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.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To explore the effect of mixed antibiotics on the intestinal flora of mice to affect the immune regulation of the body,explore the role of intestinal flora in the development of obesity,and provide new ideas and ways for the prevention and treatment of obesity.Methods Seventy-two 10-week-old male C57BL/6 mice were randomly divided into blank control(Ctrl)group,high-fat diet(HF)group,antibiotic(ABX)group,and combined(COMB)group(n=18).At the first 2 weeks(lavage intervention weeks),Ctrl and HF group were given normal saline gavage;ABX and COMB group were given mixed antibiotics gavage,and the gavage volume was 0.2 mL/animal/day.For the following 8 weeks(feeding weeks),Ctrl and ABX group were fed with ordinary diet,HF and COMB group were fed with high-fat diet.Body weight was measured weekly,and fasting blood glucose was measured before and after gavage,and at the 4th and 8th week of feeding.Oral glucose tolerance test was performed at the end of the experiment.The organ coefficient was measured and the cell morphology of white and brown adipose tissue was observed.Serum was collected for the determination of free fatty acid,high-density lipoprotein,low-density lipoprotein,triglyceride,and total cholesterol.Serum TNF-α,IL-10,IL-4,IL-13,IL-33 and MCP-1 was detected by ELISA.The stool of mice was collected for second generation sequencing.Results High-fat diet increased body weight,serum total cholesterol,low-density lipoprotein,IL-13,IL-33,TNF-α,MCP-1 content,and decreased glucose tolerance and organ coefficient in mice(P＜0.05).From the first feeding week to the end of the experiment,body weight in COMB group was significantly lower than that in HF group(P＜0.05).The level of glucose tolerance,serum total cholesterol,low density lipoprotein,IL-13,IL-33,TNF-α and MCP-1 in COMB group was lower than those in HF group(P＜0.05).The α diversity of intestinal flora in ABX group was lower than that in Ctrl group(P＜0.05).Congestion and bleeding in WAT were obvious in HF group,but not in COMB group.The microbial community composition of ABX and HF group was similar to that of Ctrl and COMB group,respectively.Conclusion High-fat diet induces obesity,disorder of glucose and lipid metabolism and inflammation in mice.Short-term mixed antibiotic use can regulate the intestinal flora of mice,mediate increased expression of related anti-inflammatory factors,up-regulate host immunity,and improve glucose and lipid metabolism in mice.

Objective To study the effects of antibiotics and high-fat diet on energy metabolism and the browning of white adipose tissue (WAT) and brown adipose tissue (BAT) in mice, so as to provide new ideas for the possible mechanism of adipose tissue in the prevention and treatment of obesity. Methods A total of 80 10-week-old C57BL/6 male mice were fed with normal diet in the early stage, and the antibiotic gavage group (AG) and antibiotic high-fat group (AFG) were given mixed antibiotics by gavage. The blank group (BG) and the high-fat diet group (FG) were given normal saline intragastric solution for 2 weeks, and after the gavage operation, the FG group and the AFG group were given high-fat diet for obesity modeling, and the BG group and AG group continued to be fed with normal diet for 8 weeks (N=20). After the experiment, each group was injected with β3-adrenergic receptor agonists for 5 days, and the high-fat/ordinary diet remained unchanged. At the end of the experiment, basal metabolic rate (BMR), fasting blood glucose (FBG) and rectal temperature were measured, and feces, blood, subcutaneous white fat, epididymis and brown adipose tissue in the scapular area of mice were collected. The automatic biochemical analyzer was used to determine the blood biochemical indexes; reverse transcription polymerase chain reaction (RT-qPCR) was used to measure the expression of genes related to browning of WAT and BAT adipose tissue, respectively. Real-time quantitative polymerase chain reaction (qPCR) was used to determine the expression of WAT mitochondrial DNA (mt DNA). Results From the 4th week to the end of the experiment, the weight of the AFG group was significantly higher than that of the AG group and significantly lower than that of the FG group (P<0.05). The body weight, organ coefficient, serum TC level, rectal temperature and WAT cell diameter in the AFG group were significantly higher than those in the AG group. The serum levels of FBG, TC and LDL in the AFG group were significantly lower than those in the FG group (P<0.05). The overall BMR(mlO2/h) FG group was significantly higher than that of BG group, and the AFG group was significantly higher than that of AG. BMR per unit body weight (mlO2/h/g) AFG was significantly higher than that of FG group (P<0.05). The expressions of RIP140, PPAR-γ and UCP-1 in BAT in the AFG group were significantly higher than those in the FG group, and the mt DNA copy number of WAT in the AFG group was significantly higher than that in the FG group (P<0.05). Conclusion Antibiotic intervention can up-regulate the expression of brown fat-related genes in high-fat diet mice, increase brown fat activity, increase the relative mitochondrial number of white fat, increase the level of browning of white fat, promote thermogenesis, increase the BMR per unit body weight of adult obese mice, and then improve the overall energy metabolism of the body, and slow down the weight gain induced by high-fat diet to a certain extent.

During the development of whole-cell microbial sensors,factors such as cellular metabolic activity and signal output modes play pivotal roles in the stability and repeatability of the sensors,presenting numerous challenges for the standardization of sensor applications. This research focused on the arsenic ion sensor based on the RepL amplifier,adjusting the reporter genes,culture media,growth stages,and induction times of arsenic ions,aiming to investigate how these factors affect the sensor's detection performance. The results indicated that the cell's culturing environment,growth status (e.g.,different growth phases),type of reporter,and induction time all had significant impacts on the performance of the arsenic ion sensor. First,the stability of the sensors varied greatly in different media,all the three sensors displayed greater stability in LB culture medium. Meanwhile,the cells in different growth stages also exhibited different performance advantages. Cells at the stationary growth phase exhibited better detection sensitivity and linearity,while cells in the logarithmic growth phase had lower limit of detection (LOD) . Moreover,there was an optimal induction time for the response of the sensor,overly long or short induction time could interfere with its response. The optimal induction time for the arsenic sensor in this work was about 2-3 h. By comparing three types of fluorescent protein reporters,it was found that although their detection limits were fairly similar,all within the range of 5-10μg/L,but their response times varied,ranging from 40 min to 2 h. The fluorescent proteins with higher brightness exhibited faster sensor response. These research outcomes provided a solid foundation for the practical application of microbes in detection. In practice,we could choose cells in specific states based on particular purpose,maximizing the performance of the cell sensors and further broadening the application scope of such sensors.

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Female ; Stroke Volume ; Stellate Ganglion/surgery* ; Ventricular Function, Left ; Cardiomyopathies/complications* ; Tachycardia, Ventricular/therapy* ; Treatment Outcome ; Catheter Ablation

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO₂) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO₂ was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO₂ for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO₂ as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO₂ and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO₂ concentration was (32.18±10.36) μg/cm³. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T₁ group of NDVI, the risk of hypertension was lower in the T₃ group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T₁ group of NO₂, the risk of hypertension was higher in the T₂ and T₃ groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO₂ was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO₂ had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO₂ are associated with hypertension in older adults.
Aged ; Humans ; Female ; Nitrogen Dioxide ; Air Pollution ; Prevalence ; Hypertension/epidemiology* ; China/epidemiology* ; Particulate Matter/analysis*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*