive protein , homocysteine , and carotid atherosclerosis  were significant risk factors for combined cerebral microbleeds with white matter lesions in patients with lacunar infarction.The elderly (81–85 years’ old, odds ratio [OR]: 2.423, 95% confidence interval [CI]: 1.795–3.271, The elderly, carotid atherosclerosis, history of hypertension were risk factors for the severity of white matter lesions. Cerebral microbleeds were positively correlated with the severity of white matter lesions. Cerebral microbleeds (CMBs) are a type of cerebral small vessel disease. It refers to the deposition of hemosiderin and ferritin around the tiny blood vessels where leakage or rupture occurs, which in turn impairs the brain parenchyma. It is more common in the cortical–cortical and deep brain tissues. CMBs in the susceptibility weighted imaging (SWI) showed a diameter of <10 mm, and there is no edema around. The incidence of CMBs in lacunar infarction was 27%. White matter lesions (WML) are also a category of cerebral small vessel disease. WML occurs mostly in the elderly population, and Inzitari et al showed that the incidence of WML was 24% in stroke patients aged 60 to 85 years. The pathogenesis of CMBs and WML is related to destruction of the blood–brain barrier,,6 with many risk factors for disease onset. At present, there are still relatively few reports on risk factors affecting the severity of WML and the relationship between CMBs and WML is unclear. This study explored risk factors for severity of WML and its correlation with CMBs in the elderly with lacunar infarction.Currently, ischemic stroke is a severe global problem with high recurrence rate that imposes severe human-health burden.22.1 rating scale (0–6 points) was used to assess severity of WML. The periventricular hyperintensities (PVH) and the deep white matter hyperintensities (DWMH) were scored separately and subsequently added as the total score. Overall, the grading was as follows. Cerebral ventricular high-signal score: 0 points, no high-signal lesions; 1 point, cap-like or pencil-thin-like lesions; 2 points, lesions showing smooth halos; and 3 points, high-signal irregularities around the ventricles. DWMH: 0 points, no high-signal lesions; 1 point, spotted lesions; 2 points, lesions beginning to fuse; and 3 points, lesions showing large-area fusion. With regard to the total score, the score was divided into 1 (1), 2 (2–3), and 3 (4–6); and per severity of CMBs, it was divided into 0 to 3 grades: Grade 0, absence of CMBs lesion; grade 1, 1 to 5 lesions; grade 2, 6 to 10 lesions; and grade 3, >10 lesions. Inclusion criteria were as follows: lacunar infarction patients who met the diagnostic criteria per 2010 Guidelines for the Prevention and Treatment of Acute Ischemic Stroke in China and were confirmed through brain MRI and carotid ultrasound examination; aged 70 to 85 years. All patients or their family members signed the informed consent form. The study was approved by the hospital's Ethics Committee. Exclusion criteria were as follows: acute large area cerebral infarction, acute cerebral hemorrhage or previous cerebral hemorrhage history; serious heart, liver, and kidney organ dysfunction; pregnant women; traumatic brain injury.Patients with lacunar infarction who were admitted to the Neurology Department of the Tai’an Central Hospital and hospitalized from September 2016 to November 2017 were included. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI) were performed. According to the results of previous clinical studies, at the level of α = 0.05, to achieve 90% of the test efficacy, a total of 175 patients were enrolled. According to the results of brain magnetic resonance imaging (MRI), the patients were divided into the WML group and non-WML group. Fazekas et al's2.2We assessed carotid Atherosclerosis by a Color Doppler ultrasound system , including carotid intima-media thickness (CIMT) and plaque Crouse score. The judgment criteria are that in longitudinal sections, CIMT value: ≤1.0 mm was considered to be healthy, >1.0 mm indicates the formation of carotid atherosclerosis. We used Crouse scoring to assess plaques. The judgment criterion of Crouse scoring is the maximum thickness (millimeter) of each plaque. The sum of the bilateral maximum CIMT values was calculated to determine Crouse score. If the CIMT value ≤1.2 mm, the Crouse score was 0. Physicians who were unaware of the clinical data recorded Carotid ultrasonography data.2.3In this study, MRI was conducted using Siemens Magnetom Skyra 3.0 T superconducting MR , and head coil was used. All patients underwent spin-echo sequence T1WI, T2WI, FLAIR, and SWI with the following scan parameters. T1WI: TR 2000 ms, TE 32 ms, FOV 240 mm, and layer thickness 5 mm; T2WI: TR 6000 ms , TE 125 ms; FOV 240 mm; and layer thickness, 5 mm. FLAIR: TR, 8500 ms; TE, 102 ms; FOV 240 mm; and layer thickness 5 mm. SWI: TR 27 ms; TE 20 ms; FOV 220 mm; and layer thickness 1.5 mm. In all patients, the acquired images were read by 2 experienced physicians in the imaging department, and related image data were recorded.2.4, t test was used for comparison between the 2 groups, and variance analysis was used for that between multiple groups. A rank comparison test was used for comparison between groups; data were expressed as frequency (or percentage), and χ2 test was applied for comparison between groups. A logistic regression model was used to analyze the related factors of severity of WML and combined CMBs with WML using a forward stepwise selection strategy. P value of <.05 was considered as significant difference.Statistical Package for the Social Sciences (SPSS) version 22.0 software  was used. In data conforming to normal distribution application 33.1P < .05), as shown in Table In this study, there were 130 cases of WML and 45 cases of no WML in patients with lacunar infarction. Patients were divided into 4 groups according to the degree of WML. The patients’ age, history of hypertension, and indicators of carotid atherosclerosis  were significantly different in patients with different degrees of WML , carotid atherosclerosis , history of hypertension  were risk factors for the severity of WML . Significant variables in univariate analysis, such as age, history of hypertension, arteriosclerosis, and according to previous studies, variables, which may be statistically significant such as sex, homocysteine (HCY), and baseline systolic blood pressure, were independent variables. The age of the patient is divided into 3 age groups, 70 to 75 years’ old, 76 to 80 years’ old, 81 to 85 years’ old. The results showed that the elderly . The comparison between the two groups showed that the difference between CMBs0 and CMBs1, CMBs0 and CMBs2, CMBs0 and CMBs3 was statistically significant (P < .01). The DWMH score increased with the severity of CMBs. There was a statistically significant difference in DWMH scores of patients in different grades of CMBs (P < .001). The comparison between the 2 groups showed that the difference between CMBs0 and CMBs1, CMBs0 and CMBs2, CMBs0 and CMBs3 was statistically significant (P < .05). WML total score increased with the severity of CMBs. There was a statistically significant difference in WML total scores of patients in different grades of CMBs (P < .001). The comparison between the 2 groups showed that the difference between CMBs0 and CMBs1, CMBs0 and CMBs2, CMBs0 and CMBs3, CMBs1 and CMBs3 was statistically significant (P < .01) . The DWMH score was higher in the CMBs combined with the WML group than in the WML group, and the difference was statistically significant (P < .001). The WML total score was higher in the CMBs combined with the WML group than in the WML group, and the difference was statistically significant (P < .001) .In a scatter plot, considering WML score as abscissa and number of CMBs as ordinate Fig. , the ave3.6P < .001 indicating statistically significant differences, as shown in Table After correcting the effects of age, the results of this study showed that there was a correlation between WML grade and CMBs grade, total WML score and CMBs’ number, total WML score and CMBs grade, WML grade, and CMBs’ number, with r-value of 0.557, 0.569, 0.570, and 0.613, respectively, and each 3.7P = 0.019; 76∼80 years’ old, OR: 1.857, 95% CI: 1.075–3.207, P = 0.031), history of hypertension , systolic blood pressure , hs-CRP , HCY , and carotid atherosclerosis  were significant risk factors for combined CMBs with WML in patients with lacunar infarction . Significant variables in univariate analysis, such as age, history of hypertension, arteriosclerosis, and according to previous studies, variables which may be statistically significant such as sex, coronary heart disease, hyperlipidemia and antithrombotic use, systolic blood pressure, diastolic blood pressure, high-sensitivity C-reactive protein (hs-CRP), HCY were used as independent variables. Logistic analysis revealed that the patients’ age  is improving. The International Stroke Conference and the European Stroke Conference of 2008 proposed the concept that small vascular disease causes big trouble.P < .05). Studies have shown that the severity of WML increases with the patients’ age, an increase of the proportion of hypertension history, and aggravation of carotid atherosclerosis the degree. Moreover, logistic regression analysis of ordered multiclassification of severity of WML revealed that the elderly, carotid atherosclerosis history of hypertension were risk factors for the severity of WML. Grueter and Schulz and Simpson et al's,11 studies have shown that age and hypertension are important risk factors for WML in patients with ischemic stroke. Also, for every 10 years of age, the incidence of WML increases by a factor of 2 to 3, since myelin necessary protein and lecithin, which constitute the myelin sheath of the white matter, are produced at an early age and show decreasing levels in adults through the aging process. Veerhaaren et al showed that the severity of hypertension was positively correlated with the occurrence of WML. Hypertension aggravated the progression of WML, and high blood pressure, and blood pressure circadian rhythm, and its variability affected the development of WML. This study showed that the increasing severity of carotid atherosclerosis results in an increasing degree of WML; however, the relationship between carotid atherosclerosis and WML is controversial. Patankar et al reported that macrovascular disease has a protective effect on distal small blood vessels, thereby reducing the occurrence of WML. However, some studies said that carotid atherosclerosis was unrelated to the occurrence of WML. This study did not indicate significant differences in sex between the WML group and the control group in patients with lacunar infarction, which is inconsistent with most reports. Most reports outside of China suggested that women were more likely to have WML than men, possibly due to changes in the hormone levels. Estrogen has a protective effect on the brain cells and can reduce their sensitivity to hypoxia. In postmenopausal women, the level of estrogen declines, which may lead to ischemia of the white matter and hypoxia.The results from analyses of clinical baseline data at different levels of WML indicated that the patients’ age, history of hypertension, carotid atherosclerosis index CIMT, and Crouse score were significantly different between the groups with different degrees of WML . As the severity of CMBs increased, the score of PVH, the score of DWMH, and the total score of WML also increased. The score of PVH, the score of DWMH, and the total score of WML were higher in the CMBs combined with the WML group than in the WML group, and the difference was statistically significant (P < .001). Partial correlation analysis between WML and CMBs showed that the severity of CMBs was positively correlated with WML. Yamada et al reported that WML and arteriosclerosis were risk factors for CMBs, and the number of CMBs was correlated with the severity of PVH and the severity of DWMH. Igose et al reported greater severity of PVH in patients with CMBs versus the control group, and positive correlation between the severity of CMBs and the PVH. Thus, the severity of CMBs was positively correlated with the severity of WML. But why is there such a correlation between them? We further explore the pathological manifestations and pathogenesis of the two. With regard to associated pathological changes of CMBs and WML, CMBs is characterized by deposition of hemosiderin around the diseased blood vessels, and WML by the demyelinated nerve fibers caused by gliosis, whereas in case of combined occurrence of both conditions, disruption of the blood-brain barrier can lead to CMBs,,19 as well as WML, and hypertension-induced vascular hyalinosis, arteriosclerosis are risk factors for CMBs and WML. Further study is needed to determine whether these are common pathways. In addition, further discussion is also needed, whether there is other pathogenesis.In this study, CMBs were classified into 0 to 3 grades according to their number, and WML was classified into 0 to 3 grades according to the WML score too. The results showed that in a scatter plot, the average value of the CMBs’ number increased corresponding to increase in the WML score ( Biffi et al reported that in patients with cerebral hemorrhage, the detection rate of WML was increased. Another study reported an increased detection rate of cerebral hemorrhage in patients with WML, suggesting that combined CMBs with WML are associated with risk of cerebral hemorrhage. Therefore, clinicians should pay close attention to the possible occurrence of cerebral hemorrhage in patients with ischemic stroke with combined CMBs with WML undergoing thrombolysis and antithrombotic therapy. Characteristics of combined CMBs with WML showed potential as an early warning sign of cerebral hemorrhage.To demonstrate the risk factors associated with CMBs and WML, 2-class logistic regression analysis was performed. As a result, the patients’ age history of hypertension, systolic blood pressure, hs-CRP, HCY, and carotid atherosclerosis were risk factors for WML combined with CMBs in patients with lacunar infarction. In patients with lacunar infarction, there are many common risk factors for CMBs combined with WML, which suggests that CMBs and WML have different pathological results under the same elements. The combined occurrence of both conditions can increase the risk of ischemic stroke, as well as lead to cerebral hemorrhage. A study has shown that patients with higher CMBs’ number were more likely to have cerebral hemorrhage.In summary, there was a significant correlation between CMBs and WML in the elderly with lacunar infarction, and the severity of the 2 was positively correlated. Risk factors were consistent between CMBs and WML. Except for the patients’ age, which is an uncontrollable factor, several of the identified factors can reverse or delay the development of disease through early detection, diagnosis, and treatment, and consequently prevent brain injury. Improved understanding of the occurrence of vascular complications improves the patients’ quality of life and allows future evidence-based prevention and treatment of patients with CSVD in clinical practice. There are some deficiencies in this study. First, the sample size is small, and second, the selected population is limited in the elderly with lacunar infarction. Therefore, future research needs to be carried out in large sample size and in a wider population.Conceptualization: Hao-yuan Gao, Fang-fang Zhao, Qing-jian Wu.Data curation: Hao-yuan Gao, Zhi-gao Wang, Qing-jian Wu.Formal analysis: Qing-jian Wu.Investigation: Fang-fang Zhao, Ying-chun Liang, Yuan Gao, Xin-hong Liu, Qing-jian Wu.Methodology: Fang-fang Zhao, Ying-chun Liang, Yuan Gao, Xin-hong Liu, Tao Wang, Qing-jian Wu.Project administration: Fang-fang Zhao, Ying-chun Liang, Tao Wang, Qing-jian Wu.Resources: Qing-jian Wu.Supervision: Xin-hong Liu, Qing-jian Wu.Writing – original draft: Yu-ni Zhou.Writing – review & editing: Yu-ni Zhou, Hao-yuan Gao.


Intensive livestock farming has become indispensable to meet the rapidly increasing demand for animal-based nutrition in low- and middle-income countries (LMICs) where antimicrobials are frequently used for treatment and prophylactic or metaphylactic purposes. However, very little is known about the trends of antimicrobial use (AMU) in dairy animals in LMICs. The objective of this study was to quantify AMU in two large commercial dairy farms in Pakistan. A retrospective study was conducted at two large corporate commercial dairy farms located in Punjab province for the year 2018. AMU was calculated using three metrics: active ingredient  and milligrams per population unit , which quantifies the amount of AI used, and antimicrobial treatment incidence , which estimates the per-day number of treatments to 1,000 cows. Total on-farm AMU was found to be 138.34 kg, 65.88 mg/kg, and 47.71 DDDA/1,000 cow-days. Measured in ATI, aminoglycosides , penicillins , and tetracyclines  were the most frequently used antimicrobial classes. A total of 42.46% of all the antimicrobials used belonged to the critically important antimicrobials for human medicine as defined by the World Health Organization. Considerably high AMU was found compared to other farm-level studies across the world. This was the first study to quantify AMU in the dairy industry in Pakistan. Our results showed that corporate commercial dairy management practices are associated with increased antimicrobial consumption and highlight the need for antimicrobial stewardship programs to encourage prudent use of antimicrobials in commercial dairy. Antimicrobial resistance (AMR) has been considered a global health problem, and the situation is worse in low- and middle-income countries (LMICs) due to lack of responsible antimicrobial use (AMU) and inadequate antimicrobial stewardship . Owing tThe dairy sector in Pakistan plays a significant role in its agriculture-based economy. Pakistan is one of the world's top milk producers, with an estimate of 45.8 million tons of milk produced in the year 2018 . The majAccording to FAOSTAT 2018, Pakistan stands at 3rd (13.6 million cattle heads) and 11th (16.8 million tons) in terms of the number of cattle and per-year milk production, respectively, but 128th (3.4 L/day) in terms of yield per animal , 15.Although NAP-AMR urged the monitoring and reduction in the level of AMU in animals, nationwide surveillance to monitor AMU in livestock has not been established yet . TherefoTo evaluate quantitative AMU, a retrospective study was conducted in two large corporate commercial dairy farms located in Punjab province for the year 2018. Both farms were automated semi-controlled and had maintained exotic cattle (Holstein-Friesian) with a total animal count of 5,588, consisting of 2,480 milking cows, 1,506 heifers, and 1,602 calves, taken as average for the year 2018 . As a stDrug inventory output records  from January 1st to December 31st for the year 2018 were accessed after signing an agreement permitting drug inventory data access and ensuring farm anonymity and secrecy in any form of publication. For the detailed product composition and dosage information, market, and respective product websites were visited. Data were maintained in columns as product name, active ingredients (AIs), concentration, and labeled dosage. Calculations were made for each AI, categorized regarding its class and the labeled treatment route using Microsoft Office Excel 2016. AMU was calculated in three different metrics: 1) AI, 2) antimicrobial treatment incidence (ATI), and 3) milligrams per population unit (mg/PU). Metrics 1 and 3 quantify the amount of AI used, whereas metric 2 estimates the number of treatments per day over 1,000 cows.The total amount of AI in milligrams (mg) for each product is determined using the labeled concentration and quantity used. For products comprising more than one AI, mg were calculated separately for each ingredient. For the prodrug compositions and the concentrations given in international units (IU), AI mg were calculated using the methodology defined by World Organization for Animal Health (OIE) and European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) [European Medicine Agency (EMA)] , 19. ForEquations 1 and 2). One DDDA (mg/cow-day) is defined as the average labeled daily dose, recommended to be administered per day, in mg per kg of the animal body weight multiplied by the approximate body weight of a dairy cow taken as 600 kg (Equation 3) (Equation 4). ANadj is used for the calculation of ATI for each AI against every product in the drug inventory  (Equations 1–4). Individual ATIs were then added up for each antimicrobial and drug class with respect to the labeled route of treatment.Total amount of AI used in terms of the number of treatments as per the defined daily dose animal (DDDA) over 1,000 cows per day is evaluated as ATI (ation 3) . For lonation 3) . For proation 3) , 22. As ation 3) , and theation 3)   is a decimal ratio between the actual numbers of treatments and the maximum possible number of treatments within the days of study, i.e., Population unit (PU) is defined as the composite weight (Wc) in kg of all the animals in the study. mg/PU is the amount of AI in mg used per kg of PU. PU was considered constant throughout the study period.A total of 42 antimicrobial products  were used, containing 28 different AIs  during the year 2018 . Of the AI analysis showed that in terms of ATI, oxytetracycline , penicillin G , and cefalonium  were the most frequently used antimicrobial AIs. Oxytetracycline , gentamicin , and enrofloxacin  were the most frequent antimicrobials used via parenteral administration. ATI values for the antimicrobials cefalonium , penicillin G , and neomycin  used in intramammary compositions were higher than those for the parenteral compositions, i.e. 0, 3, and 0 DDDA/1,000 cow-days, respectively. In terms of the AI quantities, oxytetracycline , streptomycin , and sulfadimidine  were commonly used antimicrobials . A totalA total of 21% (6/28) of the antimicrobials used at studied farms belonged to the critically important with highest priority (CIA-HtP) category of antimicrobials for human medicine, while 32% (9/28) belonged to the high priority (CIA-HhP) category according to WHO  24). AT. AT24). Globally, several initiatives have called for the prudent use of antimicrobials in food animals to prevent AMR crisis , 26. TheA shift toward intensive livestock farming due to an increase in animal-based protein demand in LMICs has been positively linked with the excessive use of antimicrobials in food animals. In this study, we found an excessive amount of antimicrobial consumption in two of the corporate dairy farms, a growing industry in Pakistan. The total AMU of 66 mg/kg identified in this report is substantially higher than the global average of 45 mg/kg in cattle  but relatively high ATI values suggests inappropriate metaphylactic or prophylactic AMU. ATI overestimation was checked by adjusting the weight of young stock to that of adult dairy cattle and by calculating per-day average DDDA for long-term preparations as reported previously , 23. HowLU/LUpop−risk/year, which would be equivalent to 3.48 DDDA/1,000 cow-days from Austria  was considerably higher than that reported from other countries, i.e., 4.2 DDDA/1,000 animal-days and 5.43 DDDA/cow/year or 14.88 DDDA/1,000 cow-days reported from Pennsylvania and Wisconsin, United States, respectively , 27; 14. Austria ; 3.24 DD Austria ; and 8.6 Austria .We identified aminoglycoside and penicillin as the most commonly used antimicrobials in our study. In contrast, similar studies from European regions have shown penicillins and cephalosporins to be the most common antimicrobials used in the dairy sector , 33–35. In this study, we observed a high intensity of AMU in the two corporate commercial dairy farms, with 91.4% of treatments consisting of critically and highly important antimicrobials for human medicine . This fiThe lack of internationally accepted standard methodology and of an abbreviation system for reporting AMU at the farm level hinders the quantification and comparison of data among different locations , 33, 37.One of the main limitations of our study is that it was based on a convenient sample of farms that are not representative of the country's commercial dairy sector. Our results are therefore not generalizable to the rest of the Pakistani dairy sector. Another limitation is that, as the AMU calculations were based on inventory record data and the animal number was adjusted for a single dairy cow, AMU for each age group  is not available, which may have led to the underestimation or overestimation of AMU in cows.This is the first attempt to calculate AMU in dairy animals in Pakistan. The total AMU was considerably higher when compared to that in international studies, with a large percentage of animal use of critically important antimicrobials for human medicine. Our baseline data will help policymakers to devise suitable antimicrobial stewardship programs for the emerging corporate commercial dairy sector in Pakistan.All datasets presented in this study are included in the article/MM: conceived and supervised the study. MM and MU: methodology. MN, RA, QA, JA, and MU: data collection and validation. MU and FF: data analysis and results interpretation. MM, MU, BA, MZ, and QA: manuscript writing and review. 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.


Background: Surgical repair of acute type A aortic dissection (ATAAD) has high risk and mortality, and there are few biomarkers of postoperative in-hospital mortality until now. This study investigated the association between WW domain–containing transcription regulator protein 1 (TAZ) and the postoperative in-hospital mortality of ATAAD patients.Methods: This is a retrospective cohort study. Data and blood samples were collected from 95 consecutive patients with ATAAD who underwent surgeries in our hospital from July 1, 2016, to December 31, 2016. The data collection included all the risk factors introduced by the modified EuroSCORE . The predictors of postoperative in-hospital death were confirmed by univariate regression analysis. Multivariable logistic regressions were used to analyze the association of the preoperative plasma level of TAZ and the postoperative in-hospital mortality of ATAAD patients. In addition, we used the generalized additive model to identify non-linear relationships.Results: Three models were used in the multivariable logistic regression analysis of the relationship between the preoperative plasma level of TAZ and postoperative in-hospital death. In the crude model, the preoperative plasma level of TAZ showed a positive correlation with postoperative in-hospital death . In adjusted model I and adjusted model II, similar results were found . The risk of postoperative in-hospital death in the preoperative plasma level of the TAZ≥12.70 ng/mL group was 10.08 times  that of the preoperative plasma level of the TAZ <12.70 ng/mL group.Conclusions: The high preoperative plasma level of TAZ suggested poor surgical prognosis for ATAAD patients. The patients with a preoperative plasma level of TAZ ≥ 12.7 ng/ml had much higher postoperative in-hospital mortality. Aortic dissection (AD), especially the acute type A aortic dissection (ATAAD) with dissected ascending aorta, is the most life-threatening vascular disease , 2. BaseWW domain–containing transcription regulator protein 1 (TAZ) is ubiquitous in the human body and mainly found downstream of the Hippo pathway, which regulates many fundamental biological processes . Our preIn this study, we investigated the preoperative plasma levels of TAZ of patients with ATAAD and studied the association between the preoperative plasma level of TAZ and the postoperative mortality of ATAAD patients.A study of the prediction and the treatment of Acute Aortic Syndrome (ChiCTR1900022637)” from July 1, 2016, to December 31, 2016, were included for the purpose of this analysis. After excluding nine patients with genetic syndrome related to aortic disease, such as Marfan, Turner, Loeys–Dietz, or Ehlers–Danlos syndrome, 95 consecutive patients were involved in the final analysis  and were consistent with the principles outlined in the Declaration of Helsinki. All patients (104) with ATAAD who underwent surgeries in our hospital and enrolled in “analysis . All theAll the patients received the surgery in 24 h after the onset of aortic dissection, and blood samples were collected from these patients before the surgical intervention was initiated.After collection, the blood sample was anticoagulated with sodium citrate and then centrifuged for 15 min at 3,500 rpm at 4°C. All the samples were divided into 0.5-ml per centrifuge tubes, stored at−80°C, and only used for this study. The mean sample storage duration was 84.50 days when ELISA was performed. The preoperative plasma levels of TAZ were determined by ELISA , as previously described . All ELIA study of the prediction and treatment of Acute Aortic Syndrome (ChiCTR1900022637),” which was established based on standardized electronic medical records from our hospital. The data collection included all the risk factors introduced by the modified EuroSCORE . All analyses were completed by the statistical software packages R  and EmpowerStats .Data were expressed as frequency and percentage, as mean ± standard deviation (SD), or as median and interquartile range (IQR). than 10% , which in = 1); septic shock (n = 1); lung infection, respiratory failure (n = 1), renal failure, paraplegia, heart failure (n = 1); cerebral infarction (n = 2); multiple-organ failure, electrolyte disorder, anemia (n = 1); cardiogenic shock, ventricular fibrillation (n = 1); distal dissection rupture, tachycardia (n = 1)]. The average preoperative plasma level of TAZ of these individuals was 11.76 ± 3.00 ng/ml. Compared with the surviving patients (11.55 ± 2.98 ng/ml), dead patients had a significantly higher preoperative plasma level of TAZ (13.80 ± 2.45 ng/ml) (P = 0.03).The results of univariate analysis showed that the preoperative plasma level of TAZ was correlated with more postoperative in-hospital death. We also found that age, gender, BMI, systolic blood pressure, diastolic blood pressure, heart rate, hypertension, smoking history, recent myocardial infarction, previous cardiac surgery, cardiac tamponade, LVEF, serum creatinine, critical preoperative state, unstable angina, d-dimer, platelet, fibrinogen, c-reactive protein, troponin I, ascending aorta diameter, pleural effusion, pericardial effusion, coronary arteries involved, cardiopulmonary bypass time, and cross-clamp time were not associated with postoperative in-hospital death in this cohort .Univariate linear regression models were used to evaluate the associations between TAZ expression and postoperative in-hospital death after adjusting for age, sex, BMI, recent myocardial infarct, serum creatinine, cardiac tamponade, and cardiopulmonary bypass time . The redP = 0.04). In adjusted model I and adjusted model II, similar results were indicated .The multiple regression analysis results are shown in P = 0.02) that of the preoperative plasma level of the TAZ < 12.70 ng/mL group P = 0.02) that of the preoperative plasma level of the TAZ < 12.7 ng/mL group.As demonstrated in In the history of ATAAD, the mortality of untreated patients with ATAAD is reported to be ~1–2% per hour after occurrence, 50% at the end of the third day, and up to 90% within 30 days –15. MediTAZ exists in most human tissue, and its functional role is critical in the cardiovascular system , 20, 21.Thus, this study relied on the clinical data to determine whether there was an association between the preoperative plasma level of TAZ and the severity of ATAAD. The plasma level of TAZ in blood had a significant positive relation to postoperative in-hospital death in all the models. In the crude model, postoperative in-hospital death increased 33% as the preoperative plasma level of TAZ increased 1 ng/ml. In adjusted model I and adjusted model II, the increase in postoperative in-hospital death was 35 and 35%, respectively, when the preoperative plasma level of TAZ experienced an increase of 1 ng/ml. In adjusted model I, basic patient data, such as age, sex, and BMI, were chosen as variables. According to our clinical experience, recent myocardial infarct, serum creatinine, cardiac tamponade, and cardiopulmonary bypass time were added to adjusted model II. After that, we determined that a preoperative plasma level of TAZ = 12.70 ng/ml was a statistically significant cutoff point using the ROC curve. The postoperative in-hospital death of patients with the preoperative plasma level of TAZ ≥ 12.70 ng/ml was 10.08 times that of patients with TAZ < 12.70 ng/ml. This outcome indicates to aortic surgeons that a high preoperative plasma level of TAZ means poor surgical prognosis for ATAAD patients.Age ≥70 years, previous cardiac surgery, cardiac tamponade, and recent myocardial infarction were reported as independent postoperative in-hospital predictors of mortality , 17. HowSeveral limitations exist in this study. First, this is a retrospective cohort study and provides only weak evidence between exposure and outcome, and it is difficult to distinguish between cause and effect. Second, some patients were diagnosed by the CTA from other hospitals before surgery, and it was difficult to get these CTA to do a detailed analysis, so we used data of clinical malperfusion, such as recent myocardial infarction, critical preoperative state, and cardiac tamponade. Finally, because the study population contains only 95 ATAAD patients who underwent surgery in a very short period (6 month), the results may not be generalizable to all ATAAD patients. Considering the fact that only 9 deaths occurred, the correlations and statistical analyses performed to associate the preoperative plasma level of TAZ with mortality could be improved with a larger prospective study population in the future.In conclusion, this study showed for the first time that a high preoperative plasma level of TAZ suggests poor surgical prognosis in ATAAD patients and that patients with the preoperative plasma level of TAZ ≥ 12.70 ng/ml had much higher postoperative in-hospital mortality. As a result, TAZ is related to surgical mortality of patients with ATAAD and merits rigorous study in the future.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Beijing Anzhen Hospital . The patients/participants provided their written informed consent to participate in this study.WJ, YZ, and HZ were expected to have made substantial contributions to the conception. YX and HL helped in sample analysis and contributed to analyzing the results. WJ, YX, and HL play major roles in writing and revising the manuscript. All authors read the manuscript and approved the final 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.


Strongly associated with obesity, non-alcoholic fatty liver disease isconsidered the hepatic manifestation of the metabolic syndrome. It presentsas simple steatosis and steatohepatitis, which can progress to cirrhosis andits complications. Among the therapeutic alternatives is bariatric surgery.To compare the effect of the two most frequent bariatric procedures (sleeveand bypass) on liver disease regarding to epidemiological, demographic,clinical and laboratory parameters. The results of intraoperative and 12 months after surgery liver biopsies wereused. The NAFLD activity score (NAS) was used to assess and compare thestages of liver disease. Sixteen (66.7%) patients underwent Bypass procedure and eight (33.3%) Sleeve.It was observed that the variation in the NAFLD activity score wassignificantly greater in the Bypass group than in Sleeve (p=0.028) and therewas a trend regarding the variation in fibrosis (p=0.054). Both surgical techniques were effective in improving the hepatic histology ofmost operated patients. When comparing sleeve and bypass groups, bypassshowed better results, according to the NAS score. Non-alcoholic fatty liver disease (NAFLD) has a global distribution and is considerednowadays the most common liver disease in the west industrialized countries,probably because of the association with obesity, type 2 diabetes (DM2),dyslipidemia and metabolic syndrome. The prevalence of NAFLD is reported as 6-35%,with an average of 20%, in the general population,There is a strong evidence that NAFLD represents the hepatic component of themetabolic syndrome, characterized by obesity, hyperinsulinemia, insulin resistance(IR), DM2, hypertriglyceridemia and systemic arterial hypertension (SAH). Obesity isa common and well-documented risk factor for NAFLD. In patients with severe obesityundergoing bariatric surgery, the prevalence of NAFLD can exceed 90%, with up to 50%of patients presenting steatohepatitis (NASH) and 5% cirrhosisAbdominal ultrasound is widely used as the first line in the investigation of NAFLDand evidence the accumulation of fat when more than 33% of hepatocytes havesteatosis. Liver biopsy is the gold standard method for the diagnosis of NAFLD,being able to assess the degree of fatty infiltration, hepatocellular damage,inflammation and fibrosis. The presence of hepatocellular ballooning in associationwith steatosis is the key to the differential diagnosis between simple steatosis andNASH,All patients with NAFLD should undergo interventions to promote a healthier lifestyleand strict control of the metabolic risk factors associated with NAFLDObesity and DM2, isolated or linked by metabolic syndrome, are the most importantrisk factors in the genesis of NAFLD. The role of bariatric surgery comes up in thiscontext. Several consistent studies over the past few years, culminating in thepublication of Philip Schauer in 2017-,,-,-,,,,-,,,Although there are still no randomized clinical trials evaluating the role ofbariatric surgery in the treatment of NAFLD, there are several retrospective andprospective studies in the literature, in addition to a few meta-analyzes, whichevaluate the effect of surgical treatment on NAFLD,,Roux-en-Y bypass (bypass) and vertical gastrectomy (sleeve) have been compared inseveral studies to determine which one has the greatest benefit in weight loss or inresolving obesity-related comorbidities. However, there is few knowledge about whichof these techniques is associated with the best results on NAFLD. There are fewcomparative studies and these are small series with a large number of biases, suchas heterogeneity of groups and assessment systemsIn a group of obese patients, the main objective of the present study was to comparethe bariatric sleeve and Roux-en-Y bypass techniques and their effects on NAFLD,also in epidemiological, demographic, clinical and laboratory parameters.The study was submitted to and approved by the Ethics Committee of the institution,where it was carried out. CAAE: 90475215500005335.A retrospective study that evaluated patients undergoing bariatric surgicalprocedures by the same surgical team, between 2014 and 2016, at Irmandade daSanta Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.Only patients with intraoperative and postoperative liver biopsy were included.The average time between biopsies was 12 months.Demographic characteristics (gender and age), clinical parameters  and laboratory , histopathological analysis and NAS scoreAll procedures were performed laparoscopically.® 2.0.The sleeve surgery was made with the dissection of the greater gastric curvature3 cm from the pylorus to the esophagogastric flexure. The gastric transectionwas calibrated with a 36F bougie and reinforcing the staple line with continuoussuture with CaprofylIn the bypass surgery, a 4 cm gastric pouch was done using a 36F bougie. The Rouxlimb used to be 100cm and the biliopancreatic limb used to be 150 cm.Gastroenteric anastomosis was performed laterally with a linear staplercalibrated by a 36F bougie.All liver samples were analyzed in the hospital’s pathology laboratory by asingle professional experienced in liver pathology. The NAFLD activity score(NAS) was used to assess and compare the stages of liver diseaseCategorical results were presented using frequency and percentage and wereanalyzed using the XTwenty-four obese patients who underwent bariatric surgery were evaluated, of which16 (66.7%) undergoing bypass and eight sleeve, with a mean segment time of 21.3±16months and 15.5±12.5 months, respectively (p=0.380). 68.8% of patients undergoingbypass were women, on the sleeve group, 75% (p=0.571); 31.3% were hypertensive vs.37.5% in the sleeve (p=0.553); in the bypass group, age and maximum weight were38.6±11.3 years and 119.1±14.1 kg respectively vs. 36.7±8.4 years, p=0.692 and119.1±13.5, p=0.999 in the sleeve group. Furthermore, the two techniques were alsosimilar in terms of weight loss  and the excess weight lost .Evaluating the evolution of the NAFLD degree on the second biopsy compared to thefirst, 19 (79.2%) patients showed improvement, two (8.3%) remained in the samedegree and three (12.5%) worsened. There was a significant association between theevolution of NAFLD and the surgical procedure performed (p=0.024). In the sleevegroup, three (37.5%) worsened the level of NAFLD vs. no patient in the bypass group.The intensity of variations was compared between groups with no significantdifference between them (p>0.05), except for the NAS score shown in In our country, bypass is still the most performed bariatric technique; but, inrecent years, there has been an important increase in the number of verticalgastrectomy, which follows the worldwide trend of technical preference nowadaysHistorically, patients with morbid obesity or those with clinical signs and symptomsof metabolic syndrome had in the operations of mixed character (bypass) - withrestrictive and disabsorptive component -, their most frequent indication. Purelyrestrictive procedure - vertical gastrectomy - a relatively newer technique, wasinitially indicated for patients with grade II obesity or very high BMI levelsgreater than 60 kg/m², those in which the necessary weight loss was not too much orthose that mixed operations has became impractical due to the great excess ofweight. Thus, sometimes it becomes difficult to compare the results between thetechniques, since the patients generally presented important clinical andepidemiological differences, making statistically different groups.In the present study, evaluating the demographic characteristics of both groups -bypass and sleeve - it was noticed that there were no statistical differencesbetween them. Gender, breed and age were similar. SAH was present in approximately30% of patients. There were no diabetic patients and the mean blood glucose waspractically the same in both groups, 100 mg/dl. Regarding weight, BMI, laboratorytests - platelets, alkaline phosphatase, ferritin, gamma-GT, glycemia, AST and ALTpreoperatively - the groups also showed similarity. This parity between the groupscontributes to a more reliable comparative analysis with a lower incidence ofbias.2 and 13.4±2.7 kg/m2 in the bypass and sleeve,respectively. This reduction represents the average loss of approximately 84% ofexcess body weight for both techniques. As previously published by several authors,and more recently by Peterli et alAlready widely discussed and consolidated in the literature, these bariatricprocedures have an important effect on weight loss. In the present study, in themean follow-up of 12 months, the BMI showed an average reduction of 16.3±5.23kg/mpeptideYY(PYY), the result of the food’s earliercontact with the ileum, would be responsible for this fact. However, more recently,although there is no established pathophysiological explanation, there are studiesshowing a similar result between the sleeve and bypass regarding glycemiccontrolAnalyzing blood glucose separately, it was observed that both surgical techniqueswere effective, statistically reducing serum glucose levels by 17.3±15.7 mg/dl and12.5±9.4 mg/dl, considering bypass and sleeve respectively. When comparing the finalresults between the techniques, there is a favorable trend towards bypass (p=0.059),probably depending on a larger sample. In recent years, it has been associated withtechniques with intestinal deviation, a condition of metabolic change that wouldprovide better results on glycemic control, compared to purely restrictivetechniques.The increase in intestinal hormones such as glucagon-like peptide-1(GLP-1) and Analyzing the other laboratory tests evaluated in the study, we observed that in thebypass group there was a significant improvement in the levels of alkalinephosphatase, ferritin, gamma-GT and ALT, which did not occur in the sleeve. AST andplatelets showed no significant changes.,,,,,,,,,As previously mentioned, the mechanism by which bariatric surgery performs potentialtreatment for NAFLD is complex and has not been fully elucidated yet. It is probablyrelated to improvement of factors such as insulin resistance, lipid profile,inflammation, weight loss and adipokines, which are directly involved in thedevelopment of metabolic syndrome and, consequently, in its hepatic phenotype,NAFLD. These changes are seen right after the surgical procedure, during the phasewhen weight loss is not yet significant. It is well established that weight lossplays a fundamental role in the control of metabolic abnormalities; however,endocrinophysiological changes resulting from the operation may have a more relevanteffect in the long term on NAFLD. These findings have been confirmed by severalstudies published in the international literature. As in the present study, NAFLD inits several stages, simple steatosis, NASH and fibrosis, showed significantimprovement after the bariatric procedure, be it bypass or sleeve ,,However, it can be noticed that part of the operated patients does not improve orcould get a worse level of NAFLD, which ranges from 7-20% of patientsIn the quantitative analysis of NAFLD, the bypass group showed between the first andsecond biopsies, significant improvement in all NAS parameters , in fibrosis and in the NAS score itself. In the sleevegroup, statistical significance was observed only in the steatosis and in the NASscore. Comparing the change in the NAS score between the first and second biopsies,it was observed that this was significantly higher in the bypass group . In line with the literature, in the present study there was a significant improvementin NAFLD after bariatric procedures, both in the purely restrictive operation(sleeve) and in the mixed operation (bypass).7 and PraveenHowever, unlike the previous findings published by FroylichThe retrospective nature of the study, the small number of patients in the groups andthe possible selection biases are important limitations that must be considered whenanalyzing these results.Sleeve and bypass were effective in restoring the liver histology of most operatedpatients. BMI and blood glucose showed significant improvement in both surgicaltechniques, with no significant difference in results between them. The levels ofalkaline phosphatase, ferritin, gamma-GT and ALT decreased significantly only in thebypass group, but they did not differ from the valuesobserved in the sleeve.However, the bypass showed significantly better results in the change of the NASscore than the sleeve.


Coronavirus disease 2019 (COVID-19) has affected more than 5 million people around the world and killed more than 300,000 people; thus, it has become a global public health emergency. Our objective was to investigate the mental health of hospitalized patients diagnosed with COVID-19.t tests, one-way ANOVA and multivariable logistic regression analysis.The PTSD checklist for DSM-5 (PCL-5), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), Trauma Exposure Scale, abbreviated version of the Connor–Davidson Resilience Scale (CD-RISC-10), Perceived Social Support Scale (PSSS) and Demographic Questionnaire were used to examine posttraumatic stress disorder (PTSD), depression, anxiety, trauma exposure, resilience and perceived social support among 898 patients who were hospitalized after being diagnosed with COVID-19 in China. The data were analyzed with The results showed that the prevalence of PTSD, depression and anxiety was 13.2, 21.0 and 16.4%, respectively. Hospitalized patients who were more impacted by negative news reports, had greater exposure to traumatic experiences, and had lower levels of perceived social support reported higher PTSD, depression and anxiety.Effective professional mental health services should be designed to support the psychological wellbeing of hospitalized patients, especially those who have severe disease, are strongly affected by negative news and have high levels of exposure to trauma. Coronavirus disease 2019 (COVID-19) has affected more than 5 million people and caused more than 300,000 deaths worldwide in just a few months. The World Health Organization (WHO) declared the outbreak a pandemic in March 2020 and stated that the world was facing a global health crisis , and resAccording to previous studies, the onset of a sudden and immediately life-threatening illness can lead to posttraumatic stress disorder (PTSD) . The psyMoreover, PTSD commonly co-occurs with other psychiatric disorders over a range of populations and trauma types . Among sEvidence has shown that when PTSD and other psychiatric disorders co-occur in populations who have experienced trauma, a combined stress model with shared vulnerabilities and similar risk factors might be involved . TherefoIn addition, resilience and perceived social support are considered protective factors against an adverse psychological response. Resilience is the ability to maintain relatively stable, healthy levels of psychological and physical functioning in the context of adversity, stress or trauma . After pThis study was performed to provide information about the prevalence rates of PTSD, depression, and anxiety among COVID-19 patients in China and to explore the associated risk factors. The related factors examined were demographic variables, trauma exposure and psychosocial variables.Starting in March 2020, we recruited patients who had been hospitalized for COVID-19 at the end of January and early February in China, primarily from Wuhan in Hubei Province. The patients began to return to the hospital for reexamination in the middle of March.SD = 14.05), with a range from 16 to 92 years. Of the participants, 123 (13.7%) were younger than 20 years old, 336 (37.4%) were between 21 and 40, 370 (41.2%) were between 41 and 60, and 62 (6.9%) were over 60 years. A total of 382 (42.5%) participants were male. In terms of educational background, 127 (14.1%) participants had a diploma from a primary or secondary school, 204 (22.7%) participants had a diploma from high school or technical secondary school, 532 (59.2%) participants had a diploma from a university or technical college, and 35 (3.9%) participants had a graduate degree or above. In terms of subjective socioeconomic status, 96 (10.7%) participants were at a low level, 316 (35.2%) participants were at a below-average level, 449 (50.0%) participants were at an average level, and 37 (4.1%) participants were at an above-average level or high level.A total of 909 hospitalized patients with COVID-19 were recruited as of May 2020. After eliminating 5 participants aged under 16 years old, 1 participant who reported a history of psychiatric disease and 5 participants who were invalidated due to incomplete or careless answers, the final number of participants was 898. The sociodemographic information is shown in Table From March 22, 2020, to May 24, 2020, medical and psychological health care workers in hospitals for COVID-19 introduced this investigation to patients with COVID-19. Due to the pandemic disease prevention and control measures, the questionnaire was completed online in the WeChat application after informed consent was obtained. The method of completing the questionnaire was very simple. The participants clicked the link shared by the psychological health care workers to access the questionnaire. After answering all the questions, the patients then clicked the submit button. If the participants had any operational questions or difficulties completing the questionnaire, the psychological health care workers provided guidance. The patients were notified that online and in-person psychological counseling services were available if needed after the survey.The study design and procedures were approved by the ethics review committee of the Institute of Psychology, Chinese Academy of Sciences .PTSD was assessed with the PTSD checklist for DSM-5 (PCL-5), which was compiled by Weathers and colleagues , translaDepression was assessed with the Patient Health Questionnaire (PHQ-9), which was compiled by Kroenke, Spitzer, and Williams  and tranAnxiety was assessed with the Chinese version of the Generalized Anxiety Disorder Scale (GAD-7) . A totalTrauma exposure was assessed with the second part of the University of California at Los Angeles (UCLA) PTSD reaction index (UCLA PTSD-RI) . A totalResilience was assessed with the abbreviated version of the Connor–Davidson Resilience Scale (CD-RISC-10), which was compiled by Connor and Davidson  and reviPerceived social support was assessed with the Chinese version of the Perceived Social Support Scale (PSSS) . A totalParticipants were asked to report their sex, age, educational background, socioeconomic status and the impact of news reports. One item was used to assess subjective socioeconomic status  ranging from 1 (low) to 4 (above-average to high). Two items were used to assess the negative impact of news reports  and the positive impact of news reports  ranging from 1  to 6 .t tests and one-way ANOVA were used to examine differences in sociodemographic information among patients with different scores for PTSD, depression and anxiety. Multivariate logistic regression analyses were performed to identify the risk factors for PTSD, depression and anxiety. All statistically significant associated variables in Table p-value of less than .05 considered statistically significant.Data were analyzed with SPSS 26.0. Independent sample Using a cutoff score of 33, 119 (13.2%) patients had probable posttraumatic stress symptoms. Using a cutoff score of 10, the prevalence of depression was 21.0%, and the prevalence of moderate, severe and very severe depression was 11.5, 6.3 and 3.2%, respectively. Using a cutoff score of 10, the prevalence of anxiety was 16.4%, and the prevalence of moderate and severe anxiety was 10.9 and 5.5%, respectively. Among the participants with PTSD, 77.3% had comorbid depression and 65.5% had comorbid anxiety. Among the participants with depression, the proportion with comorbid anxiety was 65.6%. In total, 8.2% of the participants had three disorders.The results of the multivariable logistic regression analysis are presented in Table To the best of our knowledge, this is the first study to investigate the prevalence and predictors of psychiatric symptoms among hospitalized COVID-19 patients during the acute treatment period. The current study showed that the prevalence rates of PTSD, depression and anxiety among hospitalized patients with COVID-19 were high and that these disorders often co-occurred. Negative media reports, exposure to trauma and perceived social support were shared risk and protective factors of PTSD, anxiety and depression. Resilience was a protective factor only for depression.In this study, the prevalence of PTSD, depression and anxiety among hospitalized patients with COVID-19 was 13.2, 21.0 and 16.4%, respectively. The prevalence of PTSD was lower than the prevalence in previous studies with patients with similar infectious diseases , 13 but The study showed that PTSD, depression and anxiety are often comorbid. PTSD, depression, and generalized anxiety disorder (GAD) are all thought to stem from high levels of general distress in the acute stage of trauma and are likely to become a symptom network . A netwoThis study found that negative media reports, trauma exposure and perceived social support were shared risk and protective factors of PTSD, anxiety and depression. Resilience was a protective factor only for depression. First, infection with an unknown virus for which there are no known treatments increases patients’ perception of a threat to their lives, which in turn can lead to the development of mental disorders. Second, as one aspect of trauma exposure, the degree of subjective fear plays an important role in inpatients’ susceptibility to mental health problems. Previous studies have reported that the subjective experience of fear is more strongly related to PTSD than objective exposure alone . As evidIn addition, resilience was a protective factor against depression, and perceived social support was a protective factor against PTSD, depression and anxiety. A possible reason is that external resources are more important than internal resources for patients infected with COVID-19. Social support can not only affect individuals directly by improving their health behaviors but can also affect individuals indirectly by providing resources to individuals , 28. ResThere are some limitations of this study. First, our participants were a convenience sample mainly recruited from hospitals in Wuhan. It is uncertain whether our findings can be generalized to all patients during this pandemic. Second, the data used in this study came from patients’ self-reported questionnaires. In the future, clinical diagnoses of PTSD, depression and anxiety should be used. Third, this was a cross-sectional study. Directionality cannot be determined between the “predictors”  and mental health symptoms. The pattern and long-term clinical course of the psychiatric effects of COVID-19 should continue to be investigated, and there should be widespread awareness of the possible psychiatric impacts of a future reemergence of COVID-19. Future studies should exploit existing datasets and ongoing longitudinal studies in addition to establishing new cohorts to collect detailed information on psychological factors.The findings of this study indicate that timely integrated mental health interventions are warranted for patients during the acute treatment phase of COVID-19. First, health authorities need to identify high-risk groups based on sociodemographic information and implement early psychological interventions. Females, elderly patients, patients with lower levels of education, and patients with lower socioeconomic status are target populations. Second, reducing news reports during the pandemic and disseminating accurate scientific information will help patients understand this novel virus, thereby alleviating their fear and reducing their perception of COVID-19 as a threat. Third, providing a supportive hospitalization environment will help foster resilience, enabling hospitalized patients to maintain relatively stable, healthy levels of psychological and physical functioning.The current study showed that the prevalence rates of PTSD, depression and anxiety among hospitalized patients with COVID-19 were high and that these disorders often co-occurred. Negative media reports, exposure to trauma and perceived social support were shared predictors of PTSD, anxiety and depression. Resilience was a protective factor only for depression. These findings indicate that timely integrated mental health interventions are warranted for patients during the acute treatment phase of COVID-19.


Sciatica is a syndrome characterized by sciatic nerve path and distribution area pain. Many kinds of literature reported the definite effect of warm needle acupuncture (WNA) on sciatica. However, there is no systematic review or meta-analysis on WNA for sciatica. Therefore, this study will design a protocol to comprehensively and systematically evaluate the effectiveness and safety of WNA on sciatica.The two researchers in this study will search the electronic database for randomized controlled trials, (RCTs) of WNA on sciatica, The databases we will search include PubMed, EMBASE, Cochrane Library, Web of Science, Chinese national knowledge infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Chinese biomedical literature database (CBM). Review Manager 5.4 software and Cochrane risk bias tool will be us used for data analysis and to evaluate research quality. The main clinical indicators will include visual analogue scale (VAS) and Oswestry Disability Index (ODI).This study will evaluate the efficacy and safety of WNA for sciatica.This study will provide a reliable scheme for objectively and comprehensively evaluating the efficacy and safety of WNA on sciatica.INPLASY2020110074 The prevalence of sciatica ranges from 1.2% to 43% among different studies. At present, the treatment of sciatica is a mainly conservative drug treatment and surgical therapy. However, conventional drugs for sciatica, such as non-steroidal anti-inflammatory drugs (NSAIDs), may provide short-term relief, and their long-term effects are uncertain. Furthermore, Surgical treatment is recommended only when the large disc breaks into the spinal canal, resulting in the bladder or intestinal sphincter failure.,9 In general, these treatments of sciatica is limited and imperfect. Therefore, it is urgent to find a more effective and safe treatment for sciatica, which brings significant challenges to clinical practice.Sciatica is a kind of pain syndrome caused by compression and stimulation in the sciatic nerve pathway and distribution area. It is a common clinical peripheral nerve disease. Its typical symptoms include radiating pain in one or both lower limbs, sometimes accompanied by numbness, which can be manifested as pain in the waist, buttock, back of the thigh, posterolateral leg, and lateral dorsum of the foot. Sciatica may be sudden onset and followed by days or weeks. There are many clinical reports, systematic reviews and meta-analysis on acupuncture for sciatica.–17 Among the numerous acupuncture therapies, warm needle acupuncture (WNA) can better combine the advantages of acupuncture and moxibustion, which has not only the analgesic effect of acupuncture but also has the warming effect of moxibustion Some studies have shown that WNA has better effects in relieving pain and promoting blood circulation compared with simple acupuncture or moxibustion.,19 After searching the database, the authors found that there were many RCTs about WNA in the treatment of sciatica. These literature show that WNA may be more effective than ordinary acupuncture in the treatment of sciatica.–33 Given the lack of systematic review and meta-analysis of WNA, the authors decided to design a protocol to provide evidence for a precise evaluation of the effect of warm acupuncture on sciatica and provide evidence for clinical application of WNA.Currently, as one of the most distinctive traditional Chinese medicine therapies, acupuncture has been widely used in clinical practice in China and many western countries.22.1 we will conduct and report our program.The protocol of our study has been registered on the INPLASY international prospective register of systematic reviews (INPLASY2020110074). Based on the systematic review and meta-analyses protocols (PRISMA-P) guidelines,2.22.2.1Only RCTs using WNA to relieve pain in patients with sciatica will be included. Retrospective studies, case reports, reviews, and other non RCTs studies will be excluded. For the included studies, their languages will be limited to English and Chinese.2.2.2The patients to be included in this study should be those who have been diagnosed with sciatica or have been diagnosed with synonyms of sciatica, such as nerve root injury, nerve root compression and radiation pain under the knee, or have the following symptoms and signs: radiation pain of sciatic nerve distribution, Lasegue's sign, Kernig's sign, and Bonnet's sign. Patients’ age, gender, and nationality will not be restricted.2.2.3The studies we included in the experimental group using WNA alone or in combination with other commonly clinical treatments will be included. However, If it is not clear that WNA plays a role in the combination therapy, the combination of WNA with other therapies will be excluded. Conventional acupuncture, electroacupuncture or drug therapy will be used in the control group (such as NSAIDs).2.2.42.2.4.1The primary outcome is VAS and ODI.VAS can evaluate pain intensity by measuring continuous pain, and the data is converted into 0–100 mm. And the degree of daily dysfunction of patients can be evaluated by ODI. ODI includes pain, single function and individual comprehensive function, with ten items scoring 0–5 points for each item.2.2.4.2 , valuation criteria of Traditional Chinese Medicine (TCM) syndromes and adverse reactions caused by intervention treatment, such as fatigue, dizziness, etc.The secondary outcome includes the 36-Items Short Form Health Survey (SF-36)2.32.3.1The following eight databases will be used for searching controlled clinical trials, including PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, CBM, VIP, and Wanfang Database. The retrieval period will start from the establishment of each database to November 2020. We will use “RCT, sciatica, WNA” as our search terms. Table 2.3.2Meanwhile, we also plan to search other relevant literature, such as grey literature, meeting minutes, and all reference lists of included studies. The retrieval of this literature will not be limited by date, country, publication status, or year of publication.2.42.4.1 we developed selection procedures. The selection flow chart is shown in Figure According to our previous search strategy, the retrieved literature will be imported into EndnoteX9 by two independent researchers. After removing the duplication through software, they will evaluate the title and abstract of the study based on previously established criteria. After assessing, the retained literature will be carefully read and re-selected. Any divergences between the two reviewers will be reached through third-party evaluation or group discussion. According to PRISMA guidelines,2.4.2Structured, standardized forms will be used by two researchers to collect research data independently. A third person or panel discussion will resolve any differences between the two investigators on data collection. If there is unclear or incomplete information, we will approach the lead author of the article by email or phone for details. The extracted information will include:(1)Necessary information (2)Interventions in the control and treatment groups(3)Necessary information (4)Outcome indicators(5)Randomized methods2.5Cochrane Collaboration Tool will be used to assess included studies. This will be done by two authors independently assessing the quality of the methodology, which covers seven aspects: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. After evaluation, the literature quality will be divided into “high”, “low” or “unclear”.Disputes arising from an evaluation process are discussed and resolved with the fourth author (MY).2.62.6.1Statistical management software (RevMan V5.4) will be used for data processing and meta-analysis. Mean difference (MD) and rate ratio (RR) will be used to evaluate continuous variables and dichotomous variables in extracted data respectively. Meanwhile, 95% confidence intervals (CIs) is also being used to evaluate these two variables.2.6.22 > 50%, it shows that the heterogeneity among the studies is significant, we will select the random effect model analysis and conduct further subgroup analysis. When I2 < 50%, the heterogeneity between studies is small, and the fixed effect model will be used by us.We will use I2 values according to the Cochrane Manual to assess heterogeneity and analyze valid data based on the evaluation results. If I2.6.3If the included data are highly heterogeneous, we will perform subgroup analysis according to sample size, study quality, and interventions.2.6.4If the heterogeneity between the included studies is high, we will conduct a sensitivity analysis. If the sensitivity analysis does not substantially change the results, it indicates that the results of the study are credible; if the sensitivity analysis draws different conclusions, it suggests that there are potentially important factors influencing the effectiveness of the intervention.2.6.5If we include more than ten studies, we will consider using Revman5.4 software to plot funnel plots for publication bias analysis.2.7No ethical approval is required for this study. The included data are from published literature,This study provides a comprehensive evaluation of the efficacy and safety of WNA in the treatment of sciatica and will be published in peer-reviewed journals or conferences.3 Other studies have shown that warm acupuncture can inhibit inflammation, reduce pain degree and improve clinical symptoms by increasing pain threshold and decreasing serum levels of PGE2, IL-6 and plasma levels of 5-HT, SP, TXB2, and T/K ratio.Sciatica is one of the common clinical diseases, which is easy to recur, significantly reducing the work efficiency and quality of life of patients. However, whether it is drug therapy or surgical treatment, the efficacy is not very satisfactory. Studies have shown that warm acupuncture can combine the effects of acupuncture and moxibustion. Acupuncture can stimulate nerve transmission, improve pain threshold when it is used with moxa sticks, it can penetrate the skin, direct heat to muscular layer and nerve, strengthen local blood circulation, promote the resolution of neuroedema and inflammation, and promote nerve repair.From what has been reported, this study will be the first systematic review and meta-analysis of WNA for sciatica, and our results will provide objective statistical data for WNA for sciatica, provide a reliable reference for clinicians in the treatment of WNA sciatica, and make it more widely available to the public.Conceptualization: Jing Zhang, Qianxiang Dai.Methodology: Mingxing Yuan.Resources: Yujia Xie, Jia Li.Software: Zongming Yu, Yue Su.Writing – original draft: Jing Zhang, Yuan Liu.


Rheumatoid arthritis (RA), as an autoimmune disease, can eventually lead to joint deformity and loss of function, seriously reduce the quality of life of patients and increase economic burden. As a traditional Chinese therapy, warming acupuncture and moxibustion is safe, economical, and has few side effects. At present, some studies have shown that warming acupuncture and moxibustion has a certain effect on RA, but there is no evidence of evidence-based medicine. The purpose of this study was to evaluate the efficacy and safety of warming acupuncture and moxibustion in the treatment of rheumatoid arthritis.Randomized controlled trials of warming acupuncture and moxibustion treating RA will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and China biomedical literature database (CBM) from inception to July, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies independently. Statistical analysis is performed in RevMan 5.3 software.The primary outcome is symptom evaluation including morning stiffness, pain, and joint swelling. The number of joints affected by RA, Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), anti-cyclic peptide containing citrulline (A-CCP), and adverse effects, will be evaluated as secondary outcomes.This study will compare the efficacy and safety of warming acupuncture and moxibustion with common acupuncture in the treatment of RA, providing reliable evidence for clinical application.DOI 10.17605/OSF.IO/C8RY9. Meanwhile, RA patients are often complicated with cardiovascular diseases, brittle fractures, malignant tumors, depression, etc, which not only affects the prognosis of RA patients, but also raises the mortality. The epidemiological survey shows that the current incidence of RA is 0.5% to 1% in the world and 0.42% in mainland of China. The total population of RA is about 5 million, among which women are more susceptible to RA than men and the ratio of males to females is about 1:4. With the disease progressing, the disability rate gradually increases. RA not only reduces patients’ physical function, quality of life, and social participation, but also adds huge economic burden to families and society.Rheumatoid arthritis (RA) is a common form of inflammatory autoimmune disease with unknown etiology. Bone erosion and destruction, cartilage degradation, synovial inflammation are 3 major pathways of RA pathology.,2The treatment methods of RA in western medicine involve drugs, gene therapy and surgical treatment. Drugs include nonsteroidal anti-inflammatory drug (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and corticosteroids. Currently, the preferred drug at home and abroad is conventional synthetic DMARDs, for example, Methotrexate, is the typical first-line conventional therapeutic agent in RA. Furthermore, conventional synthetic DMARDs combined with biological or targeted synthesis of DMARDs is used to treat RA while the conventional DMARDs combined with corticosteroids is used to treat moderately or highly active RA. However, drugs have some limitations like impassive to RA, severe side effects, chronic treatment, frequent medication, lack of permanent curative response, the abuse of corticosteroids and relapse after withdrawal of drug. But traditional acupuncture and moxibustion therapy for RA can provide an alternative to avoid above problems. suggest that acupuncture or moxibustion interventions may have a positive effect in pain relief, physical function in RA patients. Acupuncture exerts anti-inflammatory and analgesic effects via elevating anti-inflammatory cytokine level and reducing pro-inflammatory cytokine level and regulating Th1/Th2 balance, which reflects the dual regulatory effect of acupuncture. The moxibustion can regulate the body's immune mechanism and inflammatory factor content, relieve pain. However, there is no literature to systematically evaluate the efficacy and safety of warm acupuncture on RA. Therefore, the purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of warm acupuncture and moxibustion in RA patients and provide reliable evidence for clinical application.As a popular complementary and alternative therapy, acupuncture has a good clinical effect all over the world. Traditional acupuncture therapy includes needling and moxibustion. Warm acupuncture and moxibustion is a therapeutic combination of both. After obtaining Qi through acupuncture, the needle should be kept at an appropriate depth, and the moxa should be fixed on the needle handle and ignited, so that the heat can be transmitted to the acupuncture point through the needle body. On the basis of acupuncture, the heat can warm the meridians and promote Qi and blood circulation. Studies22.1This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P). Moreover, it has been registered on open science framework (OSF) on July 17, 2020. (Registration number: DOI 10.17605/OSF.IO/C8RY9).2.2Ethical approval is not required because there is no patient recruitment and personal information collection, and the data included in our study are derived from published literature.2.32.3.1We will collect all available randomized controlled trails (RCTs) on warming acupuncture treatment for RA, regardless of blinding, publication status, region, but Language will be restricted to Chinese and English.2.3.2All participants diagnosed as RA will be included irrespective of their country, age, race, and sex.2.3.3In the experimental group, RA patients will be treated with warm acupuncture. In the control group, RA patients will receive common acupuncture. The above 2 groups of manipulation, acupoints and the treatment courses are not restricted.2.3.4(1)Primary outcome: symptom evaluation including morning stiffness, pain and joint swelling. The number of swelling joints affected by RA; the number of painful joints affected by RA; the duration of morning stiffness.(2)Secondary outcomes: pain visual analog scale (VAS) score; rheumatoid factor; erythrocyte sedimentation rate; C reactive protein; anti-cyclic peptide containing citrulline; adverse effects.2.4(1)If the study is published repeatedly, the one with the most complete data will be included;(2)Studies with missing data, and can’t get the data after contacting the author;(3)Studies with obviously wrong data;(4)If an incorrect random method is used, the literature will be excluded.2.5Randomized controlled trials of warming acupuncture and moxibustion for the treatment of RA will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and China biomedical literature database (CBM) from inception to July, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. The search terms are as follows: “acupuncture,” “moxibustion,” “warming acupuncture,” and “rheumatoid arthritis,”, etc. The search strategy (PubMed) is shown in Table 2.6Searches will be conducted in the above databases according to guidance from The Cochrane Collaborative Network System Evaluator's Manual Version 5.0. Two researchers will select the literature by reading the title and abstract separately. Related studies will be initially included and imported into Endnote X7  for removal of duplications. Then, by reading the full text of the article, new screening is carried out by referring to the inclusion criteria and exclusion criteria. Two qualified researchers will extract data from included studies independently. Any inconsistent views will be solved by a third researcher through discussion. The following information will be extracted: basic information of included studies: study title, first author, publication year, and so on; basic characteristics: sample size, age, sex ratio, and the course of disease between experimental group and control group; Interventions: intervention measure, intervention time, frequency, treatment course; the entry of risk of bias assessment; the outcomes and relevant measurement data. The literature screening process is shown in Fig. 2.7The risk of bias for each eligible study will be assessed by 2 researchers respectively according to the Cochrane Collaboration's tool including 7 terms. According to these criteria , risk of bias is classified into the following levels: unclear, low, and high risk of bias. Any divergences will be solved through discussion by a third researcher.2.82.8.1P value and I2 statistics. If P ≥ .1, I2 ≤ 50%, there is no significant heterogeneity; thus the fixed-effect model is used. When P < .1, I2ї¿≥ 50%, the sources of heterogeneity are analyzed, and subgroup analysis may be performed. If there is statistical heterogeneity between studies but no clinical heterogeneity, the random-effect model is selected to analyze. Otherwise, we exclude the study from meta-analysis.Statistical analysis is performed in RevMan 5.3 software . For dichotomous outcome data, the risk ratio (RR) with 95% confidence intervals (CIs) is calculated. For continuous outcome data, if the measurement tool or measurement index unit is the same, the weighted mean difference (WMD) with 95% CIs is adopted; if the measurement tool or measurement index unit is different, the standard mean difference (SMD) with 95% CIs is used. Statistical heterogeneity will be checked by 2.8.2When occurring missing, incomplete, and unclear data, we will contact the corresponding author to obtain it. If data are not acquired, we will exclude this literature.2.8.3Subgroup analysis will be constructed based on the age of patients, the course of disease, and the intervention time.2.8.4In order to verify the stability of the results of each outcome indicator, we adopt the one-by-one elimination method for sensitivity.2.8.5When >10 studies are included, funnel plots are used to detect reporting bias. Egger and Begg tests are used to quantitatively assess potential publication bias.3 As a remedy of combining acupuncture and moxibustion, its functions of warming meridians to expel cold, activating blood circulation and qi, eliminating stasis and dispersing knot are in accordance with the pathogenesis of Arthralgia syndrome. Research has proved warm needle moxibustion can relieve inflammatory reactions of RA, which may be associated to its effect in modulating NF-κB signaling in the synovial tissue.–8 In addition, clinical trials have proved that warm acupuncture and moxibustion in the treatment of RA is more effective than conventional acupuncture,,10 but there is no systematic evaluation or meta-analysis on the efficacy and safety of warm acupuncture and moxibustion in the treatment of RA, so this study is of great significance. However, the study has some limitations. There are certain heterogeneity due to the difference of acupoints. And only studies published in English and Chinese are retrieved, so important studies published in other languages may be missed.In Chinese medicine, rheumatoid arthritis belongs to the category of “Bi Zheng” . The basic pathogenesis of the disease is the sense of deficiency and stagnation of meridians, and the key of its pathological changes is that phlegm, dampness, and blood stasis block the meridians. With the prolongation of the course of disease, the rate of disability is rising, which seriously affects the quality of life of patients and aggravates the economic burden. Currently, traditional Chinese medicine has a variety of treatment methods for this disease, especially acupuncture and moxibustion. Compared with oral drugs, acupuncture and moxibustion have fast onset and no side effects, and it becomes a complementary and alternative therapies for RA.Data collection: Jingwen Shang and Wei Fan.Funding support: Haifa Qiao.Literature retrieval: Wei Fan and Zhongqing Dou.Software operating: Linlin Wu and Bibo Lu.Supervision: Bibo Lu and Haifa Qiao.Writing – original draft: Jingwen Shang and Wei Fan.Writing – review & editing: Jingwen Shang and Haifa Qiao.