This paper explores the differentiation and treatment strategies for pediatric IgA vasculitis based on the correlation between blood trubidity theory and oxidative stress. It is proposed that pediatric IgA vasculitis follows an evolution of pathogenesis characterized by "deficiency of healthy qi leading to turbidity generation， accumulation of turbid toxin， and toxin damage to the collateral vessels"， which corresponds to the pathological process of oxidative stress， namely decreased antioxidant capacity with accumulation of reactive oxygen species， metabolite deposition， and endothelial cell injury. A staged treatment strategy is proposed. In the acute stage， wind-toxin invading the colla-terals and reckless movement of heat in the blood are the main manifestations， for which the treatment should focus on dispelling wind and venting pathogens， resolving toxins and unblocking the collaterals， with a modified Yinqiao Powder （银翘散） and Xijiao Dihuang Decoction （犀角地黄汤） to regulate oxidative stress burst. In the prolonged stage， intermingling of turbidity and stasis with collateral obstruction is emphasized； treatment should focus on resolving turbidity and dispelling stasis， harmonizing the blood and stabilizing the collaterals， and a modified Simiao Powder （四妙散） and Taohong Siwu Decoction （桃红四物汤） can be used to improve microcirculatory dysfunction. In the remission stage， when healthy qi remains insufficient and residual pathogens persist， treatment should focus on strengthening the root and clearing the source， reinforcing healthy qi and nourishing the collaterals， for which modified Zhibai Dihuang Pill （知柏地黄丸） and Yupingfeng Powder （玉屏风散） is suggested to rebuild the antioxidant defense system.

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 compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

Objective:To explore the expression and ultrastructure distribution of cofilin and its potential mecha-nisms in postsynaptic mitochondrial anchoring and synaptic plasticity in the pre-B?tzinger complex(pre-B?tC)in rats.Methods:Using neurokinin 1 receptor(NK1R)as a morphological marker of the pre-B?tC,we examined the expres-sion and ultrastructure distribution of cofilin in pre-B?tC neurons of normoxic(NOR)and acute intermittent hypoxic(AIH)rats by combining Western blot,RT-qPCR,immunofluorescence,and immunoelectron microscopy.Results:Cofilin was expressed in the nuclei,somata and dendrites of NK1R-positive neurons in the pre-B?tC and its expression decreased after AIH intervention in this region detected.The results of immunoelectron microscopy showed that cofilin was expressed in the dendritic spines and postsynaptic filamentous or flocculent structures of pre-B?tC neurons.A total of 317 synapses were detected in pre-B?tC(NOR:122;AIH:195).In the NOR group,65.6％of the postsynaptic had cofilin expression,while in the AIH group,the proportion decreased to 47.2％.Combining with the role of cofilin in the regulation of actin severing,it is suggested that the severing effect of cofilin on postsynaptic actin is weakened af-ter AIH intervention,which may further enhance the postsynaptic mitochondrial anchoring.Conclusion:Cofilin,an ac-tin binding protein,plays a crucial role in regulating shearing and depolymerization of actin.Decreased cofilin expres-sion induced by AIH suggests an enhanced actin polymerization,which may be involved in the postsynaptic anchoring of mitochondria and the regulation of synaptic plasticity in the pre-B?tC.

Background and purpose:Intracellular deubiquitylating enzymes,such as ubiquitin-specific peptidase 2(USP2),play a pivotal role in regulating protein degradation and cellular homeostasis by modulating protein ubiquitin deconjugation,which have been implicated in the proliferation and survival of multiple myeloma(MM)cells.Targeting the inhibition of USP2 activity in MM cells might modulate their biological behavior.This study aimed to investigate regulatory effects of the leukotriene receptor antagonist montelukast sodium on USP2 in MM cells and its subsequent biological effects.Methods:An in vitro deubiquitination reaction system was established using purified USP2 protein and its substrate,the glutathione S-transferase(GST)tagged ubiquitin A-52 residue ribosomal protein fusion product(UbA52),known as GST-UbA52 protein.This system was used to characterize inhibitory effects of montelukast sodium on USP2 deubiquitinase activity.The MM cell lines MM1.S and H929 were used as in vitro models.Cellular thermal shift assay(CETSA)was subsequently employed to test interaction mode between montelukast sodium and USP2 in MM cells.Western blot assay was applied to detect expression levels of USP2 and its targeting regulators,including cell cycle supervisors cyclin D1(CCND1)and cyclin A1(CCNA1),classical signaling transducer KRAS and glucose regulated protein 78kD(GRP78),as well as apoptotic molecule C/EBP-homologous protein(CHOP)in MM1.S and H929 cells before and after the treatment with different concentrations of montelukast sodium.MM cells with either overexpression(H929-OE,MM1.S-OE)or knockdown(H929-LE,MM1.S-LE)of USP2 were generated using a lentiviral vector.Cell counting kit-8(CCK-8)and flow cytometry were utilized to detect the proliferation and apoptotic rates of H929-OE,MM1.S-OE,H929-LE and MM1.S-LE cells treated with montelukast sodium.Results:Montelukast sodium was found to inhibit USP2 mediated degradation of GST-UbA52 protein in a concentration-dependent manner,with a half inhibitory concentration(IC50)of 3.814 μmol/L.Additionally,montelukast sodium significantly enhanced the thermal stability of USP2 at temperatures of 49.1,53.2 and 56.4℃.It was also shown that montelukast sodium could down-regulate expressions of CCND1,CCNA1 and KRAS,while increase levels of GRP78 and CHOP in MM1.S and H929 cells.Furthermore,after treating with 40 μmol/L montelukast sodium for 24 h,the proliferation inhibition and apoptotic rate of H929-OE cells reached to(37.68±1.10)%and(18.99±0.26)%,while the proliferation inhibition and apoptotic rate of MM1.S-OE cells reached to(24.48±0.49)%and(33.29±0.75)%,which were significantly lower than those in H929 and MM1.S cells[H929:(57.19±1.93)%and(45.65±0.24)%;MM1.S:(50.04±0.53)%and(40.25±0.91)%;P＜0.05,n=3].Conversely,the proliferation inhibition and apoptotic rates of H929-LE and MM1.S-LE cells were significantly higher[H929-LE-1#:(80.70±1.60)%and(89.08±0.49)%;H929-LE-2#:(75.30±3.80)%and(82.41±1.07)%;MM1.S-LE-1#:(70.64±0.84)%and(67.63±0.21)%;MM1.S-LE-2#:(68.47±1.32)%and(85.90±0.18)%;P＜0.05,n=3].Conclusion:Montelukast sodium can target ubiquitin proteasome regulator USP2 and inhibit its deubiquitylating activity,which may modulate USP2 directing protein and trigger endoplasmic reticulum stress to induce cell cycle arrest and apoptosis in MM cells.

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.

As people age, older adults experience problems such as aging and degeneration of systemic organs and skin barrier function, leading to a high incidence of dry skin and pressure injuries. Dry skin and pressure injuries interact with each other to exacerbate the failure of skin function, which not only increases suffering, mortality risk, and medical costs for the elderly but also places a heavy burden on society and families. This paper summarizes the epidemiological characteristics of dry skin in the elderly and its influencing factors, the impact of dry skin in the elderly on pressure injuries, and puts forward the prevention and control strategies of "external treatment" and "internal nourishment" to provide a reference for the development of prevention and control strategies for dry skin and pressure injuries in the elderly in China.

Objective:To search, evaluate, and synthesize the best evidence for the management of diabetes in patients after heart transplantation, in order to provide reference for blood glucose management in subsequent patients within transplant teams.Methods:Following the "6S" model, a systematic search was conducted for guidelines, expert consensus, systematic reviews, and primary studies on the management and prevention of diabetes mellitus after heart transplantation. The search period was from database inception to May 22, 2024. The articles were assessed for quality and evidence grading using the Joanna Briggs Institute Evidence-Based Health Care Center's quality appraisal standards and evidence grading and recommendation grading system.Results:A total of 11 articles were included, consisting of three guidelines, six expert consensus papers, and two systematic reviews. These studies covered six key areas: early risk factor assessment, expansion of post transplantation diabetes mellitus screening trials, management of modifiable risk factors, lifestyle changes, implementation of personalized blood sugar reduction plans, and microvascular complication management. A total of 33 relevant pieces of evidence were summarized.Conclusions:The transplant team should formulate personalized blood glucose management plans based on clinical contexts, and heart transplant recipients should also actively engage in blood glucose monitoring and management to improve prognosis.

Background and purpose:Intracellular deubiquitylating enzymes,such as ubiquitin-specific peptidase 2(USP2),play a pivotal role in regulating protein degradation and cellular homeostasis by modulating protein ubiquitin deconjugation,which have been implicated in the proliferation and survival of multiple myeloma(MM)cells.Targeting the inhibition of USP2 activity in MM cells might modulate their biological behavior.This study aimed to investigate regulatory effects of the leukotriene receptor antagonist montelukast sodium on USP2 in MM cells and its subsequent biological effects.Methods:An in vitro deubiquitination reaction system was established using purified USP2 protein and its substrate,the glutathione S-transferase(GST)tagged ubiquitin A-52 residue ribosomal protein fusion product(UbA52),known as GST-UbA52 protein.This system was used to characterize inhibitory effects of montelukast sodium on USP2 deubiquitinase activity.The MM cell lines MM1.S and H929 were used as in vitro models.Cellular thermal shift assay(CETSA)was subsequently employed to test interaction mode between montelukast sodium and USP2 in MM cells.Western blot assay was applied to detect expression levels of USP2 and its targeting regulators,including cell cycle supervisors cyclin D1(CCND1)and cyclin A1(CCNA1),classical signaling transducer KRAS and glucose regulated protein 78kD(GRP78),as well as apoptotic molecule C/EBP-homologous protein(CHOP)in MM1.S and H929 cells before and after the treatment with different concentrations of montelukast sodium.MM cells with either overexpression(H929-OE,MM1.S-OE)or knockdown(H929-LE,MM1.S-LE)of USP2 were generated using a lentiviral vector.Cell counting kit-8(CCK-8)and flow cytometry were utilized to detect the proliferation and apoptotic rates of H929-OE,MM1.S-OE,H929-LE and MM1.S-LE cells treated with montelukast sodium.Results:Montelukast sodium was found to inhibit USP2 mediated degradation of GST-UbA52 protein in a concentration-dependent manner,with a half inhibitory concentration(IC50)of 3.814 μmol/L.Additionally,montelukast sodium significantly enhanced the thermal stability of USP2 at temperatures of 49.1,53.2 and 56.4℃.It was also shown that montelukast sodium could down-regulate expressions of CCND1,CCNA1 and KRAS,while increase levels of GRP78 and CHOP in MM1.S and H929 cells.Furthermore,after treating with 40 μmol/L montelukast sodium for 24 h,the proliferation inhibition and apoptotic rate of H929-OE cells reached to(37.68±1.10)%and(18.99±0.26)%,while the proliferation inhibition and apoptotic rate of MM1.S-OE cells reached to(24.48±0.49)%and(33.29±0.75)%,which were significantly lower than those in H929 and MM1.S cells[H929:(57.19±1.93)%and(45.65±0.24)%;MM1.S:(50.04±0.53)%and(40.25±0.91)%;P＜0.05,n=3].Conversely,the proliferation inhibition and apoptotic rates of H929-LE and MM1.S-LE cells were significantly higher[H929-LE-1#:(80.70±1.60)%and(89.08±0.49)%;H929-LE-2#:(75.30±3.80)%and(82.41±1.07)%;MM1.S-LE-1#:(70.64±0.84)%and(67.63±0.21)%;MM1.S-LE-2#:(68.47±1.32)%and(85.90±0.18)%;P＜0.05,n=3].Conclusion:Montelukast sodium can target ubiquitin proteasome regulator USP2 and inhibit its deubiquitylating activity,which may modulate USP2 directing protein and trigger endoplasmic reticulum stress to induce cell cycle arrest and apoptosis in MM cells.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.