Objective To establish a method for HPLC fingerprint analysis and determine three main components of Modified Zengye Decoction.Methods The chromatographic column was Shimadzu WondaSil C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-0.3％aqueous phosphoric acid with a gradient elution procedure,the volume flow rate was 1.0 mL/min,the detection wavelengths were 265,203,310 and 290 nm,the column temperature was 25 ℃,and the injection volume was 20 μL.The HPLC fingerprints of the 10 batches of Modified Zengye Decoction were established,and the similarity analysis was performed by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine(version 2012A).The common peaks were identified and assigned,and the contents of the three main components were quantitatively determined.Results There were 17 common peaks in the fingerprints of 10 batches of Modified Zengye Decoction with similarities ranging from 0.872-0.989.The fingerprints recognized peak 9,14 and 17 as ferulic acid,aurantiamarin and harpagoside,respectively.The contents of ferulic acid,aurantiamarin and harpagoside were 0.067 3-0.174 8,0.498 8-1.522 7,0.270 9-0.802 4 mg/g,and the transfer rate were 30.74％-55.63％,11.77％-35.94％,23.15％-68.56％,respectively.Conclusion The established HPLC fingerprint analysis method combined with main components quantitative analysis method can be used for the quality analysis and control of Modified Zengye Decoction with simple analysis method and reliable results.

Objective:To investigate the clinical and genetic characteristics of a male carrier of exceptional complex chromo-some rearrangement(CCR)and the outcome of preimplantation genetic testing for chromosomal structural rearrangement(PGT-SR).Methods:Using the modified high resolution G banding technique and whole-genome low-coverage sequencing(WGLCS),we analyzed the cellular karyotype and molecular karyotype of a male carrier of CCR,performed an analysis of the single-sperm chromosome copy number and conducted PGT-SR for the patient by next-generation sequencing(NGS).In addition,we reviewed the literature on repor-ted male carriers of CCRs and summarized their normal/balanced sperm ratios and PGT-SR outcomes.Results:The karyotype of the patient was 46,XY,der(5)inv(5)(q14.3q23.2)t(5;14;11)(q23.2;q31.1;q21),der(11)t(5;14;11);der(14)t(5;14;11),with the translocation breakpoints located in the intergenic region.Single-sperm sequencing revealed 20.0%(7/35)of normal haploids in the male's spermatozoa,and the results PGT-SR showed a proportion of 25.0%(4/16)of normal/balanced embryos.After thawing and transferring of 2 euploid blastocysts,a healthy male infant was successfully delivered.Conclusion:The proportion of normal hap-loids in the spermatozoa of male CCR carriers may be higher than theoretically predicted,and PGT-SR can effectively improve the preg-nancy outcome in male CCR carriers and provide valuable data for genetic counseling.

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3^rd to May 31^st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Young Adult ; China/epidemiology* ; COVID-19/genetics* ; Nucleic Acids ; Retrospective Studies

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ²=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ²=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.
Allergens ; Animals ; Cats ; Cesarean Section ; Dander ; Dogs ; Female ; Horses ; Immunoglobulin E ; Male ; Pregnancy ; Rhinitis, Allergic

Objective:To investigate the risk factors for axial deviation in the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport.Methods:A retrospective study was performed to analyze the clinical data of 90 patients who had been treated for tibial bone defects by the Orthofix unilateral external fixator at Department of Microrepair and Reconstruction, The First Hospital Affiliated to Xinjiang Medical University from May 2012 to June 2019. There were 77 males and 13 females with a mean age of 41.2 years (from 17 to 63 years).The bone defects ranged from 4 to 13 cm in length. According to the Paley criteria for axial deviation, the 90 patients were divided into 2 groups: a deviation-free group with no axial deviation or an axial deviation ≤5° and a deviation group with an axial deviation>5°. The 2 groups were compared in terms of age, number of prior surgery, defect length, placement angle of Schanz screws, external fixation time, external fixation index and bending degree of Schanz screws at the last follow-up.The factors with P<0.05 were analyzed by multivariate logistic regression to find the risk factors for coronal axial deviation. Results:The 90 patients were followed up for an average of 23 months (from 12 to 40 months). The incidence of axial deviation in this cohort was 36.7% (33/90).The deviation group had a significantly larger number of prior surgery [5 (3, 6) times], a significantly longer defect length [8 (8, 9) cm], a significantly longer external fixation time [400.0 (341.8, 426.3) d], and a significantly greater bending degree of Schanz screws at the last follow-up [1.2° (0.4°, 3.5°)] than the deviation-free group [3 (2, 3) times, 6 (5, 8) cm, 340.8 (226.5, 422.8) d, and 0.8° (0.2°, 3.7°)] (all P<0.05). Multivariate logistic regression analysis showed that the number of prior surgery ( OR=2.581, 95% CI: 1.496-4.450, P=0.001) and the defect length ( OR=5.310, 95% CI: 1.952-14.442, P=0.001) were the risk factors for the axial deviation. Conclusion:In the treatment of tibial defect susing Orthofix unilateral external fixator and proximal tibial osteotomy for bone transport, the more prior surgeries and the longer a bone defect, the higher the risk for axial deviation.

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

The field of two-dimensional (2D) nanomaterial-based cancer immunotherapy combines research from multiple subdisciplines of material science, nano-chemistry, in particular nano-biological interactions, immunology, and medicinal chemistry. Most importantly, the "biological identity" of nanomaterials governed by bio-molecular corona in terms of bimolecular types, relative abundance, and conformation at the nanomaterial surface is now believed to influence blood circulation time, bio-distribution, immune response, cellular uptake, and intracellular trafficking. A better understanding of nano-bio interactions can improve utilization of 2D nano-architectures for cancer immunotherapy and immunotheranostics, allowing them to be adapted or modified to treat other immune dysregulation syndromes including autoimmune diseases or inflammation, infection, tissue regeneration, and transplantation. The manuscript reviews the biological interactions and immunotherapeutic applications of 2D nanomaterials, including understanding their interactions with biological molecules of the immune system, summarizes and prospects the applications of 2D nanomaterials in cancer immunotherapy.

Ligament tissue engineering is currently a novel approach to the treatment of ligament injury, which can replace the deficiency of autografts. Ligament tissue engineering consists of four basic elements:seed cells, nanoscaffolds, growth factors, and mechanical stimulation. At present, the main problem in ligament tissue engineering is how to control seed cells to ligament cells more controllly. The study found that each physical property of the natural bio ligament and mechanical stimulation (uniaxial stretching) plays an important role in the differentiation of stem cells into ligament cells. Therefore, the design of nanofiber scaffolds must consider the elastic modulus of the material and the material. Structure(material arrangement, porosity and diameter, etc.), elastic modulus and material structure in different ranges will guide cells to differentiate into different lineages. Considering that the ligament is the main force-bearing tissue of the human body, mechanical stimulation is also essential for stem cell differentiation, especially uniaxial stretching, which best meets the stress of the ligament in the body. A large number of studies have found the frequency and amplitude of stretching. And time will also lead the cells to differentiate in different directions. RhoA/ROCK plays a regulatory role in cytoskeletal remodeling and cell differentiation. It is also found that RhoA/ROCK protein participates in the process of nanofiber arrangement and uniaxial stretching to guide stem cells to differentiate into ligament cells, specifically how to influence stem cell differentiation. It is not clear at present that understanding the effects of physical properties on stem cell differentiation and understanding the mechanism of action of RhoA/ROCK protein will provide a new theoretical basis for further optimization of ligament tissue engineering.
Cell Differentiation ; Environment ; Humans ; Ligaments ; Research ; Tissue Engineering ; Tissue Scaffolds

ObjectiveNeNewly onset atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI), which is considered to be related to cardiovascular adverse events. This paper aims to discuss the relationship between atrial fibrillation and long-term cardiovascular adverse events after acute myocardial infarction.MethodsA retrospective analysis of 483 STEMI patients with multivessel disease, who underwent emergency percutaneous coronary intervention (PCI) in Beijing Chaoyang Hospital from January 2014 to May 2017, was conducted. Patients were divided into two groups: AF group: n=52(10.8%) and non-AF group: n=431(89.2%) according to including criteria. The primary endpoint event was long-term major adverse cardiovascular events, including cardiovascular death, acute heart failure or ischemia stroke. The secondary endpoint event was defined as 30-day cardiovascular death. Multivariate logistic regression analysis and Cox proportional hazards mode were performed to analyze the relationship between newly onset atrial fibrillation and cardiovascular adverse events, such as cardiovascular death. ResultsCompared with non-AF group, AF group had older age, higher levels of C-reactive protein, erythrocyte sedimentation rate, creatinine, troponin, SYNTAX score and GRACE score and lower levels of total cholesterol, low density lipoproteins and ejection fraction (P<0.01). In the multivariate logistic regression analysis model, newly onset atrial fibrillation, age, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, admission creatinine level, fasting blood glucose, and coronary SYNTAX score were all independent risk factors associated with higher risks of 30-day cardiovascular death (OR=1.983, 95% CI=1.036-3.795, P=0.04). Using Cox proportional hazards mode, newly onset atrial fibrillation following primary PCI was associated with long-term clinical adverse cardiovascular event (HR=1.983, 95% CI=1.036-3.795, P=0.04) after adjusting all covariates. The area under the ROC curve for combined prediction mode with GRACE score and newly onset AF was comparable to the one for the model with GRACE score alone (0.788 vs 0.767，P=0.08).ConclusionNewly onset atrial fibrillation in STEMI patients with multivessel disease who underwent emergency PCI is associated with 30-day cardiovascular death and long-term clinical adverse cardiovascular events. However, newly onset atrial fibrillation does not increase the predictive value of GRACE score.