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 explore the mechanism by which Cuscuta chinensis flavonoids （CCF） promote decidualization and improve recurrent spontaneous abortion （RSA）. METHODS HTR-8/SVneo cells in logarithmic growth phase were randomly divided into blank group， lipopolysaccharide （LPS） group， CCF group， SGK2 inhibitor （GSK650394， abbreviated as “GSK”） group and CCF+GSK group. Each group was treated with the corresponding agents accordingly. HTR-8/SVneo cells with SGK2 knockdown were randomly divided into small interfering RNA of SGK2 （siSGK2） group and siSGK2+CCF group； additionally， blank group and LPS group were established； each group was treated with the corresponding agents accordingly. The cell survival rate， expression levels of WNK signaling pathway- and decidualization-related proteins and mRNAs， as well as mitochondrial membrane potential levels， were assessed in each group before and after SGK2 knockdown. RSA mice model was constructed and randomly divided into model group， CCF low-dose group， CCF high-dose group， GSK group， and combined dosing group， with 4 mice in each group. Other 4 normal pregnant female mice were selected as the control group. The number of implanted embryos， viable fetuses， and lost embryos in mice was recorded. The morphological changes of endometrium and decidualization were observed， and WNK signaling pathway- and decidualization-related proteins and mRNAs expressing levels as well as mitochondrial membrane potential levels were all detected. RESULTS Compared with the blank group， the cell survival rate， as well as the protein and mRNA expression levels of SGK2， WNK1， WNK4， prolactin， insulin-like growth factor- binding protein-1， oxidative stress responsive kinase 1， and Ste20-like proline-/alanine-rich kinase were significantly reduced in the LPS group （P＜0.05）； compared with the LPS group， the cell survival rate and the expression levels of the above- mentioned proteins and mRNAs were significantly increased in the CCF group， while the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly decreased in the GSK group （P＜0.05）； compared with the CCF group， the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the CCF+GSK group （P＜0.05）. After knocking down SGK2， compared with the LPS group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the siSGK2 group （P＜0.05）； compared with the siSGK2 group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly increased in the siSGK2+CCF group （P＜0.05）. The in vivo experimental results showed that CCF treatment can significantly improve the number of implanted embryos and viable fetuses in RSA model mice and reduce lost embryos， the expression levels of the above-mentioned proteins and mRNAs in endometrial tissue were significantly increased， and the red/green fluorescence intensity ratio was significantly increased （P＜ 0.05）； the combined dosing group could reverse the effect of CCF （P＜0.05）. CONCLUSIONS CCF can activate SGK2， up- regulate the WNK signaling pathway， promote endometrial decidualization， and improve RSA.

Circadian rhythm disruption is a universal phenomenon that is associated with a combination of internal and external factors, with internal factors referring to disturbances in the intrinsic regulatory mechanisms of sleep-wake behavior, and external factors including changes in sleep habits, severe sleep deprivation, shift work, social jet lag, prolonged exposure to nighttime light, and late nighttime eating. Shift work, as a common occupational factor, can lead to disruption of the central/ peripheral biological clock which regulates the expression of almost the entire genome, and the disruption of the biological clock can lead to genetic variants, hormonal secretion abnormalities, insulin resistance, oxidative stress, and systemic inflammation, which are risk factors for obesity. In the context of rapid advancement of global economy and industrialization, the prevalence of simple obesity in the traditional cognitive category is increasing in a linear trend, while the incidence of abdominal obesity, which is closely related to metabolic disorders, is also showing an increasing trend. In recent years, the mechanism of circadian rhythm disorder and obesity associated with shift work has attracted much attention, and this article summarized the latest research progress, aiming to provide a basis for the prevention and treatment of obesity caused by circadian rhythm disruption due to shift work.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

AIM: To investigate the effect of repeated intravitreal injection of anti-vascular endothelial growth factor(VEGF)on the vitreomacular interface(VMI)and its related risk factors in patients with diabetic macular edema(DME).METHODS: The clinical data of 31 patients(55 eyes)with DME who received intravitreal injections of Conbercept(3+PRN)in the ophthalmology department of the First People's Hospital of Zunyi from January 2018 to December 2021 were analyzed retrospectively. There were 9 cases(13 eyes)in the group that has changes in VMI and 22 cases(42 eyes)in the other group that has no changes in VMI. The best corrected visual acuity(BCVA), central retinal thickness(CRT), and central choroidal thickness(CCT)of the two groups were compared, and the risk factors of VMI change were analyzed.RESULTS: The patients were followed up for an average of 9.58±8.32mo, received an average of 4.07±2.17 times of anti-VEGF therapy, and the number of intravitreal injections in VMI changed group was more than that in VMI unchanged group(5.77±2.09 times vs. 3.55±1.93 times, P=0.001). At the last follow-up, compared with before treatment, the BCVA of both patients improved significantly after treatment(both P<0.05), while CCT had no significant change(both P>0.05). CRT of patients in the VMI unchanged group decreased significantly(P=0.039), but there was no significant change in patients of VMI changed group(P=0.627). Logistic regression analysis showed that BCVA was a risk factor for VMI change before treatment(P=0.049, OR=6.210, 95%CI 1.006～38.346).CONCLUSIONS: The VMI of DME patients may change during repeated intravitreal injections of anti-VEGF drugs. The worse the BCVA before treatment, the higher the risk of change in VMI, and the patients with VMI change have a poor response to anti-VEGF treatment.

Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.
Humans ; Percutaneous Coronary Intervention/methods* ; Acute Coronary Syndrome/drug therapy* ; Coronary Disease ; Treatment Outcome ; Stents/adverse effects*

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*