ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

Curettage is the main treatment method for oral maxillofacial cystic lesions,but simple curettage may easily damage surrounding structures such as adjacent teeth and nerves,leading to incomplete removal of the cyst and large jaw defects.The curettage assisted by endoscopy can provide a good surgical field for the surgeons,can clearly identify the important anatomical structure during the operation and can remove the cyst wall tissue as much as possible,thereby reducing the damage and reducing the recurrence rate of the lesion.This article combines the characteristics of maxillofacial surgery with clinical treatment experience,summarizes relevant literature from both domestic and international sources,and engages in discussions with experts in order to provide reference for the clinical treatment of jaw cystic lesions with endo-scope assisted curettage.

Objective To investigate the effect and potential mechanisms of α-cyperone(CYP)on Crohn's disease(CD)-like colitis induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)in mice.Methods The mice were randomly and evenly divided into wild type(WT),TNBS,CYP and 5-aminosalicylic acid(5-ASA)groups,with 10 mice in each group.The symptoms of enteritis,the function and structure of the intestinal barrier,and the expression levels of inflammatory factors,including interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and gamma-interferon(IFN-γ),in the colon were assessed.The lipopolysaccharide(LPS)-induced inflammation model of Caco2 cells was constructed and the cells were divided into Control,LPS and LPS+CYP groups.The expression levels of tight junction protein and inflammatory factors in each group were assessed.Gene Ontology(GO)functional enrichment analysis was conducted to predict the possible pathways of action and potential molecular mechanisms of CYP,and to verify them in vivo and in vitro.Results In the in vivo study,compared with those of the TNBS group,the body mass and colon length of mice in the CYP group and the 5-ASA group were significantly increased,while the disease activity scores and histological inflammation scores were significantly decreased(P＜0.05).The level of lucifcein-glucan isothiocyanate and the bacterial translocation rate(in the liver,the spleen,and mesenteric lymph nodes)were significantly decreased,while the transepithelial electric resistance(TEER)value and the expression levels of zonula occluden protein-1(ZO-1),and claudin-1 were significantly increased(P＜0.05).The expression of inflammatory factors was significantly decreased(P＜0.05).In the in vitro study,compared with those of the LPS group,the TEER value and the expression of ZO-1 and claudin-1 in the Caco2 cells in the LPS+CYP group were significantly increased(P＜0.05).The expression of inflammatory factors was significantly decreased(P＜0.05).Enrichment analysis showed that CYP was correlated with inflammatory response(P＜0.001).Western blot results showed that CYP could significantly reduce the expression of key proteins in toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway in vivo and in vitro(P＜0.05).Conclusion CYP may protect the intestinal barrier by antagonizing the inflammatory response of the intestinal mucosa through regulating the expression of the TLR4/NF-κB signaling pathway,thereby alleviating TNBS-induced CD-like colitis in mice.

Objective The study was conducted to investigate the expression of protein-L-isoaspartate(D-aspartate)O-methyltransferase(PCMT1)in gastric cancer and its effect on the prognosis,and to analyze its potential mechanism.Methods UALCAN,a cancer data analysis platform,was used to conduct online analysis of the expression of PCMT1 in gastric cancer tissues.Through the Database for Annotation,Visualization and Integrated Discovery(DAVID),Gene Ontology(GO)annotation and signaling pathway enrichment by Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed to analyze the possible functions and signaling pathways.A total of 120 patients who underwent radical gastrectomy for gastric cancer between January 2014 and December 2017 in our hospital were enrolled for the study.Immunohistochemical staining was performed to determine the expression of PCMT1 and Ki67 in gastric cancer tissues.Cox regression,Kaplan-Meier curve,and receiver operating characteristic(ROC)curves were used for prognostic analysis of 5-year survival in gastric cancer patients after surgery.Lentivirus was used to construct PCMT1-interfering or PCMT1-overexpressing vectors,which were then used to transfect human gastric cancer cell lines of MGC-803 and HGC-27 cells.The interfering empty vector(sh-NC)group,the interfering PCMT1 vector(sh-PCMT1)group,the overexpressing empty vector(LV-Vec)group,and the overexpressing PCMT1 vector(LV-PCMT1)group were set up.Western blot was performed to determine the protein expression levels of PCMT1,CyclinB1,and CDC20.CCK-8 assay was performed to measure the proliferation of gastric cancer cells.Flow cytometry was performed to determine the cell cycle.MGC-803 cells were injected in four groups of nude mice to construct a subcutaneous xenograft tumor model,with three nude mice in each group.The body mass of the nude mice was measured.The nude mice were sacrificed after 14 days and the tumor volume was monitored.The expression levels of CyclinB1 and CDC20 proteins in the tumor tissues were determined by Western blot assay.Results Analysis with UALCAN showed that PCMT1 was highly expressed in gastric cancer tissues.Moreover,elevated expression was found in gastric tumor tissues of different pathological stages and grades and those with lymph node metastasis(P＜0.05).GO and KEGG enrichment analyses showed that PCMT1 was mainly involved in the signal regulation of mitosis,spindle assembly checkpoints,and cell cycle.The immunohistochemical results showed that PCMT1 and Ki67 were highly expressed in gastric cancer tissues and that they were positively correlated with each other(P＜0.05).Cox multivariate analysis showed that high PCMT1 expression(hazard ratio[HR]=2.921,95％confidence interval[CI]:1.628-5.239)was one of the independent risk factors affecting the 5-year survival rate of gastric cancer patients after surgery.Kaplan-Meier curve showed that patients with high PCMT1 expression had a lower 5-year survival after surgery(16.7％,HR=4.651,95％CI:2.846-7.601)than patients with low PCMT1 expression(70.0％,HR=0.215,95％CI:0.132-0.351)did.The ROC curve showed that PCMT1 had an area under the curve(AUC)of 0.764(95％CI:0.674-0.854)for predicting 5-year patient survival after surgery.Western blot results showed that lentiviral interference or overexpression of PCMT1 cell lines was successfully constructed.The results of CCK-8 showed that the proliferative ability of MGC-803 and HGC-27 cells was weakened with the downregulation of PCMT1,and the overexpression of PCMT1 promoted cell proliferation(P＜0.05).With the interference of PCMT1,the expression of CDC20 protein was decreased,the expression of CyclinB1 protein was increased,and the cell cycle was arrested in the G2/M phase.In contrast,the overexpression of PCMT1 led to the opposite trends(P＜0.05).In the sh-PCMT1 group,the tumor volume and mass were decreased and the expression of CDC20 protein was decreased and the expression of CyclinB1 protein was increased in the tumor tissues of the nude mice(P＜0.05,compared with those of the sh-NC group.In contrast,the LV-PCMT1 group showed the opposite trends(P＜0.05,compared with those of the LV-Vec group).Conclusion The high expression of PCMT1 in gastric cancer tissues is associated with poor prognosis in patients and may affect tumor cell malignant proliferation via regulating spindle checkpoints in the process of mitosis.

BACKGROUND: The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. METHODS: Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. RESULTS: In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P  = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P  = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P  = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P  = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P  = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P  = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P  = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P  = 0.002), musculoskeletal damage (P  = 0.023), cardiovascular impairment (P  = 0.009), and CYC use (P  = 0.001); while leukopenia (P  = 0.017), arthritis (P  = 0.014), and mycophenolate usage (P  = 0.013) rates were lower. CONCLUSIONS Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.
Humans ; Female ; Male ; Cross-Sectional Studies ; Sex Characteristics ; East Asian People ; Severity of Illness Index ; Lupus Erythematosus, Systemic/diagnosis* ; Lupus Nephritis/pathology* ; Registries ; Cyclophosphamide/therapeutic use* ; Thrombocytopenia ; Leukopenia/drug therapy* ; Arthritis

Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited childhood white-matter disorders, and the pathogenic gene has been confirmed as EIF2B gene. VWM is characterized by chronic progressive neurological deterioration with cerebellar ataxia, usually less prominent spasticity and relatively mild mental decline. There are episodes of rapid and major neurological deterioration provoked by stresses, such as fever, minor physical trauma and acute fright, which is a characteristic clinical feature of VWM. Brain magnetic resonance imaging findings are diagnostic in almost all patients,and the disappearance of the cerebral white matter occurs in a diffuse "melting away" pattern. The onset of VWM can be at any age from fetal stage to adult stage, and the clinical phenotypes vary immensely. Gene diagnosis is the golden standard for VWM. This article reported a patient with a course of 17 years, who was misdiagnosed as Wilson′s disease because of low serum ceruloplasmin, and was finally diagnosed as VWM by reinterpretation of whole exome sequencing, which is worthy of clinicians′ vigilance and consideration.

Objective To compare the difference of volatile organic compounds (VOCs) in the urine of diabetic patients comorbid with or without depression. Methods Patients with type 2 diabetes who met the diagnostic criteria of prevention and treatment guidelines and were treated in inpatient department of Sixth People’s Hospital South Campus, Shanghai Jiaotong University, from November 2019 to November 2020 were included in the study. Depression screening was performed using PHQ9 scale. According to the scores, the patients were divided into two groups: diabetic patient group and diabetic patient comorbidity depression group. The morning urine was collected and VOCs in urine were detected using a miniature gas tester. Results A total of 161 patients with diabetes mellitus, including 141 patients in the diabetic group and 20 patients in the diabetic comorbidity depression group. The results indicated that the sensitivity, specificity and accuracy of the method are 80%, 98% and 92.8% respectively. There were differences in urine volatile organic compounds between the two groups. Conclusions Compared with diabetic patients, the composition of volatile organic compounds in urine may change after diabetic comorbidity depression, which can provide experimental reference for early clinical diagnosis of depression.

Objective:To investigate the cognitive status of fatigue among patients with coronary heart disease (CHD) in the community and analyze its influencing factors.Methods:From May to July 2020, a total of 250 patients with CHD in the community were selected as the research objects by multi-stage sampling method. The general information questionnaire and Fatigue Cognition Questionnaire for Patients with CHD were used for investigation. Multiple linear regression analysis was used to analyze the influencing factors. A total of 250 questionnaires were distributed and 245 were effectively recovered.Results:The total score of fatigue cognition of 245 patients with CHD in the community was 6 (4, 7) . Univariate analysis showed that there were statistically significant differences in the total scores of fatigue cognition among community CHD patients with different education level, duration of disease, grading of cardiac function, whether pay attention to fatigue knowledge, number of combined chronic diseases and treatment methods ( P<0.05) . Multiple linear regression analysis showed that education level, duration of disease, whether pay attention to fatigue knowledge, number of combined chronic diseases and treatment methods were the main influencing factors on fatigue cognition of CHD patients in the community ( P<0.05) . Conclusions:The cognition of patients with CHD in the community on fatigue needs to be improved, and community medical workers should take corresponding measures to increase the attention and active response of patients with CHD to fatigue.