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 evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Objective To isolate a Acinetobacter baumannii(Ab)phage from underground sewage,study its prop-erties,and to provide a theoretical basis for phage treatment of Ab infection.Methods Double-layer agar tech-nique was used to isolate phages by using Ab GY-6 as the host strain.Biological characterization and therapeutic effect of the phage was tested.Genetic information of the phage was analyzed.Results Ab phage Abgy202162 was isolated.Transmission electron microscopy(TEM)analysis showed that the morphology of Abgy202162 exhibited an icosahedral structure.Biological characteristic analysis showed that the optimal multiplicity of infection was 1,the latent period was 5 min,and the burst size was approximately 520 PFU per cell.In addition,Abgy202162 re-mained stable at different concentrations of chloroform,pH,and temperatures.Sodium dodecyl sulfate-polyacryl-amide gel electrophoresis(SDS-PAGE)analysis showed that it contained 10 proteins with molecular weights ran-ging from 15 to 100 ku.The double-stranded(ds)DNA genome of Abgy202162 consisted of 40 889 bp and its G+C content was 38.85％.It contained 47 open reading frames(ORFs),of which 26 had specific functions,but no virulence related genes or antibiotic resistance genes were found.Phylogenetic analysis showed that Abgy202162 was a new phage in the Autographiviridae family,Beijerinkvirinae subfamily,and Friunavirus genus.Abgy202162 showed the ability to prevent Ab infection in the Galleria mellonella in vivo model.Conclusion The phage Ab-gy202162 has strong environmental tolerance and high safety,indicating its potential as an antibiotic alternative used in the treatment of infections caused by Ab.

mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by in vitro cytotoxicity and in vivo biosafety. First, we characterized the chemical composition of the cationic lipid peptides by nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) and time-of-flight mass spectrometry (MS). The results of particle size and potential tested by dynamic light scattering particle size analysis showed that at a nitrogen/phosphorus (N/P) ratio of 20, the RLS/mRNA composite assemblies formed homogeneous nanoparticles with an average particle size of about 220 nm and a surface ζ potential of about +21 mV. In vitro gene transfection, the transfection experiments demonstrated that RLS exhibited 1.2-fold higher transfection efficiency in human embryonic kidney 293 cells (HEK293) and 3-fold higher transfection efficiency in rat mesenchymal stem cells (MSC) compared to Lipofectamine 2000. In addition, after microinjection of RLS into zebrafish embryos, we evaluated the survival, hatching, and teratogenicity rates, all of which confirmed its favorable in vivo safety profile. Thus, this amphiphilic cationic lipid peptide RLS, enriched with branched arginine, exhibits excellent mRNA delivery properties and safety. These findings highlight its potential as a promising gene therapy tool.

Objective : To explore the role of Argonaute ( Ago) gene and RNA⁃Dependent RNA Polymerase (RDRP) gene of Aspergillus flavus in the growth and development about the RNAi mechanism . Methods : A. flavus Ago1 , Ago2 , RDRP1 , RDRP3 gene mutant strains were constructed by homologous recombination . The growth and development of the mutant strains were observed on potato dextrose agar(PDA) + uracil uridine (UU) medium inoculated with 3 μl 106 CFU/mL spores . 200 , 400 μg cell wall pressure agent conidored ( CR) , 0. 8 mol/L , 1 . 6 mol/L osmotic pressure agent NaCl , 2 mmol/L , 4 mmol/L oxidative pressure agent hydrogen peroxide (H2 O2 ) and 0. 01% , 0. 02% genomic damage agent methyl mesylate (MMS) were added to the Yeast extract Glucose Minimum (YGM) + UU medium to analyze the stress response of the mutant strains . Results : A. flavus mutant strains about ΔAgo1 , ΔAgo2 , ΔRDRP1 , ΔRDRP3 were successfully constructed and its growth and development were normal . The ΔAgo1 and ΔAgo2 strains reduced the stress effects on cell wall and osmotic pressure compared to the control . Ago1 gene deletion reduced the effect of H2 O2 , and conversely RDRP3 gene deletion increased the inhibition of H2 O2 . The Ago2 and RDRP1 strains reduced the effect on genetic damage agent . In addition , ΔRDRP1 increased the effect of osmotic stress . Conclusion The Ago1 , Ago2 , RDRP1 and RDRP3 genes of A. flavus are not in⁃ volved in the regulation of growth rate and asexual reproduction and can participate in the regulating of the host stress response to the environment .

The purpose of this study was to explore the clinical efficacy and safety of Gynostemma pentaphyllum (G. pentaphyllum) in the treatment of hyperlipidemia, and to provide systematic evaluation basis for clinical application. CNKI, Wanfang Data, VIP, Web of science, PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) about G. pentaphyllum in the treatment of hyperlipidemia. Review Manager 5.4 were used for statistical analysis. Through reading topics, abstracts, and full texts, 27 papers with 2311 cases involved that met the inclusion and exclusion criteria were finally included for the analysis. In terms of curative effect, the effect of G. pentaphyllum alone in increasing high density lipoprotein (HDL) index was better than that of conventional treatment, and the effect of reducing total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) was similar to that of conventional treatment. There was a synergistic effect between G. pentaphyllum and conventional drugs, and the combination of G. pentaphyllum and conventional drugs was superior to conventional treatment in reducing TG and increasing HDL. G. pentaphyllum can also decrease the levels of serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in the treatment of hyperlipidemia, indicating a certain protective function of the liver. In terms of safety, there were fewer cases of adverse reactions in the G. pentaphyllum treatment group, and the adverse reaction events reported in the literature was mild. According to the results of meta-analysis, G. pentaphyllum was effective in the treatment of hyperlipidemia, and it has the potential to be combined with traditional drugs, has a certain liver protection function, and was superior to traditional drugs in the treatment of hyperlipidemia.

Postoperative radiotherapy increase the overall survival rate offor breast cancer improves overall survivalpatients, but. Nevertheless, the heart is at risk of radioactive heart damageradiation-induced cardiac injury due to its anatomical location, which is inevitably exposed to radiation during radiotherapy. The heart is considered a "high-risk organ" sensitive to radiation, and its radiation dose should be as low as possible. Previous studies have evaluated the effect of overall heart radiation dose on long-term cardiovascular events, but the. However, new study has found that the average heart dose does not accurately reflect the degree of heart radiation exposure. In recent years, more and morewidespread attention has been paid to subclinical cardiac injury after radiotherapy, aiming at early identification of latent cardiac injury. In addition, the relationship between specific cardiac substructural doses and arrhythmias is unclear. This paper focuses onIn this article, the limitations of average cardiac dose in predicting radioactive heart injuryradiation- induced cardiac injury, the indicators of early identification of the indicators for cardiac injury and the influencing factors of radiation-induced cardiac injury in breast cancer radioactive heart injurywere illustrated, and focuses on the relationship between radiation damage of different cardiac substructures and arrhythmia was evaluated, so asaiming to achieve fine cardiac risk management in breast cancer patients and reduce the non-cancer mortality in breast cancer patients.

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.
China/epidemiology* ; Cohort Studies ; Female ; Humans ; Proportional Hazards Models ; Risk ; Sample Size