ObjectiveTo analyze the metabolomic characteristics of platelets in fibrinogen（FIB） overexpression rats of coronary heart disease with blood stasis syndrome（CHD-BSS）， explore potential biomarkers， and investigate the mechanism of FIB overexpression on CHD-BSS. MethodsSD rats were randomly divided into BSS group and BSS+FIB overexpression group（BSS+FIB group）， with 10 rats in each group. Both the BSS+FIB group and the BSS group were fed a high-fat diet combined with oral administration of vitamin D₃ and subcutaneous injection of isoproterenol， but rats in the BSS+FIB group were overexpressed with FIB during the initial modeling stage by transfection with adeno-associated virus（AAV）. The overexpression level of FIB in rat liver and plasma samples was detected by enzyme-linked immunosorbent assay（ELISA） and real-time fluorescence quantitative polymerase chain reaction（Real time PCR）， as well as the expression level of liver FIB A（FGA） mRNA. The characteristics of metabolites in rat platelet samples were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and the differential metabolites between groups were screened by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and the enriched pathways were analyzed. The accuracy of potential biomarkers in the diagnosis of CHD-BSS was evaluated by receiver operating characteristic（ROC） curve. The expression of autophagy related proteins phosphorylated adenosine monophosphate（AMP） activated protein kinase（p-AMPK）/AMPK， phosphorylated mammalian target of rapamycin（p-mTOR）/mTOR， microtubule-associated protein 1 light chain 3（LC3） Ⅱ/Ⅰ and p62 in platelets were detected by Western blot. ResultsCompared with the BSS group， the expression levels of FIB in liver and plasma samples of the BSS+FIB group were significantly increased（P<0.05， P<0.01）， and the expression level of FIB mRNA in the liver was remarkably increased（P<0.01）， indicating successful overexpression of FIB. Platelet metabolomics results showed significant differences in metabolic profiles between the BSS+FIB group and the BSS group， and a total of 25 significantly enriched metabolic pathways and 8 metabolites involved in these metabolic pathways， among which uric acid， guanosine and ribose 1-phosphate levels were up-regulated， while adenosine diphosphate（ADP）， AMP， guanosine diphosphate（GDP）， adenylosuccinate and norepinephrine levels were down-regulated. The diagnostic ability analysis of differential metabolites showed that all 8 differential metabolites had good diagnostic ability， with an area under the curve（AUC）>0.85. Western blot results showed that compared with the BSS group， the expression levels of p-mTOR/mTOR and p62 proteins in platelets of the BSS+FIB group was significantly reduced（P<0.01）， while the expression levels of p-AMPK/AMPK and LC3Ⅱ/Ⅰ proteins were increased， but the difference was not statistically significant. ConclusionOverexpression of FIB can change the metabolic characteristics of CHD-BSS rat model， involving multiple aspects such as vascular endothelial injury， platelet activation and myocardial function damage. Among them， overexpression of FIB may enhance the occurrence of platelet autophagy， thereby inducing platelet activation and promoting thrombus formation.

ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the short-term outcome of transoral robotic thyroidectomy.Methods:This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960 th Hospital of People′s Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results:All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized ( M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection ( n=1), left submandibular perforation ( n=1), skin scald ( n=1), and perioral numbness ( n=1), oral tear ( n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion:For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective To analyze the registered clinical trials of headache treated by TCM;To discuss the current research status;To provide reference for the optimization of subsequent clinical trial research plans.Methods All clinical trials of headache treated by TCM were retrieved from the ChiCTR and the ClinicalTrials.The retrieval time was from the database establishment to May 22,2023.The general characteristics,study types,intervention measures and outcome indicators of the trials were analyzed respectively.Results A total of 104 registered studies were included,with the number of registered studies increasing since 2004 and reaching a peak in 2020,involving 25 provincial administrative regions or countries and 69 clinical trial institutions;the funding sources were mainly scientific research funds of universities,national finance and local finance.The research type was mainly intervention research;the designing scheme was mainly randomized parallel control study;the high frequency random method was simple random method;45 registered studies used blind methods.Exploratory studies/pre-trials were the most commonly used in the phases of clinical researches.Most of the registered studies were single-center clinical trials with a total sample size of 9 648 patients.The main interventions were acupuncture and oral Chinese medicines.The high frequency outcome indicators included life quality of score,headache attack frequency,headache attack days and headache severity,etc.There were some problems in outcome indicators,such as non-standard,lack of TCM characteristic advantages,and insufficient patient participation.Conclusion The number of registered studies of headache treated by TCM has increased by year,but there are some problems in design elements,such as random method,blind method,number of research centers,sample size and the setting of outcome indicator.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule(XFC)on interleukin(IL)-1β-induced impairment of chondrocytes.Methods XFC-medicated serum was collected from SD rats with XFC gavage,and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry.Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2.In cultured human chondrocytes induced with IL-1β,the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum,alone or in combination,on expression levels of IL-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 were examined with ELISA,and the changes in the expressions of collagen type Ⅱ alpha 1(COL2A1),matrix metalloproteinase 13(MMP13),adisintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR,Western blotting,and immunofluorescence assay.Results In cultured human chondrocytes,treatment with IL-1β significantly decreased the cell viability,increased cell apoptosis rate,lowered miR-502-5p,IL-4,IL-10,and COL2A1 expressions,and enhanced IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 expressions(P<0.05),and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20％(P<0.05).Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 and lowered expressions of miR-502-5p,IL-4,IL-10,and COL2A1,and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor.Conclusion XFC can inhibit IL-1β-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.