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.

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Nasopharyngeal carcinoma (NPC) is a common head and neck malignant tumor with high incidence in southern China. Local recurrence is one of the main failure modes of locally advanced NPC. The dose-escalation after radical radiotherapy for locally advanced NPC remains controversial. In the era of modern radiotherapy, the mainstream treatment mode of locally advanced NPC is neoadjuvant chemotherapy plus concurrent chemoradiotherapy. There is no consensus on whether to prescribe dose-escalation, how and when to conduct dose-escalation, how much dose to prescribe for patients with residual lesion proved by MRI or pathology. How to accurately determine the target volume and dose / fraction to maximize the local control of the tumor are the directions of clinical practice for locally advanced NPC, which remain to be further studied.

Objective:To investigate epithelial-mesenchymal transition and to explore the effects of mitochondrial dysfunction and increased expression of TGF-β1 pathway on epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma after X-ray irradiation.Methods:Split-dose irradiations of total 40 Gy (2 Gy × 20 and 4 Gy × 10) of 6 MV X-rays were performed on PATU1 988 t cells. The migration of the cells were examined through transwell filter chambers. Real-time PCR was adopted to detect the expression of EMT-related factors E-cadherin, Vimentin, N-cadherin, and MMPs (MMP2 and MMP9), critical subunits of mitochondrial complex I, and TGF-β1. The expression of EMT-related factors and content of TGF-β1 was detected after carbonylcyanide-m-chlorophenylhydrazone(CCCP) treatment. Meanwhile, the migration potential of pancreatic cells was detected after small interfering RNA (siRNA) knockdown of the expression of TGF-β1.Results:After irradiation, the migration capacities of the cancer cells increased ( t=21.90, 35.64, P<0.05). The expression of N-cadherin ( t=4.42, 4.77, P<0.05), Vimentin ( t=4.57, 3.02, P<0.05), MMP2 ( t=7.27, 26.08, P<0.05), and MMP9 ( t=13.26, 7.29, P<0.05) all increased, while the expression of E-cadherin deceased ( t=8.37, 6.77, P<0.05). The expression of TGF-β1 ( t=90.49, 35.17, P<0.05) increased. The expression of TGF-β1 decreased with small interfering RNA, which paralleled the inhibition of the epithelial-mesenchymal transition and migration ( t=38.66, 11.54, P<0.05). Mitochondrial dysfunction was reflected by the decline in the membrane potential ( t=6.94, 29.71, P<0.05) and complex-related subunits. The expression of TGF-β1 ( t=47.93, P<0.05) and EMT-related factors further increased after mitochondrial function was destroyed ( t=16.51, P<0.05). Conclusions:Radiation-induced mitochondrial dysfunction can increase the expression of TGF-β1, which promotes epithelial-mesenchymal transition, and result in the migration of pancreatic cancer cell line.