Objective To understand the status of quality control in occupational medical examination (OME) institutions in Guizhou Province. Methods A total of 124 registered OME institutions actively conducting OME in Guizhou Province were selected as the study subjects using the judgment sampling method. The evaluation was conducted by on-site document reviews, practical skill assessments, and investigation of OME practices for quality evaluation and analyzing their quality control performance. Results The public institutions accounted for 71.0% with a 41.5% of OME workload, while private institutions accounted for 29.0% with a 58.5% of OME workload among these 124 OME institutions. The overall pass rate for quality evaluation of OME institutions was 16.9% (21/124), with a total of 1 296 items failed to pass the quality evaluation. Among the unqualified items, organizational structure, quality control management systems, OME quality control, and information reporting accounted for 15.2%, 21.7%, 52.8%, and 10.3%, respectively. The unqualified rate of quality assessment items of OME institutions was 24.5% (1 296/5 288), and the unqualified rate was lower in public institutions compared with private institutions (22.4% vs 29.3%, P<0.01). The rates of the three key unqualified items, including chest radiography conclusion evaluation, audiogram calculation and conclusion evaluation, and blood lead comparison were 9.8%, 74.8% and 71.4%, respectively. The rates of unqualified audiometry operation test and chief physician theory test were 74.8% and 9.7%, respectively. Conclusion The quality of OME institutions in Guizhou Province requires continuous improvement, particularly in enhancing the abilities of audiometry operation, calculating audiogram results and conducing right conclusion, and blood lead inter-laboratory comparision.

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

ObjectiveTo investigate the incidence of hypertension and its influencing factors in community-dwellers at risk for high blood pressure in Minhang District of Shanghai， and to provide scientific evidence for the community management. MethodsA retrospective cohort study was conducted using the electronic health records of community-dwellers at risk for high blood pressure in Minhang District， Shanghai from January 1， 2011 to December 31， 2017. The study end-point was the occurrence of hypertension，and the followup was finished in December 2021. A total of 17 265 community-dwellers at risk for high blood pressure were enrolled in our study. Log-rank test and Cox regression analysis were used to determine the influencing factors. ResultsAfter 6.04 years of follow-up， the hypertension incidence among community-dwellers at risk for high blood pressure in Minhang District of Shanghai was 25.5%. Family history of hypertension （HR=1.250， 95%CI： 1.168‒1.338）， family history of stroke （HR=1.295， 95%CI： 1.080‒1.553）， history of diabetes （HR=1.203， 95%CI： 1.076‒1.345）， daily smoking （HR=1.187， 95%CI： 1.087‒1.296）， overweight （HR=1.393， 95%CI：1.308‒1.484）， obesity（HR=1.903， 95%CI： 1.719‒2.106）， high values of normal blood pressure （HR=1.275， 95%CI： 1.195‒1.359） and advanced age （HR=1.033， 95%CI： 1.030‒1.036） were all risk factors. Emaciation （HR=0.649， 95%CI： 0.500‒0.840） was a protective factors. ConclusionBlood pressure monitoring should be strengthened for people elderly， with family history of hypertension， family history of stroke， diabetes or high values of normal blood pressure， so as to diagnose hypertension early. Timely intervention measures should be taken for community-dwellers with unhealthy lifestyles such as smoking， overweight and obesity.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

BACKGROUND:Peripheral nerves play an important role in bone metabolism.In clinical practice,the specific impact of nerve injury on bone transport technology needs further study. OBJECTIVE:To investigate the effect of tibial nerve injury on the treatment of tibial slip by single-plane osteotomy. METHODS:Thirty-two patients with tibial bone defects admitted to Tangshan Second Hospital from May 2011 to June 2022 were selected.According to the presence or absence of tibial nerve injury,patients were divided into the tibial nerve injury group(n=16)and the non-tibial nerve injury group(n=16).Both groups were treated with single-plane osteotomy and bone slip.After treatment,the patients were followed up to collect the mineralization zone healing index,external fixation index,docking point healing and needle infection.After the removal of external fixation,the bone healing and functional evaluation were evaluated by a classification of the Association for the Study and Application of the Method of Ilizarov(ASAMI). RESULTS AND CONCLUSION:(1)All 32 patients were followed up for(25.28±4.79)months.There were no significant differences in bone healing time,external fixation time,healing index and external fixation index between the two groups(P＞0.05).Needle infection occurred in two cases of the tibial nerve injury group and one case of the non-tibial nerve injury group,all of which were PALEY I,and there was no significant difference between the two groups(P＞0.05).The non-union rate of the occlusal end of the tibial nerve injury group was 31%,and that of the non-tibial nerve injury group was 13%;there was no statistical difference between the two groups(P＞0.05).The excellent and good rate of ASAMI bone healing score in the two groups was 100%;the excellent and good rate of limb score was 81%in the tibial nerve injury group and 94%in the non-tibial nerve injury group;there was no statistical difference between the two groups(P＞0.05).(2)Our research shows that tibial nerve injury has no significant effect on the mineralization speed,external fixation time,union of the occlusal end,infection of the needle tract,and the quality of bone formation in the mineralized area of the single-plane osteotomy.

Objective:To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients.Methods:We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison.Results:The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM ( P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM ( P=0.035) . Conclusion:This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.