This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

ObjectiveTo evaluate the efficacy and safety of traditional Chinese exercises (TCE) in patients with diabetic peripheral neuropathy (DPN) and to recommend best practices for using TCE to improve neurological function, glycemic control, and psychological well-being.MethodsNine databases were searched from the inception to October 2024. Effect relationships were assessed using meta-analysis with Stata 17, and the methodological quality and certainty of the evidence were evaluated using standard tools.ResultsTwelve studies comprising three study designs (nine randomized controlled, one quasi-experimental controlled, and two single-arm clinical trials), were identified. Compared with usual care, TCE improved various indicators and enhanced the nerve conduction velocities of the peroneal motor (mean difference [MD] = 3.86 m/s, 95% confidence interval [CI]: 0.38 to 7.34, P = .03), sural sensory (MD = 4.15 m/s, 95% CI: 0.68 to 7.63, P = .02), median motor (MD = 3.84 m/s, 95% CI: 2.14 to 5.54, P .001), and median sensory nerves (MD = 6.14 m/s, 95% CI: 4.54 to 7.74, P .001). TCE practices also reduced glycosylated hemoglobin level (MD = −0.59%, 95% CI: −0.91 to −0.27, P .001) and fasting blood glucose (standardized mean difference [SMD] = −1.08, 95% CI: −1.79 to −0.37, P .001). The overall quality of evidence was very low.ConclusionThe results indicate that TCE therapy improves certain outcomes in patients with DPN. Although the optimal type, intensity, frequency, and duration of TCE interventions are uncertain, these preliminary findings suggest that TCE should be further studied as a potentially affordable and effective treatment for DPN.

AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Objective: To evaluate the effect of Tai Chi and Qigong on patients with lumbar disc herniation (LDH). Methods: Relevant data were retrieved from nine English and Chinese databases, including Cochrane Library, PubMed, and Wanfang Data, etc. from inception to June 2024. All published randomized controlled trials assessing the effect of Tai Chi and Qigong on visual analog scale (VAS), Japanese Orthopedic Association (JOA) score, and other health indicators in participants with LDH compared to usual medical care or other treatments were included. Grey literature, trials involving the pushing of hands (Tui Shou) or Tai Chi with weapons, and trials with co-interventions (Tai Chi/Qigong plus another treatment) were excluded. Methodological quality was analyzed using the Cochrane risk of bias tool, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Results: Fourteen trials (954 patients) were included in this study. Tai Chi and Qigong were associated with lower VAS pain scores (standardized mean difference −0.55, 95% confidence interval [CI] −0.95 to −0.15, P = .01), higher JOA scores (mean difference [MD] 4.40, 95% CI 2.62 to 6.18, P < .001) and straight leg raise test results (MD 9.40°, 95% CI 7.64 to 11.15, P < .001) in patients with LDH. Furthermore, compared with usual care, Tai Chi and Qigong showed enhanced effects on pain and JOA scores. When compared to other exercises or massage, the effect on pain scores was similar but that on JOA scores was significant. Conclusions Tai Chi and Qigong may have favorable effects on VAS pain and JOA scores compared with usual care, and on JOA scores compared with other exercises or massage in patients with LDH. Given the overall poor quality of the evidence, the results of current study should be interpreted cautiously.