AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

Background With the continuous development of the healthcare industry, healthcare workers face increasing pressure, including long-term shift work and workplace violence from patients or their relatives. This not only affects the physical and mental health of healthcare workers but may also negatively impact the quality of patient care and the efficiency of medical services. Objectives To analyze the pathways through which shift work and workplace violence affect healthcare workers' self-rated health and depression symptoms, explore potential mediating role of job burnout, and conduct subgroup analyses to reveal differences among various groups. Methods Data were collected from 3706 frontline healthcare workers across 23 provinces from January 10 to February 5, 2019, using a snowball sampling method. The survey included basic demographic information, self-rated health, depression symptoms [assessed using the Patient Health Questionnaire-2 (PHQ-2)], workplace violence experience assessed using the Workplace Violence Scale), and job burnout (assessed using the Chinese Maslach Burnout Inventory). Data were analyzed using logistic regression, structural equation modeling (for mediating effects), and subgroup analysis to examine the impacts of shift work and workplace violence on health and depression symptoms. Results Among the subjects, 2700 workers (73.29%) reported shift work experience, 2079 workers (56.43%) experienced workplace violence, 633 workers (17.18%) reported poor self-rated health, and 687 workers (18.65%) reported depression symptoms. Shift work was associated with self-rated health (OR=0.572, 95%CI: 0.461, 0.710) and depression symptoms (OR=1.519, 95%CI: 1.190, 1.938), while workplace violence also associated with self-rated health (OR=0.566, 95%CI: 0.471, 0.681) and depression symptoms (OR=2.096, 95%CI: 1.740, 2.525). Job burnout significantly mediated the effects of shift work and workplace violence on self-rated health (indirect effects: −0.023, −0.027) and depression symptoms (indirect effects: 0.032, 0.037) (all P < 0.001). The subgroup analysis revealed that age, marital status, physical exercise, smoking, and alcohol consumption influenced the impacts of shift work and workplace violence on health. Conclusion Shift work and workplace violence significantly affect healthcare workers' self-rated health and depression symptoms, with job burnout playing a key mediating role in this process. This suggests that healthcare institutions should improve resource allocation, provide flexible scheduling systems, ensure adequate rest time, and increase psychological support and safety measures to help healthcare workers better cope with work-related stress and violence.

Objective To assess the current state and influencing factors of multi-site work-related musculoskeletal disorders (WMSDs) among front-line employees in the assembly workshop of an automobile manufacturing enterprise. Methods A total of 394 front-line workers in the assembly workshop of an automobile manufacturing enterprise in Beijing City were selected as the research subjects using the judgmental sampling method. The Chinese version Musculoskeletal Disorders Questionnaire was used to assess the presence of WMSDs over the past 12 months in nine body regions: neck, shoulders, upper back, lower back, elbows, wrists, hips and thighs, knees, ankles and feet. The multivariable logistic regression was employed to investigate the influencing factors. Results The detection rate of overall WMSDs was 32.7% (129/394), with the top three single-site WMSDs being in the neck, shoulders, and lower back, and their detection rates were 14.0%, 12.7% and 9.6%, respectively. The detection rate of multi-site WMSDs was 17.8% (70/394). The result of multivariable logistic regression analysis revealed that workers who turned or bent their upper body while keeping their legs stationary, frequently performed wrist flexion/extension/lateral bending/rotation, or stood for prolonged period of time had significantly higher risks of developing multi-site WMSDs compared with those who did not (all P<0.05). Workers who perceived uncomfortable workplace lighting had higher risk of multi-site WMSDs than those who perceived it as comfortable (P<0.01). Conclusion The development of multi-site WMSDs among workers in the assembly workshop of this automobile manufacturing enterprise is strongly related to poor working postures at work.

Objective:To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy. Methods:A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by Medical Ethics Committee of the Peking University First Hospital (Ethics No. 2016[1029]).Results:The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c. 737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+ PM2_Supporting+ PM3+ PP3+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b. Conclusion:The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.