As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To study the epidemiological characteristics of human brucellosis in Ordos City and provide reference and theoretical guidance for prevention and control of the disease.Methods:The surveillance data of human brucellosis cases and the serological surveillance data of key occupational populations reported by the Ordos City Center for Disease Control and Prevention from 2013 to 2022 were collected and analyzed descriptively. ArcGIS 10.8 software was used to draw a spatial distribution map of human brucellosis in Ordos City, and SPSS 26.0 software was used to conduct Spearman correlation analysis to further explore the impact of economic factors on human brucellosis.Results:From 2013 to 2022, a total of 8 676 cases of human brucellosis were reported in Ordos City, with an average annual incidence rate of 40.93/100 000. In 2022, 2 570 cases were reported, with an incidence rate of 116.78/100 000, reaching the peak in the past 10 years. The cases were mainly distributed in Dalad Banner, Hangjin Banner, and Otog Front Banner, with a total of 6 415 cases, accounting for 73.94% of the total number of cases. The spatial distribution spread from north to south and from north to east. The majority of cases were in the age group of 40 to 65 years old (6 061 cases, accounting for 69.86%), male (6 089 cases, accounting for 70.18%), and farmers and herdsmen (7 367 cases, accounting for 84.91%). The median time interval between onset and diagnosis was 16 days. The positive rate of serological surveillance in key occupational groups was 5.38% (7 058/131 229). The results of Spearman correlation analysis showed that the number of agricultural legal entities, the number of animal husbandry legal entities, regional gross domestic product, per capita disposable income of rural and pastoral residents, total agricultural output value, the number of cattle and sheep at the end of the year, milk production, and mutton production were important factors affecting the incidence of brucellosis ( P < 0.05). Conclusions:The incidence of brucellosis in Ordos City is on the rise, and the epidemic situation is severe. It is necessary to strengthen the surveillance and joint prevention and control of human brucellosis to prevent the spread and expansion of the epidemic.

Objective:To study the effects of arsenic exposure on neurological function including voluntary motor ability, anxiety, and short-term memory ability of rats, as well as its impact on the expression levels of synaptic function related genes such as neuropeptide 1 (NLGN1), glutamate receptor 2A (NR2A), and postsynaptic density protein 95 (PSD95).Methods:Forty 3-week-old male specific pathogen free (SPF) grade Wistar rats [weighing (453.97 ± 35.68) g] were selected and divided into four groups using a random number table: 0 (control group) and 2, 10, and 50 mg/L arsenic exposure groups, with 10 rats in each group. They were given deionized water and 2, 10, and 50 mg/L sodium arsenite solutions for 12 weeks, respectively. The open field experiment and Y-maze experiment were used to test the voluntary motor ability, anxiety, and short-term memory ability of rats. Nissl staining was used to observe the pathological damage of the hippocampus in the brain. Real time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of NLGN1, NR2A, and PSD95 in the hippocampus, respectively.Results:The results of the open field experiment revealed that the horizontal movement distances of rats in the 2 and 10 mg/L arsenic exposure groups were reduced compared to the control group, the movement distances in the central area in the 2, 10, and 50 mg/L arsenic exposure groups were reduced compared to the control group, and the residence time in the central area in the 10 and 50 mg/L arsenic exposure groups was reduced compared to the control group ( P < 0.05). The results of Y-maze experiment showed that the retention time of new arms in rats of the 2 and 10 mg/L arsenic exposure groups was shorter than that in the control group ( P < 0.05). The pathological examination results of Nissl staining showed that the control group had abundant Nissl bodies in hippocampal tissues of the cytoplasm with intact neuronal structures, tightly arranged cells, appearing blue purple in color and clear visible nuclei. However, the number of Nissl bodies decreased, intercellular gaps increased, disordered arrangement increased, cytoplasmic staining was lighter, and nuclear shrinkage phenomenon increased in the hippocampal tissues of rats in the 2, 10 and 50 mg/L arsenic exposure groups. The real-time fluorescence quantitative PCR detection results showed that there was a statistically significant difference in the mRNA expression levels of NLGN1, NR2A, and PSD95 in the hippocampal tissues of the four groups ( F = 13.85, 44.94, 4.63, P < 0.05). The results of Western blot analysis showed that the protein expression levels of NLGN1 and NR2A in the hippocampal tissues of rats in the 10 and 50 mg/L arsenic exposure groups were lower than those in the control group (0.65 ± 0.07, 0.69 ± 0.03 vs 1.00 ± 0.04, 0.51 ± 0.11, 0.51 ± 0.13 vs 1.00 ± 0.07, P < 0.05), and the expression level of PSD95 in the hippocampal tissues of rats in the 50 mg/L arsenic exposure group was lower than that in the control group (0.51 ± 0.09 vs 1.00 ± 0.05, P < 0.05). Conclusion:Arsenic may affect synaptic function and cause neurological dysfunction in rats by adjusting the expression levels of NLGN1, NR2A, and PSD95.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Rheumatoid arthritis(RA)is a chronic autoimmune disease of unknown etiology that can cause joint destruction and deformity.As a small molecule cytokine,the chemokine C-X-C motif chemokine ligand 12(CXCL12)regulates the pathogenesis of rheumatoid arthritis by binding to the specific receptor CXC chemokine receptor 4(CXCR4).Therefore,based on the bio-logical characteristics of CXCL12 and CXCR4,this paper intro-duces the pathogenesis of CXCL12/CXCR4 in RA and summari-zes the progress in RA-related research,with the aim of providing clinical value for understanding the pathogenesis of RA and de-veloping novel therapeutic targets.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To study the epidemiological characteristics of human brucellosis in Ordos City and provide reference and theoretical guidance for prevention and control of the disease.Methods:The surveillance data of human brucellosis cases and the serological surveillance data of key occupational populations reported by the Ordos City Center for Disease Control and Prevention from 2013 to 2022 were collected and analyzed descriptively. ArcGIS 10.8 software was used to draw a spatial distribution map of human brucellosis in Ordos City, and SPSS 26.0 software was used to conduct Spearman correlation analysis to further explore the impact of economic factors on human brucellosis.Results:From 2013 to 2022, a total of 8 676 cases of human brucellosis were reported in Ordos City, with an average annual incidence rate of 40.93/100 000. In 2022, 2 570 cases were reported, with an incidence rate of 116.78/100 000, reaching the peak in the past 10 years. The cases were mainly distributed in Dalad Banner, Hangjin Banner, and Otog Front Banner, with a total of 6 415 cases, accounting for 73.94% of the total number of cases. The spatial distribution spread from north to south and from north to east. The majority of cases were in the age group of 40 to 65 years old (6 061 cases, accounting for 69.86%), male (6 089 cases, accounting for 70.18%), and farmers and herdsmen (7 367 cases, accounting for 84.91%). The median time interval between onset and diagnosis was 16 days. The positive rate of serological surveillance in key occupational groups was 5.38% (7 058/131 229). The results of Spearman correlation analysis showed that the number of agricultural legal entities, the number of animal husbandry legal entities, regional gross domestic product, per capita disposable income of rural and pastoral residents, total agricultural output value, the number of cattle and sheep at the end of the year, milk production, and mutton production were important factors affecting the incidence of brucellosis ( P < 0.05). Conclusions:The incidence of brucellosis in Ordos City is on the rise, and the epidemic situation is severe. It is necessary to strengthen the surveillance and joint prevention and control of human brucellosis to prevent the spread and expansion of the epidemic.

Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.

Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.