Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Primary biliary cholangitis （PBC） is a chronic progressive autoimmune liver disease that is often comorbid with other connective tissue diseases （CTDs）， and such comorbidity can significantly alter the natural course or clinical phenotype of PBC or CTDs， limiting available therapeutic drugs and complicating clinical decision-making. Due to the involvement of the interdisciplinary subjects of hepatology， rheumatology， and clinical immunology and a paucity of large-scale cohort data and in-depth basic research， there is a limited understanding of such comorbidity in clinical practice， which increases the complexity of clinical diagnosis and treatment. This article summarizes the comorbidity of PBC with common CTDs such as Sjögren’‍s syndrome， systemic sclerosis， systemic lupus erythematosus， and idiopathic inflammatory myopathies， and analyzes related immune mechanisms， clinical manifestations， diagnostic challenges， treatment strategies， and prognosis. It is expected to establish PBC-CTD comorbidity cohorts through future multidisciplinary collaborations， focus on genetic background， immune mechanisms， and multi-omics approaches， elucidate pathogenesis and novel therapeutic targets， and improve the prognosis of patients by optimizing treatment strategies through precision medicine and artificial intelligence.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Non-suicidal self-injury behavior and suicidal ideation are important risk factors for suicide attempts in patients with depression.At present,studies have found that there are obvious differences in electroencephalogram(EEG)characteristics between these two.Resting-state EEG analysis reveals that the absolute power of Gamma in specific electrode points is significantly increased in patients with depression accompanied by suicidal ideation.The Beta and Gamma activities of those with non-suicidal self-injury behavior changed.EEG microstate research shows that there are differences in microstates between those with non-suicidal self-injury behavior and those with suicidal ideation.Among them,short segments of microstate sequences have certain potential.In event-related potentials,these two show specific characteristics in components such as P3 wave and N2 wave.The amplitude of N2 wave in patients with depression accompanied by non-suicidal self-injury behavior is lower.Although there are few machine learning-related studies on EEG technology,it has shown certain application prospects.Therefore,this article will summarize the progress of EEG research related to the two,aiming to provide a basis for early prediction of suicide in depression.

Objective To investigate the effect of mechanical stretch on the proliferation and differen-tiation of skeletal satellite cells in mice,and explore its mechanism.Methods The research was divid-ed into two parts.In the first part,all mice were not given osteogenic or adipogenic induction,and randomly divided into a control group,a mechanical stretch(MS)group,a solvent control group[Di-methyl sulfoxide(DMSO)+mechanical stretch],a Notch inhibitor(KY-02111)+mechanical stretch group and a Wnt inhibitor(FLI-06)+mechanical stretch group,with the aim to evaluate cell prolifera-tion and migration,and the effect of mechanical stretch on the Wnt and Notch signaling pathway.In the second part,all mice were randomly divided into 6 groups:a control group,an induced differentia-tion(ID)group,an induced differentiation+mechanical stretch(IDMS)group,an induced differentia-tion+DMSO+mechanical stretch(IDDMS)group,an induced differentiation+Notch inhibitor(KY-02111)+mechanical stretch(IDNMS)group,and an induced differentiation+Wnt inhibitor(FLI-06)+mechanical stretch(IDWMS)group.All groups except the control group were induced differenti-ation using osteoblastic or adipogenic medium,and the IDMS group was applied tensile stress to the cell basement membrane,with the IDDMS and IDNMS groups given DMSO and KY-02111 or FLI-06 with a final concentration of 5 μM into the culture medium,respectively.On the 7th and 14th days af-ter culture,cell proliferation was detected using CCK-8,while on the 14th day after culture,cell mi-gration was observed using the streak method.Alkaline phosphatase and oil red staining were per-formed on all cells.Moreover,the mRNA expression of osteogenic[alkaline phosphatase(ALP)and Runt-related transcription factor(Runx)-2]and adipogenic[fatty acid-binding protein(FABP)4 and li-poprteinlipase(LPL)]differentiation marker genes were quantitatively detected by using the real-time PCR.Meanwhile,while the expression of c-Myc and Cyclin B(CCNB)1 proteins was measured using Western blotting.Results Cell proliferation increased significantly in MS group compared with the con-trol group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group.As to cell migration,MS group was significantly better than the control group(P<0.01),while there was a significant decrease in both IDMMS and IDNMS groups compared with MS group(P<0.01).According to ALP and oil red staining,a significant increase in ALP activity and lipid droplet secretion was observed in skeletal muscle satellite cells of ID groups compared with the control group,with the increase in IDMMS and IDNMS groups significantly greater than MS group.More-over,the results of real-time PCR showed that the expression of ALP and Runx-2mRNA in the osteo-genic induction group and the FABP4 and LPL mRNA in the adipogenic induction group increased sig-nificantly compared with the control group(P<0.05),with a significant decrease in the above measure-ments of IDMS group compared with ID group,but a significant increase in IDMMS and IDNMS groups compared with IDMS group(P<0.01).Meanwhile,according to Western blotting,the expres-sion of c-Myc and CCNB1proteins increased significantly in the skeletal muscle satellite cells of MS group compared with the control group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group(P<0.01).Conclusion Mechanical stretch can promote the prolif-eration and migration of skeletal satellite cells in mice,but inhibit osteogenic and adipogenic differenti-ation.Its mechanism is related to the activation of Wnt and Notch signal pathways.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Objective:To investigate the clinical features of patients with coexisting connective tissue disease (CTD) and sarcoisosis and to avoid misdiagnosis and mistreatment.Methods:To analyze the clinical manifestations, laboratory data, imaging and pathological features of patients with CTD combined with sarcoidosis in Peking Union Medical College Hospital from January 1985 to December 2021.Results:There were 17 patients with CTD(including 10 SS, 2 DM, 2 PBC, 1 SLE, 1 RA and 1 UCTD), combined with sarcoidosis, with a mean age of (55±10) years old and the ratio of male-to-female was 1:16. Eight patients were diagnosed as CTD before sarcoidosis, while 3 patients after sarcoidosis. The other 6 patients were diagnosed with the two diseases almost simultaneously. Lymphadenopathy(12/17), pulmonary nodules (8/17), subcutaneous nodules (4/17), rash (4/17) and blurred vision (1/17) were the main manifestations of patients with the onset of nodular disease. Nine patients were treated based on the presentation of sardoisis and 5 patients for CTD; 3 patients were treated for both diseases at the same time. All 17 patients discharged with improvement after treatment.Conclusion:When sarcoidosis do coexists with CTD, occult CTD might occur. It is important to investigate specific manifestations including pathological features of sarcoidosis and differentiate it from CTD.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.