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

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To explore whether metformin preconditioning can protect brain injury after cardiac arrest/cardiopulmonary resuscitation(CA/CPR)and its possible mechanisms and signaling pathways.Methods Constructed a CA model by using electrical stimulation.Rats were randomly divided into the sham group(0.9％NaCl gavage daily for 14 days,without inducing CA),model group(CA model was induced after 0.9％NaCl gavage daily for 14 days),experimental group(CA model was induced after 200 mg·kg-1 Met+0.9％NaCl gavage daily for 14 days),Cc group[200 mg·kg-1 Met+0.9％NaCl gavage daily for 14 days,adenosine 5'-monophosphate kinase-activated protein(AMPK)inhibitor Compoud C(Cc)was injected intraperitoneally at 1 hour before modeling],chloroquine(CQ)group(daily 200 mg·kg-1 Met+0.9％NaCl gavage for 14 days,intraperitoneal injection of autophagy inhibitor CQ at 1 hour before modeling)and AICAR group(continuous daily 200 mg·kg-1 Met+0.9％NaCl gavage for 14 days,intraperitoneal injection of AMPK agonist AICAR at 1 hour before modeling).The 7-day survival rate after CA/CPR via using survival curves was recorded;the neurological function 7-days after CA/CPR was scored by using the neurological disability scale;the protein malondialdehyde(MDA)level were measured using the Coomassie Brilliant Blue method;detection of reactive oxygen species(ROS)levels in brain tissue by using ROS fluorescent probe DHE;Western blotting was used to determine the expression levels of related proteins such as AMPK,p-AMPK,microtubule associated protein 1 light chain 3 Ⅰ(LC3 Ⅰ),LC3 Ⅱ,and p62 in brain tissue.Results The 7-day survival rates of sham,model,experimental,Cc,CQ and AICAR groups rats were 100％,40％,70％,40％,40％and 65％,respectively;the 7-day neurological function scores were 78.35±1.65,46.50±4.41,67.93±4.64,49.50±3.53,52.00±2.83 and 68.33±1.53,respectively;the ROS levels were(417.60±8.37),(748.60±36.05),(575.80±10.73),(713.80±18.85),(668.20±9.58)and(566.00±24.48)U·mg-1,respectively;the MDA levels were(4.38±0.33),(8.06±0.76),(5.50±0.48),(7.18±0.29),(6.82±0.31)and(5.20±0.34)nmol·mg-1,respectively;the brain tissue p-AMPK/AMPK were 0.74±0.04,0.87±0.01,1.61±0.01,0.55±0.05,1.09±0.09 and 1.27±0.07,respectively;the p62 values were 0.42±0.02,0.86±0.05,0.61±0.04,0.98±0.04 and 0.78±0.03,respectively;the LC3 Ⅱ/LC3 1 were 0.29±0.32,0.37±0.26,0.96±0.78,0.58±0.26,0.43±0.03 and 1.40±0.10,respectively.Compared with the model group,the differences of above indexes in the experimental group,AICAR group were statistically significant(all P＜0.05);compared with the experimental group,the differences of above indexes in the Cc group,CQ group were statistically significant(all P＜0.05).Conclusion Metformin preconditioning can play a protective role in brain injury after cardiac arrest/cardiopulmonary resuscitationin in rats by activating the AMPK signaling pathway,regulating mitochondrial energy metabolism and promoting autophagy.

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

Objective: The investigate the effects and mechanism of exosomes derived from human umbilical vein endothelial cells (HUVECs) on wound healing in diabetes rabbits. Methods: The experimental research methods were used. The primary vascular endothelial cells (VECs) and human skin fibroblasts (HSFs) were extracted from skin tissue around ulcer by surgical excision of two patients with diabetic ulcer (the male aged 49 years and the female aged 58 years) admitted to Xiangya Third Hospital of Central South University in June 2019. The cells were successfully identified through morphological observation and flow cytometry. The HUVEC exosomes were extracted by ultracentrifugation and identified successfully by morphological observation, particle size detection, and Western blotting detection. Twenty female 3-month-old New Zealand rabbits were taken to create one type 2 diabetic full-thickness skin defect wound respectively on both sides of the back. The wounds were divided into exosomes group and phosphate buffer solution (PBS) group and treated accordingly, with 20 wounds in each group, the time of complete tissue coverage of wound was recorded. On PID 14, hematoxylin-eosin staining or Masson staining was performed to observe angiogenesis or collagen fiber hyperplasia (n=20). The VECs and HSFs were co-cultured with HUVEC exosomes for 24 h to observe the uptake of HUVEC exosomes by the two kinds of cells. The VECs and HSFs were divided to exosome group treated with HUVEC exosomes and PBS group treated with PBS to detect the cell proliferation on 4 d of culture with cell count kit 8, to detect and calculate the cell migration rate at 24 and 48 h after scratch by scratch test, to detect the cell migration number at 24 h of culture with Transwell test, and to detect the mRNA expressions of nuclear factor-erythroid 2-related factor 2 (NRF2) and transcription activating factor 3 (ATF3) by real time fluorescence quantitative reverse transcription polymerase chain reaction. Besides, the number of vascular branches and vascular length were observed in the tube forming experiment after 12 h of culture of VECs (n=3). The VECs and HSFs were taken and divided into PBS group and exosome group treated as before, and NRF2 interference group, ATF3 interference group, and no-load interference group with corresponding gene interference. The proliferation and migration of the two kinds of cells, and angiogenesis of VECs were detected as before (n=3). Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and least significant difference test. Results: The time of complete tissue coverage of wound in exosome group was (17.9±1.9) d, which was significantly shorter than (25.2±2.3) d in PBS group (t=4.54, P<0.05). On PID14, the vascular density of wound in PBS group was significantly lower than that in exosome group (t=10.12, P<0.01), and the collagen fiber hyperplasia was less than that in exosome group. After 24 h of culture, HUVEC exosomes were successfully absorbed by VECs and HSFs. The proliferative activity of HSFs and VECs in exosome group was significantly higher than that in PBS group after 4 d of culture (with t values of 54.73 and 7.05, respectively, P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs (with t values of 3.42 and 11.87, respectively, P<0.05 or P<0.01) and VECs (with t values of 21.42 and 5.49, respectively, P<0.05 or P<0.01) in exosome group were significantly higher than those in PBS group. After 24 h of culture, the migration numbers of VECs and HSFs in exosome group were significantly higher than those in PBS group (with t values of 12.31 and 16.78, respectively, P<0.01). After 12 h of culture, the mRNA expressions of NRF2 in HSFs and VECs in exosome group were significantly higher than those in PBS group (with t values of 7.52 and 5.78, respectively, P<0.05 or P<0.01), and the mRNA expressions of ATF3 were significantly lower than those in PBS group (with t values of 13.44 and 8.99, respectively, P<0.01). After 12 h of culture, the number of vascular branches of VECs in exosome group was significantly more than that in PBS group (t=17.60, P<0.01), and the vascular length was significantly longer than that in PBS group (t=77.30, P<0.01). After 4 d of culture, the proliferation activity of HSFs and VECs in NRF2 interference group was significantly lower than that in PBS group and exosome group (P<0.05 or P<0.01); the proliferation activity of HSFs and VECs in ATF3 interference group was significantly higher than that in PBS group (P<0.05 or P<0.01) and significantly lower than that in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in ATF3 interference group were significantly higher than those in PBS group (P<0.05 or P<0.01) and significantly lower than those in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in NRF2 interference group were significantly lower than those in PBS group and exosome group (P<0.05 or P<0.01). After 24 h of culture, the migration numbers of VECs and HSFs in ATF3 interference group were significantly more than those in PBS group (P<0.05) and significantly less than those in exosome group (P<0.05 or P<0.01); the migration numbers of VECs and HSFs in NRF2 interference group were significantly less than those in PBS group and exosome group (P<0.01). After 12 h of culture, the vascular length and number of branches of VECs in NRF2 interference group were significantly decreased compared with those in PBS group and exosome group (P<0.01); the vascular length and number of branches of VECs in ATF3 interference group were significantly increased compared with those in PBS group (P<0.01) and were significantly decreased compared with those in exosome group (P<0.01). Conclusions: HUVEC exosomes can promote the wound healing of diabetic rabbits by promoting the proliferation and migration of VECs and HSFs, and NRF2 and ATF3 are obviously affected by exosomes in this process, which are the possible targets of exosome action.
Animals ; Female ; Humans ; Male ; Rabbits ; Collagen/metabolism* ; Diabetes Mellitus ; Exosomes/metabolism* ; Human Umbilical Vein Endothelial Cells ; Hyperplasia/metabolism* ; NF-E2-Related Factor 2/metabolism* ; RNA, Messenger/metabolism* ; Ulcer ; Wound Healing ; Middle Aged

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.
Female ; Humans ; Aminopyridines/adverse effects* ; Antineoplastic Agents/adverse effects* ; Breast Neoplasms/drug therapy* ; Consensus ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Protein Kinase Inhibitors/adverse effects* ; Cyclin-Dependent Kinase 6/antagonists & inhibitors*

Objective　To explore the clinical and electrophysiological characteristics of cardiac-respiratory dysfunction during the peri-epileptic seizure period.Methods　A retrospective analysis was made from 12 000 patients with long-term video electroencephalograph （EEG）monitoring from October 2016 to April 2022 in the Department of Neurology,Xijing Hospital.Epilepsy patients with cardiac and respiratory dysfunction during peri- epileptic seizure period were enrolled,and their clinical and electrophysiological changes during the peri- epileptic seizure period were analyzed.Results　Three patients experienced five seizures with cardiopulmonary dysfunctions during the EEG monitoring.Two of them were female and one was male,and their age was from 23 to 55 years old with epilepsy history of 9~40 years.One patient experienced sGTCS (secondly generalized tonic-clonic seizures) followed by generalized EEG suppression (PGES),during which respiratory movements disappeared for 74 s and the heart rate was as low as 25 bpm.One patient experienced ictal asytole lasting for 15 s during a seizure induced by flash stimulation;one patient experienced ictal asytole during two seizures,which lasted for 5 s and 3 s respectively.Follow-up time ranged from 6 months to 7 years,and all the three patients were seizure free.Conclusion 　Cardiopulmonary dysfunction occurs during PGES after seizures,and ictal asytole occurs during seizures,which maybe related with sudden unexpected death in epilepsy (SUDEP).

Objective:To develop a framework for a national system of elderly health standards in response to population aging in China and to meet the need for health service standards for elderly care, thus providing a roadmap for the development of elderly health standards.Methods:Preliminary indicators for a framework of a Chinese elderly health standards system were established by literature review and expert consultations.Using the Delphi method, we invited 23 experts to form a consultation panel.After two rounds of expert consultations, the preliminary framework was updated and the weight of each indicator was calculated by using the analytic hierarchy process.Results:A framework of the Chinese elderly health standards system was established after two rounds of expert consultations.The expert authority coefficient was 0.847.The framework proposed four primary indicators, including basic health standards, medical service standards, public health standards and social support standards, for the elderly, with a weight of 0.204, 0.346, 0.260 and 0.189 for each indicator.There were 22 secondary indicators, including standardized terminologies, medical services, health education, geriatrics personnel training, etc., for elderly care.Conclusions:Our research has generated a preliminary framework of an elderly health standards system that incorporates China's specific issues, takes into consideration of the needs of various parties and covers many relevant aspects.It will provide the basis for decision-making in the elderly health standardization process in China and safeguard the implementation of the Healthy China strategy.

Objective To study the reliability and validity of the Chinese version of the Lymphedema Quality of Life Questionnaire (LYMQOL) in lymphedema patients. Methods LYMQOL was translated into Chinese. The Chinese version of the LYMQOL was distributed with the official Wechat account "Lymphedema Channel" to lymphedema patients who were recruited from October 28
China ; Humans ; Lymphedema ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires