Objective To analyze the expression levels of a-smooth muscle actin (α-SMA) and Vimentin in spindle cells and their relationship with the prognosis of patients with myxofibrosarcoma (MFS). Methods The imaging, clinical, and pathological data of 61 patients with MFS were collected. All patients were confirmed by surgical and postoperative pathological examination. Immunohistochemical methods were used to determine the positive proportion of α-SMA and Vimentin. The correlation between the expression levels of α-SMA and Vimentin in spindle cells and prognosis was analyzed. Results The positive rates of α-SMA and Vimentin expression in MFS tissues were 68.85% and 60.66%, respectively. The expression of Vimentin was not significantly correlated with 3-year OS and DFS (P=0.351, P=0.284). The expression of α-SMA was significantly correlated with OS and DFS (P=0.030, P=0.017), and patients with high expression of α-SMA have shorter OS and DFS. Conclusion Determining α-SMA level can help evaluate the prognosis of patients with MFS and guide clinical treatment.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

BACKGROUND:Fluorosis is a disorder of enamel development caused by long-term intake of large amounts of fluoride during enamel development. OBJECTIVE:To further explore the molecular mechanism of dental fluorosis formation by screening the differentially expressed genes associated with calcium homeostasis in ameloblasts by transcriptome sequencing technology. METHODS:LS8 cells were treated with 0,0.4,0.8,1.6,3.2 and 6.4 mmol/L sodium fluoride(NaF)for 24,48 and 72 hours to observe the effects of different concentrations of NaF on the morphology,cell activity and intracellular Ca2+ concentration of LS8 cells.The differentially expressed genes were screened by transcriptome sequencing and validated. RESULTS AND CONCLUSION:After 24 hours of treatment,the cells treated with 0,0.4,and 0.8 mmol/L NaF were in good growth condition,with increased cell number and clear cell outline.When the NaF concentration was≥1.6 mmol/L,the cells were gradually shrunken and became smaller and the number of cells decreased with the increase of NaF concentration.After 48 and 72 hours of treatment,the number of cells increased in the 0,0.4 mmol/L NaF groups,while gradually decreased in the 0.8,1.6,3.2 mmol/L NaF groups,with rounded and smaller cell morphology.The cells in the 6.4 mmol/L NaF group were shrunken,rounded and suspended in the medium,with almost no adherent cells.When treated with the same concentration of NaF,LS8 cells were in optimal growth after 24 hours of treatment.Results from cell counting kit-8 assay showed that when treated with the same concentration of NaF,the cell activity decreased with the increase of treatment time;when the treatment time was the same,the cell activity decreased with the increase of NaF concentration.After 24 hours of treatment,the intracellular Ca2+ concentration increased with the increase of NaF concentration.Transcriptome sequencing analysis identified genes involved in the regulation of cellular calcium homeostasis:Hsp90b1,Canx,Calr,and Hspa5 that were significantly upregulated(P＜0.05)and Cacna1a that was significantly downregulated(P＜0.05).To conclude,the inhibitory effect of NaF on LS8 cell proliferation may be related to the abnormal increase in intracellular Ca2+ concentration,and the mechanism may be caused by the upregulation of the expression of protein processing and synthesis pathways Hsp90b1,Canx,Calr,and Hspa5 and the downregulation of the expression of calcium signaling pathway Cacna1a.

The application of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin(PA-MSHA)in the field of an-titumors has been increasing.PA-MSHA has been found to promote tumor cell apoptosis,inhibit tumor cell invasion and migration,differentiation,and change drug resistance and epithelial-mesenchymal transformation(EMT)by inhibiting the EGFR pathway.Meanwhile,PA-MSHA also enhances the immune killing and inhibition of macrophages and T cells to tumor cells through toll-like receptors(TLRs).In this paper,we reviewed the reported anti-tumor mechanism and clinical application of PA-MSHA,suggesting that PA-MSHA may alter the glycosylation of EGFR and TLR proteins by acting on the regulatory process of the cellular mannosy-lation process.PA-MSHA can act on cell membrane proteins,including more receptors with high-mannosylation of signaling path-ways.Elucidating the deep relationship between PA-MSHA and mannosylation is of great significance for the mechanism research and clinical application of PA-MSHA.

Objective:To understand the characteristics of sexual behaviors in the elderly aged ≥60 years and provide evidence for AIDS prevention and control in the elderly.Methods:Local residents who were aged ≥60 years and had lived in Yongchuan District of Chongqing for more than half a year were recruited by multi-stage sampling with a sample size of 2 721 from September to December 2022 for a face to face questionnaire survey to collect the information about their demographic characteristics, awareness of AIDS related knowledge and sexual behaviors, and the incidence of non-marital sexual behaviors. Multivariate logistic regression model was used to analyze related factors non-marital sexual behaviors in the elderly aged ≥60 years. SPSS 23.0 software was used for statistical analysis.Results:A total of 2 974 valid questionnaires were collected from 3 000 old persons aged ≥60 years, the male to female ratio of the elderly who returned the questionnaires was about 1∶1 (1 488∶1 486). The average age of them was (69.3± 7.0) years, and the awareness rate of AIDS related knowledge was 78.5% (2 336/2 974), 26.9% of them (801/2 974) had sexual behavior in the past year, 20.9% (493/2 350) of them had sexual behaviors with their spouses in the past year, and 10.8% (322/2 974) of them had non-marital sexual behaviors. The proportions of the elderly with commercial sexual behaviors and non-marital/non-commercial sexual behaviors were 10.2% (304/2 974) and 1.2% (36/2 974). The results of multivariate logistic regression analysis showed that being man (a OR=89.08, 95% CI: 36.30-218.60), age 70-79 years (a OR=1.93, 95% CI:1.44-2.59) and ≥80 years (a OR=2.41, 95% CI: 1.56-3.74), and unawareness of AIDS related knowledge (a OR=2.72, 95% CI: 2.04-3.64) were associated with the incidence of non-marital sex. Conclusions:The proportions of non-marital sexual behaviors were higher among the elderly aged ≥60 years in Yongchuan District of Chongqing. It is necessary to pay attention to the sexual needs and sexual health of the population, improve the awareness rate of AIDS prevention and treatment knowledge, advocate safe sex, and improve the sexual health and quality of life in the elderly.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Objective To understand the use situation of Rush among the men who have sex with men(MSM)in Chongqing City and its influencing factors,so as to provide a basis for the formulation of relevant prevention and control measures.Methods The cross-sectional survey was adopted.The MSM population in Chongqing City were recruited through the network recruitment and referral of social organizations to conduct an anonymous electronic questionnaire survey to obtain the information such as demographic characteristics,sexual partners and sexual behavior characteristics in the past 6 months,Rush use,HIV and syphilis antibody testing.The X2 test and non-conditioned multi-factor Logistic regression analysis were used to analyze the in-fluencing factors of Rush use.Results A total of 494 MSM were surveyed,the Rush usage rate was 22.1％.The results of the multi-factor logistic regression analysis showed that the age of first time homosexuality be-havior＜18 years old(OR=2.715,95％CI:1.353-5.451),unprotected homosexual anal intercourse in near-ly 6 months(OR=2.237,95％CI:1.355-3.693),having multiple same-sex partners in nearly 6 months(OR=3.610,95％CI:1.449-8.993),same-sex casual partners in the nearly 6 months(OR=3.734,95％CI:2.221-6.280)were the risk factors for MSM using Rush.Conclusion The RUSH use rate among the MSM population in Chongqing City is high.The targeted intervention measures should be carried out,especially to strengthen the propaganda and education of the population who first have homosexual behavior under 18 years old,have unprotected homosexual anal intercourse in the nearly 6 months,have multiple homosexual perma-nent partners in the last 6 months,and have homosexual temporary partners,in order to reduce the use rate of Rush and thereby reduce the risk of HIV infection and transmission in this population.

Objective To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology,which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails'entry point,and to verify its clinical value through clinical tests.Methods After matching the locating module with the developing board,which are the two components of the locating device,they were placed on the skin surface of the proximal femur of the affected side.Anteroposterior fluoroscopy was performed.The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image,and then the yaw angle of the locating module was reset to zero.After resetting,the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire.The ideal direction of entry point was accurately located based on the angle guidance.By setting up an experimental group and a control group for clinical surgical operations,the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss with or without the locating device was recorded.Results Compared to the control group,the experimental group showed significant improvement in the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss,with a statistically significant difference(P<0.01).Conclusion The locating device can assist doctors in quickly locating the entry point of intramedullary nail,effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot,improving surgical efficiency,and possessing certain clinical value.