Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Objective To explore the effectiveness and safety of hypofractionated radiotherapy(HFRT)combined with transcatheter arterial chemoembolization(TACE)for metachronous hepatic oligometastasis from nasopharyngeal carcinoma(NPC).Methods The clinical data of patients with metachronous hepatic oligometastasis from NPC,who received HFRT combined with TACE treatment at the Sichuan Provincial Cancer Hospital of China from January 2012 to October 2022,were retrospectively analyzed.The 3-year and 5-year overall survival(OS),progression-free survival(PFS),local recurrence-free survival(LRFS),no extrahepatic distant metastasis survival(EMFS),and treatment-related adverse reactions were analyzed.Results A total of 55 patients were enrolled in this study,including 36 males and 19 females,the median age at the time of occurring metachronous hepatic oligometastasis was 44(27-75)years.The 3-year and 5-year OS,PFS,LRFS,EMFS were 67.8％and 40.0％,55.8％and 30.0％,72.7％and 56.5％,63.6％and 56.5％,respectively.The subgroup analysis indicated that the treatment course of TACE ≥3 cycles could significantly improve the PFS of patients with oligometastasis.HFRT combined with TACE treatment was well tolerated by all patients,and the incidence of Grade Ⅲ-Ⅳadverse reactions was quite low.Conclusion For the treatment of metachronous hepatic oligometastasis from NPC,HFRT combined with TACE is clinically effective,besides,the patients can well tolerate the therapeutic scheme.

Objective To investigate the mechanism of action of Guizhi Fuling pill in treating chro-nic prostatitis(CP)using network pharmacology and molecular docking techniques.Methods Compo-nents of Guizhi Fuling pill were collected from the Traditional Chinese Medicines Systems Pharmacolo-gy Platform(TCMSP),and target information was obtained from the SwissTarget database.Targets for chronic prostatitis were screened from the GeneCards,OMIM,CTD,and DisGeNET disease data-bases.A protein-protein interaction(PPI)network was established and analyzed.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analysis were performed using the DAVID database.The Cytoscape software was employed to construct an association network linking the components of Guizhi Fuling Pill,their targets,and the targets of chronic prostatitis.Molecular docking was conducted using AutoDock Vina software to verify the binding stability between the components of Guizhi Fuling pill and their targets.Results After screening and deduplication in the TCMSP database,76 components of Guizhi Fuling Pill were iden-tified,and 655 component targets were retrieved from the SwissTarget database.There were 190 intersecting targets between GuizhiFuling Pill and chronic prostatitis.GO analysis indicated that Guizhi Fuling Pill may treat chronic prostatitis by participating in processes such asapoptosis,ATP binding,and signal transduction.KEGG analysis suggested that Guizhi Fuling Pill can regulate pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and mitogen-acti-vated protein kinase(MAPK)to intervene in chronic prostatitis.Molecular docking data demonstra-ted that the components of Guizhi Fuling pill exhibited stable conformations with their targets.Con-clusion The components of Guizhi Fuling Pill can stably bind to their targets and exert therapeutic effects on chronic prostatitis through multiple targets and pathways.

Objective:To investigate the anti-aging and antioxidant effect of the heat shock transcription factor 1 (HSF1) on human retinal pigment epithelial cells.Methods:Two HSF1-deficient ARPE cells (ARPE/Hsf1 -/-) were constructed by using the clustered regularly interspaced short palindromic repeat and associated protein 9 (CRISPR/Cas9) gene editing system and named H8, H9 konckout cell strains.Experiments were operated on the 3 cell strains: wild-type, H8 and H9 cells.The content of reactive oxygen species in ARPE-19 cell was measured by DHE probe staining combined with flow cytometry technology, and the cell cycle was measured by flow cytometry technology.The cell viability at different time points was measured using cell counting kit-8 (CCK-8).Crystal violet staining assay was used to measure the relative ratio of cell survival.SA-β-gal staining assay was used to detect the ratio of ARPE-19 senescent cells.The expressions of HSP70, HSP27, clusterin (CLU), p53, p21 and interleukin (IL)-1β proteins were measured by Western blot technology.The expressions of p53, p21, IL-6, IL-8, IL-1β and monocyte chemoattractant protein 1 (MCP1) mRNA were measured by quantitative real-time PCR technology.Relative expression of heat shock response protein under different heat shock treatment conditions and HSP90 inhibitor IPI504, relative survival with different concentrations of H 2O 2, relative expression of p21 protein after treatment with or without ROS scavenger N-acetylcysteine (NAC) were compared in each cell strain. Results:Gene sequencing showed that H8 and H9 cell strains successfully carried mutated genes.Western blot experiment results showed that H8 and H9 cell strains did not express HSF1 protein, and HSF1 was successfully knocked out in ARPE-19 cells.Compared with wild-type cell, the expression levels of HSP70, HSP27 and CLU proteins in H8 and H9 cell strains significantly decreased, with statistically significant differences (all at P<0.05), and no significant difference was found in the relative HSP90 protein expression level ( F=0.29, P>0.05).Under different heat shock stimulation and IPI504 induction, the HSP70, HSP27, and CLU protein levels significantly increased in wild-type cells compared with before treatment, and the HSP70, HSP27, and CLU protein levels were significantly lower in H8 and H9 cell strains than in corresponding treated wild-type cells (all at P<0.05).Compared with wild-type cell strains, cell viability significantly decreased in H8 and H9 cell strains at 24, 48, 72, and 96 hours (all at P<0.05).Compared with wild-type cell strains, the percentage of cells in G1 phase was significantly higher and the mRNA and protein levels of the cell cycle inhibitors p53 and p21 significantly increased in H8 and H9 strains, showing statistically significant differences (all at P<0.05), and the ratio of positive cells for SA-β-gal staining significantly increased, showing statistically significant differences (all at P<0.001).The relative expression of aging-related inflammatory factors IL-6, IL-8, IL-1β, and MCP1 mRNA decreased, and the differences were statistically significant (all at P<0.001).In addition, compared with wild-type cell strains, the content of reactive oxygen species (ROS) was higher in H8 and H9 cell strains, and the differences were statistically significant (all at P<0.001).The expression of p21 protein in H8 and H9 cell strains wtih NAC treatment decreased significantly compared with non-NAC treatment cells (both at P<0.05).Compared with wild-type cell strains, H8 and H9 cell viability decreased at 200, 400, 600, and 800 μmol/L H 2O 2 treatment conditions, and the differences were statistically significant (all at P<0.05). Conclusions:Knockdown of HSF1 can downregulate the expression of heat shock proteins, activate the ROS/P53/P21 pathway, induce senescence in RPE cells, and increase the sensitivity of RPE to oxidative stress stimuli.HSF1 may have anti-senescence and anti-oxidant regulatory effects in RPE cells.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To compare the accuracy of different stone scoring systems for predicting the stone-free rate (SFR) after retrograde intrarenal surgery (RIRS).Methods:The clinical data of 227 patients with lithiasis undergoing RIRS from June 2017 to December 2020 in Affiliated Benq Hospital of Nanjing Medical University and Qingdao Fuwai Hospital were retrospectively analyzed. There were 152 males and 75 females. The average age was (53.0±10.4) years old. The average body mass index was (26.9±2.1)kg/m 2. The maximum diameter of the stone was (22.7±12.8)mm. The stone is located in left side in 133 cases and in right side in 94 cases. The stones of 44 cases were located in upper ureter, upper calyceal or renal pelvis, that of 23 cases were in medium calyceal, 157 cases in lower calyceal, and 3 cases in calyceal diverticulum.The average CT value of stone was (778.3±350.4)HU. American Society of Anesthesiology (ASA)scores: 86 cases of grade Ⅰ, 129 cases of grade Ⅱ, 12 cases of grade Ⅲ. Preoperative non-contrast CT was conducted and three-dimensional data were constructed. A single observer reviewed and entered the modified S.T.O.N.E., RUSS, modified S-ReSC, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E., stone free index (SFI) scores. Logistic analysis were performed between every score and SFR. Receiver operating characteristic (ROC) curve was drawn to detect sensitivity and specificity of every score in predicting the SFR. The predictive accuracies of all scores were compared. Results:The SFR was 83.0%(189/227). There were statistically significant differences in modified S. T.O.N.E.(10.5±1.9 vs. 12.7±1.8), RUSS[1(0, 4) vs. 3(0, 6)], modified S-ReSC (8.2±5.6 vs. 11.8±6.0), R.I.R.S.(6.2±1.4 vs. 8.1±1.2), SHA.LIN (9.9±2.4 vs. 13.0±2.1), Ito nomogram (12.1±5.8 vs. 4.3±3.3), S. O.L.V.E. (6.8±1.6 vs. 8.7±1.2), SFI score (7.9±1.1 vs. 6.3±0.9) between the stone-free group and the stone remaining group ( P <0.05). Logistic regression revealed that modified S.T.O.N.E., RUSS, modified S-ReSC, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E. and SFI score were significantly associated with SFR( P<0.05). There were no significant differences in the area under the curve (AUC) between the modified S. T.O.N.E., RUSS, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E. and SFI score( P>0.05), but there were significant differences in the AUC between modified S-ReSC score and other score ( P<0.05). When the cutoff of SHA.LIN, SFI and R. I.R.S. score was determined as 10, 6 and 6 scores, the specificity of SHA.LIN, SFI and R. I.R.S. score was 94.7%, 92.6% and 89.5%, respectively. Conclusions:All score could predict the postoperative SFR of RIRS, while the SHA.LIN, SFI and R.I.R.S. score were more accurate than the other scores. The accuracy of the modified S-ReSC in predicting SFR after RIRS was slightly worse than other scores.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:To investigate the utilization of sexual health services among community-based older adults in Chongqing and explore its potential correlates.Methods:A cross-sectional survey using multistage sampling among community-based older adults aged ≥50 years was conducted in Chongqing between June 2020 and December 2022. A questionnaire including information on demographic characteristics, general health, sexual health status, and sexual health services utilization was collected. Sexual health and reproductive services utilization was defined as having ever been tested for human immunodeficiency virus (HIV), or having had a male/gynecological reproductive health examination in the past year. Logistic regression was used to examine the correlates of the utilization of sexual health services.Results:A total of 794 community-based older adults participated in the study (482 were male, and 312 were female). The mean age was (62.8±8.2) years. The proportion of HIV testing was 18.0%, and the proportion of reproductive health examination was 10.1% among community-based older adults. The results of multivariate logistic regression analysis showed that the age group of 60-69 years (a OR=0.37, 95% CI: 0.18-0.76), female (a OR=11.34, 95% CI: 5.71-22.52), monthly income ≥5 000 yuan (a OR=3.05, 95% CI: 1.01-9.27), being sexual activity (a OR=4.99, 95% CI: 2.23-11.15) was significantly associated with had a reproductive health examination in the past year. Conclusions:The proportion of sexual health services utilization among older adults was low. Older sexual health education should be further strengthened, the close relationship between older adults should be correctly guided and dealt with, and the sexual health services suitable for the older population should be formulated.

Objective:To understand the current status of condom use and its correlates among community-based older adults in Chongqing, China.Methods:Cross-sectional study based on a multistage sampling method was conducted in Chongqing from June 2020 to December 2022. The estimated sample size was 735. Through face-to-face interviews, the investigators collected the sociodemographic characteristics, sexual behavior characteristics, awareness of AIDS prevention knowledge, etc. A multivariable logistic regression model was used to explore the correlates of condom use during the last sexual behavior among the participants. Results:A total of 761 participants were included in this study, with 476 males and 285 females, whose average age was (63.8±8.2) years old, mainly in the age group of 60-69 years (44.5%). Among the participants, the rate of condom use during the last sexual behavior was 9.7%. The multivariable logistic regression analysis indicated that correlates of condom use during the last sexual behavior included urban household registration (a OR=2.34, 95% CI: 1.12-4.89), monthly income of 1 000-4 999 Yuan, and 5 000 Yuan and above (a OR=4.49, 95% CI: 1.31-15.41; a OR=16.33, 95% CI: 4.30-62.00), self-assessed sexual behavior risk as very risky/relatively risky (a OR=3.97, 95% CI: 1.40-11.31), awareness of AIDS prevention knowledge (a OR=0.36, 95% CI: 0.21-0.62). Conclusions:The rate of condom use among community-based older adults in Chongqing is low. Comprehensive intervention measures should be taken in combination with the characteristics and needs of community-based older adults to improve awareness of AIDS prevention knowledge and perception of AIDS risk and promote condom use among this population.