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.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

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.

Objective:To compare the clinical outcomes and prognosis of transabdominal opening of the left diaphragm and traditional thoracoabdominal combination approach for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:A retrospective cohort study was conducted. The clinical data of 59 patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction who underwent radical total gastrectomy in Shanxi Provincial People's Hospital from January 2018 to March 2020 were retrospectively analyzed, and all patients were divided into the transabdominal opening of the left diaphragm group (30 cases) and the thoracoabdominal combination group (29 cases) according to surgical access. The general data, perioperative indexes, postoperative complications and postoperative survival of patients in the two groups were compared. Factors influencing the overall survival were analyzed by using Cox proportional hazards model.Results:The differences in terms of gender, age, tumor diameter, pT staging, and pN staging between the two groups were not statistically significant (all P > 0.05). The length of esophageal invasion was (3.5±1.1) cm and (3.7±1.1) cm, respectively in the transabdominal opening of the left diaphragm group and the thoracoabdominal combination group, and the difference was not statistically significant ( t = -0.70, P = 0.486). Compared with the thoracoabdominal combination group, the transabdominal opening of the left diaphragm group had less operative time, intraoperative bleeding, postoperative bedtime, chest tube extraction time and postoperative hospitalization days, and the differences were statistically significant (all P < 0.05); the differences in the number of lymph nodes cleared, the number of positive lymph nodes, the number of thoracic lymph node dissection, and the number of positive thoracic lymph node were not statistically significant in the two groups (all P > 0.05). The total incidence of postoperative complications in the transabdominal opening of the left diaphragm group and the thoracoabdominal combination group were 53.3% (16/30) and 72.4% (21/29), respectively, and the difference was not statistically significant ( χ2 = 2.30, P = 0.130), while the incidence of lung infection and pleural effusion in the thoracoabdominal combination group was higher than that in the transabdominal opening of the left diaphragm group (both P<0.05). The 1- and 3-year postoperative overall survival rates were 80.0%, 63.3% in the transabdominal opening of the left diaphragm group, and 79.3%, 62.1% in the thoracoabdominal combination group, respectively, and the difference in overall survival between the two groups was not statistically significant ( χ2 = 0.01, P = 0.934). Multivariate analysis showed that pT staging ( HR = 4.009, 95% CI: 1.851-8.683, P < 0.001) and pN staging ( HR = 2.338, 95% CI: 1.435-3.811, P = 0.001) were the independent influencing factors of overall survival. Conclusions:For patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction with esophageal invasion length > 3 cm, transabdominal opening of the left diaphragm approach can reduce intraoperative bleeding and postoperative chest complications, and it has the advantages of shorter operation, hospitalization time, and less trauma, which can help to accelerate the recovery of the patients; pT and pN staging are the independent factors influencing the prognosis of patients.

OBJECTIVE: To explore risk factors for infections after arthroscopic rotator cuff repair, and improve the under standing for reducing infection. METHODS: Clinical data of 2 591 patients who underwent arthroscopic rotator cuff repair from January 2019 to January 2022 were retrospectively analyzed, including 1 265 males and 1 326 females, aged from 25 to 82 years old with an average age of (51.5±15.6) years old. They were divided into infection group(n=18) and uninfected group(n=2 573) according to whether or not patients had postoperative infection. Gender, age, smoking, diabetes, body mass index, local closure within 1 month before operation, operation time, preventive use of antibiotics, and internal fixation implantation between two groups were recorded. Univariate Logistic regression analysis screened factors associated with infections after arthroscopic rotator cuff repair. Theresultswere entered into the multivariate logistic regression analysis, screening the high risk factors for infections after arthroscopic rotator cuff repair. RESULTS: In 2 591 patients, 18 patients were infected after operation, infection rate was 0.69%. Univariate Logistic regression analysis showed that gender, age, operation time, antibiotic prophylaxis, internal fixation implantation were risk factors for infections after arthroscopic rotator cuff repair. Multivariate Logistic regression analysis showed male(OR=14.227), age≥65 years(OR=34.313), operation time≥2 h (OR=15.616), without antibiotic prophylaxis(OR=4.891), and internal fixation implantation(OR=5.103) were major risk factors for infection after arthroscopic rotator cuff repair(P<0.05). CONCLUSION Male, age≥65 years, operation time≥2 h, without antibiotic prophylaxis and internal fixation implantation were independent risk factors for infection after arthroscopic rotator cuff repair. Early diagnosis and timely treatment should be carried out to reduce the incidence of infection.
Female ; Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Rotator Cuff ; Rotator Cuff Injuries/surgery* ; Retrospective Studies ; Arthroscopy/adverse effects* ; Risk Factors ; Treatment Outcome

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) has played an important role in screening occupational contraindications and preventing occupational diseases since its implementation. However, during the use of occupational health examination, we found that the use of occupational contraindication on cardiovascular disease was not "homogenized" due to the differences in the understanding of various physical examination institutions. Therefore, this paper mainly discussed the connotation and quantitative standards of organic heart disease, arrhythmia, hypertension in the occupational contraindication cardiovascular disease in the specification for "homogenization".
Humans ; Occupational Health ; Cardiovascular System ; Cardiovascular Diseases ; Contraindications ; Occupational Diseases

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To explore the effect of pretreatment body mass index (BMI) on the prognosis of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy.Methods:The clinical data of 711 patients with locally advanced NSCLC treated with radiotherapy, sequential chemoradiotherapy or concurrent chemoradiotherapy from January 2013 to December 2017 in Cancer Hospital of Chinese Academy of Medical Science and Peking Union Medical College were retrospectively analyzed. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), and the chemotherapy regimens were paclitaxel+carboplatin, pemetrexed+cisplatin or etoposide+cisplatin. The effects of pretreatment BMI and other clinical factors on overall survival (OS) of patients were analyzed. Survival analysis was performed by using Kaplan-Meier method; univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:According to the World Health Organization (WHO) recommended BMI grouping method for Asian, the median OS time of low BMI group (<18.5 kg/m 2, 23 cases), normal BMI group (18.5-23.9 kg/m 2, 293 cases) and high BMI group (≥24.0 kg/m 2, 395 cases) was 17 months (95% CI 11-29 months), 29 months (95% CI 22-36 months) and 30 months (95% CI 27-34 months), respectively. OS in the low BMI group was poorer than that in the normal BMI group and high BMI group ( χ2 = 11.20, P = 0.004). Maximally selected rank statistics was used to determine the optimal cut-off value of BMI for prediction of survival as 21.31 kg/m 2, according to which patients were divided into low BMI group (BMI<21.31 kg/m 2, 130 cases) and high BMI group (BMI≥21.31 kg/m 2, 581 cases), the median OS time of the two groups was 20 months (95% CI 17-27 months) and 32 months (95% CI 28-35 months), respectively. OS in the low BMI group was poorer than that in the high BMI group ( χ2 = 12.30, P < 0.001). Multivariate analysis showed that age ≥ 65 years old, male, Karnofsky score < 80 points, low BMI, smoking, histological type of squamous cell carcinoma and radiotherapy alone were independent risk factors for OS (all P < 0.05). Conclusions:For patients with unresectable locally advanced NSCLC who received chemoradiotherapy, those with low pretreatment BMI have poor prognosis.

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
Colorectal Neoplasms ; Humans ; Liver/pathology* ; Lung/pathology* ; Prospective Studies ; Radiosurgery/methods*