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 investigate the effects of Carthamus tinctorius L.extract(CTLE)on the levels of oxidative stress and inflammation in mice with ethanol-induced alcoholic liver disease and its mechanism of action.Methods SPF-grade C57BL/6 male mice were randomly divided into four groups:control group,model group,low-CTLE group(50 mg·kg-1),and high-CTLE group(100 mg·kg-1).The control group was given Lieber-Decarli liquid diet,and the other groups were given Lieber-Decarli alcohol diet to construct a chronic alcoholic liver injury model in mice.Serum and liver tissues of mice were collected and serum biochemical indexes of mice were detected.HE and oil red O staining were applied to observe pathological changes in mouse liver tissues.Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of Keap1/Nrf2 and STAT3/NF-κB pathway-related factors.Results Compared with the model group,the ALT,AST,LDL-C,and MDA levels were significantly reduced(P＜0.05,P＜0.01),while the levels of HDL-C,SOD,and GSH were increased dramatically in the administered group(P＜0.05,P＜0.01),which indicated that CTLE has specific protective and antioxidant effects on alcoholic liver injury in mice.HE staining and oil red O staining showed that the hepatic lesions and lipid deposition of mice were ameliorated.It enhances the antioxidant and anti-inflammatory effects of the body by activating the mRNA and protein expression levels of antioxidant factors related to the Keap1/Nrf2 pathway and inhibiting the mRNA and protein expression levels of inflammatory factors related to STAT3/NF-κB pathway(P＜0.05,P＜0.01).Conclusion It was shown that CTLE could exert anti-oxidative stress and anti-inflammatory effects through regulating Keap1/Nrf2 and STAT3/NF-κB signaling pathways to attenuate alcoholic liver injury in mice.This study may provide a new idea for the treatment of alcoholic liver disease and the subsequent study of molecular mechanisms.

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.

Objective:To identify the risk factors for hypoxemia during painless gastrointestinal endoscopy (PGIE) in patients with COVID-19.Methods:Clinical data of COVID-19 patients who underwent PGIE in our hospital from December 2022 through April 2023 were retrospectively collected. The patients were divided into hypoxemia group ( n=201) and non-hypoxemia group ( n=747) based on the occurrence of intraoperative hypoxemia. The logistic regression analysis was used to identify the influencing factors for intraoperative hypoxemia. Results:There were significant differences in age ratio, American Society of Anesthesiologists Physical Status classification ratio, ratio of smoking degree, ratio of hypertension course, ratio of PGIE type, period of implementing PGIE, MAP before induction, time to diagnosis of COVID-19, COVID-19 classification ratio and cough ratio between the two groups ( P<0.05). Multivariate logistic regression analysis showed that age 51-65 yr, age >65 yr, smoking degree-mild, smoking degree-moderate to severe, COVID-19 related signs and symptoms-cough not healed until PGIE, COVID-19-related signs and symptoms-cough healed until PGIE were independent risk factors for intraoperative hypoxemia; the PGIE type-colonoscopy, time to diagnosis of COVID-19 and PGIE 43-56 days, time to diagnosis of COVID-19 and PGIE 57-70 days, and time to diagnosis of COVID-19 and PGIE >70 days were independent protective factors for intraoperative hypoxemia. Conclusions:Age>50 yr, having smoking habit and cough shown during COVID-19 are independent risk factors for intraoperative hypoxemia; PGIE type-colonoscopy and time to diagnosis of COVID-19 and PGIE >42 days are independent protective factors for intraoperative hypoxemia.

Objective To investigate the changes of cortical thickness in patients with insomnia disorder(ID).Methods High-resolution MRI data were collected from 32 ID patients(ID group)and 30 healthy controls(HC)(HC group).The cortical thickness of both groups were analyzed using statistical parametric mapping 12(SPM12)software,while considering age,gender,and educational level as covariates.The cortical thickness in brain regions showed statistically significant differences was extracted for Pearson's correla-tion analyses with sleep and mood-related scales.Results Compared with the HC group,the ID group exhibited significantly decreased cortical thickness in brain regions such as the left insula,fusiform gyrus,orbitofrontal lobe,superior temporal gyrus,middle temporal gyrus,lateral occipital lobe and right caudal anterior cingulate gyrus[P＜0.05,family-wise error(FWE)correction].Furthermore,reduced cortical thickness of the cingulate gyrus was negatively correlated with the Pittsburgh sleep quality index(PSQI)score(r=-0.437,P=0.012).Conclusion The cortical thickness of several brain regions associated with sleep and mood are significantly reduced in patients with ID,providing potential neuroimaging evidence for understanding the pathophysiological mechanism of ID.

Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.