Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective To explore the effect of exercise-induced fatigue on intra-and interhemispher-ic functional connectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.Meth-ods Twenty-four healthy adult males(age:21.6±2.2 years;all right-side dominant)were selected as participants for the study.They ran on a treadmill at an individualized constant speed until fatigue.Fatigue was determined when all the following criteria were met:(1)participants failing to maintain the individualized constant speed despite the strong verbal encouragement from the experimenters;(2)reaching a rating of perceived exertion(RPE)score of at least 19;and(3)their heart rate reaching 90%of their age-predicted maximal heart rate(220-age).Moreover,EEG signals from four channels(C1,C2,C3,and C4)of the primary motor cortex were collected during unilateral ankle dorsi-plan-tarflexion movements before and after fatigue,followed by EEG coherence analyses on the collected da-ta.Results Compared to the pre-fatigue state,the coherence values of the intra-hemispheric primary motor cortex electrode pairs C1-C3 and C2-C4 during unilateral ankle plantar-dorsiflexion decreased significantly in the alpha and gamma bands after fatigue(both P<0.05).Conversely,the value of the interhemispheric primary motor cortex electrode pair C1-C2 increased significantly in the beta band(P<0.05).Conclusion Exercise-induced fatigue significantly weakens the intra-hemispheric functional con-nectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.However,it may en-hance the interhemispheric functional connectivity and potentially collaborate to strengthen the regula-tion of fatigued muscles.

Objective To explore the effect of exercise-induced fatigue on intra-and interhemispher-ic functional connectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.Meth-ods Twenty-four healthy adult males(age:21.6±2.2 years;all right-side dominant)were selected as participants for the study.They ran on a treadmill at an individualized constant speed until fatigue.Fatigue was determined when all the following criteria were met:(1)participants failing to maintain the individualized constant speed despite the strong verbal encouragement from the experimenters;(2)reaching a rating of perceived exertion(RPE)score of at least 19;and(3)their heart rate reaching 90%of their age-predicted maximal heart rate(220-age).Moreover,EEG signals from four channels(C1,C2,C3,and C4)of the primary motor cortex were collected during unilateral ankle dorsi-plan-tarflexion movements before and after fatigue,followed by EEG coherence analyses on the collected da-ta.Results Compared to the pre-fatigue state,the coherence values of the intra-hemispheric primary motor cortex electrode pairs C1-C3 and C2-C4 during unilateral ankle plantar-dorsiflexion decreased significantly in the alpha and gamma bands after fatigue(both P<0.05).Conversely,the value of the interhemispheric primary motor cortex electrode pair C1-C2 increased significantly in the beta band(P<0.05).Conclusion Exercise-induced fatigue significantly weakens the intra-hemispheric functional con-nectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.However,it may en-hance the interhemispheric functional connectivity and potentially collaborate to strengthen the regula-tion of fatigued muscles.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

Advanced gastric cancer(AGC)includes locally unresectable gastric cancer(GC),metastatic GC,and postoperative recurrent GC.Due to delayed diagnosis and lack of effective treatment for AGC,the median survival time of AGC patients is only 6-12 months.At present,the main treatment goal of AGC is to improve symptoms and prolong the survival time of patients receiving sequential chemotherapy.Although the therapeutic effect of systemic therapy on AGC is gradually becoming apparent,the patient's prognosis is far from expected.In addition,targeted therapy and novel immunotherapy have drawbacks such as high incidence of drug resistance,high toxic side effects,and heavy economic burden on patients.Therefore,finding new therapeutic targets and developing anti-tumor drugs is a key issue that urgently needs to be addressed.According to reports,abnormal activation of the hepatocyte growth factor(HGF)/cellular-mesenchymal epithelial transition factor(c-MET)pathway plays a crucial role in the progression of GC and the occurrence of multi-line resistance and may be a potential therapeutic target for GC.In recent years,some HGF/c-MET-targeting small molecule tyrosine kinase inhibitors(TKIs)have been found to show good clinical effects in the treatment of GC.Meanwhile,new HGF/c-MET inhibitors(such as monoclonal antibodies,bispecific antibodies,antibody drug conjugates,etc.)have shown good anti-tumor activity in preclinical studies,but they are all at different stages of clinical research,and their efficacy and safety still need further confirmation.This review elaborates on the latest research progress of HGF/c-MET inhibitors in the treatment of AGC and discusses the main reasons and strategies for drug resistance,aiming to provide better guidance for the treatment of AGC and provide reference for future research.

Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the autoimmune system attacking hepatocytes， and its chronic progression may lead to liver cirrhosis and even hepatocellular carcinoma. Currently， pharmacotherapy and liver transplantation are the main treatment methods for AIH， but both methods have their own limitations， which limits the clinical benefits of patients. Therefore， it is a critical issue to search for new therapeutic agents and methods. Recent studies have shown that mesenchymal stem cells （MSC） and their exosomes can improve the symptoms of patients with AIH by suppressing inflammatory response， enhancing the regeneration of hepatocytes， and regulating the immune system and thus have wide application prospects in the treatment of AIH. By summarizing related articles， this article reviews the possible mechanisms and application of MSC and their exosomes in the treatment of AIH， in order to provide new ideas for the clinical treatment of AIH.

Objective To investigate the expression of Sema4D in peripheral blood T cells and serum of patients with hepatitis B cirrhosis and its correlation with clinical indicators. Methods A total of 20 patients with chronic hepatitis B (CHB), 68 patients with hepatitis B cirrhosis, and 20 healthy controls who attended The 940 th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from October 2020 to November 2021 were enrolled. According to Child-Pugh class, the patients with hepatitis B cirrhosis were divided into Child-Pugh class A group with 24 patients, Child-Pugh class B group with 24 patients, and Child-Pugh class C group with 20 patients. After peripheral blood samples were collected to isolate serum and peripheral blood mononuclear cells (PBMCs), flow cytometry was used to measure the expression of membrane-bound Sema4D (mSema4D) + CD4 + T cells and mSema4D + CD8 + T cells in PBMCs, and ELISA was used to measure the expression of soluble Sema4D (sSema4D) in serum; their correlation with viral replication and liver inflammation markers was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; a Spearman correlation analysis was also performed. Results There were significant differences in the expression of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells between the CHB group, the hepatitis B cirrhosis group, and the control group ( F =43.092 and 13.344, both P < 0.001), while there were significant differences between any two groups ( P < 0.05). The expression levels of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells gradually decreased with increasing Child-Pugh class ( F =14.093 and 17.154, both P < 0.05), and there were significant differences between any two groups ( P < 0.05). The content of sSema4D was 1.54(1.42-1.71) ng/mL in the control group, 1.08(1.07-1.38) ng/mL in the CHB group, and 4.87(2.13-14.97) ng/mL in the hepatitis B cirrhosis group, with a significant difference between the three groups ( H =32.366, P < 0.001) and between any two groups ( P < 0.05). The content of sSema4D was 2.42(0.59-5.65) ng/mL in the Child-Pugh class A group, 4.92(2.75-12.73) ng/mL in the Child-Pugh class B group, and 14.18(4.59-18.43) ng/mL in the Child-Pugh class C group, with a significant difference between the three groups ( H =11.889, P =0.003) and between any two groups ( P < 0.05). In patients with hepatitis B cirrhosis, the level of sSema4D was positively correlated with the levels of alanine aminotransferase (ALT) and HBV DNA quantification ( r =0.294 and 0.430, both P < 0.05). Conclusion Sema4D is lowly expressed on T cell membrane and highly expressed in serum of patients with hepatitis B cirrhosis, and sSema4D may be involved in the development and progression of hepatitis B cirrhosis by affecting the levels of ALT and HBV DNA.