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 study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

Aim To investigate the regulatory mecha-nism of arrhythmia of sodium channel ubiquitination af-ter MI and to study the electrophysiological remodeling mechanism of lncRNA-CCRR after MI for the preven-tion and treatment of arrhythmia after MI.Methods LncRNA-CCRR transgenic mice and C57BL/6 mice injected with lncRNA-CCRR overexpressed adeno-asso-ciated virus were used.Four weeks after infection,the left anterior descending branch of the coronary artery was ligated for 12 h to establish a mouse acute myocar-dial infarction model,and the incidence of arrhythmia was detected by programmed electrical stimulation.Ln-cRNA-CCRR overexpression/knockdown adeno-associ-ated virus and negative control were transfected into neonatal mouse cardiomyocytes(NMCMs),and the model was prepared by hypoxia for 12 h.LncRNA-CCRR expression was detected by FISH,Nav1.5 and UBA6 protein and Nav.1.5 mRNA expression were de-tected by Western blot and real-time quantitative poly-merase chain reaction(qRT-PCR),Nav1.5 and UBA6 expressions were detected by immunofluores-cence,and the relationship between lncRNA-CCRR and UBA6 was detected by RIP.INa current density af-ter CCRR overexpression and knockdown was detected by Whole-cell clamp patch.Results In MI mice,the expression of lncRNA-CCRR decreased,the incidence of arrhythmia increased,the expression of CCRR and Nav1.5 mRNA was down-regulated,the protein ex-pression of Nav1.5 was down-regulated,and the pro-tein expression of UBA6 was up-regulated compared with sham group.Overexpression of CCRR could re-verse the above changes.AAV-CCRR could reverse the down-regulated CCRR and Nav1.5 mRNA levels af-ter hypoxia,and improve the expression of Nav1.5 and UBA6 protein.The direct relationship between ln-cRNA-CCRR and UBA6 was identified by RIP analy-sis.The INa density increased after transfection with AAV-CCRR.The INa density decreased after transfec-tion with AAV-si-CCRR.Conclusions The expres-sion of lncRNA-CCRR decreases after MI,and ln-cRNA-CCRR can improve arrhythmia induced by MI by inhibiting UBA6 to increase the protein expression level of Nav1.5 and the density of INa.

Objective To investigate the early diagnostic value of serum double cortin-like kinase 1(DCLK1),latent transforming growth factor binding protein 2(LTBP2)combined with transvaginal real-time shear wave elastography(SWE)for cervical cancer.Methods A total of 155 patients with cervical lesions treated in our hospital from August 2021 to December 2022 were selected as the research objects.Seventy-five patients with cervical cancer(the cervical cancer group)and 80 patients with cervical intraepithelial neoplasia(the CIN group)were diagnosed by surgical pathology,another 80 volunteers without cervical related diseases who participated in physical examinations at our hospital during the same period were selected as the control group.All subjects of each groups underwent serum DCLK1 and LTBP2 levels detection and transvaginal SWE examination.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum DCLK1 and LTBP2 for cervical cancer;the diagnostic value of serum DCLK1 and LTBP2 combined with transvaginal SWE for cervical cancer was analyzed by fourfold table analysis.Results The serum levels of DCLK1 and LTBP2 of patients in the cervical cancer group were obviously higher than those in the CIN group and the control group(P<0.05).Compared with before surgery,the serum levels of DCLK1 and LTBP2 1,3,and 6 months after surgery in cervical cancer patients gradually decreased,and there were statistical differences in pairwise comparisons at each time point(P<0.05).The area under the curve of serum DCLK1 and LTBP2 for diagnosing cervical cancer were 0.868 and 0.754,respectively,with sensitivity of 86.67% and 78.67%,specificity of 81.25% and 60.00%,and optimal cutoff values of 1.49 ng/mL and 19.02 μg/mL.The maximum and average elastic modulus of lesion tissue in the cervical cancer group were obviously higher than those in the CIN group(P<0.05).The positive rates of serum DCLK1,serum LTBP2,and transvaginal SWE in the diagnosis of cervical cance were 86.67%,78.67%,and 82.67%,respectively,which were consistent with the gold standard(Kappa=0.624,0.501,0.673,P<0.001),and the positive rate of the combination of them in the diagnosis of cervical cancer was 97.33%,which was highly consistent with the gold standard(Kappa=0.846,P<0.001).The sensitivity and accuracy of the three combined diagnosis were obviously higher than those of the single indicator diagnosis of serum DCLK1,LTBP2,and transvaginal SWE,the specificity of the three combined diagnosis was obviously higher than that of the single indicator diagnosis of serum DCLK1 and LTBP2,the misdiagnosis rate of the three combined diagnosis was obviously lower than that of the single indicator diagnosis of serum DCLK1 and LTBP2,and the differences were all statistically significant(P<0.05).Conclusion Serum DCLK1 and LTBP2 combined with transvaginal SWE has high application value in the diagnosis of cervical cancer,which can further improve the sensitivity and accuracy of diagnosis,and reduce the misdiagnosis rate.

Objective To explore association between childhood trauma,resilience and non-suicidal self-injury in adolescents.Methods One hundred and fifty-eight first-episode adolescent patients with mood disorders were selected and divided into NSSI group(n=94)and non-NSSI group(n=64)based on presence or absence of NSSI.The Hamilton depression scale(HAMD),Hamilton anxiety scale(HAMA),childhood trauma questionnaire(CTQ-SF)and Connor-Davidson resilience scale(CD-RISC)were used to evaluate the depression and anxiety symptoms,childhood trauma and resilience.Results There were more cases of younger age(16.17±1.67 vs.16.73±1.37),lower education level(30.9% vs.15.6% ),left behind experience(48.9% vs.29.7% ),school bullying(46.8% vs.25.0% ),suicide ideation(85.1% vs.37.5% )and history of attempted suicide(29.8% vs.6.3% )in the group with NSSI compared to those without NSSI.The HAMD score(27.99±5.94 vs.24.19±5.19),HAMA score(18.02±5.94 vs.15.45±4.99),CTQ total score(48.43±15.40 vs.41.97±9.75),emotional abuse score(12.77±6.06 vs.10.19±4.06),and emotional neglect score(11.40±5.34 vs.9.14±3.55)were higher in the group with NSSI,and the differences between the two groups were significant(P<0.05).The total scores of psychological resilience(39.83±10.27 vs.28.66±12.75),resilience(19.59±4.92 vs.12.28±6.47),strength(12.03±3.98 vs.9.99±4.67),and optimism(8.98±2.97 vs.6.47±3.73)in the group without NSSI were higher than those in the group with NSSI(P<0.05).Logistic regression analysis showed that left behind experience(OR=4.494,95% CI:1.192-16.940),school bullying(OR=5.983,95% CI:1.329-26.945),suicidal ideation(OR=13.225,95% CI:2.908-60.146),history of attempted suicide(OR=16.769,95% CI:1.845-152.379),HAMD(OR=1.264,95% CI:1.046-1.626),emotional abuse(OR=1.327,95% CI:1.093-1.612),and resilience(OR=0.468,95% CI:0.266-0.823)were significantly associated with adolescent mood disorders with NSSI(P<0.05).Conclusion Left behind experience,campus bullying,suicidal ideation and attempted suicide,emotional abuse,degree of depression,and psychological resilience may be associated with NSSI behavior in adolescents with mood disorders.

Objective This study systematically evaluated the clinical efficacy of Shangke Jiegu tablet in the treatment of fracture,and explored the mechanism of action of Shangke Jiegu tablet and the compatibility of each efficacy group from the"Disease-Symptom-Formula"perspective.Methods Clinical research literatures on the use of Shangke Jiegu tablet for fracture intervention were retrieved from Chinese databases(CNKI,Wanfang Database,VIP database)and English databases(PubMed,Cochrane Library,EMbase),covering the period from the inception of the databases to January 2024.Risk assessment tools were used to evaluate the literature's quality,and the data were extracted and analyzed using Stata 16.0 software.Gene sets associated with fracture symptoms were identified through the TCMIP platform(version 2.0).Differential gene expression related to fractures was obtained from the GEO database.Chemical composition and candidate target profiles of the 12 herbs in Shangke Jiegu tablets were collected from TCMIP v 2.0.An interaction network between fracture-related genes and drug candidate targets was established,and core network targets were screened based on topological features,with functional enrichment analysis performed.Results A total of 14 articles were incorporated into the Meta-analysis,encompassing a total sample size of 1 293 cases,indicating an overall response rate of Shangke Jiegu tablets in fracture therapy(RR=1.24,95%CI:1.18-1.31,P<0.001).The"Disease-Symptom-Formula"association network analysis indicated that the pathways related to the putative targets of Shangke Jiegu tablet were primarily involved in bone healing,nerve and blood system regulation,and immune-inflammation regulation.Different efficacy groups within the prescriptions showed varying emphases on these roles.Conclusions Shangke Jiegu tablet may facilitate fracture healing by regulating blood and nervous systems,correcting immune-inflammatory imbalances,and maintaining bone and energy metabolism.The comprehensive effects include the dissipation of blood stasis,the promotion of blood circulation,the alleviation of swelling and pain,the regeneration of muscles and bones,and the clearance of heat and detoxification.These findings support the clinical advantages and positioning of Shangke Jiegu tablet.

Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models,and to analyze its clinical value.Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease,the patients were divided into the severe group(n=88)and the non-severe group(n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features.Results In the training set,the area under curve(AUC)of the improved machine learning model was 0.922.In the testing set,the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein,blood chlorine,blood magnesium and fibrinogen level,which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis.Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.