It is proposed that yangming （阳明） turbid heat and dysfunction of the chong and ren （冲任） vessels are the key pathogenesis underlying abnormal uterine bleeding caused by polycystic ovary syndrome （PCOS）. The general principle of treatment is to clear and drain the yangming channel and resolve turbid heat. During the acute bleeding phase， the approach is to clear heat， cool the blood， consolidate the chong vessel， and stop bleeding. During the chronic phase， the focus shifts to resolving phlegm and removing stasis， unblocking and purging qi movement. And during the late stage， the method of boosting qi and nourishing yin， consolidating the root and regulating menstruation is suggested. In clinical practice， the self-formulated Yishen Quzhuo Formula （益肾祛浊方） serves as the foundation， with flexible modifications and adjustments made according to disease stage and individual clinical presentation.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To explore the relationship between the ferroptosis-related molecules heme oxygenase-1(HMOX1)and mitogen-activated protein kinase 14(MAPK14)with the onset and prognosis of acute lung injury(ALI)in children with sepsis.Methods A total of 102 children with sepsis were selected,including 54 in the ALI group and 48 in the non-ALI group.Clinical data,laboratory tests,organ function scores and serum levels of HMOX1 and MAPK14 were compared between the two groups.The mortality rates of children with different levels of HMOX1 and MAPK14 at 28-day and 90-day were analyzed.Results Compared with the non-ALI group,procalcitonin(PCT),lactate(Lac),pediatric organ dysfunction Logistic-2 score(PELOD-2),pediatric risk of mortality score version 3(PRISM III)and sequential organ failure assessment(SOFA)scores were increased in the ALI group(P＜0.05).Serum levels of HMOX1 and MAPK14 were significantly higher in the ALI group than those in the non-ALI group(P＜0.05).HMOX1 and MAPK14 showed good predictive value for the occurrence of ALI in sepsis patients,with AUC values of 0.872(95%CI:0.791-0.930)and 0.825(95%CI:0.737-0.893),and the optimal cutoff values were 3.1 μg/L and 3.8 μg/L,respectively.After grouping by the cutoff values of HMOX1 and MAPK14,there were no significant differences in the 28-day and 90-day mortality rates in children with different levels of HMOX1 and MAPK14(P＞0.05).Conclusion The expression levels of serum HMOX1 and MAPK14 increase in the early stage of sepsis-related ALI,which may serve as biomarkers for the onset of ALI,and they have no significant impact on the prognosis of children.

Objective To comprehensively and systematically evaluate the clinical effect of Chuanzhi Tongluo capsule combined with western medical treatment in patients with cerebral infarction using meta-analysis.Methods Domestic databases were searched,including China Knowledge Network,Wanfang,and Wipu databases,and foreign databases were mainly PubMed.The qualified literature was screened according to the inclusion and exclusion criteria,and was evaluated using the software of RevMan5.3 and Stata14.0 after quality assessment.Results Eight randomized controlled trials(RCTs)on the combination of Chuanzhi Tongluo capsule and western medicine were included,with a total of 728 patients with cerebral infarction,among which 365 cases were in the group of Chuanzhi Tongluo capsule combined with western medicine and 363 cases were in the group of western medicine alone.The results were analyzed in terms of the total effective rate,neurological deficit score such as the National Institutes of Health Stroke Scale(NIHSS),daily living scores,such as the Barthel Index and Activities of Daily Living(ADL)scores and inflammation level(Inflammatory mediator IL-6,ultrasensitive C-reactive protein)as the outcome indexes.Meta-analysis results showed that the total effective rate[95%CI,1.18(1.12,1.25),P<0.00001],neurological function impairment score[95%CI,-1.37(-2.08,-0.67),P=0.0001],daily life score[95%,0.88(0.51,1.25),P<0.00001],and inflammation level[95%CI,-0.75(-0.96,-0.54),P<0.00001]were better than those of the control group and showed significant differences.The incidence of adverse events[95%CI,0.89(0.37,2.15),P=0.80],and the difference was not statistically significant with that of western medicine treatment alone.Conclusion Compared with the control group which only used western medicine,the treatment effect of Chuanzhi Tongluo capsule combined with western medicine in the treatment of cerebral infarction is more significant,and the combined treatment can improve the neurological function of the patients,enhance the quality of daily life,and reduce the level of inflammation more effectively.

Objective This study aims to investigate the effects of FGL2 on the immune response of EBV-infected T cells,including their activation,proliferation,exhaustion,and cytokine profile changes.Methods Primary T cells were infected with EBV at different multiplicities of infection(MOI).Expression of FGL2 in T cells,as well as T-cell activation,proliferation,exhaustion,and cytokine levels,were detected using RT-qPCR,Western blot,ELISA,CCK8,and flow cytometry(FCM),respectively.Further experiments involving FGL2 knockdown and overexpression were conducted to elucidate its specific regulatory role in EBV-infected T cells.Results FGL2 expression was significantly upregulated in EBV-infected T cells(P＜0.05).EBV infection also induced enhanced T cell activation(P＜0.001),proliferation(P＜0.001),and exhaustion(P＜0.01).Compared to the T cells+EBV group,the T cells+EBV+FGL2 overexpression group exhibited higher exhaustion levels(P＜0.01),reduced activation(P＜0.05)and proliferation(P＜0.05),decreased pro-inflammatory cytokine levels(P＜0.05),and increased anti-inflammatory cytokine levels(P＜0.05).Conversely,the T cells+EBV+FGL2 knockdown group demonstrated the opposite trends,with elevated activation(P＜0.01),proliferation(P＜0.05),pro-inflammatory cytokine levels(P＜0.05),and reduced exhaustion(P＜0.01)and anti-inflammatory cytokine levels(P＜0.05).Conclusion FGL2 suppresses T cell activation and proliferation,exacerbates T cell exhaustion,inhibits pro-inflammatory cytokine release,and promotes anti-inflammatory cytokine secretion during EBV infection,thereby modulating the immune response of T cells.

Objective This study aims to investigate the effects of FGL2 on the immune response of EBV-infected T cells,including their activation,proliferation,exhaustion,and cytokine profile changes.Methods Primary T cells were infected with EBV at different multiplicities of infection(MOI).Expression of FGL2 in T cells,as well as T-cell activation,proliferation,exhaustion,and cytokine levels,were detected using RT-qPCR,Western blot,ELISA,CCK8,and flow cytometry(FCM),respectively.Further experiments involving FGL2 knockdown and overexpression were conducted to elucidate its specific regulatory role in EBV-infected T cells.Results FGL2 expression was significantly upregulated in EBV-infected T cells(P＜0.05).EBV infection also induced enhanced T cell activation(P＜0.001),proliferation(P＜0.001),and exhaustion(P＜0.01).Compared to the T cells+EBV group,the T cells+EBV+FGL2 overexpression group exhibited higher exhaustion levels(P＜0.01),reduced activation(P＜0.05)and proliferation(P＜0.05),decreased pro-inflammatory cytokine levels(P＜0.05),and increased anti-inflammatory cytokine levels(P＜0.05).Conversely,the T cells+EBV+FGL2 knockdown group demonstrated the opposite trends,with elevated activation(P＜0.01),proliferation(P＜0.05),pro-inflammatory cytokine levels(P＜0.05),and reduced exhaustion(P＜0.01)and anti-inflammatory cytokine levels(P＜0.05).Conclusion FGL2 suppresses T cell activation and proliferation,exacerbates T cell exhaustion,inhibits pro-inflammatory cytokine release,and promotes anti-inflammatory cytokine secretion during EBV infection,thereby modulating the immune response of T cells.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

In recent years,the prevalence of porcine infectious pleuropneumonia caused by Actinoba-cillus pleuropneumoniae(APP)has significantly increased in large-scale pig farms in China.The i-solation,identification,and biological characteristic testing of newly prevalent strains have impor-tant clinical significance.This study isolated four suspected APP strains(named XB2T-56,JMTLP-443,YD-THB-755,SYZJ-291)from lung samples of pig farms suspected of outbreaks of porcine infectious pleuropneumonia in Hubei Province.They were identified by PCR amplification,and multiplex PCR serological typing,the biological properties were tested by detecting the growth a-bility,hemolytic activity and biofilm forming ability.The drug resistance of the strains was ana-lyzed by drug sensitivity testing,and the virulence of one strain(XB2T-56)in mice and piglets was evaluated.The PCR identification result showed that all four clinical isolates were APP serotype 15 strains.These four strains grew slower than serotype 1 standard strains,had weaker hemolytic activity,but could form stronger biofilms.These strains are all less sensitive to cephalosporin,tylo-sin,sulfamethoxazole,and doxycycline,but sensitive to cefotaxime and enrofloxacin.The mice and piglet infection experiments showed that the isolated strain XB2T-56 has strong virulence.Artifi-cial intranasal infection causes acute death in piglets,with typical symptoms of pleuropneumonia in the lungs,and serotype 15 strains can be isolated from the lesion site.This study indicates that the APP serotype 15 strain has strong virulence,providing new date for the clinical epidemiological characteristics of APP.

Aim To compare the differences in the in vitro anti-precancerous lesions of gastric cancer(PL-GC)activities of different polar extracts from Bombyx batryticatus.Methods Bombyx batryticatus was ex-tracted by ethanol reflux,and the extract was further partitioned using different polarity organic solvents to obtain four fractions:petroleum ether(SYM),ethyl acetate(YSYZ),n-butanol(ZDC),and aqueous phase(SX).The PLGC cell model was established by inducing malignant transformation in GES-1 cells using N-methyl-N-nitro-N-nitrosoguanidine(MNNG).The optimal concentration of four extracts were determined by CCK-8 assay.The proliferation,migration and in-vasion of cells in each group were detected by plate cloning,scratch healing and Transwell assay,respec-tively.The expression levels of E-cadherin,Vimentin and key proteins of the PI3 K/AKT/mTOR signaling pathway in cells of each group were detected by West-ern blot.Meanwhile,chemical components of the four extracts were analyzed by UPLC-Q-TOF-MS/MS.Re-sults Compared with the normal group,the prolifera-tion,migration and invasion abilities of cells in the PL-GC group were significantly enhanced,the expression levels of E-cadherin proteins of PLGC cells were down-regulated,and the expression levels of Vimentin,p-PI3K,p-AKT and p-mTOR proteins of PLGC cells were up-regulated.Compared with the PLGC group,the four extracts attenuated the proliferation,migration and invasion abilities of PLGC cells,down-regulated the protein expression levels of Vimentin,p-PI3K,p-AKT and p-mTOR,and upregulated E-cadherin ex-pression in cells of the SYM,YSYZ,and ZDC groups.There was no statistical significance in the SX group.In addition,there were significant differences in the chemical components of the four different polar extracts of Bombyx batryticatus.The differential compounds were cysteine,histidine,etc.Conclusions The four different polar extracts of Bombyx batryticatus all can exert in vitro anti-PLGC effects by regulating the PI3K/AKT/mTOR signaling pathway to inhibit the EMT process.Among them,the extract of n-butanol had the strongest activity,followed by the extracts of ethyl ace-tate and petroleum ether.The aqueous phase had the weakest activity,and the difference in activity may be related to the different compounds such as Cysteine and Histidine.