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.

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.

ObjectiveTo investigate the expression features of HBsAg and HBcAg in liver tissue and their correlation with HBV serum markers in children with chronic hepatitis B （CHB）. MethodsA total of 257 patients who were consecutively admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2023 and underwent liver biopsy to achieve a confirmed diagnosis of CHB were enrolled in this study. The NIS-Elements system was used to capture the immunohistochemical images of HBsAg and HBcAg in liver tissues， and Image J software was used for quantitative analysis. The one-sample chi-square test was used for within-group comparison of continuous data， and the Pearson/Spearman/Kendall’s Tau-b correlation analysis was used to investigate the correlation between viral antigen expression and serological markers. ResultsAmong the 257 CHB patients， there were 162 children （76 children aged<5 years and 86 children aged 5 — 18 years） and 95 adults. There were significant differences in the expression pattern， area， and intensity of HBsAg and the area and intensity of HBcAg in liver tissue between different age groups and between the children with different HBeAg statuses （all P<0.05）. In the children aged<5 years， HBsAg staining area was significantly negatively correlated with anti-HBs and HBeAg （both P<0.05）and was significantly positively correlated with ALT and AST （both P<0.05）， and HBsAg staining intensity was significantly positively correlated with qHBsAg （P<0.05） and was significantly negatively correlated with anti-HBs （P<0.05）. In the children group， HBsAg staining area was negatively correlated with anti-HBs and HBeAg （both P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg （P<0.05） and was negatively correlated with anti-HBs （P<0.05）. In the adult group， HBsAg staining area was positively correlated with ALT， AST， and liver inflammatory activity （all P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05） and was negatively correlated with liver inflammatory activity and fibrosis degree （both P<0.05）. In the children aged<5 years， HBcAg staining area was positively correlated with qHBsAg and HBV DNA （both P<0.05）， and HBcAg staining intensity was significantly positively correlated with HBV DNA （P<0.001）. In the children aged 5 — 18 years， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）. In the children group， HBcAg staining area was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）， and HBcAg staining intensity was positively correlated with qHBsAg and HBV DNA （both P<0.05）. In the adult group， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.001）， and HBcAg staining area was positively correlated with the serum level of ALT （P=0.043）. ConclusionThe expression levels of HBsAg and HBcAg in liver tissue of children with CHB are significantly correlated with serological markers， and in clinical practice， HBsAg and HBcAg combined with serological markers can help to assess the condition of the liver， determine the immune stage， and provide evidence-based guidance for treatment timing.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

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.