ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Antibody-negative autoimmune encephalitis （AE） in children poses certain challenges for clinical diagnosis and treatment due to the lack of characteristic autoantibodies. This study conducts a retrospective analysis of the clinical data of a boy， aged 7 years， who had the main manifestations of “irritability， vomiting， pyrexia， and lethargy”. Video electroencephalography showed diffuse slow waves， with the presence of type 2 cerebrospinal fluid oligoclonal bands， and the boy was tested negative for related autoantibodies in blood and cerebrospinal fluid. Finally the boy was diagnosed with antibody-negative AE. After admission， the boy received first-line immunotherapy with methylprednisolone and intravenous immunoglobulin， combined with tocilizumab for intensive treatment， and the symptoms were rapidly relieved. At 1 week after discharge， the boy experienced memory loss， and head MRI suggested cerebral atrophy. After 1 month of adjuvant hyperbaric oxygen therapy， the boy’s memory recovered to the level before disease onset， and reexaminations of MRI and video electroencephalography obtained normal results.No recurrence was observed during follow-up for 6 months， and the boy achieved satisfactory academic performance.This case suggests that for children with antibody-negative AE， first-line immunotherapy combined with tocilizumab can rapidly control inflammation， and the addition of hyperbaric oxygen therapy can effectively improve subsequent cerebral structural and cognitive abnormalities， with few adverse reactions， which provides a new clinical approach for the treatment of this type of disease.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Objective:Through imaging analysis, the association between the degree of paravertebral muscle fat infiltration (fat infiltration, FI), trabecular bone score (TBS) and the fracture risk of postmenopausal osteoporosis (OP) patients was explored.Methods:A retrospective selection was made of 110 postmenopausal female patients diagnosed with OP at Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University from Mar. 2023 to Mar. 2024. Additionally, healthy postmenopausal individuals who underwent physical examinations during the same period were included in the healthy postmenopausal group. The levels of paravertebral muscle FI and TBS in the two groups were compared. Postmenopausal patients with OP were followed up for one year, and the incidence of fractures in the patients was analyzed by Kaplan-Meier curve. The patients were divided into the fracture group ( n=29) and the non-fracture group ( n=81). The clinical data of the two groups of patients at admission were compared. Binary Logistic regression was used to analyze the independent risk factors for fractures in patients. Spearman was used to analyze the correlation of fracture risk within one year among FI, TBS and postmenopausal OP patients. ROC was used to evaluate the predictive value of each independent risk factor. Results:The proportion of severe paraverteal muscle FI in the postmenopausal OP group was significantly higher than that in the healthy physical examination group (multifisis FI, erector spinae FI, psoas major muscle FI, χ2=14.96, 17.17, 16.08, all P=0.00), and the lumbar TBS level was significantly lower (t=4.52, P=0.00). The Kaplan-Meier curve indicated that the degree of paravertebral muscle FI affected the incidence of fractures in patients ( χ2=14.58, P=0.00), and the level of lumbar TBS also affected the incidence of fractures in patients ( χ2=6.02, P=0.01). The bone mineral density (BMD), cross-sectional area of the multifidus muscle (CSA), erectus spinae muscle area (CSA), and psoas major muscle area (CSA) of patients in the fracture group were significantly lower than those in the non-fracture group ( t=10.72, 3.40, 3.46, 2.12). P=0.00, 0.00, 0.00, 0.04), while the indicators of TNF-α, IL-6 and PCT were higher than those in the non-fracture group ( t=4.11, 4.96, 5.48, all P=0.00). Binary Logistic regression analysis showed that high-level BMD ( OR=0.52, 95%CI: 0.27-0.77, P=0.01) and TBS ( OR=0.68, 95 %CI: 0.48-0.93 ,P=0.02) were protective factors for fractures in postmenopausal patients with OP. Multifidus FI ( OR=1.73, 95 %CI: 1.48-1.98, P=0.03), erector spinae FI ( OR=1.25, 95%CI:1.10-1.50, P=0.01), and psoas major FI ( OR=1.96, 95 %CI: 1.71-2.21, P=0.03) is the risk factor. Spearman analysis indicated that the paravertebral muscle FI of patients at the first diagnosis of OP was positively correlated with the risk of fracture within one year after diagnosis ( r=0.88, 0.91, 0.82, P=0.01, 0.01, 0.02), while the BMD and TBS values were negatively correlated ( r=-0.92, -0.77, P=0.00, 0.02). ROC showed that the values of multifidus FI, erector spinae FI, psoas major FI, BMD and TBS at admission all had good predictive efficacy for fractures within one year in patients [area under the ROC curve (AUC) =0.88, 0.84, 0.86, 0.73, 0.82]. Moreover, the predictive efficiency of the joint model is higher (AUC=0.89) . Conclusions:Higher BMD and TBS levels protect against fractures in postmenopausal OP patients ( OR=0.523-0.675), while severe paraspinal muscle FI (multifidus: OR=1.726; erector spinae: OR=1.248; psoas: OR=1.961) increases risk. The combined model shows excellent predictive value (AUC=0.890), serving as effective clinical warning indicators for fracture risk assessment.

Objective:Through imaging analysis, the association between the degree of paravertebral muscle fat infiltration (fat infiltration, FI), trabecular bone score (TBS) and the fracture risk of postmenopausal osteoporosis (OP) patients was explored.Methods:A retrospective selection was made of 110 postmenopausal female patients diagnosed with OP at Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University from Mar. 2023 to Mar. 2024. Additionally, healthy postmenopausal individuals who underwent physical examinations during the same period were included in the healthy postmenopausal group. The levels of paravertebral muscle FI and TBS in the two groups were compared. Postmenopausal patients with OP were followed up for one year, and the incidence of fractures in the patients was analyzed by Kaplan-Meier curve. The patients were divided into the fracture group ( n=29) and the non-fracture group ( n=81). The clinical data of the two groups of patients at admission were compared. Binary Logistic regression was used to analyze the independent risk factors for fractures in patients. Spearman was used to analyze the correlation of fracture risk within one year among FI, TBS and postmenopausal OP patients. ROC was used to evaluate the predictive value of each independent risk factor. Results:The proportion of severe paraverteal muscle FI in the postmenopausal OP group was significantly higher than that in the healthy physical examination group (multifisis FI, erector spinae FI, psoas major muscle FI, χ2=14.96, 17.17, 16.08, all P=0.00), and the lumbar TBS level was significantly lower (t=4.52, P=0.00). The Kaplan-Meier curve indicated that the degree of paravertebral muscle FI affected the incidence of fractures in patients ( χ2=14.58, P=0.00), and the level of lumbar TBS also affected the incidence of fractures in patients ( χ2=6.02, P=0.01). The bone mineral density (BMD), cross-sectional area of the multifidus muscle (CSA), erectus spinae muscle area (CSA), and psoas major muscle area (CSA) of patients in the fracture group were significantly lower than those in the non-fracture group ( t=10.72, 3.40, 3.46, 2.12). P=0.00, 0.00, 0.00, 0.04), while the indicators of TNF-α, IL-6 and PCT were higher than those in the non-fracture group ( t=4.11, 4.96, 5.48, all P=0.00). Binary Logistic regression analysis showed that high-level BMD ( OR=0.52, 95%CI: 0.27-0.77, P=0.01) and TBS ( OR=0.68, 95 %CI: 0.48-0.93 ,P=0.02) were protective factors for fractures in postmenopausal patients with OP. Multifidus FI ( OR=1.73, 95 %CI: 1.48-1.98, P=0.03), erector spinae FI ( OR=1.25, 95%CI:1.10-1.50, P=0.01), and psoas major FI ( OR=1.96, 95 %CI: 1.71-2.21, P=0.03) is the risk factor. Spearman analysis indicated that the paravertebral muscle FI of patients at the first diagnosis of OP was positively correlated with the risk of fracture within one year after diagnosis ( r=0.88, 0.91, 0.82, P=0.01, 0.01, 0.02), while the BMD and TBS values were negatively correlated ( r=-0.92, -0.77, P=0.00, 0.02). ROC showed that the values of multifidus FI, erector spinae FI, psoas major FI, BMD and TBS at admission all had good predictive efficacy for fractures within one year in patients [area under the ROC curve (AUC) =0.88, 0.84, 0.86, 0.73, 0.82]. Moreover, the predictive efficiency of the joint model is higher (AUC=0.89) . Conclusions:Higher BMD and TBS levels protect against fractures in postmenopausal OP patients ( OR=0.523-0.675), while severe paraspinal muscle FI (multifidus: OR=1.726; erector spinae: OR=1.248; psoas: OR=1.961) increases risk. The combined model shows excellent predictive value (AUC=0.890), serving as effective clinical warning indicators for fracture risk assessment.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Autoimmunity diseases(AIDs) involve the entire body's tissue systems and pose a serious threat to the normal immune system and health of the human body. Researches have shown that AID is caused by the complex interaction between genetic susceptibility and environmental factors. Enterovirus(EV) infection often accompanies certain AID and is an important type of virus infection related to AID. Coxsackievirus(CV), a member of the EV family, is an important pathogen among the pathogenic factors of type 1 diabetes(T1D). EV infection causes damage to the activity of pancreatic β cells and accelerates the disease progression of T1D. In terms of treatment, recent reports have shown that antiviral therapy for T1D is effective in preserving the function of β pancreatic cells. In celiac disease and Crohn's disease(CD), EV infection can induce inflammatory pathogenic changes in the intestinal microbiota, increase intestinal barrier permeability, and may trigger the occurrence of such AIDs. However, the relationship and mechanism between EV infection and many AIDs remain unclear.This paper summarizes the research conclusions on the correlation between EV infection and AIDs to facilitate a deeper exploration of their pathogenic patterns.