ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

Multiple myeloma (MM) is a hematological malignancy that poses significant treatment challenges due to its heterogeneity and propensity for relapse and progression. In the last two decades, the therapeutic landscape of MM has changed dramatically, but the disease remains largely incurable, with many patients facing treatment resistance. This review evaluates the current status of MM treatments, emphasizing the limitations of traditional therapies and the emerging role of immunotherapy in improving patient outcomes. It highlights the importance of achieving and maintaining minimal residual disease negativity and a balanced immune response as key treatment goals. Furthermore, it discusses the advancements in immunotherapies that are improving the prospects for patients, particularly those with relapsed or refractory disease. Innovative strategies, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and bispecific T cell engagers, have shown significant promise by targeting the malignant cells and the bone marrow microenvironment, which are essential for disease persistence and resistance to therapy. Future research should focus on refining MM treatment strategies, including the integration of immunotherapy into earlier treatment lines and the development of predictive biomarkers for personalized treatment approaches, ultimately enhancing patient outcomes.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To explore the relationship between Metabolic Score of Visceral Fat(METS-VF)and new-onset stroke in Chinese middle-aged and elderly individuals aged ≥45 years.Methods:This study is a prospective cohort study that included 3 311 participants from the China Health and Retirement Longitudinal Study(CHARLS)database, with new-onset stroke as the primary endpoint.The association between METS-VF and new-onset stroke was evaluated by Cox proportional hazards model, subgroup analysis and restricted cubic spline(RCS)analysis.Additionally, mediation analysis was used to assess the mediating effect of remnant cholesterol(RC)on the association between METS-VF and stroke.Results:During the 9-year follow-up period, 138(4.2%)middle-aged and elderly individuals experienced stroke.Compared with the lowest quartile group of METS-VF, the fully adjusted HR and 95% CI of new-onset stroke in the second, third and fourth quartiles were 1.78(1.03-3.08), 1.96(1.12-3.44)and 2.19(1.17-4.10), respectively with a statistically significant trend( P for trend<0.05). Mediation analysis indicated that the indirect effect mediated by RC accounted for 13.51% of the association between METS-VF and new-onset stroke( P=0.03), and RCS analysis revealed a linear dose-response relationship between METS-VF and stroke( P for overall=0.022, P for non-linearity=0.198); The results of the subgroup analyses were consistent with the main analyses( P interaction>0.05). Conclusions:METS-VF may serve as a potential biomarker in risk stratification of stroke, with RC partially mediating this association.

Objective:To understand the prevalence of hearing loss among individuals aged 60 and above undergoing physical examinations and to explore the feasibility of using pure tone audiometry (PTA) for hearing screening in the elderly population, as well as to establish screening criteria suitable for our country.Methods:The study was a cross-sectional study, a total of 1 066 elderly individuals (619 males and 447 females; Age range: 60-90 years old, with an average of 66.5 years old) who underwent physical examinations at the Peking Union Medical College Hospital physical examination center from February to December 2023, were screened using PTA and the Chinese version Hearing Handicap Inventory for the Elderly Screening (CHHIE-S). Different screening criteria were applied to calculate the proportion of individuals who did not pass the PTA screening in the elderly population. The consistency between these results and the screening outcomes of the CHHIE-S scale was analyzed to explore reasonable screening standards. We performed statistical analysis using SPSS 27.0.Results:It was found that 18.39% of the elderly population had moderate or severe hearing loss. The positive rate determined by the detection of pure tones at a fixed dB level was significantly higher than that based on the average hearing threshold across 0.5, 1, 2, and 4 kHz frequencies (4-frequency pure-tone average, 4fPTA), and the difference was statistically significant ( χ2=136.56, P<0.001). The criterion of 4fPTA>35 dB HL in the better ear showed the highest consistency with the criterion of CHHIE-S>8, with a Kappa value of 0.554 ( P<0.001), and this criterion resulted in a positive rate of 15.57% (166/1 066). Conclusions:Conducting hearing screening based on PTA among the elderly population undergoing physical examinations is an effective and feasible approach. Given the subjective perceptions of the elderly population being screened, a 4fPTA greater than 35 dB HL in both ears might be a reasonable criterion.

Objective To investigate the differences in speech recognition in noise between patients with con-genital and acquired single-sided deafness.Methods Sixty-two patients with single-sided deafness were included in this study,which included 31 congenital single-sided deafness(CSSD)cases and 31 acquired single-sided deafness(ASSD)cases according to the onset of deafness.Thirty-one normal hearing(NH)subjects were also included in this study as the control group.The ability of speech recognition in noise were tested and compared among the three groups,meanwhile the differences between patients with left and right single-sided deafness were compared.Results The speech recognition threshold in noise of ASSD patients was significantly higher than that of CSSD patients,and both of them were significantly higher than that of the NH subjects.Under the 0 and-2 dB signal-to-noise ra-tio conditions,the speech recognition score was significantly lower in ASSD patients compared to CSSD patients,but only in ASSD patients it was significantly lower than that of the NH group,with no significant difference be-tween CSSD patients and the NH group.A significant difference in speech recognition thresholds was observed be-tween left and right CSSD patients.Conclusion CSSD have better speech recognition in noise than ASSD patients,suggesting better central function compensation.In addition,the side of deafness affects the speech recognition per-formance of CSSD patients.

Objective:To investigate the impact of internationalization at home medical education on clinical medical undergraduate abilities based on value-added assessment, and to provide a reference for deepening education and teaching reform in medical colleges and universities.Methods:The study subjects consisted of undergraduate students enrolled in 2020 at Chongqing Medical University majoring in clinical medicine (five-year program) and clinical medicine (Sino-foreign cooperative education program). The questionnaire in the 2023 China Medical Students Survey, initiated by the National Medical Education Development Center, was used in this study. SPSS 27.0 was used for independent samples t-test and hierarchical linear regression. Results:Compared with the control group, the clinical medical undergraduates who received internationalization at home medical education had higher scores in academic article writing ability [(3.89±0.73) vs. (2.87±0.80)], literature retrieval and information management ability [(3.98±0.64) vs. (3.43±0.65)], and international communication and global health concept [(3.81±0.68) vs. (3.52±0.69)]. Controlling for individual-level student variables, internationalization at home medical education had a positive effect on clinical medicine undergraduate abilities based on value-added assessment ( β=5.003, P<0.001). Conclusions:The internationalization at home medical education in Chongqing Medical University enhances the abilities of clinical medical undergraduates, and provides a reference for the comprehensive improvement of the education quality of medical talents.

Objective To investigate the differences in speech recognition in noise between patients with con-genital and acquired single-sided deafness.Methods Sixty-two patients with single-sided deafness were included in this study,which included 31 congenital single-sided deafness(CSSD)cases and 31 acquired single-sided deafness(ASSD)cases according to the onset of deafness.Thirty-one normal hearing(NH)subjects were also included in this study as the control group.The ability of speech recognition in noise were tested and compared among the three groups,meanwhile the differences between patients with left and right single-sided deafness were compared.Results The speech recognition threshold in noise of ASSD patients was significantly higher than that of CSSD patients,and both of them were significantly higher than that of the NH subjects.Under the 0 and-2 dB signal-to-noise ra-tio conditions,the speech recognition score was significantly lower in ASSD patients compared to CSSD patients,but only in ASSD patients it was significantly lower than that of the NH group,with no significant difference be-tween CSSD patients and the NH group.A significant difference in speech recognition thresholds was observed be-tween left and right CSSD patients.Conclusion CSSD have better speech recognition in noise than ASSD patients,suggesting better central function compensation.In addition,the side of deafness affects the speech recognition per-formance of CSSD patients.

Objective:To investigate the impact of internationalization at home medical education on clinical medical undergraduate abilities based on value-added assessment, and to provide a reference for deepening education and teaching reform in medical colleges and universities.Methods:The study subjects consisted of undergraduate students enrolled in 2020 at Chongqing Medical University majoring in clinical medicine (five-year program) and clinical medicine (Sino-foreign cooperative education program). The questionnaire in the 2023 China Medical Students Survey, initiated by the National Medical Education Development Center, was used in this study. SPSS 27.0 was used for independent samples t-test and hierarchical linear regression. Results:Compared with the control group, the clinical medical undergraduates who received internationalization at home medical education had higher scores in academic article writing ability [(3.89±0.73) vs. (2.87±0.80)], literature retrieval and information management ability [(3.98±0.64) vs. (3.43±0.65)], and international communication and global health concept [(3.81±0.68) vs. (3.52±0.69)]. Controlling for individual-level student variables, internationalization at home medical education had a positive effect on clinical medicine undergraduate abilities based on value-added assessment ( β=5.003, P<0.001). Conclusions:The internationalization at home medical education in Chongqing Medical University enhances the abilities of clinical medical undergraduates, and provides a reference for the comprehensive improvement of the education quality of medical talents.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.