BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis. OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components. METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention. RESULTS AND CONCLUSION:A total of 28 active ingredients from Cibotium barometz and Epimedium were selected,yielding 288 intersection targets for rheumatoid arthritis.The main ingredients included isobavachalcone,cibotium,and epimedium.The main targets included protein kinase 1 for serine/threonine(AKT1),tumor necrosis factor,and vascular endothelial growth factor A.Gene ontology analysis yielded 2 232 biological processes,mainly related to serine protein phosphorylation,positive regulation of serine/threonine protein kinase,and reactive oxygen metabolism.Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways,mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway,which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors.Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1,which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT.Cibotium barometz and Epimedium reduced the expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models.Cibotium barometz and Epimedium reduced the expression of p-PI3K,p-AKT,and p-FOXO1 in the synovium of collagen-induced arthritis rat models.The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway.This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis,and provides a reference for the rational use and development of new drugs in clinical practice.

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 analyze the efficacy and safety of integrase inhibitor-based single-tablet regimens bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and lamivudine/dolutegravir (3TC/DTG) in the treatment-na?ve patients with acquired immunodeficiency syndrome (AIDS).Methods:This study was a retrospective cohort study. The clinical data of treatment-na?ve AIDS patients initiating anti-retroviral therapy (ART) with B/F/TAF or 3TC/DTG and on ART for greater than or equal to 24 weeks from October 2020 to July 2023 in Shanghai Public Health Clinical Center, Fudan University were collected. The baseline human immunodeficiency virus (HIV)-1 RNA, CD4 + T lymphocyte counts at baseline and 12 weeks of treatment, and the rates of virological suppression and virological failure at 24 weeks of treatment, and levels of total cholesterol, serum creatinine, uric acid before and after treatment were compared between the B/F/TAF group and 3TC/DTG group. Independent sample t test, corrected t test, Mann-Whitney U test, Wilcoxon signed rank test, chi-square test were used for statistical analysis. Results:Among 189 treatment-na?ve AIDS patients, 141 cases were in B/F/TAF group and 48 cases in 3TC/DTG group. The HIV-1 RNA level at baseline was 1.77(0.78, 4.52)×10 5 copies/mL in the B/F/TAF group and 0.97(0.24, 2.20)×10 5 copies/mL in the 3TC/DTG group. There was a statistically significant difference between the two groups ( U=2 221.00, P=0.006).There were 77.3%(109/141) patients on B/F/TAF achieved complete virological suppression with no virological failure at week 24, and 85.4%(41/48) on 3TC/DTG achieved complete virological suppression with one (2.1%) virological failure at week 24. At 12 weeks of treatment, 92.2%(130/141) of the patients in the B/F/TAF group and 85.4%(41/48) of the patients in the 3TC/DTG group had an increase in CD4 + T lymphocyte count by more than 30% compared with baseline. The proportion of CD4 + T lymphocyte count increased by more than 100/μL from baseline in the B/F/TAF group was 67.4%(95/141), and that in the 3TC/DTG group was 52.1%(25/48). There were no significant differences between the two groups ( χ2=1.91 and 3.61, respectively, P=0.167 and 0.733).The levels of total cholesterol ( W=2 036.00, t=-5.42, respectively), serum creatinine ( W=1 098.00, 234.00, respectively), uric acid ( W=2 188.00, 299.00, respectively) and the proportion of patients with mild to moderate renal insufficiency ( χ2=22.29, 8.22, respectively) in the B/F/TAF group and 3TC/DTG group after 24 weeks of treatment were significantly higher than those before treatment (all P<0.01). Conclusions:Both B/F/TAF and 3TC/DTG are effective in terms of virological suppression and immunological recovery and have good safety profiles in treatment-na?ve patients with AIDS.

Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

Objective:To examine the clinical effect of endovascular treatment for patients with non-acute symptomatic anterior circulation distal medium artery disease (aDMAD).Methods:This is a retrospective case series study.Retrospective analysis was conducted on the clinical data of 28 patients(29 lesions) with non-acute symptomatic aDMAD who underwent endovascular treatment at the Department of Neurosurgery,Beijing Hospital from May 2018 to March 2024. There were 15 males and 13 females,with an age of (63.4±10.2) years (range:36 to 82 years). The course of disease were more than 72 hours of all the patients. Confirmed by digital subtraction angiography,the lesion was located in distal anterior circulation and (or) medium arteries. Among them, 21 lesions (72.4%) located at middle cerebral artery and 8 lesions (27.6%) located at anterior cerebral artery.The median degree of stenosis before surgery ( M(IQR)) was 90%(23%) (range:70% to 100%).After standardized drug treatment,there was still a transient ischemic attack or cerebral infarction in the vascular related area.The therapeutic effects and complications were analyzed,and the differences in the occurrence of target vessel restenosis under different interventional treatment methods were collected. Results:A total of 28 patients with 29 lesions underwent endovascular treatment, with a treatment success rate of 96.6% (28/29). The course of disease was 60(66)days (range:9 to 210 days). Simple plain balloon angioplasty was performed in 12 cases (13 lesions), drug-coated balloon (DCB) angioplasty in 7 cases (7 lesions), and stent placement in 9 cases (9 lesions). The median degree of stenosis after surgery was 20%(39%) (range:0 to 50%). There was no new cerebral infarctions,cerebral hemorrhages,or other complications during the perioperative period.Imaging follow-up was conducted on 23 lesions for 12(15)months(range:3 to 34 months),with 10 cases (43.5%) of restenosis,3 cases (13.0%) of symptomatic restenosis,and 4 cases (17.4%) of re-treatment. There were no new cases of cerebral hemorrhage or death during the follow-up process.The restenosis rate was 6/10 for the conventional balloon group,1/6 for the DCB group, and 3/7 for the stent group; the rate of symptomatic restenosis was 1/10 for the conventional balloon group,0/6 for the DCB group, and 2/7 for the stent group.Conclusions:Endovascular treatment for non-acute symptomatic aDMAD is relatively effective,but there is a high rate of restenosis postoperatively. DCB may reduce the occurrence of postoperative restenosis.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective:To examine the clinical effect of endovascular treatment for patients with non-acute symptomatic anterior circulation distal medium artery disease (aDMAD).Methods:This is a retrospective case series study.Retrospective analysis was conducted on the clinical data of 28 patients(29 lesions) with non-acute symptomatic aDMAD who underwent endovascular treatment at the Department of Neurosurgery,Beijing Hospital from May 2018 to March 2024. There were 15 males and 13 females,with an age of (63.4±10.2) years (range:36 to 82 years). The course of disease were more than 72 hours of all the patients. Confirmed by digital subtraction angiography,the lesion was located in distal anterior circulation and (or) medium arteries. Among them, 21 lesions (72.4%) located at middle cerebral artery and 8 lesions (27.6%) located at anterior cerebral artery.The median degree of stenosis before surgery ( M(IQR)) was 90%(23%) (range:70% to 100%).After standardized drug treatment,there was still a transient ischemic attack or cerebral infarction in the vascular related area.The therapeutic effects and complications were analyzed,and the differences in the occurrence of target vessel restenosis under different interventional treatment methods were collected. Results:A total of 28 patients with 29 lesions underwent endovascular treatment, with a treatment success rate of 96.6% (28/29). The course of disease was 60(66)days (range:9 to 210 days). Simple plain balloon angioplasty was performed in 12 cases (13 lesions), drug-coated balloon (DCB) angioplasty in 7 cases (7 lesions), and stent placement in 9 cases (9 lesions). The median degree of stenosis after surgery was 20%(39%) (range:0 to 50%). There was no new cerebral infarctions,cerebral hemorrhages,or other complications during the perioperative period.Imaging follow-up was conducted on 23 lesions for 12(15)months(range:3 to 34 months),with 10 cases (43.5%) of restenosis,3 cases (13.0%) of symptomatic restenosis,and 4 cases (17.4%) of re-treatment. There were no new cases of cerebral hemorrhage or death during the follow-up process.The restenosis rate was 6/10 for the conventional balloon group,1/6 for the DCB group, and 3/7 for the stent group; the rate of symptomatic restenosis was 1/10 for the conventional balloon group,0/6 for the DCB group, and 2/7 for the stent group.Conclusions:Endovascular treatment for non-acute symptomatic aDMAD is relatively effective,but there is a high rate of restenosis postoperatively. DCB may reduce the occurrence of postoperative restenosis.

Objective:To explore the benefits of transradial diagnostic cerebral angiography in elderly patients and its correlation with morphometric parameters of the aortic arch.Methods:Clinical data and aortic arch CTA imaging parameters of patients who underwent cerebral angiography at the Department of Neurosurgery, Beijing Hospital, between May 2022 and April 2023 were retrospectively analyzed.The study aimed to compare the time taken for angiography via radial artery access in elderly patients versus younger patients, as well as via femoral artery access, and to evaluate the associated aortic arch morphology parameters.Results:A total of 101 patients' data were analyzed, with 67 males(66.3%)and an average age of 63.4±12.0 years.Among them, 69 patients(68.3%)were aged 60 and above.The arterial approach for 44 patients(43.6%)was radial, while 57 cases(56.4%)used the femoral artery approach.In the elderly group, 14 cases(20.6%), 31 cases(45.6%), and 23 cases(33.8%)had type Ⅲ aortic arch, respectively.For younger patients, 17 cases(53.1%), 12 cases(37.5%), and 3 cases(9.4%)fell into these categories.The distribution difference was statistically significant( χ2=12.765, P=0.002).Elderly patients had a larger aortic arch width angle compared to younger patients(106°±12°and 100°±12°, t=2.334, P=0.022).The time for whole-brain angiography via radial artery was shorter for elderly patients than via femoral artery(39.8±29.5 minutes and 52.2±28.4 minutes, respectively, t=1.845, P=0.070).In young patients, there was no significant time difference between the two approaches(42.3±30.4 minutes for radial artery and 34.6±11.2 minutes for femoral artery, t=1.026, P=0.313).In the type Ⅱ aortic arch group, the average times for transradial and transfemoral approaches were 38.1±21.7 minutes and 46.7±32.2 minutes, respectively( t=1.020, P=0.314).The average times for the type Ⅲ aortic arch group were 41.9±37.3 minutes and 48.9±20.7 minutes, respectively.Correlation analysis revealed a significant negative correlation between the duration of radial artery access and the distance from the origin of the innominate artery to the left subclavian artery(Pearson correlation coefficien( r=-0.372, P=0.014). Conclusions:In elderly patients, particularly those with type Ⅱ or Ⅲ aortic arch or a wide aortic arch, diagnostic cerebral angiography using transradial access is preferable to femoral access.The distance between the innominate artery and the left subclavian artery origin could impact the duration of the procedure.