ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

【Objective】 To investigate the physical and neuropsychological development of the offspring born to mothers with gestational diabetes mellitus (GDM) at 2 years of age, and to provide evidence to enhance the physical and neuropsychological development of GDM offspring. 【Methods】 A retrospective analysis was conducted on neonates born in the Department of Obstetrics at Qinzhou Maternal and Child Health Hospital from January 2018 to December 2018 and regularly followed at the outpatient service. The neonates were categorized into two groups based on whether their mothers were diagnosed with GDM during pregnancy: the GDM group (n=243) and the control group (n=362). The general clinical data, follow-up information on physical development and neuropsychological development at 1 year and 2 years of age for all children were collected. Their height, head circumference, body weight, BMI, and Gesell developmental quotients (DQs) at 1 year and 2 years of age for both groups were analyzed. 【Results】 1) There were no significant differences in height, head circumference, body weight, and body mass index (BMI) between the two groups at 1 year and 2 years of age during the follow-up period (P>0.05). 2) At 1 year of age, the GDM group exhibited higher rates of abnormal language development (8.6% vs. 3.3%, χ²=7.854), adaptive behavior(11.4% vs. 5.0%,χ²=8.605), and personal social behavior(8.2% vs. 3.0%, χ²=8.062) compared to the control group (P<0.05), and lower DQs for these Gesell subscales (language development 87.6±7.7 vs. 89.4±9.2, t=2.591; adaptive behavior: 88.4±7.8 vs. 90.5±8.9, t=2.957; personal social behavior: 89.1±7.0 vs. 91.2±7.5, t=3.495, P<0.05). 3) At 2 year of age, the GDM group also showed higher rates of adaptive behavior (8.2% vs. 4.1%, χ²=3.927) and personal social behavior (7.3% vs. 3.0%, χ²=4.093) compared to the control group (P<0.05), and lower DQs for these Gesell subscales (adaptive behavior: 89.5±6.5 vs. 91.9±6.9, t=3.878; personal social behavior: 89.9±7.1 vs. 92.1±6.9, t=3.311, P<0.05). 【Conclusions】 The development of adaptive behavior and personal social behavior in offspring born to mothers with GDM remains delayed. Follow-up for GDM offspring should prioritize achieving a balanced development of adaptive behavior and personal social behavior.

Objective:To evaluate the efficacy of Yiqi Yangyin Jiedu Decoction in the treatment of patients with pulmonary nodules and qi-yin deficiency syndrome after early lung cancer surgery.Methods:Randomized controlled trial was conducted. A total of 76 patients with lung nodules and qi-yin deficiency syndrome after early lung cancer surgery at the Oncology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March to September 2020 were selected and randomly divided into two groups using a random number table method, with 38 cases in each group. The control group received symptomatic treatment, while the treatment group took Yiqi Yangyin Jiedu Decoction from the first day after enrollment. Both groups were treated for 6 months and followed up for 2 years. TCM syndrome scores before and after treatment were evaluated; the patients' activity status was evaluated using the Eastern Oncology Collaborative Group Activity Status (ECOG PS) score in the United States, and electrochemiluminescence was used to detect carcinoembryonic antigen (CEA) and neuron specific enolase (NSE). Flow cytometry was used to detect the percentage of T lymphocyte subsets CD3 +and CD4 +, and ELISA was used to detect TGF-β Horizontal. The patients' weight was recorded and their weight changes after treatment were observed. Adverse reactions during treatment were observed and recorded, the efficacy of TCM syndromes and pulmonary nodules was evaluated. Results:During the observation period, one case was lost to follow-up in the treatment group and three cases were lost to follow-up in the control group. Finally, 37 cases in the treatment group and 35 cases in the control group completed the observation. After the treatment, the panting (0.27±0.07 vs. 0.68±0.12, t=17.66), spontaneous sweating and night sweating (0.16±0.16 vs. 0.79±0.16, t=16.55) score of the treatment group were lower than those in the control group ( P<0.01); insomnia (0.15±0.08 vs. 0.54±0.13, t=15.52) score of the control group was lower than that of the treatment group ( P<0.01). The effective rate of TCM syndrome in treatment group was 81.08% (30/37), higher than 54.29% (19/35) in control group ( Z=-2.00, P=0.040). After the treatment, the ECOG PS score stability rate in the treatment group was 89.19% (33/37), higher than 82.86% (29/35) in control group, without statistical significance ( χ2=0.19, P>0.05). The increase and stable rate of body weight was 88.10% (32/37) in treatment group and 62.86% (22/35) in control group ( χ2=5.36, P<0.05). After 2-year follow-up, the control rate of pulmonary nodules in the treatment group was 91.89% (34/37), while in the control group it was 65.71% (23/35). The difference between the two groups was statistically significant ( χ2=7.47, P<0.01). After the treatment, the level of NSE [(12.54±2.52)ng/L vs. (13.85±2.71)ng/L, t=-2.12], TGF-β [(218.38±102.63)ng/L vs. (301.24±193.69)ng/L, t=-2.29] in treatment group were lower than those in the control group ( P<0.05), and the level of CD3 +T cells [(70.60±7.90)% vs. (65.99±9.27)%, t=2.32] in treatment group was higher than that of the control group ( P<0.05). Conclusion:Yiqi Yangyin Jiedu Decoction can delay the development of pulmonary nodules in patients after early lung cancer surgery, increasing the body weight of patients, relieving the TCM syndromes and improve the immune function of patients, with the potential to prevent and treat the occurrence and development of early lung cancer.

Objective To investigate the consistency analysis between multimodal MRI in determining vaginal involvement and parametrial infiltration in cervical cancer patients and pathological examination.Methods Ninety-two patients with cervical cancer were regressively selected and who underwent preoperative multimodal MRI examination.Using pathological results as the gold standard,the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)alone and in combination in predic-ting vaginal involvement and parametrial infiltration.Results(1)Vaginal involvement:the diagnostic sensitivity of conventional MRI was 65.96％,the specificity was 91.11％,and the area under the curve(AUC)was 0.775[95％confidence interval(CI)0.676-0.873].The sensitivity of DCE-MRI was 61.70％,the specificity was 95.56％,and the AUC was 0.797(95％CI 0.702-0.892).The sensitivity of DWI was 72.34％,the specificity was 88.89％,and the AUC was 0.817(95％CI 0.725-0.908).At the optimal cut-off point,the sensitivity of parallel combined detection was 97.87％,the specificity was 93.33％,and the AUC was 0.956(95％CI 0.907-0.918).(2)Parametrial infiltration:the diagnostic sensitivity of conventional MRI was 67.24％,the specificity was 91.18％,and the AUC was 0.783(95％CI 0.688-0.879).The sensitivity of DCE-MRI was 62.07％,the specificity was 94.12％,and the AUC was 0.781(95％CI 0.686-0.875).The sensitivity of DWI was 75.86％,the specificity was 97.06％,and the AUC was 0.865(95％CI 0.788-0.941).At the optimal cut-off point,the sensitivity of parallel combined detection was 98.28％,the specificity was 91.18％,and the AUC was 0.947(95％CI 0.888-1.000).Conclusion Combined multimodal MRI can improve the positive detection rate of vaginal involve-ment and parametrial infiltration in patients with cervical cancer,allowing for timely treatment adjustments,improved quality of life and longer survival.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.

Adipose progenitor cells(APCs) represent a prominent stromal cellular component of adipose tissue and are now identified as highly heterogenous populations. However, the role of APCs in regulating systemic metabolism remains unknown. Using single cell RNA-sequencing, we investigated the role of the APC subpopulations in regulating development of type 2 diabetes. CD9 + CD55 low APCs are the novel subset identified in this study, which is significantly increased in type 2 diabetic patients. Transplantation of these cells from type 2 diabetic patients into adipose tissue caused glycemic disturbance in mice. Depletion of pathogenic APCs improved obesity-related glycemic disturbance. Collectively, our data provide deeper insights into human APC functionality and highlights APCs as a potential therapeutic target to combat type 2 diabetes. This study has been published in Nature Communications, 2024, 15(1): 4827.

AIM To explore the clinical effects of Polygonum cuspidatum Sieb.et Zucc.on patients with type 2 diabetes mellitus of Dampness-Heat Pattern.METHODS One hundred and forty patients were randomly assigned into control group(70 cases)for 8-week intervention of conventional treatment,and observation group(70 cases)for 8-week intervention of both P.cuspidatum granules and conventional treatment.The changes in body weight,BMI,blood glucose indices(FBG,2 h PG,HbA1C,GA),blood lipid indices(TC,TG,HDL-C,LDL-C,ApoA-I,ApoB,ApoA,ApoE,sdLDL-C),liver function indices(ALT,AST),fatty liver progression,TyG,HSI,TCM syndrome score and effects were detected.RESULTS The observation group demonstrated higher total effective rates of TCM syndromes than the control group(P＜0.01),along with slighter fatty liver progression(P＜0.01).After the treatment,the observation group displayed decreased body weight,BMI,FBG,GA,TG,ApoE,TyG,HSI,ALT and TCM syndrome score(P＜0.05,P＜0.01),and 2 h PG,TyG,HSI,ALT,TCM syndrome score were lower than those in the control group(P＜0.05,P＜0.01).CONCLUSION For the patients with type 2 diabetes mellitus of Dampness-Heat Pattern,P.cuspidatum can improve glucose and lipid metabolism disorders,which is worthy of clinical popularization and application.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.