Liver transplantation, hepatocyte transplantation, and bioartificial liver are means of treating end-stage liver disease and acute liver failure. However, insufficient liver resources and immune rejection after transplantation, as well as a shortage of liver tissue or cell donors, are challenges faced in clinical treatment. The research progress of liver organoid technology in recent years may provide new ways to solve the above problems. Organoids are a kind of three-dimensional cell condensates formed by the self-organization of pluripotent or adult stem cells through three-dimensional culture in vitro, which can imitate the spatial structure and physiological function characteristics of the original organs, can be sub-cultured in vitro, replicated on a large scale, and have the ability of self-renewal. The emergence of organoid technology has brought new hope for providing mechanism exploration models and resolution of hepatocyte resources. In particular, induced pluripotent stem cell-derived organoids do not involve ethical concerns, and are combined with emerging technologies such as gene editing and organ chips, thereby overcoming the constraint of traditional disease research models and establishing a new platform for translational medicine. Additionally, it has expansive application prospects in building disease models, screening drugs, precision medicine, regenerative medicine, and organ transplantation. Thus, this paper summarizes the technical principles, preclinical research, and application progress and challenges of liver organoid technology.

Hepatitis B virus (HBV) infection is a major global public health problem. There will be about 257 million chronic HBV-infected patients worldwide, according to the World Health Organization's estimation by 2025. Currently, the main drugs for the treatment of chronic HBV infection are nucleos(t)ide analogues and pegylated interferon (PEG-IFN). However, previous research results show that whether it is nucleos(t)ide analogues and PEG-IFN-α monotherapy or combination therapy, or sequential combination therapy, the rate of hepatitis B surface antigen seroconversion in patients is low, and there is still a high risk of disease progression after a certain course of antiviral treatment. Therefore, to achieve the ambitious target of "eliminating viral hepatitis by 2030" set by the World Health Organization and help more hepatitis B patients achieve functional cure, a large number of new drugs have been developed and entered clinical trials. This paper summarizes and reviews the types, safety, and efficacy of new drugs to further promote advancements in the field of treatment of chronic HBV infection.

Objective:To explore the demographic composition of type 2 diabetes mellitus (T2DM) with metabolic associated fatty liver disease (MAFLD) and the role of energy metabolism in the progression of MAFLD in order to provide theoretical support for improving the prognosis of MAFLD.Methods:A cross-sectional study was conducted. Ninety-four cases with T2DM combined with MAFLD admitted to the Endocrinology Department of Tianjin Third Central Hospital from July 2014 to July 2019 were selected. Patients were divided into three groups: non-metabolic associated steatohepatitis (MASH) group (25 cases), borderline MASH group (49 cases), and MASH group (20 cases) according to the non-alcoholic fatty liver disease activity score (NAS). Patients were further divided into two groups: non/mild fibrosis (F0-1) group (74 cases) and the significant fibrosis (F2-4) group (20 cases) in accordance with liver fibrosis scores. The differences in general clinical and biochemical indicators, body composition, and energy metabolism indicators among the groups were compared. Binary logistic regression analysis was conducted to explore factors affecting liver inflammation and fibrosis severity degree in patients with MAFLD.Results:The visceral fat area (VFA) and body fat percentage (PBF) were significantly higher in the MASH group than in the non-MASH group ( P<0.05), while the skeletal muscle mass index and body mass index (SMI-BMI) were significantly lower in the MASH group than in the marginal MASH group ( P<0.05) during the comparison of body composition and substrate metabolism at different stages of MASH. Alanine aminotransferase (ALT) and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the fibrotic group than in those in the no/mild fibrosis group ( P<0.05) when comparing clinical and biochemical indicators, body composition, and substrate metabolism at different stages of fibrosis. The skeletal muscle mass (SMM), SMI-BMI, SMM-Weight, resting energy expenditure (REE), and fat oxidation rate (FAT OXR) were significantly lower in the fibrotic group than those in the no/mild fibrosis group ( P<0.05). The respiratory quotient and carbohydrate functional ratio (%CHO) were significantly higher in the fibrotic group than in the no/mild fibrosis group ( P<0.05). Correlation analysis indicated a positive correlation between the NAS score, reflecting the severity of liver inflammatory lesions, with VFA and PBF ( r=0.258 and 0.323, P<0.05); while the F score was positively correlated with the respiratory quotient, %CHO, and VFA ( r=0.292, 0.303, and 0.239, P<0.05), and negatively correlated with REE, the energy ratio from fat, FAT OXR, SMM, SMI-Weight, and SMI-BMI ( r=-0.209, -0.214, -0.333, -0.240, -0.250, and -0.305, P<0.05). Logistic regression analysis indicated that SMI-Weight and FAT OXR were independent factors affecting the progression of liver fibrosis. Conclusion:The reduction of skeletal muscle, particularly because of energy metabolism, is a factor affecting the progression of fibrosis in MAFLD.

Liver transplantation, hepatocyte transplantation, and bioartificial liver are means of treating end-stage liver disease and acute liver failure. However, insufficient liver resources and immune rejection after transplantation, as well as a shortage of liver tissue or cell donors, are challenges faced in clinical treatment. The research progress of liver organoid technology in recent years may provide new ways to solve the above problems. Organoids are a kind of three-dimensional cell condensates formed by the self-organization of pluripotent or adult stem cells through three-dimensional culture in vitro, which can imitate the spatial structure and physiological function characteristics of the original organs, can be sub-cultured in vitro, replicated on a large scale, and have the ability of self-renewal. The emergence of organoid technology has brought new hope for providing mechanism exploration models and resolution of hepatocyte resources. In particular, induced pluripotent stem cell-derived organoids do not involve ethical concerns, and are combined with emerging technologies such as gene editing and organ chips, thereby overcoming the constraint of traditional disease research models and establishing a new platform for translational medicine. Additionally, it has expansive application prospects in building disease models, screening drugs, precision medicine, regenerative medicine, and organ transplantation. Thus, this paper summarizes the technical principles, preclinical research, and application progress and challenges of liver organoid technology.

Hepatitis B virus (HBV) infection is a major global public health problem. There will be about 257 million chronic HBV-infected patients worldwide, according to the World Health Organization's estimation by 2025. Currently, the main drugs for the treatment of chronic HBV infection are nucleos(t)ide analogues and pegylated interferon (PEG-IFN). However, previous research results show that whether it is nucleos(t)ide analogues and PEG-IFN-α monotherapy or combination therapy, or sequential combination therapy, the rate of hepatitis B surface antigen seroconversion in patients is low, and there is still a high risk of disease progression after a certain course of antiviral treatment. Therefore, to achieve the ambitious target of "eliminating viral hepatitis by 2030" set by the World Health Organization and help more hepatitis B patients achieve functional cure, a large number of new drugs have been developed and entered clinical trials. This paper summarizes and reviews the types, safety, and efficacy of new drugs to further promote advancements in the field of treatment of chronic HBV infection.

Objective:To explore the demographic composition of type 2 diabetes mellitus (T2DM) with metabolic associated fatty liver disease (MAFLD) and the role of energy metabolism in the progression of MAFLD in order to provide theoretical support for improving the prognosis of MAFLD.Methods:A cross-sectional study was conducted. Ninety-four cases with T2DM combined with MAFLD admitted to the Endocrinology Department of Tianjin Third Central Hospital from July 2014 to July 2019 were selected. Patients were divided into three groups: non-metabolic associated steatohepatitis (MASH) group (25 cases), borderline MASH group (49 cases), and MASH group (20 cases) according to the non-alcoholic fatty liver disease activity score (NAS). Patients were further divided into two groups: non/mild fibrosis (F0-1) group (74 cases) and the significant fibrosis (F2-4) group (20 cases) in accordance with liver fibrosis scores. The differences in general clinical and biochemical indicators, body composition, and energy metabolism indicators among the groups were compared. Binary logistic regression analysis was conducted to explore factors affecting liver inflammation and fibrosis severity degree in patients with MAFLD.Results:The visceral fat area (VFA) and body fat percentage (PBF) were significantly higher in the MASH group than in the non-MASH group ( P<0.05), while the skeletal muscle mass index and body mass index (SMI-BMI) were significantly lower in the MASH group than in the marginal MASH group ( P<0.05) during the comparison of body composition and substrate metabolism at different stages of MASH. Alanine aminotransferase (ALT) and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the fibrotic group than in those in the no/mild fibrosis group ( P<0.05) when comparing clinical and biochemical indicators, body composition, and substrate metabolism at different stages of fibrosis. The skeletal muscle mass (SMM), SMI-BMI, SMM-Weight, resting energy expenditure (REE), and fat oxidation rate (FAT OXR) were significantly lower in the fibrotic group than those in the no/mild fibrosis group ( P<0.05). The respiratory quotient and carbohydrate functional ratio (%CHO) were significantly higher in the fibrotic group than in the no/mild fibrosis group ( P<0.05). Correlation analysis indicated a positive correlation between the NAS score, reflecting the severity of liver inflammatory lesions, with VFA and PBF ( r=0.258 and 0.323, P<0.05); while the F score was positively correlated with the respiratory quotient, %CHO, and VFA ( r=0.292, 0.303, and 0.239, P<0.05), and negatively correlated with REE, the energy ratio from fat, FAT OXR, SMM, SMI-Weight, and SMI-BMI ( r=-0.209, -0.214, -0.333, -0.240, -0.250, and -0.305, P<0.05). Logistic regression analysis indicated that SMI-Weight and FAT OXR were independent factors affecting the progression of liver fibrosis. Conclusion:The reduction of skeletal muscle, particularly because of energy metabolism, is a factor affecting the progression of fibrosis in MAFLD.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

BACKGROUND:There is no consensus on the optimal bone tunnel position in the lateral clavicle,which guides coracoclavicular ligament reconstruction.Postoperative complications such as enlargement of the lateral clavicle bone tunnel,bone osteolysis,clavicle fracture,and failure of internal fixation are likely to occur.Bone mass density plays an important role in the strength and stability of endophytic fixation.Regional differences in the bone mass density of the distal clavicle should not be overlooked in the repair and reconstruction of acromioclavicular dislocation.Currently,there are no quantitative clinical studies in humans regarding the bone mass density of the distal clavicle. OBJECTIVE:To measure the magnitude of bone mass density in different regions of the distal clavicle by quantitative CT to provide a reference for surgeons to repair and reconstruct the coracoclavicular ligament. METHODS:101 patients undergoing quantitative CT checking in Fuyang People's Hospital Affiliated to Anhui Medical University from October to December 2022 were enrolled,from which 1 616 samples of subdivisional bone mass density of the distal clavicle were measured.For each of the quantitative CT samples,firstly,the distal clavicle was divided medially to laterally into the following four regions:conical nodal region(region A),inter-nodal region(region B),oblique crest region(region C)and distal clavicular region(region D).Secondly,each region was divided into the first half and the second half to determine eight subdivisions,then setting semiautomatic region of interest(ROI)in each subdivision:(ROI A1,A2,B1,B2,C1,C2,D1,and D2).Thirdly,each quantitative CT scan was transferred to the quantitative CT pro analysis workstation,and cancellous bone mass density was measured in the distal clavicle ROI.Finally,the clavicular cortex was avoided when measuring. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in bone mineral density on the different sides of the shoulder(P＞0.05).(2)The analysis of bone mineral density in eight sub-areas of the distal clavicle A1,A2,B1,B2,C1,C2,D1,and D2 showed statistically significant differences(P＜0.05).It could be considered that there were differences in bone mineral density in different areas of the distal clavicle.After pairwise comparison,there was no statistically significant difference in bone mineral density between A1 and A2,D1 and D2,A2 and B1(P＞0.05),and there was a statistically significant difference in bone mineral density between the other sub-areas(P＜0.05).(3)The bone mineral density in the region A2 of the anatomical insertion of the conical ligament was significantly higher than that in the inter-nodular area(region B)(P＜0.05).The bone mineral density in the region A1 was higher than that in the region A2,but the difference was not statistically significant(P＞0.05).The bone mineral density in the region C1 of the anatomical insertion of the trapezium ligament was higher than that in regions C2,D1 and D2,and the bone mineral density in the inter-nodular area(region B)was significantly higher than that in regions C and D(P＜0.05).(4)These results have suggested that there are differences in bone mass density in different regions of the distal clavicle;regional differences in bone mass density in the distal clavicle during repair and reconstruction of acromioclavicular dislocation cannot be ignored.Consideration should be given not only to biomechanical factors but also to the placement of implants or bone tunnels in regions of higher bone mass density,which could improve the strength and stability of implant fixation and reduce the risk of complications such as bone tunnel enlargement,osteolysis,fracture and implant failure.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To study the correlation between patients with type 2 diabetes mellitus combined with nonalcoholic steatohepatitis in order to provide theoretical support for the treatment of NAFLD through aerobic exercise performance.Methods:253 cases with T2DM combined with NAFLD were selected. 93 cases consented to undergo a liver biopsy. Among them, 74 cases with liver biopsy successfully passed the symptom-limited cardiopulmonary exercise test (CPET) and respiratory quotient (RQ)≥1.05. Patients were divided into two groups according to the NAFLD activity score (NAS) of the pathological biopsy: the non-NASH group (NAS < 4) and the NASH group (NAS≥4). The differences in general clinical and biochemical indicators and exercise parameters were compared between the two groups. The relevant factors that affect aerobic exercise performance in NAFLD patients were explored by correlation and regression analysis.Results:The peak oxygen uptake [VO2 @ peak, (17.82 ± 5.61) ml·kg -1·min -1 and (23.14 ± 5.86) ml·kg -1·min -1] and anaerobic threshold [VO2 @ AT, (11.47 ± 3.12) ml·kg -1·min -1 and (13.81 ± 3.53) ml·kg -1·min -1] were lower in the NASH group than those in the non-NASH group in T2DM patients, with P < 0.01, indicating a significant decrease in aerobic exercise performance in NASH patients compared to non-NASH patients. Correlation analysis showed that patients with T2DM combined with NAFLD VO2@peak was positively correlated with RQ, carbohydrate oxidation rate (%CHO), daily carbohydrate energy supply (CHO Kcal/d), high-density lipoprotein cholesterol (HDL-C), and maximal voluntary ventilation (MVV) ( r 0.360, 0.334, 0.341, 0.255, 0.294, P < 0.05 or P < 0.01, respectively) and negatively correlated with NAS score, fat attenuation, liver stiffness, fat oxidation rate (%FAT), daily fat energy supply (FAT Kcal/d), aspartate aminotransferase (AST), alanine aminotransferase (ALT), body mass, and body mass index (BMI) ( r -0.558, -0.411, -0.437, -0.340, -0.270, -0.288, -0.331, -0.295, -0.469, P < 0.05 or P < 0.01, respectively). VO2@AT were positively correlated with RQ, %CHO, total cholesterol (TC), and HDL-C ( r 0.351, 0.247, 0.303, 0.380, P < 0.05 or P < 0.01, respectively), while it was negatively correlated with NAS score, fat attenuation, liver stiffness, %FAT, FAT (Kcal/d), ferritin (Fer), ALT, AST, body weight, and BMI ( r -0.330, -0.384, -0.428, -0.270, -0.318, 0.320, -0.404, -0.416, -0.389, -0.520, P < 0.05 or P < 0.01, respectively). Stepwise multiple regression analyses revealed that BMI, RQ, and NAS scores were independent correlated factors of aerobic exercise performance. Conclusion:Hepatic inflammation and fibrosis affect the aerobic exercise performance of patients with T2DM combined with NAFLD.