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.

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.

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.

Objective:To investigate the status of corneal epithelial remodeling and changes in corneal aberration after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and FS-LASIK combined with corneal collagen cross-linking (FS-LASIK Xtra), and to analyze the relationship between corneal epithelial thickness (CET) and corneal aberration.Methods:A cohort study was conducted.A total of 172 patients (172 eyes) who underwent FS-LASIK at Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine were enrolled from June 2021 to February 2022.The 172 eyes were divided into FS-LASIK group (94 eyes) and FS-LASIK Xtra group (78 eyes) according to the surgical procedure, with a total follow-up of 6 months.The cornea was divided into a central 2-mm ring and a ring of 2-5 mm centered on the central cornea.CET at 9 regions in the central 0-5 mm area was measured by OCT before and at 1, 3 and 6 months after surgery, and the corneal higher-order aberration (HOA) was measured by the iTrace visual function analyzer.The main outcomes were the increase in CET (ΔCET), and corneal HOA at 6 months after surgery.The relationship between central corneal ΔCET and corneal aberration was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-009). Written informed consent was obtained from each subject.Results:At 1, 3 and 6 months after surgery, the central, superior, superior nasal, nasal, inferior nasal, inferior, inferior temporal, temporal and superior temporal ΔCET were significantly smaller in FS-LASIK Xtra group than in FS-LASIK group (all at P<0.05). In FS-LASIK Xtra group, 6-month postoperative central, superior, superior nasal, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 3- and 6-month postoperative temporal ΔCET were significantly larger than that at 1 month after surgery, and 6-month postoperative superior temporal ΔCET was significantly larger than those at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, 3- and 6-month postoperative central, superior, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 6-month postoperative superior nasal ΔCET was significantly larger than that at 3 months after surgery, and 6-month postoperative nasal, inferior nasal, temporal, superior temporal ΔCET were significantly larger than those at 1 and 3 months after surgery (all at P<0.05). There was no significant difference in vertical trefoil, vertical and horizontal coma changes at different time points after surgery between both groups (vertical trefoil: χ2group=4.27, P=0.118; χ2time=0.01, P>0.05.vertical coma: χ2group=5.74, P=0.057; χ2time=0.08, P=0.957.horizontal coma: χ2group=3.97, P=0.137; χ2time=0.51, P=0.773). The tilted trefoil changes at 1, 3 and 6 months after surgery of FS-LASIK Xtra group were significantly larger than those of FS-LASIK group (all at P<0.05). The 6-month spherical aberration change in FS-LASIK Xtra group was significantly higher than that at 1 month after surgery, and the 6-month spherical aberration change in FS-LASIK group was significantly higher than that at 1 and 3 months after surgery (all at P<0.05). The 6-month total HOA change in FS-LASIK group was significantly lower than that at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, central corneal ΔCET was weakly positively correlated with spherical aberration at 1 and 6 months after surgery ( rs=0.257, P=0.008; rs=0.244, P=0.012), and was weakly positively correlated with total HOA ( rs=0.253, P=0.009; rs=0.279, P=0.004). Conclusions:The postoperative ΔCET after FS-LASIK Xtra is smaller than that after FS-LASIK, but the homogeneity of ΔCET in each region is similar between the two groups.The changes in corneal HOA after surgery are similar in both groups, and there is a certain association between the overall epithelial distribution and corneal aberration.

Objective:To observe the effect of nutrition intervention and exercise rehabilitation treatment on the sarcopenia in elderly patients with type 2 diabetes.Methods:It was a cross-sectional study. From March 2019 to September 2020, 101 elderly patients with type 2 diabetes complicated with sarcopenia treated in the Department of Endocrinology of Tianjin Third Central Hospital were enrolled in this study. The patients were divided into four groups with propensity score matching method: sarcopenia education group without nutrition and resistance training group (group A, n=22), simple nutrition intervention group (group B, n=28), nutritional intervention combined with resistance training group (group C, n=27) and nutritional intervention combined with aerobic and resistance training group (group D, n=24). All the patients were intervened for 24 weeks, two patients in groups C and D dropped due to their own reasons. The 25-dihydroxy vitamin D3 (25(OH)D 3), grip strength, muscle mass of the limbs and short physical performance battery (SPPB) scores were measured before and 24 weeks after the intervention in all the participants. Results:After the intervention, the 25(OH)D 3 levels in the B, C, D groups was (33.45±4.05), (33.68±4.69), (34.28±5.58) μg/L, respectively, all were higher than those before the treatment (all P<0.01), and there was no significant differences among the three groups ( P>0.05). The muscle mass in the B, C, D groups after intervention was 5.650 (5.102, 6.658), 6.601 (6.007, 7.156) and 6.520 (6.017, 7.302) kg/m 2, respectively, all were significantly higher than those before the treatment (all P<0.01); the muscle mass in group C and D increased more significantly than that in group B ( P<0.01), but there was no significant differences between group C and D ( P>0.05). After the intervention, the muscle strength in the C and D groups was 20.60 (19.20, 24.55) kg and 21.15 (19.43, 26.63) kg, and the SPPB scores was 8.00 (7.00, 9.00) points and 8.00 (8.00, 9.00) points, respectively, all were higher than those before the intervention (all P<0.01), but there was no significant differences between the two groups(both P>0.05). The SPPB function score in group D was better than that in group C, the difference was statistically significant ( P<0.05). Conclusions:Nutritional intervention can improve the muscle mass in elderly type 2 diabetes patients with sarcopenia. Combined with rehabilitation training, the muscle strength and muscle function of these patients could also be improved, and the improvement of muscle mass is better than that in patients receiving nutritional intervention only. In terms of increasing muscle strength, the two kinds of rehabilitation training are equivalent. If combined with aerobic exercise, it can also improve the muscle function of these patients.