Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

[Purpose]To analyze the cost-effectiveness of endoscopic screening for upper gastroin-testinal cancer in Yangcheng County of Shanxi Province.[Methods]People aged from 40 to 69 who participated in upper gastrointestinal cancer screening in Yangcheng County in 2018 were se-lected as the study subjects to participate in upper gastrointestinal cancer screening in 2018,and endoscopic examination with iodine staining and indicative biopsy were performed for screening.The detection rates of precancerous lesions and upper gastrointestinal malignancies,and early di-agnosis rates were calculated,and compared among different groups.The data of screening cost were collected;and the per capita screening cost,the average cost of early case detection and ear-ly detection cost index(EDCI)were calculated.[Results]Among 2 950 subjects undergoing en-doscopy,pathological biopsy was completed in 2 073 cases(70.27％),374 cases of precancerous le-sions(12.68％)and 52 cases of malignancies(1.76％)were detected,among which 17 cases were up-per gastrointestinal cancer with a detection rate of 0.58％,there were 44 early cases with an early diagnosis rate of 84.62％.The detection rate of precancerous lesions and positive cases in men was higher than that of women,but the early diagnosis rate of upper gastrointestinal cancer was lower than that of women;the detection rate of positive cases and digestive tract cancer of 50 years and above were higher than those of people aged 40 to 49.The cost of screening for one positive lesion was 25 528.85 CNY,the cost of screening for one early case was 30 170.46 CNY.The EDCI was 0.52,indicating a good cost-effective value.[Conclusion]The study shows that the early diagnosis and early treatment screening program of upper gastrointestinal cancer has achieved remarkable re-sults in Yangcheng County.The follow-up screening work should focus on men and people over 50 years old,and strengthen the publicity of upper gastrointestinal screening for cancer.

Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7nAChR) in thymic T follicular helper cells (TFH) and its significance in patients with myasthenia gravis (MG). Methods Fifteen MG patients who underwent surgical treatment at the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People’s Hospital from June 2022 to June 2023 were selected as a MG group, including 7 males and 8 females, aged 12-30 years. Twelve patients who underwent partial thymectomy to optimize surgical field exposure during cardiac surgery at Fuwai Central China Cardiovascular Hospital from June 2022 to June 2023 were selected as a control group, including 5 males and 7 females aged 20-35 years. Thymus single cell suspension was obtained by grinding the thymus tissue, and flow cytometry was used to detect the expression of α7nAChR in TFH cells. The thymus cell suspension was purified using density gradient centrifugation, followed by immunomagnetic bead separation to obtain CD4+T cells. CXCR5 antibody and coupled magnetic beads were added to isolate TFH cells. Real-time fluorescent polymerase chain reaction and Western blotting were performed to further investigate the expression of α7nAChR in TFH cells. Results Compared with the control group, the proportion of thymic TFH cells in the MG group was significantly increased (P<0.05), along with significantly decreased mRNA and protein expression levels of α7nAChR within these cells (P<0.01). Conclusion The findings suggest that there is a reduced expression of α7nAChR within thymic TFH cells in MG patients, leading to weakened immunosuppressive function which may indirectly contribute to disease onset and progression.

Objective:To explore the activation characteristics and synergistic mode of lumbar and abdominal core muscle group during abdominal breathing training.Method:Thirty-two healthy college students were recruited and randomly divided into the control group and the experimental group with 16 cases in each group.The control group received stan-pile training,while the experimental group received abdominal breathing and stan-pile training 5 times a week for 8 weeks.The sur-face electromyography of the lumbar and abdominal core muscles was collected before and after the interven-tion.Non-negative matrix factorization(NMF)was used to extract extract muscle synergy patterns from the EMG data.Result:In terms of cooperative elements,the number of cooperative elements increased after intervention in both groups compared with baseline,but there was no significant difference in the number of cooperative ele-ments between the two groups before intervention(P>0.05),and there was a significant difference in the num-ber of cooperative elements after intervention(P<0.05).In terms of cooperative patterns,the cooperative pat-terns before intervention in the two groups were similar.After intervention,the cooperative patterns in the two groups were different,the control group showed coactivation of the right transversus abdominis,left internal oblique,right erector spinae,and bilateral multifidus throughout the breathing cycle.In contrast,the experimen-tal group exhibited pronounced activation of bilateral erector spinae and multifidus during inhalation,and bilater-al transversus abdominis,left external oblique,and left erector spinae during exhalation.The activation curves before intervention in the two groups were similar,and the activation curves after intervention in the two groups trended towards slowing down,with the time feature of the activation curve in the experimental group being more obvious.Conclusion:Abdominal breathing training can increase the number of cooperative tuples of the waist and abdo-men muscles,and the muscles perform efficient division of labor after training to form an adaptive coopera-tive mode.

Objective:To explore the activation characteristics and synergistic mode of lumbar and abdominal core muscle group during abdominal breathing training.Method:Thirty-two healthy college students were recruited and randomly divided into the control group and the experimental group with 16 cases in each group.The control group received stan-pile training,while the experimental group received abdominal breathing and stan-pile training 5 times a week for 8 weeks.The sur-face electromyography of the lumbar and abdominal core muscles was collected before and after the interven-tion.Non-negative matrix factorization(NMF)was used to extract extract muscle synergy patterns from the EMG data.Result:In terms of cooperative elements,the number of cooperative elements increased after intervention in both groups compared with baseline,but there was no significant difference in the number of cooperative ele-ments between the two groups before intervention(P>0.05),and there was a significant difference in the num-ber of cooperative elements after intervention(P<0.05).In terms of cooperative patterns,the cooperative pat-terns before intervention in the two groups were similar.After intervention,the cooperative patterns in the two groups were different,the control group showed coactivation of the right transversus abdominis,left internal oblique,right erector spinae,and bilateral multifidus throughout the breathing cycle.In contrast,the experimen-tal group exhibited pronounced activation of bilateral erector spinae and multifidus during inhalation,and bilater-al transversus abdominis,left external oblique,and left erector spinae during exhalation.The activation curves before intervention in the two groups were similar,and the activation curves after intervention in the two groups trended towards slowing down,with the time feature of the activation curve in the experimental group being more obvious.Conclusion:Abdominal breathing training can increase the number of cooperative tuples of the waist and abdo-men muscles,and the muscles perform efficient division of labor after training to form an adaptive coopera-tive mode.

Objective:To develop the Hypoglycemia Prevention Knowledge, Attitude and Practice Questionnaire for Homebound Elderly Patients with Diabetes Mellitus to inform the development of targeted interventions for caregivers.Methods:The first draft of the questionnaire was formed through literature analysis, group discussion, semi-structured interviews, Delphi expert consultation and pre-testing based on the theory of knowledge, attitude and practice. Convenience sampling was applied to select homebound elderly diabetic patients within the Shangcheng District of Hangzhou City from August to September 2022, and the questionnaire was subjected to item analysis, reliability test and exploratory factor analysis. Patients within Gongshu District of Hangzhou City were selected from October to November 2022 for questionnaire survey and validation factor analysis.Results:The questionnaire included 31 entries in three dimensions of knowledge, attitude, and practice. The content validity index was 0.96 at the questionnaire level and 0.83 to 1.00 at the entry level. The overall Cronbach's α coefficient for the questionnaire was 0.933, the folded reliability was 0.836, and the retest reliability was 0.913. The exploratory factor analysis cumulative variance contribution was 68.917% and the validation factor analysis showed a good model fit.Conclusions:The Hypoglycemia Prevention Knowledge, Attitude and Practice Questionnaire for Homebound Elderly Patients with Diabetes Mellitus is scientific and practical and can be used to investigate the hypoglycemia prevention knowledge, attitude and practice among homebound elderly diabetic patients.

[Purpose]To analyze the cost-effectiveness of endoscopic screening for upper gastroin-testinal cancer in Yangcheng County of Shanxi Province.[Methods]People aged from 40 to 69 who participated in upper gastrointestinal cancer screening in Yangcheng County in 2018 were se-lected as the study subjects to participate in upper gastrointestinal cancer screening in 2018,and endoscopic examination with iodine staining and indicative biopsy were performed for screening.The detection rates of precancerous lesions and upper gastrointestinal malignancies,and early di-agnosis rates were calculated,and compared among different groups.The data of screening cost were collected;and the per capita screening cost,the average cost of early case detection and ear-ly detection cost index(EDCI)were calculated.[Results]Among 2 950 subjects undergoing en-doscopy,pathological biopsy was completed in 2 073 cases(70.27％),374 cases of precancerous le-sions(12.68％)and 52 cases of malignancies(1.76％)were detected,among which 17 cases were up-per gastrointestinal cancer with a detection rate of 0.58％,there were 44 early cases with an early diagnosis rate of 84.62％.The detection rate of precancerous lesions and positive cases in men was higher than that of women,but the early diagnosis rate of upper gastrointestinal cancer was lower than that of women;the detection rate of positive cases and digestive tract cancer of 50 years and above were higher than those of people aged 40 to 49.The cost of screening for one positive lesion was 25 528.85 CNY,the cost of screening for one early case was 30 170.46 CNY.The EDCI was 0.52,indicating a good cost-effective value.[Conclusion]The study shows that the early diagnosis and early treatment screening program of upper gastrointestinal cancer has achieved remarkable re-sults in Yangcheng County.The follow-up screening work should focus on men and people over 50 years old,and strengthen the publicity of upper gastrointestinal screening for cancer.

Objective:To develop the Hypoglycemia Prevention Knowledge, Attitude and Practice Questionnaire for Homebound Elderly Patients with Diabetes Mellitus to inform the development of targeted interventions for caregivers.Methods:The first draft of the questionnaire was formed through literature analysis, group discussion, semi-structured interviews, Delphi expert consultation and pre-testing based on the theory of knowledge, attitude and practice. Convenience sampling was applied to select homebound elderly diabetic patients within the Shangcheng District of Hangzhou City from August to September 2022, and the questionnaire was subjected to item analysis, reliability test and exploratory factor analysis. Patients within Gongshu District of Hangzhou City were selected from October to November 2022 for questionnaire survey and validation factor analysis.Results:The questionnaire included 31 entries in three dimensions of knowledge, attitude, and practice. The content validity index was 0.96 at the questionnaire level and 0.83 to 1.00 at the entry level. The overall Cronbach's α coefficient for the questionnaire was 0.933, the folded reliability was 0.836, and the retest reliability was 0.913. The exploratory factor analysis cumulative variance contribution was 68.917% and the validation factor analysis showed a good model fit.Conclusions:The Hypoglycemia Prevention Knowledge, Attitude and Practice Questionnaire for Homebound Elderly Patients with Diabetes Mellitus is scientific and practical and can be used to investigate the hypoglycemia prevention knowledge, attitude and practice among homebound elderly diabetic patients.

Objective To investigate the effects of qigong abdominal breathing training on human brain function.Methods Seventy-two university students were recruited and randomly divided into the control and treatment groups in a 1:1 ratio. Both the control and treatment groups underwent the same standing pile work operation. However,only the treatment group received additional abdominal breathing training. The intervention process comprised two phases:2 weeks of intensive training and 6 weeks of counseling training. Electrocardiogram and electroencephalogram (EEG) tests were performed before (baseline period) and after training respectively. Sample entropy algorithm and empirical mode decomposition were used to analyze the EEG signals. The sample entropy complexity index and the correlation between EEG changes and respiratory curves were calculated to explore the brain function regulation effect. Results The complexity of different brain regions in the treatment group was higher than that of the control group after training. A large difference was observed when comparing the brain complexity in the temporoparietal junction,posterior temporal,parietal,parietal-occipital junction,and occipital regions. The brain complexity in the posterior temporal region of the treatment group was significantly higher than that of the control group after the intervention,with a significant difference (P<0.05). In the control group,the brain complexity in the frontal pole,anterior temporal,frontal reion,frontal-temporal junction,frontal-central junction,middle temporal,central,and temporal-parietal junction regions decreased to different degrees. However,the comparison between before and after was not significant. Furthermore,brain complexity in the central-parietal junction,posterior temporal,parietal,parietal-occipital junction,and occipital regions increased to different degrees in the control group;however,the difference was not significant. The brain complexity of the treatment group in the frontotemporal junction,middle temporal,and temporoparietal junction areas decreased slightly;however,the before-and-after comparison was not significant. The brain complexity of the treatment group in the frontal pole,frontotemporal,frontal,frontal-central junction,central,central-parietal junction,posterior-temporal,parietal,parietal-occipital junction,and occipital areas increased. The posterior-temporal,parietal,parietal-occipital junction,and occipital areas had more significant increases than the other areas. However,the before-and-after comparison was not significant. In both groups,brain complexity decreased in the frontotemporal junction,middle temporal,and temporoparietal junction areas and increased in the parietal,parieto-occipital junction,and occipital areas. The comparison of complexity between the treatment and control groups in P3 and PO3 leads after training was significant. P3 and PO3 are situated in the parietal region and parieto-occipital junction areas,respectively,indicating that antebellum breathing also affects brain function in these regions. The correlation between the respiratory curve and EEG components was enhanced after training. Conclusion Abdominal breathing training can significantly increase the complexity of the corresponding brain regions (posterior temporal,parietal,and parieto-occipital junction regions),and a significant correlation was observed between the two.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.