Objective:To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage.Methods:The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ2 test between groups. Results:This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery ( P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence ( HR =181.92, 95% CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95% CI 1.289~20.889, P = 0.020), and a high dosage of HBIG ( HR = 1.012, 95% CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion:High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

SIRT6,a member of the sirtuin family of histone deacetylases,belongs to the class Ⅲ longevity proteins and exhibits NAD+-dependent deacetylase and mono-ADP-ribosyltransferase activities.SIRT6 is primarily located in the cell nucleus and plays a pivotal role in regulating genomic stability and relative gene expression,participating in the control of key processes such as energy metabolism and aging.Given its crucial role in maintaining cellular homeostasis and organismal health,SIRT6 has emerged as a potential therapeutic target,sparking significant research interest in the development of targeted modulators.Activating the longevity protein with drugs may provide therapeutic strategies for age-associated diseases,including aging,metabolic syndrome,inflammation,and reproductive health issues.The review elaborates the structural characteristics,enzymatic activities,and biological functions of SIRT6,as well as the mechanisms of action,pharmacological activities,and clinical applications of various SIRT6 activators.

Objective To establish and evaluate chemotherapeutic phlebitis model rats induced by vinorelbine via the dorsalis pedis vein.Methods Rats were divided randomly into control and 4 different concentration of vinorelbine-induced model groups.Control rats were injected with 0.1 mL normal saline via the dorsalis pedis vein of the hind limb,while other rats were injected with different concentrations of vinorelbine(2,3,4,5 mg/mL),as above.General observations were performed and the hind limb volume was measured daily for 7 consecutive days to calculate the swelling rate.The rats were then killed and histological changes in the dorsalis pedis vein were observed by hematoxylin and eosin staining.Microstructural changes on the surface of the vascular endometrium were observed by scanning electron microscopy.Results Injection of 2,3,4,5 mg/mL vinorelbine via the dorsalis pedis vein significantly induced hind limb swelling in a concentration-dependent manner,peaking on day 3 in each group.The phlebitis rates on day 7 were 50%in the 2 mg/mL group and 83.3%in the 3 mg/mL group.Phlebitis was also induced in the 4 mg/mL and 5 mg/mL groups,including grade Ⅲ in 66.6%and grade Ⅳ in 83.3%.Histopathology showed inflammatory cell infiltration,wall thickening,lumen stenosis,and thrombosis in the tissues surrounding the veins.Scanning electron microscopy showed destruction of tight junctions of venous endothelial cells,and a rough surface of the vascular lining,resultsing in blood cell adhesion.Conclusions Injection of 0.1 mL of 3～5 mg/mL vinorelbine via the dorsalis pedis vein could induce red,swollen,and cord-like veins,as well as infiltration of inflammatory cells around the vein,thickened vein walls,lumen stenosis,and thrombosis.In addition,the surface of the venous intima was rough and adhered to numerous blood cells.All these features are consistent with those of clinical chemotherapeutic phlebitis in terms of the symptoms and pathological structure.

Objective:To evaluate the immunogenicity of a quadrivalent influenza virus subunit vaccine in a healthy population aged 3-64 years.Methods:Healthy people aged 3-64 years old were selected as the study subjects, and a randomized, blind, positive controlled, non-inferiority test was adopted. The subjects were randomly inoculated with one dose of the corresponding experimental vaccine or control vaccine in a ratio of 1∶1. Blood samples were collected from all subjects before and at 28 d after immunization, and hemagglutination inhibition (HI) test was used to measure the levels of antibodies against H1N1, H3N2, B/Victoria (BV) and B/Yamagata (BY) in serum. The geometric mean titers (GMT), geometric mean increase (GMI), positive conversion rates and protection rates of antibodies against the four types of viruses were analyzed.Results:A total of 2 157 subjects aged 3-64 years were included, including 1 074 in the experimental group and 1 083 in the control group. There were no significant differences in the GMT or protection rates of antibodies against H1N1, H3N2, BV or BY before immunization between the two groups ( P>0.05), and the two groups were balanced at baseline. After full immunization, the GMI of antibodies to H1N1, H3N2, BV and BY in the experimental group was 11.16, 17.77, 9.61 and 15.13, respectively; the positive conversion rates were 84.08% (903/1 074), 92.46% (993/1 074), 86.03% (924/1 074) and 91.71% (985/1 074), respectively; the protection rates were 96.74% (1 039/1 074), 97.58% (1 048/1 074), 88.08% (946/1 074) and 94.97% (1 020/1 074), respectively. In the experimental group, the GMT of each antibody increased by more than 2.5 times after immunization; the lower limit of the 95%CI of the positive conversion rate was higher than 40%, and the lower limit of the 95%CI of the protection rate was higher than 70%. The lower limit of the 95%CI of the difference in the positive conversion rate of each antibody between the experimental group and the control group was >-10%, and the lower limit of the 95%CI for GMT (experimental group)/GMT (control group) was over 2/3. Conclusions:The experimental vaccine had good immunogenicity and was non-inferior to the control vaccine in the population aged 3-64 years.

Objective:To investigate the effects of Neibu Huangqi Decoction combined with Kangfuxin Liquid on wound healing after hemorrhoid fistula.Methods:Randomized controlled trial. A total of 90 patients with hemorrhoid fistula surgery in Tangshan Hospital of Traditional Chinese Medicine from January 2020 to June 2021 were selected as the observation objects and divided into 2 groups by random number table method, with 45 cases in each group. The control group was treated with Kangfuxin Liquid after surgery, and the observation group was treated with Neibu Huangqi Decoction. Both groups were treated continuously for 14 days. Wound symptom score was performed before and after treatment. The levels of TNF-α, IL-6 and IL-8 were determined by ELISA. The wound healing time was observed and the wound healing rate was calculated. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 93.33% (42/45) in the observation group and 66.67% (30/45) in the control group, with statistical significance ( χ2=9.89, P=0.002). After treatment, the scores of pain [(0.63±0.14) vs. (0.97±0.27), t=7.50], exudation [(0.67±0.12) vs. (1.09±0.31), t=8.48], edema [(0.78±0.17) vs.(1.25±0.36), t=7.92], pruritus [(0.78±0.20) vs. (1.32±0.33), t=9.39] were lower than those in the control group ( P<0.01); serum TNF-α [(33.46±2.86) μg/L vs. (45.78±3.92) μg/L, t=25.39], IL-6 [(41.86±5.84) μg/L vs. (56.12±6.75) μg/L, t=15.98], IL-8 [(27.40±3.58) ng/L vs. (36.16±3.84) ng/L, t=16.69] were lower than those in the control group ( P<0.01). The wound healing time of the observation group was shorter than that of the control group ( t=8.60, P<0.01), and the wound healing rate was higher than that of the control group ( t=24.65, P<0.01). During treatment, the incidence of adverse reactions was 11.11% (5/45) in the observation group and 6.67% (3/45) in the control group, without statistical significance ( χ2=0.14, P=0.711). Conclusion:Neibu Huangqi Decoction combined with Kangfuxin Liquid can promote wound healing, reduce inflammatory cytokines, relieve pain and exudation, improve clinical efficacy, and have few adverse reactions.

ObjectiveTo investigate the effect of Zuoguiwan on pancreatic islet function in offspring of gestational diabetes mellitus （GDM） maternal rat model and explore the mechanisms of Zuoguiwan in improving pancreatic islet function based on postpartum pancreatic regeneration. MethodHealthy female SD rats with normal blood glucose levels were paired with male rats in a 2∶1 ratio and housed together. Pregnancy was confirmed based on vaginal plugs or vaginal smears. The pregnant rats were divided into the following groups： normal group， model group， insulin group （insulin Detemir， 20 U·kg^-1）， low-dose Zuoguiwan group （1.89 g·kg^-1）， and high-dose Zuoguiwan group （3.78 g·kg^-1）. The GDM rat model was induced using streptozotocin in rats except for those in the normal group. The model was confirmed by blood glucose testing in the maternal rats. Except for the normal and model groups， the other groups received daily administration of corresponding treatments. At 21 days after birth， fasting blood glucose （FBG） and fasting serum insulin （FINS） levels were measured in 6 offspring from each group. The homeostasis model assessment of insulin resistance （HOMA-IR） was calculated， and an oral glucose tolerance test （OGTT） was performed on additional 12 offspring from each group. Blood samples were taken from the abdominal aorta of the offspring at postnatal day 22， and enzyme-linked immunosorbent assay （ELISA） was used to measure insulin， glucagon （GC）， pancreatic polypeptide （PPY）， and somatostatin （SS） levels in the serum. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the pancreatic tissue of the offspring. Immunofluorescence （IF） was used to observe the area and structure of the pancreatic islets. Western blot was used to detect the expression of key proteins involved in the development and functional expression of pancreatic β-cells， namely pancreatic and duodenal homeobox factor 1 （Pdx1）， Nkx6.1， and Glucose transporter 2 （Glut2）. ResultCompared with the normal group， the model group showed significant increases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the model group， the insulin group showed significant decreases in FBG levels and HOMA-IR （P<0.01）， the low-dose Zuoguiwan group showed a significant decrease in FBG levels （P<0.05）， and the high-dose Zuoguiwan group showed significant decreases in FBG and FINS levels， and HOMA-IR （P<0.01）. Compared with the normal group， the model group showed significant increases in OGTT 60-min blood glucose levels and AUC index （P<0.05， P<0.01）. Compared with the model group， the high-dose Zuoguiwan group showed significant decreases in OGTT60-min blood glucose levels and area under the curve（AUC） index （P<0.05， P<0.01）. HE staining of pancreatic tissue showed that compared with the normal group， the model group had a reduced number of islets and a loose arrangement of acinar cells. Compared with the model group， the groups with drug treatment showed increased number of islets and a compact arrangement of acinar cells. Compared with the normal group， the model group had significantly increased levels of insulin， GC， PPY， and SS in the serum （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups and the insulin group showed significantly decreased serum levels of insulin， GC， PPY， and SS （P<0.05， P<0.01）. IF results showed that compared with the normal group， the model group had a significantly lower positive rate of insulin （P<0.05）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed a significant increase in the positive rate of insulin （P<0.05）. There was no significant difference in the positive rate of GC among the groups. In terms of the proportion of insulin and GC in individual islets， compared with the normal group， the model group showed a significant decrease in the proportion of insulin （P<0.01） and a significant increase in the proportion of GC （P<0.01）. Compared with the model group， the low-dose and high-dose Zuoguiwan groups showed significantly increased proportion of insulin （P<0.01） and significantly decreased proportion of GC （P<0.01）. Compared with the normal group， the model group showed significantly decreased expression levels of Pdx1， Nkx6.1， and Glut2 proteins in the pancreatic tissue of GDM offspring （P<0.05）. Compared with the model group， the insulin group and the low-dose Zuoguiwan group showed significant increases in the expression levels of Pdx1 and Nkx6.1 proteins in the pancreatic tissue of GDM offspring （P<0.05）， and the low-dose and high-dose Zuoguiwan groups showed significant increases in the expression levels of Glut2 protein （P<0.05）. ConclusionZuoguiwan can promote pancreatic islet development in offspring of GDM maternal rat model， improve pancreatic islet morphology and function， and alleviate insulin resistance. Its mechanism of action may be related to the regulation of Pdx1， Nkx6.1， and Glut2 protein expression in the pancreatic tissue of offspring.

Objective:To explore the independent predictive factors of cirrhosis in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, and establish a nomogram model based on clinical laboratory data and analyze the predictive value of this model.Methods:The laboratory data of 596 patients with HBeAg-negative chronic HBV infection and 677 patients with hepatitis B cirrhosis, who were hospitalized in the First Hospital of China Medical University from 2011 to 2021, were retrospectively analyzed. Patients were randomly divided into training group ( n=892) and validation group ( n=381) at the ratio of 7∶3. The independent predictive factors of cirrhosis were analyzed by univariate logistic regression, multiple collinearity test and multivariate logistic regression. The nomogram model was established and the prediction value of this model was evaluated. Results:According to multivariate logistic regression analysis, hepatitis B core antibody ( OR=1.492, 95% CI 1.316-1.706), glutamine transpeptidase ( OR=1.015, 95% CI 1.010-1.022), platelet ( OR=0.986, 95% CI 0.982-0.988) and albumin ( OR=0.853, 95% CI 0.824-0.882) were independent predictors of cirrhosis ( P<0.05), and the nomogram was established based on the four indicators. Receiver operating characteristic curves showed that area under the curve of the nomogram was 0.933 (95% CI 0.916-0.950), and that of the validation group was 0.931 (95% CI 0.905-0.956). The calibration curves indicated the nomogram model was highly consistent with the actual outcome. Decision curves and clinical impact curves confirmed that the model had high net benefit and good clinical application performance. Conclusions:Hepatitis B core antibody, glutamine transpeptidase, platelet and albumin are independent predictors of cirrhosis among patients with HBeAg-negative chronic HBV infection. The newly developed nomogram model based on these factors could be used to predict cirrhosis risk in these patients.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*

Objective:This multicenter clinical evaluation analyzed the clinical performance of five fast nucleic acid detection systems for 2019-nCoV.Methods:Clinical performance of the five fast nucleic acid detection reagents approved in China was evaluated in the present study. Fifty-seven throat swabs samples from COVID-19 patients and fifteen throat swabs samples from healthy people were collected from the First Affiliated Hospital of Zhejiang University school of Medicine, Tongji Hospital of Tongji Medical College of HUST, and National Institute of Viral Disease Control and Prevention of CDC to evaluate the positive coincidence rate, negative coincidence rate, total coincidence rate, the detection time and retest rate as well as the relation between positive intensity and positive coincidence rate of the five fast nucleic acid detection systems in November 2020.Results:The positive coincidence rates of the five kits were 92.59% (50/54), 83.64% (46/55), 98.25% (56/57), 94.44% (51/54) and 98.18% (54/55); and the negative coincidence rates were 93.33% (14/15), 93.33% (14/15), 86.67% (13/15), 100% (14/14) and 93.33% (14/15); and the total coincidence rates were 92.75% (64/69), 85.71% (60/70), 95.83% (69/72), 94.20% (65/69) and 97.14% (68/70), respectively. The positive coincidence rate of the five kits reached 100% for the strong-positive (90/90) and medium-positive samples (84/84), but only 82.18% (83/101) for weak-positive samples (cycle threshold value>33), and the retest rate of two kits were 15.28% (11/72) and 12.50% (9/72), which were both higher than 10%. Total time from sample extraction to amplification was between 32.33-65.33 minutes for these five kits.Conclusion:The five fast nucleic acid detection reagents have good performance and can be used as a supplement to routine nucleic acid detection reagents.

Objective:The risk factors for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-positive cirrhosis patients were screened based on commonly used laboratory indexes for the purpose of establishing a predictive model and the prediction efficacy of established model was validated in a validation patient cohort.Methods:The clinical data of 661 male patients with HBV-positive cirrhosis (cirrhosis group) and 694 male patients with HBV-positive HCC admitted to the First Hospital of China Medical University from 2010 to 2020 were retrospectively analyzed, age and complete blood count,liver function index (aspartate transaminase/alanine transaminase,glutamine transpeptidase,total protein, prealbumin, total bile acid, total bilirubin,direct bilirubin,cholinesterase), HBV markers, alpha-fetoprotein (AFP), fibrinogen,calcium were compared between the two groups. Multivariate Logistic regression was used to analyze the independent risk factors of HCC. The prediction model of high risk HCC ( P<0.05) was constructed and validated by receiver operating characteristic (ROC) curve and calibration curve. Results:There was significant difference in complete blood count, liver function index, HBV core antibody, HBV core antibody IgM, alpha-fetoprotein, fibrinogen, calcium between the two groups ( P<0.05). Multivariate analysis showed that calcium ( OR=35.770,95% CI 13.39-99.304),HBV core antibody ( OR=0.878,95% CI 0.816-0.944), AFP ( OR=1.002, 95% CI 1.001-1.003), fibrinogen ( OR=1.369, 95% CI 1.202-1.564) were the independent risk factors for HCC ( P<0.05), and were used for the nomogram. The AUC of the nomogram was 0.750 (95% CI 0.720-0.781) and the AUC of the validation group was 0.752 (95% CI 0.705-0.798). Conclusions:Based on calcium, hepatitis B virus core antibody, AFP, fibrinogen, a nomogram of the HCC is established and verified by ROC curve, which could be used to predict the risk of HBV-positive HCC.