OBJECTIVE: To investigate a family with hereditary coagulation factor XI (FXI) deficiency, identify its possible genetic etiology, analyze the bleeding risk of the proband, and provide a blood transfusion regimen. METHODS: The blood samples from the family members were collected, and the coagulation parameters of the proband and her family members were detected. Whole-exome sequencing was performed on the blood samples of the proband to identify gene variants, and validate the variants in the family using Sanger sequencing. Bioinformatics softwares were used to analyze the conservation of amino acid variant sites and the impact of the variations on protein function. The pathogenicity of the variant sites was analyzed according to the genetic variation classification criteria and guidelines of the American College of Medical Genetics and Genomics (ACMG). Thromboelastography (TEG) was used to assess the coagulation function of the family members and evaluate the transfusion regimen and its efficacy in the proband. RESULTS: The activated partial thromboplastin time (APTT) of the proband was significantly prolonged to 96.7 seconds, and FXI activity (FXI: C) and FXI antigen (FXI: Ag) decreased to 1.3% and 1%, respectively, both of which were extremely reduced. The FXI: C of the proband's father was also significantly lower than the normal value. The TEG results showed that the coagulation function of the proband was reduced, while the coagulation function of other family members was normal. The F11 gene of the proband exhibited compound heterozygous variants of c.738G>A (p.Trp246 *) and c.1288G>A (p.Ala430Thr). The proband's father carried a heterozygous missense variant of c.1288G>A (p.Ala430Thr), while her mother, her eldest daughter, and her youngest daughter carried a heterozygous nonsense variant of c.738G>A (p.Trp246 *). According to the ACMG genetic variation classification criteria and guidelines, c.738G>A (p.Trp246 *) is classified as a pathogenic variant (PVS1+PS3-Moderate+PP4), and c.1288G>A (p.Ala430Thr) is classified as a possible pathogenic variant (PS3-Moderate+PM1+PM3_Srong+PP4). p.Trp246 and p.Ala430 are highly conserved across different species. Swiss PdbViewer software analysis showed that p.Ala430Thr variant caused a change in the number of hydrogen bonds in FXI protein, affecting protein function. The following transfusion regimen was determined through TEG evaluation in vitro: 600 ml of fresh frozen plasma (FFP) was administered 24 hours before surgery to prevent bleeding. And there was no significant bleeding during or after the surgery. CONCLUSION The heterozygous nonsense variant ofc.738G>A (p.Trp246 *) and the heterozygous missense variant of c.1288G>A (p.Ala430Thr) in the F11 gene are the pathogenic factors of this hereditary FXI deficiency family.
Humans ; Factor XI Deficiency/therapy* ; Factor XI/genetics* ; Blood Transfusion ; Pedigree ; Female ; Male ; Mutation ; Thrombelastography ; Partial Thromboplastin Time ; Blood Coagulation ; Adult

This study aimed to determine the drug resistance phenotype and genetic characteristics of Listeria monocytogenes ST5 LK100 isolated from a neonate,which provided a basis for the diagnosis and treatment of L.monocyto-genes infection and to enhance the understanding of the genomic characteristics of this strain.A suspected L.monocytogenes strain was isolated from the gastric juice sample of an infected neonate,and identified with a VITEK2 Compact automatic mi-crobial identification instrument and 16S RNA sequencing.Five drug sensitivity tests were conducted on the identified strain with the E-test method.Additionally,the whole genome of the strain was sequenced using a third-generation sequencing plat-form.The antibiotic resistance elements of the strain were identified by BlastN with the CARD antibiotic resistance gene data-base.The multilocus sequence typing(MLST),serotyping,and virulence genes of the strain was determined by Pasteur da-tabase,the virulence gene distribution was analyzed using the virulence analysis website.The prophages of the strain were predicted and annotate by PHASTER online website.The strain(LK100)isolated from the neonate was identified as L.monocytogenes.This strain was sensitive to penicillin,ampicil-lin,meropenem,erythromycin,and trimethoprim-sulfame-thoxazole antibiotics.The MLST type and serotype was ST5 and 1/2b-3b,respectively.The total length of the chromoso-mal genome of LK100 was 3 032 582 bp with a GC content of 37.91％,and it contained a complete circular plasmid with a se-quence length of 52 822 bp.The strain LK100 carried complete InlA protein,LIPI-1 pathogenicity island,SSI-1 stress survival island,and an LGI2 genomic island.The intrinsic antibiotic resistance genes were mainly located on the chromosome.Five prophage sequences were predicted in the LK100 genome.This study identified a strain of ST5 L.monocytogenes LK100 from an infected neonate and characterized its genome and antibiotic sensitivity,laying the foundation for further research on ST5 L.monocytogenes.

AIM To screen anti-inflammatory activity Q-markers for Glycyrrhizae Radix et Rhizoma.METHODS Lipopolysaccharide was used for stimulating RAW264.7 macrophages to establish inflammatory model,after which the NO inhibitory rates of different grades of medicinal materials were determined.The UHPLC-QTOF-MS fingerprints were established,after which chemical constituents were identified,heatmap was drawn,and orthogonal partial least squares analysis was performed.RESULTS Grade 1 and grade 2 medicinal materials demonstrated higher NO inhibitory rates than gradeless and uniformly-priced goods(P＜0.05,P＜0.01).There were 211 common peaks in the fingerprints of 47 batches of medicinal materials,total 56 compounds were identified,containing 17 saponins,6 flavonoids,8 flavanones,4 chalcones,12 isoflavones and 9 other kinds.The relative contents of isoflavones,coumarins,kaempferol and licoflavonol in grade 1 and grade 2 medicinal materials were higher than those in gradeless and uniformly-priced goods,while the relative contents of flavanones,chalcones and saponins in wild products were higher than those in cultivated products.Neoliquiritin,isoliquiritin,kaempferol,hedysarimcoumestan E,licorice saponin C2,licoarylcoumarin,glicoricone and liconeolignan were taken as Q-markers.CONCLUSION This stable and reliable method has a certain reference value for the quality control of Glycyrrhizae Radix et Rhizoma.

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.
Humans ; Antipyretics/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Influenza, Human/drug therapy* ; Nucleic Acids/therapeutic use* ; Oseltamivir/therapeutic use* ; Phosphates/therapeutic use* ; Treatment Outcome ; Double-Blind Method

Objective:To evaluate the value of shear wave elastography (SWE) in skin assessment of Systemic sclerosis (SSc).Methods:A total of 58 SSc patients admitted to Peking University Third Hospital from May 2021 to October 2022 and 41 healthy volunteers were included in the study. Skin shear wave elastography (SWE) was performed at 17 sites defined in modified Rodnan skin score (mRSS) measurement, and shear wave velocity values were recorded to evaluate skin hardness. SPSS 22.0 software was used to analyze the skin hardness of SSc patients and healthy controls, and the correlation between skin hardness of SSc patients and clinical data was analyzed. A logistic regression model was constructed to evaluate the diagnostic efficacy of skin hardness at different sites of SSc patients, and to further select the most practical measurement site.Results:The SWE value of SSc patients was significantly higher than that of healthy control group ( P<0.05). There was a positive correlation between SWE and mRSS in the measurement of bilateral fingers, bilateral dorsal hands, bilateral forearms, fore-chest, abdomen, bilateral thighs, and bilateral dorsal feet. Skin stiffness measured by SWE was significantly correlated with SSc disease activity score (EScSG-DAI), ( r=0.71, P<0.001), disease injury score (SCTC-DI), (P=0.55, P=0.005) and functional score (HAQ-DI), ( r=0.46, P=0.003). Reducing the number of measurement sites to 12 (bilateral fingers, bilateral hands, bilateral forearms, bilateral upper arms, forehead, fore-chest, bilateral dorsum of feet) performs as well as all 17 measurement sites simultaneously in assessing disease activity. Conclusion:SWE is a good evaluation tool to reflect the skin lesions of SSc, which is of great value for the diagnosis and evaluation of the disease. We can further standardize the measurement sites and select the most appropriate evaluation strategy, so as to achieve better clinical application.

Humans ; Herpesvirus 4, Human ; Wiskott-Aldrich Syndrome ; Epstein-Barr Virus Infections/complications* ; Smooth Muscle Tumor/therapy* ; Hematopoietic Stem Cell Transplantation

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.
Humans ; Caustics ; Lung Injury/chemically induced* ; Gastrointestinal Tract ; Burns, Chemical/therapy* ; Eating

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the modified application of orbicularis oculi muscle-levator aponeurosis composite tissue flap fixation technique (modified Park method) in double-eyelid surgery.Methods:From June 2019 to March 2021, 823 patients included 92 males and 731 females, aged from 18 to 45 years with mean (31.4±7.9) years, in which 142 patients with slightly ptosis were selected to receive the treatment in the Department of Plastic Surgery of the Affiliated Hospital of Nangjing University of TCM. The symmetry of bilateral double eyelids after operation was evaluated by the third party. The marginal reflex distance (MRD1) was measured before and 6 months after operation, and the difference between preoperative and postoperative MRD1 (ΔMRD1) was calculated. And the postoperative complications were counted. The patients were followed up from 6 to 12 months after surgery to evaluate the long-term results.Results:The patients were followed up for 4-22 months (mean 10 months) after operation. And the incisions of all the 823 cases had primary healling. Most patients had smooth upper eyelid crease, upturned lashes and dynamic fold. The skin tended to spread evenly without dimple. The symmetry evaluation by the third party showed that there were 764 patients with symmetry and basic symmetry after operation, the symmetry rate was 92.8%; 59 patients with asymmetry, the asymmetry rate was 7.2%. The data of MRD1 increased significantly 6 months after operation, from (3.25±0.72) mm to (3.64±0.61) mm, and the ΔMRD1 was (0.38±0.76) mm ( t=-20.41, P<0.05). The difference between the two groups was statistically significant. The double eyelid line became shallow in 8 cases and disappeared completely in 3 cases. The double eyelid curve of the patients was natural and smooth after the operation. And there was no obvious sunken scar and pretarsal fullness. Conclusions:The " modified Park technique" blepharoplasty can obtain a more firm, symmetrical and natural appearance. And the mild ptosis could be corrected by this method. The anatomical structure can be identified clearly, and the surgical results are highly repeatable. It is worth promoting.

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4⁺T lymphocytes (CD4) counts >500 cells/μl (compared with having recent CD4 counts <200 cells/μl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.
Acquired Immunodeficiency Syndrome/epidemiology* ; Adolescent ; Adult ; Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; HIV Infections/epidemiology* ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Marriage ; Young Adult