Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To analyze the relationship between serum cystatin C(CysC),β2-microglobulin(β2-MG)and the efficacy of demethylation therapy in patients with acute myeloid leukemia(AML).Methods:A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022.All patients were treated with decitabine(DAC)+HAG regimen,28 days as a course and treated for 3-4 courses.At the end of each course of treatment,the treatment effect of the patients was evaluated,and the patients who achieved complete remission(CR)transferred to consolidation therapy,while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure.The examination items before treatment include routine blood parameters,serum CysC,and β2-MG,and general clinical data of the patients were collected.According to the statistical results,logistic regression model was used to analyze the relationship between serum CysC,β2-MG and the efficacy of demethylation therapy in AML patients.The ROC curves were drawn,and the predictive efficacy of serum CysC,β2-MG on demethylation therapy in AML patients was evaluated by the area under the curve(AUC).Results:Of the 98 AML patients enrolled in the study,5 cases were excluded during the treatment period,and 93 cases finally completed the chemotherapy courses.Among them,23 patients achieved CR after the initial induction chemotherapy(course 1-2),and 11 patients achieved CR after the re-induction chemotherapy(course 3-4).The success rate of demethylation therapy was 36.56％(34/93).Compared with the patients in treatment success group,patients in treatment failure group had a higher proportion of intermediate-and adverse-risk,lower levels of platelet(PLT)and hemoglobin(Hb),and higher expression levels of serum CysC and β2-MG,all of which were statistically significant(P＜0.05).Logistic regression analysis showed that high expression of serum CysC,β2-MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients(OR＞1,P＜0.05).The ROC curves showed that the AUC values of serum CysC,β2-MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788,0.785 and 0.834,respectively.Conclusion:The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and β2-MG,and detection of serum CysC and β2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the role and mechanism of epithelial-mesenchymal transition(EMT)in a rat model of bronchopulmonary dysplasia(BPD).Methods The experiment consisted of two parts.(1)Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group,with 24 rats in each group.The hyperoxia group was exposed to 85%oxygen to establish a BPD model,while the normoxia group was kept in room air at normal pressure.Lung tissue samples were collected on days 1,4,7,and 14 of the experiment.(2)Rat type II alveolar epithelial cells(RLE-6TN)were randomly divided into a normoxia group(cultured in air)and a hyperoxia group(cultured in 95%oxygen),and cell samples were collected 12,24,and 48 hours after hyperoxia exposure.Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs,and immunofluorescence was used to detect the co-localization of surfactant protein C(SPC)and α-smooth muscle actin(α-SMA)in preterm rat lung tissue and RLE-6TN cells.Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells.Results(1)Compared with the normoxia group,the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure.Co-localization of SPC and α-SMA was observed in lung tissue,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group.In the hyperoxia group,the mRNA and protein levels of TGF-β1,α-SMA,and N-cadherin were increased,while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group(P<0.05).(2)SPC and α-SMA was observed in RLE-6TN cells,with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group.Compared to the normoxia group,the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased,while the mRNA and protein levels of TGF-β1,α-SMA,and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure(P<0.05).Conclusions EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD,leading to simplified alveolar structure and abnormal development,and is involved in the development of BPD.

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.