Objective: To analyze the process of handling a pulmonary tuberculosis(TB) outbreak among senior high school students in a boarding school in Chongqing, as well as to investigate the underlying causes of the outbreak, so as to provide evidence to inform TB prevention and control strategies in school settings. Methods: From November 2023 to April 2024, an epidemiological investigation was conducted into the TB outbreak in a grade 12 class from a boarding high school. Suspected cases were screened using symptom screening, tuberculin skin test (TST), and chest X-ray examinations. Confirmed cases underwent individual epidemiological interviews and sputum culture; Cultured positive mycobacterial strains were subjected to whole genome sequencing after identification as Mycobacterium tuberculosis. Results: A total of 10 active pulmonary TB cases were identified, all from the same class, yielding a student attack rate of 16.67%. Three isolates were culture positive, as well as all strains were of L2 type，and the WGS analysis of the strains suggested a common transmission chain. Excluding the index case, four additional cases were detected through symptom driven health care visits. Notably, 70% of patients presented with "chest tightness and chest pain" symptoms, and 50% had "cough" symptoms,but none were detected during morning health checks or tracking of absences due to illness. A total of 326 contacts were identified and underwent three rounds of screening and one follow up examination. In the initial screening, 35 close contacts from the same class showed strong TST positivity, corresponding to a strong positivity rate of 55.56%, significantly higher than the 20.76% observed among casual contacts ( χ 2=29.80, P <0.01). Among the 35 strongly TST positivvity close contacts and five individuals with moderate TST positivity whose induration had increased by ≥10 mm over two years, none received timely preventive treatment initially; five of them were subsequently diagnosed with active TB within three months. Following this, 25 individuals initiated preventive therapy, resulting in a preventive treatment initiation rate of 62.50%. Among TST negative classmates who converted to strong positivity on repeat TST testing at three months, 75.00% started preventive treatment, but only 22.22% completed the full course. Conclusion Inadequate implementation of morning health checks and cause tracking for absenteeism due to illness, poorly standardized screening procedures, and delayed preventive treatment may have been key factors contributing to the spread of the outbreak.

ObjectiveTo evaluate the public health governance capacity in Jiangsu Province and provide an optimized pathway for the construction of a “strong, rich, beautiful, and high-quality” new Jiangsu. MethodsA total of 806 policy documents, 658 public information reports, and 148 research literatures related to public health governance capacity in Jiangsu Province from January 1995 to December 2023 were collected. The status of current public health goverance was assessed based on the evaluation criteria suitable for public health systems, and the strengths and the weaknesses of the system were identified. ResultsThe public health governance capability of Jiangsu Province was scored at 738.3 points, ranking 3rd nationally. Maternal health care and emergency response capacities achieved leading positions nationwide, both ranking 2nd. Jiangsu had exhibited a standardized guidance in the strategic level, a well-established management mechanism, an extensive coverage in information collection, and a scientifically established health targets setting. However, bottlenecks remained, including an unclear division of responsibilities across organizational departments, an insufficient public-health workforce, the absence of a stable growth mechanism for government funding investment, and difficulties in promptly identifying public needs. ConclusionJiangsu’s public-health system demonstrates leading nationally, yet several components remain underdeveloped. Future efforts should consolidate advantages while addressing weaknesses, further diversify content and forms, establish a stable funding increase mechanism, and clarify departmental functions, thereby providing solid health support for realizing the developmental goals of a “strong, rich, beautiful and high-quality” new Jiangsu.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

OBJECTIVE: To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations. METHODS: One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.（2021）GSFY（65）]. RESULTS: The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c.413dupA (p.Tyr138*) frameshift mutation in exon4 and c.573G>A (p.Trp191*) nonsense mutation in exon5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+PM2_Supporting+PM3) and likely pathogenic variant (PVS1+PM2_Supporting), respectively. And the nonsense mutation c.6972C>A (p.Tyr2264*) was detected in exon46 of the NF1 in the fetus, inherited from the mother maternal grandfather. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A (p.Tyr2264 *) was classified as pathogenic variant (PVS1+PS4_Supporting+PP4+PM2_Supporting). CONCLUSION The mutations in the DUOXA2 gene c.413dupA (p.Tyr138*) and c.573G>A (p.Trp191*), and the NF1 gene c.6972C>A (p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c.573G>A (p.Trp191*) enriches the spectrum of pathogenic gene variations.
Humans ; Female ; Pedigree ; Pregnancy ; Neurofibromatosis 1/complications* ; Male ; Genetic Testing ; Adult ; Thyroid Dysgenesis/genetics* ; Fetus ; Exome Sequencing ; Mutation

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with primary infertility accompanied by Oocyte maturation defect (OOMD). METHODS: A 24-year-old female patient who visited the Reproductive Medicine Center of Gansu Provincial Maternity and Child Care Hospital in April 2024 was selected as the study subject. Whole-exome sequencing (WES) was performed on the proband and her husband. Candidate gene variants were validated in the family using Sanger sequencing, and compound heterozygous variants were confirmed through vector construction. Candidate variants were classified for pathogenicity according to the "Standards and Guidelines for the Interpretation of Sequence Variants" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: (2023) GSFYLS(78)]. RESULTS: The proband, a 24-year-old female, had been unable to conceive for four years without contraception after marriage. She had undergone two ovarian stimulation cycles using the antagonist protocol and the PPOS protocol, respectively. A total of 74 oocytes were retrieved, with all showing OOMD and some oocytes exhibiting abnormal morphology and poor quality. WES results revealed two heterozygous missense variants in exons 14 and 16 of the PATL2 gene: c.1127G>A (p.R376Q) and c.1388C>G (p.A463G). Family validation results indicated that the missense variant in exon 14 was inherited from the proband's father, while the variant in exon 16 was de novo. CONCLUSION The compound heterozygous variants of the PATL2 gene probably underlay the OOMD and infertility in this proband. Further analysis based on the variant sites and protein structures is needed to determine whether PATL2 gene variants can fully affect oocyte development, thereby providing a personalized treatment plan for the proband.
Female ; Humans ; Young Adult ; Exome Sequencing ; Infertility, Female/genetics* ; Oocytes/metabolism* ; Pedigree ; Phenotype

UNLABELLED: OBJECTIVE：To explore the clinical characteristics and genetic etiology of a child with CAKUTHED syndrome. METHODS: A child who was admitted to the neonatal department of Gansu Provincial Maternal and Child Health Care Hospital due to "neonatal asphyxia" in May 2021 was selected as the study subject. Genomic DNA was extracted from peripheral venous blood samples from the child and his parents, and whole exome sequencing (WES) was carried out. Sanger sequencing was used to verify the candidate variant of the PBX1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital [Ethics No.: 2021GSFY (65)]. RESULTS: The proband, a male neonate, manifested renal dysplasia, congenital heart disease, pulmonary dysplasia, mediastinal hernia, cryptorchidism, and clavicle dysplasia. WES revealed that he had harbored a heterozygous c.863G>A (p.Arg288Gln) missense variant in exon 6 of PBX1 gene, which resulted substitution of Arginine at position 288 by Glutamine, for which both parents were of the wild type. The variant was unreported previously and rated as pathogenic (PS2+PM1+PM2_Supporting+PP2+PP3) based on the ACMG guidelines. CONCLUSION The c.863G>A variant of the PBX1 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PBX1 gene.
Humans ; Male ; Pre-B-Cell Leukemia Transcription Factor 1/genetics* ; Phenotype ; Infant, Newborn ; Exome Sequencing ; Mutation, Missense ; Heart Defects, Congenital/genetics* ; Abnormalities, Multiple/genetics*

AIM To investigate the renal protective effects of Qizhi Tongluo Formula on a mouse model of diabetic nephropathy.METHODS The male db/db mice were randomly divided into the model group,the dapagliflozin group(0.76 mg/kg)and the low,medium and high dose Qizhi Tongluo Formula groups(7.83,15.65 and 31.3 g/kg),with 6 mice in each group,in contrast to the 6 db/m mice of the control group.When the mice of the control group and the model group were given distilled water by gavage,those of the other administration groups were dosed with the corresponding drug by gavage once daily for 8 weeks.After the drug administration,the mice had their levels of FBG,BUN,Scr and 24 h-UTP detected;their renal pathological changes observed by transmission electron microscopy(TEM)and HE staining;their levels of serum Nrf2,HO-1,Keap1 and renal oxidative stress assessed by ELISA;their renal Nrf2 protein expression observed by immunofluorescence(IF);their renal protein expressions of Nrf2,HO-1 and Keap1 detected by Western blot;and their renal Nrf2,HO-1,and Keap1 mRNA expressions detected by RT-qPCR.RESULTS Compared with the control group,the model group displayed increased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);decreased renal activities of SOD,CAT and GSH-Px(P＜0.01);mild glomerular mesangial hyperplasia,vacuolated renal tubular epithelial cells,widely fused podocyte foot processes,disappearance of tear film,decreased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.05,P＜0.01);and decreased secretion levels of serum Keap1 and renal Keap1 protein and mRNA expressions(P＜0.01).Compared with the model group,the high-dose Qizhi Tongluo Formula group demonstrated decreased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);increased renal activities of SOD,CAT and GSH-Px(P＜0.01);alleviated renal pathological damage,increased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.01);and increased level of serum Keap1 secretion and renal Keap1 protein and mRNA expressions(P＜0.01).CONCLUSION Qizhi Tongluo Formula can inhibit oxidative stress and alleviate kidney damage in db/db mice by activating Nrf2/Keap1/ARE signaling pathway.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.