OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins （PACs） on steroid-induced osteonecrosis of the femoral head （SONFH） in rabbits based on the receptor-interacting protein kinase 1 （RIPK1）/RIPK3/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group （normal saline）， low-dose PACs group （PACs-L group， 11 mg/kg）， high-dose PACs group （PACs-H group， 22 mg/kg）， high-dose PACs+ RIPK1 activator （rRIPK1） group （PACs-H+rRIPK1 group， 22 mg/kg PACs+4 μg/kg rRIPK1）， along with a control group （normal saline）， with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection， for 4 consecutive weeks. After the last administration， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rabbit serum were measured. The changes in the microstructure of rabbit femurs， including bone mineral density （BMD）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular separation （Tb. Sp） were examined. The histopathological features of rabbit femoral tissues were observed， and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor （VEGF） and bone morphogenetic protein 2 （BMP2） in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group， serum contents of TNF-α and IL-6， Tb.Sp， empty bone cavity rate， cell apoptosis rate， phosphorylation levels of RIPK1， RIPK3 and MLKL in femoral tissue were significantly increased in the Model group （P＜0.05）. BMD， Tb.Th， Tb.N， as well as the mRNA expression of VEGF and BMP2， along with protein expression of caspase-8， in the femoral tissues were all decreased （P＜0.05）. The bone cells in the femoral tissue were unevenly distributed， and the trabeculae were arranged sparsely. Compared with the Model group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits， and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway， suppression of apoptosis in femoral tissue cells， and promotion of angiogenesis.

BACKGROUND: China is one of the countries with the highest burdens of stomach cancer. The objective of this study was to analyze long-term trends in the incidence and mortality of stomach cancer in Chinese mainland from 1990 to 2019 and to make projections until 2030. METHODS: Data on stomach cancer were extracted from the Global Burden of Diseases Study 2019. Population data were extracted from the Global Burden of Diseases Study 2019 and World Population Prospects 2019. An age-period-cohort framework and decomposition analysis were used in this study. RESULTS: The net drift for the incidence of stomach cancer was 0.2% (95% confidence interval [CI]: 0, 0.4%) per year for men and -1.8% (95% CI: -2.0%, -1.6%) for women. The net drift for mortality was -1.6% (95% CI: -1.8%, -1.3%) per year for men and -3.3% (95% CI: -3.5%, -3.1%) for women. In the last 10-15 years, the risk of stomach cancer occurrence and death has continued to decline for both sexes. Regarding birth cohorts, although the risk of stomach cancer death decreased in general among women and men born after 1920, the risk of occurrence increased in recent birth cohorts (men born after 1970 and women born after 1985). It is expected that the age-standardized incidence will increase among men and decrease among women, and age-standardized mortality will decrease for both sexes. The largest contributor to the projected increase in incident cases and deaths is population aging, and elderly individuals are projected to have an increased proportion of occurrence and death. CONCLUSIONS In the past three decades, the incidence of stomach cancer among men has increased in Chinese mainland, and this trend is projected to continue. Aging will be the main contributor to future increased stomach cancer occurrence and deaths. To reduce the health impact of stomach cancer, more efforts are needed.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Incidence ; Stomach Neoplasms/mortality*

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe²⁺ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe²⁺ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
Ferroptosis/drug effects* ; Dental Pulp/drug effects* ; Animals ; Pulpitis/pathology* ; Rats ; Thymalfasin/pharmacology* ; Humans ; Male ; Thymosin/pharmacology* ; Disease Models, Animal ; Rats, Sprague-Dawley

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective:To discuss the effect of knock down of gene of kinesin family member 3B(KIF3B),an important component of primary cilia(PC)of in mouse embryonic palatal mesenchymal on the autophagy level of cells(mEPMCs)cells,and to clarify its mechanism.Methods:The mEPMCs from gestational day 14.5 C57BL/6J mice cultured in vitro were collected and divided into control group(administered normal saline),empty lentivirus transfected cell group(sh-NC group)(administered lentivirus transfection),KIF3B knockdown group(sh-KIF3B group)(administered KIF3B gene knockdown),and KIF3B knockdown plus Smoothened receptor agonist(SAG)group(sh-KIF3B+SAG group)(administered KIF3B gene knockdown followed by SAG addition),based on whether the KIF3B gene was knocked down and whether the SAG was used to activate the sonic hedgehog(Shh)signaling pathway and its downstream coreceptor Smo,with 5 rats in each group.Transmission electron microscope was used to observe the morphology and the number of autophagosomes/autolysosomes in the mEPMCs in various groups;Western blotting method was used to detect the expression levels of autophagy-related proteins Beclin-1 and p62,and the Shh signaling pathway proteins Shh and Smo in the mEPMCs in various groups.Results:The transmission electron microscope observation results showed that compared with control group,the number of autophagosomes/autolysosomes in sh-KIF3B group was significantly increased(P<0.05);compared with sh-KIF3B group,the number of autophagosomes/autolysosomes in the mEPMCs in sh-KIF3B+SAG group was significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the Beclin-1 protein expression level in the mEPMCs in sh-KIF3B group was significantly increased(P<0.05),and the KIF3B,p62,Shh,and Smo protein expression levels were significantly decreased(P<0.01);compared with sh-KIF3B group,the Shh,Smo,and p62 protein expression levels in the mEPMCs in sh-KIF3B+SAG group were significantly increased(P<0.01),and the Beclin-1 protein expression level was significantly decreased(P<0.01).Conclusion:Knockdown of KIF3B gene can promote autophagy of the mEPMCs,and the mechanism may be related to its inhibition of the Shh signaling pathway.

Yttrium-90(90Y)selective internal radiation therapy(SIRT)is an emerging modality for the treatment of hepatocellular carcinoma(HCC),leveraging the nuclide 90Y to deliver targeted radiation therapy.90Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays.It has high biological effectiveness and robust local control capabilities.In recent years,with the continuous advancement of basic and clinical research,the application of 90Y-SIRT in the conversion treatment of unresectable HCC(uHCC)has made significant progress.However,challenges remain in the clinical application of 90Y-SIRT,including how to improve the efficacy of conversion therapy and how to optimize therapy regimens.This review aims to summarize the research progress of90Y-SIRT in the conversion therapy of uHCC.

Objective To evaluate the application of evidence-based perioperative patient-controlled analgesia(PCA)management in patients with liver cancer receiving transcatheter arterial chemoembolization(TACE)treatment.Methods By using the application model of clinical evidence-based practice,the review indicators were formulated based on the best evidence.The baseline assessment was conducted,the barrier factors were analyzed,the best clinical decision was made,the implementation steps of PCA management,including training,monitoring,education,etc.were refined,and two rounds of clinical review were carried out.The knowledge-belief-practice level and the implementation of review indicators in 50 medical and nursing staff engaged in PCA management,as well as the changes in pain scores,the incidence of adverse reactions due to PCA management,and the patient's satisfaction in 159 patients after the application of evidence were compared with their corresponding values determined before the application of evidence.Results After implementing the evidence-based practice plan and applying the evidence,at multiple time points the pain scores and the incidences of adverse reactions were decreased significantly(P＜0.05),the patient's satisfaction increased remarkably(P＜0.01),the execution rate of medical and nursing staff for the review indicators were strikingly increased(P＜0.01),and the knowledge-belief-practice level concerning PCA management was prominently improved(P＜0.01).Conclusion The implementation of perioperative PCA management in patients with liver cancer receiving TACE treatment can help to reduce the perioperative pain level,improve the patient discomfort,increase the patient's satisfaction degree,and improve the ability of medical staff in performing PCA management and evidence-based practices.

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

Objective:To explore the factors influencing the supportive communication ability of medical undergraduates, and to propose strategies to improve supportive communication.Methods:By cluster sampling, we selected 388 medical undergraduates of grades 2017 and 2018 from Harbin Medical University for a questionnaire survey on supportive communication, general self-efficacy, and health education abilities. SPSS 22.0 was used for descriptive statistical analysis. AMOS 22.0 was used to construct a structural equation model to verify the relationship between the three variables. Mediating effects were also tested.Results:The students showed good supportive communication ability, with a total score of (74.28±10.84) points. The general self-efficacy score was (27.81±5.58) points, and the total score of health education ability was (25.50±4.76) points. General self-efficacy had direct positive effects on supportive communication and health education abilities ( β=0.75, 0.31, both P<0.001). Health education ability had a direct positive effect on supportive communication ability ( β=0.14, P<0.001). Health education ability played a significant mediating role in the influence of general self-efficacy on supportive communication ability (standardized mediating effect value=0.042, P<0.01), with the mediating effect accounting for 5.1%. Conclusions:The health education competency of medical undergraduates can mediate the effect of general self-efficacy on supportive communication ability. By strengthening medical humanities education to increase general self-efficacy and also emphasizing the cultivation of health education competency, the supportive communication ability of students can be improved.