[Objective]To explore the effects of astragalin(AST)on autophagy and apoptosis of astrocytes in the L4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant(CFA).[Methods]Twenty-four male C57BL/6 mice,aged six months,were randomly assigned to four groups:control group,saline group,CFA model group,and CFA+AST group,six mice in each group.The inflammatory pain model was established by injection of 10 μL CFA into the right lateral malleolus fossa.The saline group were injected with an equal amount of normal saline at the same site.The inflammatory pain mice in CFA+AST group were further treated with AST(60 mg/kg)intraperitoneally once a day for 21 consecutive days.Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1,apoptosis-related factors including Cleaved-Caspase3 and Caspase9,and the astrocyte marker such as GFAP in the L4-5 spinal dorsal horn of the mice in each group.Western blot was used to examine the protein expression levels of autophagy-related proteins(ATG12,Beclin-1)and apoptosis-related proteins(Caspase 3,Caspase 9)in the L4-5 spinal dorsal horn of mice.[Results]Immunofluorescent staining showed that in the L4-5 dorsal horn of the spinal cord,the fluorescence intensity of ATG12(P<0.000 1)and Beclin-1(P<0.000 1)was significantly increased,while that of Cleaved-Caspase 3(P<0.001)and Caspase 9(P<0.000 1)was decreased in the CFA+AST group when compared to the CFA model group.Furthermore,AST could inhibit the activation of astrocytes.Western blot further confirmed that AST significantly upregulated the expression of ATG12(P<0.000 1)and Beclin-1(P<0.000 1)in the L4-5 spinal cord of CFA mice,and downregulated the expression of Caspase 3(P<0.01)and Caspase 9(P<0.001).[Conclusions]AST promotes autophagy of astrocytes and inhibits their apoptosis in the L4-5 spinal dorsal horn of CFA mice.

Objective To explore the time cross-lagged effect between carotid intima-media thickness(CIMT)and bone mineral density(BMD)and to assess whether CIMT can be used as an early predictor of osteoporosis.Methods Based on the retrospective cohort study involved,people who underwent health checkups at The First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2023 were selected,and data related to CIMT and BMD were collected.The time-series relationship between CIMT and BMD was explored by cross-lagged modeling.Meanwhile,the effects of CIMT on BMD and its dose-response relationship were assessed using multiple linear regression and restricted cubic spline regression models.Results Analysis of 2 453 study subjects revealed a significant negative relationship between prior physical examination CIMT and subsequent BMD,and this relationship remained significant after controlling for confounders.For every 1-unit increase in CIMT,there was a mean decrease in second-stage BMD T-values of 0.113.Restricted cubic spline regression analysis showed a maximum decrease in BMD T-values of 0.121 for every 1.00 mm increase in CIMT.Conclusion The present study found that there was a significant negative cross-lag effect between CIMT and BMD,and that there was a dose-response between an increase in CIMT and a decrease in BMD.CIMT,as an easy-to-measure indicator,may be a potential marker for early prediction of osteoporosis,especially in the elderly population.

In this study,we aim to evaluate the immunogenicity of the whole-cell proteins isolated from Mycobacterium marinum(MM).The findings of this research may provide scientific basis for the development of new candidate tuberculosis vaccines.Both MM 95014 and Mycobacteriumtuberculosis(MTB)H37Rv cells were routinely cultured and collected.After inactivation,whole-cell proteins were extracted by low-temperature ultrasonic fragmentation and mixed with DDA/Poly:IC adjuvant.The mixture was administered to BALB/c mice subcutaneously with 50 mg/mouse twice with an interval of 10 days.Blood sample was collected before each immunization,as well as 10 days after the last immunization.Blood samples and spleen tissue extracts were measured for serum antibody potency and cytokine levels by an enzyme-linked immunosorbent assay.An in vitro growth inhibition assay(MGIA)was used to assess the ability of mouse bone marrow-derived macrophages,collected after immunization with MM whole-cell proteins,to inhibit MTB growth.A MTB whole mycobacterium proteome microarray was applied to analyze the interaction between the serum in MM immunization group and MTB proteins.Our results indicated that,compared with the adjuvant group,MM whole-cell proteins induced higher levels of Th1 cytokines(IL-2,IFN-γ,IL-12,TNF-α)in the mice.The IgG and IgM antibody titers induced by MM immunization group reached 1∶608 874 and 1∶304 437,respectively.The MGIA results showed that the MM immunization group was able to significantly inhibit MTB growth in vitro.The MTB proteome microarray results indicated that there were 226 and 324 cross-proteins with IgG and IgM antibodies,respectively.This study suggested that MM whole-cell proteins can induce high levels of cellular and humoral immune responses in mice and exhibit strong inhibition of MTB growth in vitro.The results may suggest potential application value of MM whole-cell proteins as a novel candidate vaccine for tuberculosis.

Traditional Chinese medicine （TCM） has unique advantages in alleviating the symptoms of diabetic kidney disease （DKD） and slowing its progression. However， traditional clinical trials often use the occurrence of end-stage renal disease as the end point， requiring long-term follow-up， which increases trial complexity and costs， thereby limiting the feasibility of TCM clinical studies. This paper suggested that in clinical trials of TCM for DKD， both the estimated glomerular filtration rate （eGFR） change rate （≥30%） and eGFR slope can serve as potential surrogate outcome measures. If the intervention course is short （＜1 year）， the eGFR change rate （≥30%） is recommended as a surrogate outcome measure， whereas in long-term interventional studies （≥1 year）， the eGFR slope may be more appropriate. Furthermore， based on biochemical indicators such as eGFR slope and urinary albumin-to-creatinine ratio （UACR） change rate， integrating TCM symptom evaluation， TCM syndrome evaluation， and quality of life scales can help develop internationally recognized patient-reported outcome measures （PROMs） for TCM clinical trials， which will be a key step in enhancing the evaluation system for the effectiveness of TCM in treating DKD.

The prevention and research of military training injuries(MTI)are crucial for reducing non-battle casualties,ensuring combat readiness,and enhancing the effectiveness of military training.In-depth analyses of the prevention and treatment strategies of MTI and related research can provide concrete guidance for scientific training practices.As a critical component of national defense,the Chinese Navy has experienced rapid development in recent years,and the prevention and research of MTI in naval forces have become a key focus.In recent years,rehabilitation medicine has been increasingly recognized for its importance in areas such as physical capability enhancement and injury prevention.The comprehensive adoption of rehabilitation concepts and the early implementation of rehabilitation measures have been widely accepted.It has important guiding significance for further strengthening the application of rehabilitation in preventing and treating injuries in naval training.This article discusses how to further strengthen the rehabilitation strategies for the prevention and research of MTI in the Navy,so as to provide insights and prospects for this field.

In this study,we aim to evaluate the immunogenicity of the whole-cell proteins isolated from Mycobacterium marinum(MM).The findings of this research may provide scientific basis for the development of new candidate tuberculosis vaccines.Both MM 95014 and Mycobacteriumtuberculosis(MTB)H37Rv cells were routinely cultured and collected.After inactivation,whole-cell proteins were extracted by low-temperature ultrasonic fragmentation and mixed with DDA/Poly:IC adjuvant.The mixture was administered to BALB/c mice subcutaneously with 50 mg/mouse twice with an interval of 10 days.Blood sample was collected before each immunization,as well as 10 days after the last immunization.Blood samples and spleen tissue extracts were measured for serum antibody potency and cytokine levels by an enzyme-linked immunosorbent assay.An in vitro growth inhibition assay(MGIA)was used to assess the ability of mouse bone marrow-derived macrophages,collected after immunization with MM whole-cell proteins,to inhibit MTB growth.A MTB whole mycobacterium proteome microarray was applied to analyze the interaction between the serum in MM immunization group and MTB proteins.Our results indicated that,compared with the adjuvant group,MM whole-cell proteins induced higher levels of Th1 cytokines(IL-2,IFN-γ,IL-12,TNF-α)in the mice.The IgG and IgM antibody titers induced by MM immunization group reached 1∶608 874 and 1∶304 437,respectively.The MGIA results showed that the MM immunization group was able to significantly inhibit MTB growth in vitro.The MTB proteome microarray results indicated that there were 226 and 324 cross-proteins with IgG and IgM antibodies,respectively.This study suggested that MM whole-cell proteins can induce high levels of cellular and humoral immune responses in mice and exhibit strong inhibition of MTB growth in vitro.The results may suggest potential application value of MM whole-cell proteins as a novel candidate vaccine for tuberculosis.

OBJECTIVES: To evaluate the clinical value of CD4⁺ cell percentage (CD4⁺%) and NK cell percentage (NK%) in predicting treatment outcomes in children with aplastic anemia (AA), providing a reference for precise diagnosis and treatment. METHODS: This retrospective study analyzed the clinical data of AA children treated with cyclosporine A at the First Affiliated Hospital of Xinjiang Medical University from January 2019 to April 2024. The study involved 48 AA children as the observation group and 50 children undergoing medical check-ups during the same period as the control group. Lymphocyte subset data were collected from both groups to analyze differences and their relationship with treatment efficacy. Based on hematological responses, the observation group was divided into an effective group of 18 patients (HR group, including complete and partial remission) and an ineffective group of 30 patients (NHR group, including non-remission). RESULTS: Univariate analysis showed that NK% in the observation group was significantly lower than that in the control group (P<0.05). The observation group was followed up for 3 months. The HR group had a lower CD4⁺% than the NHR group (P=0.018) and a higher NK% than the NHR group (P=0.029). Multivariate logistic regression analysis indicated that a high CD4⁺% was a risk factor for poor treatment efficacy (OR=1.062), whereas a high NK% was a protective factor (OR=0.820). The area under the curve for the prediction of HR in pediatric AA by combining CD4⁺% and NK% was 0.812. CONCLUSIONS A higher CD4⁺% at diagnosis is a predictor of poor treatment response, whereas a higher NK% is associated with better outcomes.
Humans ; Anemia, Aplastic/blood* ; Male ; Female ; Killer Cells, Natural ; Child ; Retrospective Studies ; Child, Preschool ; Prognosis ; Adolescent ; CD4-Positive T-Lymphocytes ; Infant

Objective:To improve the clinical diagnostic ability of antiphospholipid syndrome (APS) with onset of autoimmune hemolytic anemia (AIHA).Methods:The diagnosis and treatment of one APS patient with AIHA as the initial manifestation were reported and discussed.Results:A young female patient admitted to Peking Union Medical College Hospital on October 15, 2022 suffered from AIHA and persistent lupus anticoagulant (LA) positivity. After being treated with high-dose glucocorticoid, both symptoms and indicators were improved. However, relapses occurred when the glucocorticoid was tapered. Subsequent attempts to combine multiple immunosuppressants and biologics for treatment was ineffective. During the course of the disease, the patient had experienced intermittent intracranial hypertension which was revealed as cerebral venous sinus thrombosis(CVST) by MRV. Laboratory test revealed that antiphospholipid antibodies and antiphospholipid serine/prothrombin antibodies (aPS/PT) were all positive. She was finally diagnosed with APS. After being treated with high-dose glucocorticoids and immunosuppressants, combined with warfarin and aspirin, the patient′s clinical symptoms were significantly improved.Conclusion:AIHA is one of the extra-criteria manifestations of APS. Patients with AIHA and persistent antiphospholipid antibody profiles should be alerted to the possibility of thrombotic events. It is difficult to control APS-CVST-AIHA patients′disease development and recurrence. Early and adequate antithrombotic therapy is essential for improvement of prognosis. Furthermore, some drugs may lead to false positive in LA testing, making aPS/PT a viable alternative method for assessing LA.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the clinical characteristics of children with cervicothoracic hemivertebra at different ages and evaluate the surgical outcomes of hemivertebra resection.Methods:This retrospective cohort study analyzed clinical and radiographic data of 35 children (under 18 years old) with cervicothoracic hemivertebra who underwent one-stage posterior hemivertebra resection at the Department of Spine Surgery, Second Xiangya Hospital of Central South University, from June 2005 to June 2022. The cohort included 19 males and 16 females, with a surgical age of (9.7±4.1) years (range: 3 to <18 years). Patients were divided into three groups based on initial surgical age: preschool group (≤5 years, n=10), school-age group (6 to 10 years, n=10), and adolescent group (11 to <18 years, n=15). The intraoperative blood loss, operative time, number of fixed vertebrae, and perioperative and postoperative complications were recorded. Radiographic measurements were taken preoperatively, postoperatively, and at final follow-up, including the Cobb angle of the primary curve, curve length, distal curve Cobb angle, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, and local kyphosis. Statistical analyses included one-way ANOVA, Kruskal-Wallis H test, chi-square test, and Fisher′s exact test. Results:The operative time was (333±74) minutes (range:200 to 450 minutes), the intraoperative blood loss was (419±132) ml (range:200 to 650 ml), and the number of fixed vertebrae was (6.0±2.7) segments (range:2 to 12 segments). Preoperatively, the preschool group had a smaller primary curve Cobb angle compared to the adolescent group (33.6°±8.4° vs. 43.0°±9.4°, F=3.394, P=0.046) and distal curve Cobb angle (6.4°±2.4° vs.11.9°±4.5°, F=6.550, P=0.038). The preschool group had better coronal balance ((8.8±4.3) mm vs. (20.2±11.7)mm, F=9.448, P=0.009) and trunk tilt (4.0°±2.0° vs.7.0°±3.0°, F=4.343, P=0.029) than the school-age group. The preschool group had fewer fused vertebrae than the school-age and adolescent groups (3.8±1.6 vs. 7.0±2.6 vs. 6.8±2.6, F=10.480, P=0.005). The preschool group also had less intraoperative blood loss than the adolescent groups ((320±125) ml vs. (480±113) ml, F=8.666, P=0.013). However, no significant differences were found in postoperative and final follow-up measurements of primary and distal curve Cobb angles, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, local kyphosis, or complication rates (all P>0.05). Conclusions:Children with cervicothoracic hemivertebra across different age groups exhibit similar surgical outcomes and complication rates. But the preschool group had fewer fixed segments and less intraoperative blood loss, suggesting that this age group is an ideal time for surgery.