This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ²/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ²/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P<0.05) in overall subjects. For traffic police and firefighters, professional efficacy was not correlated with depressive symptoms or sleep disorders (P>0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups. Conclusion The GBS shows high reliability and validity, as well as good application effects in different occupational groups.

Background Healthcare workers suffer from great internal and external pressure and are prone to burnout. Existing studies have shown that depressive symptoms are important influencing factors of burnout, both of which are closely related to job stress. Objective To analyze overall prevalence of burnout among healthcare workers using a new survey tool developed by our team, and to reveal potential influencing factors related to burnout. Methods A cross-sectional multi-center study was conducted in August–October 2019 and June–September 2020, using multi-stage stratified cluster sampling. A total of 8738 healthcare workers from 22 hospitals in 5 provinces (Shandong, Hubei, Hunan, Guangdong, and Chongqing) of China were selected in this study. A set of survey questionnaires, including the general information questionnaire and the Chinese versions of General Burnout Scale, Core Occupational Stress Scale, Patient Health Questionnaire-9, and Self-administered Sleep Questionnaire were distributed. Independent samples t-test or one-way ANOVA were employed for inter-group comparison of burnout. Spearman correlation was used to evaluate correlations among burnout, depressive symptoms, and occupational stress. Stepwise linear regression was conducted to identify factors independently associated with burnout. Process plug-in was used to test potential mediating effect of depressive symptoms on occupational stress and burnout. Results Of the 8738 questionnaires distributed, 8456 valid questionnaires were collected, and the recovery rate was 96.77%. Among the 8456 healthcare workers, the prevalence of burnout was 58.0%, that of occupational stress was 31.8%, and that of depressive symptoms was 31.0%. Among those with depressive symptoms and occupational stress, the proportions of burnout were 86.7% and 83.7%, respectively. According to the stepwise linear regression analysis, depressive symptoms, occupational stress, work experience, drinking, and marital status were all independent influencing factors of burnout. Especially, depressive symptoms, social support, and organization and reward had significant influences on burnout (b'=0.455, −0.183, 0.220, P<0.001). Depressive symptoms showed mediating effects on occupational stress (and its subscales) and burnout, and the contribution rates of the mediating effects were 41.00%, 47.02%, 43.44%, 56.62%, and 59.45%, respectively. Conclusion Burnout is a prominent problem among healthcare workers in the 5 provinces, with the prevalence of 58.0%. And nearly 1/3 suffering from depressive symptoms and occupational stress, which has a great impact on burnout.

Objective:To understand the research progress and quality of lung cancer screening guidelines and consensus in China and abroad, and to provide reference for the formulation of high-quality lung cancer screening guidelines in China.Methods:Databases including PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP and Wanfang Data were searched, websites and important references were also searched by hand retrieval. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to assess the quality of newly published or updated guidelines and consensus.Results:A total of 9 guidelines and consensus published between 2015 and 2020 were included in this study, with countries including the United States, China, Canada, Saudi Arabia and South Africa. The field of scope and purpose and clarity of presentation scored relatively high but the rigor of development and applicability scored low. Five guidelines were judged to be A-level, all of which were published abroad, and the remaining four were B-level, including three guidelines and consensus issued by China and 1 guideline issued by South Africa. The report rate of RIGHT were higher in basic information and background, lower in review and quality assurance, funding and declaration and management of interests. There were 5 guidelines with a good level and 4 guidelines and consensus with a moderate level. The best overall quality guidelines were those published by the American College of Chest Physicians in 2018 and by the Canadian Task Force on Preventive Health Care in 2016.Conclusions:The number of countries and institutions that issue lung cancer screening guidelines and consensus had been increasing gradually, but the quality in China remained low. It is necessary to develop high-quality lung cancer screening guidelines suitable for China's national conditions in combination with evidence-based methods to guide practice.

Objective:To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis.Methods:The binding structures of ZOL and VEGF were preprocessed and the molecular dockings were simulated through AutoDockTools, Discovery studio4 and AutoDockVina. The best binding conformation was accurately screened. The effects of various concentrations of ZOL (group A was 0 μmol/L, groups B, C and D were 25, 50 and 100 μmol/L, respectively) on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis and angiogenic molecules were detected by using cell counting kit-8 (CCK-8) in vivo and in vitro angiogenesis, immunofluorescence and Western blotting. Results:There was a ZOL binding site on the target protein VEGF conformation. The affinity was -5.2 kcal/mol. This binding site consisted of the hydrophobic region composed of amino acids Cys26, 51, 57, etc. and the hydrogen bond binding region of the A chain (ASP34, SER50) and B chain (CYS61, 68, LEU66, GLY59). The results of CCK-8 showed that the levels of value A in groups B, C and D were significantly lower than that in group A at each time point from 3 to 6 days ( P<0.05). In vitro vascular experiments demonstrated that the numbers of budding in groups B, C and D [(208±28), (151±21) and (62±9), respectively] were significantly lower than that in group A (276±30) ( P<0.05). In vivo vascular experiments displayed that the ratio of Matrigel gel/plasma fluorescence in group A (0.003 1±0.000 3) was significantly higher than those in group B (0.002 1±0.000 2), group C (0.001 6±0.000 2) and group D (0.000 6±0.000 1) ( P<0.05). The results of Western blotting revealed that the expression of VEGF in groups B, C and D [(0.72±0.11), (0.41±0.07) and (0.24±0.04), respectively] were significantly lower than that in group A (1.01±0.02) ( P<0.05), and the expression levels of hypoxia-inducible factor-1α (HIF-1α) in groups B, C and D [(0.68±0.09), (0.55±0.06) and (0.43±0.08), respectively] were significantly lower than that in group A (0.96±0.04) ( P<0.05). Conclusions:ZOL could inhibit cell proliferation, in vivo and in vitro vascularization and expression of VEGF/HIF-1α. The binding site of ZOL with the conformation of VEGF was located in the hydrophobic region and hydrogen-bonding region of amino acids. Designing an antagonist targeting this site might potentially alleviate the effect of ZOL in inhibiting angiogenesis.

Objective To explore the relationship between the serum neuropeptide Y (NPY) levels and the pathogenesis,therapeutic intervention of schizophrenia. Methods One hundard twenty-five patients with schizophrenia (case group) with no medication for at least 4-week and 136 healthy controls (control group) were evaluated by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Positive and Negative Syndrome Scala (PANSS). Simultaneously blood tests were performed to detect serum NPY levels. In the case group, PANSS was evaluated and blood collected again after 4 weeks of treatment with olanzapine. Result At the baseline,the serum NPY concentration was significantly lower in the case group than in control group (t=-5.79, P<0.01). The scores of RBANS and its factors were significantly lower in the case group than in control group (all P<0.01). The concentration was positively correlated with the score of the attention factor for RBANS scale (r=0.20, P=0.04). After treatment with olanzapine for 4 weeks,the serum NPY level in the case group was significantly increased (t=-2.23,P=0.03).The scores of PANSS total scale and subscale were significantly decreased(all P<0.01).There was no significant correlation between alterations of the serum level of NPY and PANSS total or subscale scores from baseline to 4-week (all P>0.05). Conclusion The present study has revealed a significant decrease in serum NPY levels in patients with schizophrenia which can be attenuated by treatment of Olanzapine.The action of Olanzapine may be related to the mechanism of action of Olanzapine.However,there is no correlation between alterations of the serum level of NPY and the improvement in the patientˊs clinical symptoms.

Objective To evaluate the prognostic value of preoperative neutrophil-to lymphocyte ratio (NLR) in invasive breast carcinomas of no special type.Methods we retrospectively analyzed the clinical and pathological data of all breast cancer patients at Shanghai Huangpu District Cental Hospital from Jan.2012 to Dec.2012.The optimal cutoff value was obtained by ROC.The difference among variables was calculated by chi-square test.DFS and OS were estimated using Kaplan-Meier method.Cox analysis was performed to analyze clinical parameters for their prognostic relevance.Results A total of 493 were eligible.The optimal cutoff value of NLR was 2.057.The sensitivity was 0.767 and specifity was 0.327 at the optimal cutoff point.Univariate analysis showed that patients with NLR higher than 2.057 had significantly lower DFS (P=-0.001) than patients with NLR equal or lower than 2.057,while the overall survival rate was not statistically different (P=0.131).The Cox proportional multivariate hazard model revealed that higher NLR was independently related with poor DFS with hazard ratio 5.649(95％ confidence interval 3.128-10.201,P=0.002).Conclusions Preoperative NLR is an independent predictor of DFS in breast cancer patients.Further validation and a feasibility study are required before it can be considered for clinical use.

Objective To explore the diagnosis and treatment of biotinase deficiency (BTD) manifested as encephalomyelopathy.Methods The clinical data of one child with BTD were retrospectively analyzed.The pertinent literatures were reviewed.Results A six-year-old male child suffered from progressive spastic paralysis of lower limbs for 3 months before admission.A similar symptoms occurred after a cold in 3-year-old.It was easy to peel skin on her hands and she had angular stomatitis.Audio visual evoked potential was detected to be abnormal in other hospital.After hospitalizion,the cerebrospinal fluid examination was normal,and MRI showed long T1 long T2 signals bilateral occipital lobe and basal ganglia region.Because the child represented medulla palsy,and so the tracheal intubation ventilator was administrated to assist ventilation.Urine gas chromatography/mass spectrometry (GC/MS) analysis showed increases of lactic acid,3-hydroxy acid,3-tiglyl glycine,methylcitric acid,and ethylene lactic acid.Serum MS/MS analysis showed that the concentrations of propionyl camitine and 3-hydroxyisovaleryl carnitine were increase obviously.The serum biotinase level was significantly decrease to 0.076 pmol/(min·mm3).The diagnosis of BTD was confirmed.After supplementation biotin,40 mg/d,the ventilator was successfully weaned on the third day,the child walked again after 2 weeks,and the rash was vanished.After 3 weeks,the head MRI showed disappearance of the original lesion,and there was no abnormal in spinal cord.The BTD gene detected by PCR direct sequencing showed a heterozygosis mutation of T172T/C in the second exon and a homozygous mutation of T1413C in the fourth exon,which was confirmed as a pathogenic mutation by pedigree verification and database query.After discharge,the oral administration of biotin 20 mg/d continued,and no abnormality was found in 2 years of follow-up.Conclusions The manifestations of BTD are complex and diverse.The analysis of urine GC/MS and serum MS/MS can assist the diagnosis.The determination of biotinase activity and gene detection of BTD can further confirm the diagnosis.Timely biotin supplementation has significant treatment efficacy.

Objective To apply the optical coherence tomography(OCT) to detect the characteristics of coronary artery plaque and to investigate its correlation with levels of serum matrix metalloproteinase 7(MMP 7),MMP9 and MMP12.Methods The patients undergoing coronary arterial angiography for diagnosing coronary arterial lesions in the cardiology department of our hospital from October 2014 to March 2016 were collected and included into the research subjects.The subjects were divided into the stable plaque group and unstable plaque group based on the results of OCT scanning.The neovascularization characteristics such as the fibrous cap thickness of plaque,angle of lipid pool,macrophage infiltration and plaque cracks were detected by using OCT.ELISA was used to measure serum MMP7,MMP9 and MMP12 levels.Results (1) The fibrous cap thickness in the stable plaque group was more than that in the unstable plaque group(P＜0.01);the lipid pool angle,microphage infiltration,intima erosion and plaque cracks in the unstable plaque group were more than those in the stable plaque group(P＜0.05).(2) The MMP7 and MMP9 levels in the unstable plaque group were higher than those in the stable plaque group and control group(P＜0.05).(3) The fibrous cap thickness had significantly negative correlation with serum MMP9 level(r=-0.336,P=0.034);the MMP7 and MMP9 levels in the microphage infiltration group were higher than those in the non-microphage infiltration group(P＜0.05);the MMP9 level in the intima erosion group was higher than that in the non-intima erosion group(P＜0.01).Conclusion OCT can detect and find unstable plaque and the serum levels of MMP7 and MMP9 are significantly elevated in the patients with unstable plaque,which can be used as an important basis for predicting unstable plaque and guiding the treatment decisions.