In March 2024,the World Health Organization released the latest version of guidelines for the prevention,diagnosis,care and treatment for people with chronic hepatitis B infection.The guidelines were updated in several aspects,including expanding and simplifying the indications for chronic hepatitis B treatment,adding alternative antiviral treatment regimens,broadening the indications for antiviral therapy to prevent mother-to-child transmission,improving the diagnosis of hepatitis B virus,and adding hepatitis D virus(HDV)testing.This article summarizes and gives an excerpt of the recommendations in the guidelines.

The global chronic hepatitis B (CHB) guidelines have gradually expanded treatment indications in order to accelerate the elimination and improve the treatment rate of hepatitis B virus (HBV) infection. This article analyzes the new treatment concepts for chronic hepatitis B at home and abroad from two aspects: expanding treatment by paying more attention to the long-term prognosis of the disease and maximizing the use of existing drugs in order to achieve the early goal of the World Health Organization's of eliminating viral hepatitis by 2030.

BACKGROUND: The addition of growth factiors is commonly applied to improve the osteogenic differentiation of stem cells. However, for human pluripotent stem cells (hPSCs), their complex differentiation processes result in the unknown effect at different stages. In this study, we focused on the widely used bone forming peptide-1 (BFP-1) and investigated the effect and mechanisms of its addition on the osteogenic induction of hPSCs as a function of the supplementation period. METHODS: Monolayer-cultured hPSCs were cultured in osteogenic induction medium for 28 days, and the effect of BFP-1 peptide addition at varying weeks was examined. After differentiation for varying days (0, 7, 14, 21 and 28), the differentiation efficiency was determined by RT–PCR, flow cytometry, immunofluorescence, and alizarin red staining assays. Moreover, the expression of marker genes related to germ layers and epithelial-mesenchymal transition (EMT) was investigated at day 7. RESULTS: Peptide treatment during the first week promoted the generation of mesoderm cells and mesenchymal-like cells from hiPSCs. Then, the upregulated expression of osteogenesis marker genes/proteins was detected in both hESCs and hiPSCs during subsequent inductions with BFP-1 peptide treatment. Fortunately, further experimental design confirmed that treating the BFP-1 peptide during 7–21 days showed even better performance for hESCs but was ineffective for hiPSCs. CONCLUSION The differentiation efficiency of cells could be improved by determining the optimal treatment period.Our study has great value in maximizing the differentiation of hPSCs by adding osteogenesis peptides based on the revealed mechanisms and promoting the application of hPSCs in bone tissue regeneration.

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

In order to reduce the disease burden of chronic hepatitis B (CHB) and improve the treatment rate of CHB, the indications for anti-viral therapy have been gradually expanded and simplified in guidelines for the prevention and treatment of CHB released by Chinese Medical Association from 2005 to 2022. This article elaborates on the evolution in the indications for anti-viral therapy in CHB from the five aspects of converging indications of HBeAg-positive and HBeAg-negative CHB, reduction in the treatment threshold of HBV DNA, reduction in the treatment threshold of serum alanine aminotransferase, emphasis on the risk factors for disease progression, and gradual loosening of the requirements for virological indicators in patients with liver cirrhosis.

Objective:To investigate the effect of paeoniflorin on toll-like receptor 4(TLR4)/nuclear transcription factor(NF-κB) signaling pathway of streptozotocin combined with ovariectomized mice, and to explore whether it can improve the cognitive impairment of ovariectomized diabetic mice.Methods:Ninety female C57BL/6J mice were divided into SHAM group, ovariectomy group, diabetes group(intraperitoneal injection of STZ 50 mg·kg -1·d -1 for 5 consecutive days), dual model group(DM modeling and OVX operation), paeoniflorin low-dose intervention group(OVX+ STZ+ L-PF 50 mg·kg -1·d -1), paeoniflorin high-dose intervention group(OVX+ STZ+ H-PF 100 mg·kg -1·d -1; all groups n=15). After 8 weeks of paeoniflorin intervention, their cognitive function was tested by behavioral experiments(Morris water maze and Y maze). The pathological changes of hippocampal tissue were observed by HE and Nissl staining. The mRNA expressions of TLR4, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in hippocampal tissues were detected by real-time fluorescence quantitative PCR. The expression of TLR4, NF-κB P65, TNF-α, IL-6, IL-1β, β-amyloid protein(Aβ), tau proteins, and p-tau proteins were detected by Western blot. Results:Compared with SHAM group, the learning and memory ability of ovariectomy group, diabetes group and dual model group decreased, hippocampal cells were damaged, and the expression of related gene mRNA and protein were increased, especially in dual model group; Compared with dual model group, paeoniflorin intervention could delayed the learning and memory impairment, improve cognitive function, reduce the degree of hippocampal injury, and decrease the expression levels of related gene mRNA and protein, The above changes were the most pronounced at paeoniflorin high-dose intervention group.Conclusion:Paeoniflorin improves cognitive dysfunction in ovariectomized diabetic mice by inhibiting TLR4/NF-κB signaling pathway.

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective To investigate the regulatory effect of Jiedu Huayu Tongfu prescription on intestinal homeostasis in patients with hepatitis B cirrhosis with liver-gallbladder damp-heat syndrome, as well as its effect on endotoxin, inflammatory factors, and cellular immune function. Methods A total of 72 patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from June 2019 to January 2021 and met the diagnostic and inclusion criteria were enrolled as subjects and then randomly divided into observation group and control group, with 36 patients in each group. In the treatment group, 2 patients were lost to follow-up, 2 patients were excluded, and 32 patients completed the study; in the control group, 2 patients were lost to follow-up, 1 patient was excluded, and 33 patients completed the study. In addition to the basic treatment including antiviral therapy and liver-protecting treatment, the patients in the observation group were given Jiedu Huayu Tongfu granules, and those in the control group were given oral administration of Bifidobacterium tetravaccine tablets; the course of treatment was 4 weeks for both groups. The 16S rDNA sequencing technique was used for sequencing of fecal flora, and the two groups were measured in terms of the changes in liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and albumin (Alb)], endotoxin (ET), levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and T lymphocyte subsets (CD3 + T, CD4 + T, CD8 + T, and CD4 + /CD8 + ) after treatment. For normally distributed continuous data with homogeneity of variance, the paired t -test was used for comparison within each group, and the independent samples t -test was used for comparison between two groups; the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data. The chi-square test was used for comparison of categorical data. Results The observation group had a significantly higher overall response rate than the control group (87.5% vs 60.6%, χ 2 =-2.299, P =0.022). After treatment, both groups had significant reductions in ALT, AST, and TBil and a significant increase in Alb (all P < 0.05), and compared with the control group, the observation group had a significantly greater reduction in TBil ( Z =-2.165, P =0.030). After treatment, both groups had significant improvements in the levels of CD3 + T, CD4 + T, and CD4 + /CD8 + , and the observation group had significantly greater improvements than the control group ( Z =-2.146, -2.940, and 3.157, P =0.032, 0.003, and 0.002). After treatment, both groups had significant reductions in the levels of TNF-α, IL-6, and ET, and the observation group had significantly greater reductions than the control group ( Z =-2.139, -1.982, and -2.062, P =0.032, 0.048, and 0.043). Both groups had an increase in the number of operational taxonomic units after treatment. As for the abundance of intestinal flora at the phylum level, the observation group had a significant increase in the abundance of Firmicutes and a significant reduction in the abundance of Bacteroidetes after treatment ( Z =-3.181 and -2.215, P =0.001 and 0.027); compared with the control group, the observation group had significantly greater increases in the abundance of Firmicutes and Cyanobacteria and significantly greater reductions in the abundance of Bacteroidetes, Cercozoa, and ε-Proteobacteria (all P < 0.05). At the genus level, the observation group had a significant increase in the abundance of Bifidobacterium after treatment ( Z =-2.045, P =0.041). The alpha-diversity analysis showed that the observation group had significant increases in Chao1 and Ace indices after treatment ( t =-4.263 and -3.328, P =0.001 and 0.005) and a significantly greater increase in Ace index than the control group ( t =2.292, P =0.030). The beta-diversity analysis showed that the two groups had a similar composition of flora without significant difference (all P > 0.05). Conclusion Jiedu Huayu Tongfu prescription, in combination with etiological and basic treatments, can alleviate clinical symptoms, reduce liver injury, and improve cellular immune function in patients with hepatitis B cirrhosis with liver-gallbladder damp-heat syndrome. Jiedu Huayu Tongfu prescription can improve the imbalance of intestinal flora by increasing the abundance of the probiotic bacteria such as Firmicutes, Lactobacillus, and Bifidobacterium and the pathogenic bacteria such as Bacteroidetes and Cercozoa, and its effect in further improving liver and immune function may be associated with the regulation of intestinal microecology.

This article reports a case of using immediate implant placement and immediate restoration combined with measurable implant surgical guides to restore compromised maxillary incisors caused by dental trauma. Target restoration was designed in the exoCAD software preoperatively, intraoral measurements were obtained in three directions, and the correct position of virtual implants was determined in BlueSky Plan 4. Afterward, measurable implant guides were designed and fabricated by 3D printing. Under the guidance of the measurable implant surgical guides and intraoperative measurement, the entry point was determined, the axial direction was verified when drilling to half the depth, and the 3D position was verified when drilling to total depth. Implants were inserted followed by verification once again. The temporary restoration, which was designed based on the target restoration and emergence profile of the original teeth and milled preoperatively, was connected to the implant immediately after surgery. Postoperative accuracy analysis showed that the mean linear deviations between the actual implant position and the pre-planned position were (0.57±0.17) mm at the entry point and (0.82±0.27) mm at the apex, and the mean angular deviation was (1.86±0.89) °, demonstrating that precise implant placement and immediate restoration were implemented.
Humans ; Dental Implantation, Endosseous ; Dental Implants ; Surgery, Computer-Assisted ; Imaging, Three-Dimensional ; Software