Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

OBJECTIVE: To evaluate the effects of Chinese patent medicine Huatuo Zaizao Pill (HTZZ) on neurological function and limb motor in ischemic stroke (IS) patients during convalescence. METHODS: This is a prospective, open-labelled, randomized controlled trial. Patients with IS were recruited from the Neurology Department of Xiyuan Hospital of China Academy of Chinese Medical Sciences from May 2021 to June 2023. Eligible participants were randomly assigned to the HTZZ (40 cases) or control group (40 cases) at a ratio of 1:1. The HTZZ group was treated with oral HTZZ (8 g, thrice daily) combined with conventional treatment, while the control group received only conventional treatment. The treatment duration was 12 weeks. The primary outcome was the change in Modified Ashworth Scale (MAS) score from baseline to week 6 and 12. Secondary outcomes included changes in scores of National Institute of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FM), and Barthel Index (BI) from baseline to week 6 and 12, as well as lipid indices after 12 weeks. All adverse events (AEs) were recorded and liver and kidney indices were evaluated. RESULTS: A total of 72 patients completed the study (38 in the HTZZ group and 34 in the control group). Compared with the control group, the HTZZ group demonstrated significant improvements in MAS, NIHSS, FM, and BI scores following 6 and 12 weeks of treatment in both intent-to-treat and per-protocol analyses (all P<0.05). No significant differences were noted between groups in lipid indices, AEs, and liver and kidney dysfunction after 12 weeks (P>0.05). CONCLUSIONS HTZZ alleviated spasticity and enhanced neurological function and prognosis of IS patients during convalescence. However, further evaluation of HTZZ's effect on IS outcomes is warranted in clinical trials with larger sample sizes and extended observation periods. (Trial registration No. NCT04910256).
Humans ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Ischemic Stroke/physiopathology* ; Middle Aged ; Aged ; Recovery of Function/drug effects* ; Convalescence ; Extremities/physiopathology* ; Treatment Outcome ; Prospective Studies

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To explore whether dexmedetomidine(DEX)can alleviate exertional heatstroke(EHS)-induced rhabdomyolysis(RM)in rats by activating adrenergic α2 receptors,and to explore its potential mechanism based on the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/interleukin-1β(IL-1β)pathway.Methods Thirty-six male Sprague-Dawley(SD)rats,after a 7-day acclimatization training,were randomly divided into six groups:control group(CN group),EHS group,low-dose DEX group(EHS+low DEX group),high-dose DEX group(EHS+high DEX group),DEX combined with yohimbine(YOH)group(EHS+high DEX+YOH group),and YOH group(EHS+YOH),with six rats in each group.Before modeling,EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg,while the other four groups were injected intraperitoneally with an equal dose of physiological saline(0.9%NS).During modeling,except for CN group,the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model.After successful modeling,EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg,EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg,and CN group,EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline.After 6 h of observation,all rats were anesthetized,and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β and myoglobin(MB)in rats;biochemical assay kit was used to measure the level of creatine kinase(CK)in rat serum;HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues;transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle;2′,7′-dichlorofluorescent yellow diacetate(DCFH-DA)fluorescent probe was used to detect the level of reactive oxygen species(ROS);and Western blotting was performed to detect the expression levels of NOD-like receptors 3(NLRP3),aspartic protease-1(caspase-1)and adrenergic α2A receptor(ADRA2A).Results Compared with CN group,the levels of serum IL-6,IL-1β,TNF-α,CK and MB in EHS group rats were significantly elevated(P<0.01).HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure,hemorrhage,edema,and infiltration of inflammatory cells.Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size,cytoplasmic vacuolization,and mitochondria with obvious swelling,degranulation,and disappearance of double cristae.Compared with CN group,the expression levels of ROS,NLRP3,and caspase-1 in gastrocnemius of rats in EHS group significantly increased(P<0.01);Compared with EHS group,the levels of TNF-α,IL-6,IL-1β,CK,MB and the expression levels of ROS,NLRP3,caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX.After YOH pretreatment,compared with the EHS+high DEX group,the serum levels of TNF-α,IL-6,IL-1β,CK,MB and ROS,NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated.The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group(P<0.01),and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group(P<0.05).Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A,potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

The patient,a male newborn,was admitted to the hospital 2 hours after birth due to prematurity(gestational age 27+5 weeks)and respiratory distress occurring 2 hours postnatally.After admission,the infant developed fever and elevated C-reactive protein levels.On the fourth day after birth,metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis(9 898 reads).On the eighth day,a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis(56 806 reads).The diagnosis of purulent meningitis caused by Mycoplasma hominis was established,and the antibiotic treatment was switched to moxifloxacin[5 mg/(kg·day)]administered intravenously for a total of 4 weeks.After treatment,the patient's cerebrospinal fluid tests returned to normal,and he was discharged as cured on the 76th day after birth.This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis,introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.[Chinese Journal of Contemporary Pediatrics,2024,26(4):432-436]

Objective To study the composition,abundance,and functional profiles of the intestinal microbiota in infants and young children with Kawasaki disease(KD)during the acute phase,and to explore the potential role of intestinal microbiota in the pathogenesis of KD.Methods Six children aged 0-3 years with acute KD admitted to the Department of Cardiology,Children's Hospital Affiliated to Capital Institute of Pediatrics from July to October 2021 were prospectively included as the KD group.Six age-and sex-matched healthy children who underwent physical examinations at the hospital during the same period were selected as the healthy control group.Metagenomics sequencing was used to detect and compare the differences in the microflora structure and functional profiles of fecal samples between the two groups.Results There were significant differences in the structural composition and diversity of intestinal microbiota between the two groups(P<0.05).Compared with the healthy control group,the abundance of Listeria_monocytogenes(family Listeriaceae and genus Listeria),Bifidobacterium_rousetti,Enterococcus_avium,and Enterococcus_hirae was significantly higher in the intestinal microbiota in the KD group(|LDA|>2.0,P<0.05).The steroid degradation and apoptosis pathways were significantly upregulated in the KD group compared with the healthy control group,while the Bacterial_secretion_system,Sulfur_metabolism,Butanoate_metabolism,Benzoate_degradation,β-alanine metabolism,and α-linolenic acid pathways were significantly downregulated(|LDA|>2,P<0.05).Conclusions There are significant differences in the structure and diversity of intestinal microbiota between children aged 0-3 years with acute KD and healthy children,suggesting that disturbances in intestinal microbiota occur during the acute phase of KD.In particular,Listeria_monocytogenes,Enterococcus_avium,and Enterococcus_hirae may be involved in the pathogenesis of KD through steroid degradation and apoptosis pathways.

Objective To express recombinant Burkholderia pseudomallei(B.pseudomallei)type Ⅲ secretion system BipD protein,prepare its polyclonal antibodies and verify their immunological traits.Methods The recombinant pET-28a-BipD plasmid was generated,and the pET-28a-BipD-carried E.coli BL21(DE3)bacteria were induced with isopropyl-β-d-thiogalactoside(IPTG)to express recombinant BipD(rBipD)protein.The rBipD was obtained by affinity chromatography using His Trap column,then mixed with Fredrick's adjuvant to immunize BALB/c mice by intraperitoneal injection in order to obtain anti-rBipD polyclonal antibodies.The immunoreactivity of rBipD was detected by Western blot assay using rabbit anti-melioidosis serum and the serum from melioidosis patients.The immunogenicity of rBipD was evaluated using Western blotting and immunofluorescence staining.Finally,rBipD was used to establish an indirect ELISA to detect serum antibodies of clinical melioidosis patients.Results The recombinant plasmid pET-28a-BipD was successfully constructed and transformed into E.coli BL21(DE3)to induce rBipD expression with IPTG treatment.The obtained rBipD had a relative molecular weight of 36×103 and a purity of 95.4％,and had good immunogenicity and immunoreactivity.It could induce the production of specific antibodies after immunizing mice,and mouse polyclonal antibodies against rBipD were prepared with the titer of 1∶512 000.rBipD of 5.0 μg/mL produced specific immune response with the serum of melioidosis patients,but had no specific reaction with the serum of tuberculosis patients,with statistical difference(P＜0.01).Conclusion rBipD with immunological activity is successfully prepared and purified,and its polyclonal antibodies are also developed,which provide a good tool for clinical immunological diagnosis and study of immune mechanism of B.pseudomallei infection.