ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Objective To observe the expression of Galectin-3 in peritoneal dialysis (PD) fluid in patients with different dialysis ages, and to conduct correlation analysis with vascular endothelial growth factor (VEGF) , fi-bronectin (FN) and related clinical indicators.Methods A total of 109 PD patients who were regularly followed up in the department of nephrology were divided into four groups according to different peritoneal dialysis ages.The concentrations of Galectin-3, VEGF and FN were determined by enzyme-linked immunosorbent assay.The expres-sion of Galectin-3 in peritoneal dialysate of the 4 groups was compared, the correlation with VEGF, FN and clinical related indexes was analyzed, and the correlation was analyzed by Spearman test.Results The concentration of VEGF in peritoneal dialysis patients in group D significantly increased (P<0.05) .Galectin-3 expression levels were positively correlated with VEGF (r =0.358 , P =0.022) , but not significantly correlated with FN (r =0.121, P=0.452).Galectin-3 was positively correlated with clinical indicators parathyroid hormone (PTH) (r=0.201, P=0.037), C-reactive protein (CRP) (r=0.357, P<0.001), left ventricular posterior wall dimensions (LVPWD) (r=0.213, P=0.026), and negatively correlated with clinical indicators total cholesterol (TC) (r=-0.316, P=0.001).Conclusion The concentration of Galectin-3 in the dialysate of long-term peritoneal dialy-sis patients is significantly elevated, indicating that the expression of galectin-3 increases with the extension of peri-toneal dialysis time, suggesting that the detection of galectin-3 levels may be helpful for the evaluation of early peri-toneal fibrosis.The positive correlation with VEGF may suggest its role in promoting peritoneal angiogenesis and fi-brosis.Moreover, it is positively correlated with clinical indicators PTH, CRP and LVPWD, suggesting that it has certain clinical guiding significance on microinflammatory state and myocardial remodeling.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Background and purpose:Breast cancer is a major global public health problem.Bone is the most common site of distant metastasis of breast cancer,accounting for about 70%of all metastatic cases.Bone metastasis of breast cancer can cause a series of complications,including severe pain,pathological fracture,hypercalcemia,spinal cord compression,etc.,which bring great inconvenience to patients'physical activities and affect their quality of life.Metastatic recurrence is the leading cause of death in breast cancer patients.Therefore,there is an urgent need to build a diagnostic model of bone metastasis in breast cancer to identify patients with a high risk of bone metastasis.The aim of this study was to develop a predictive model based on machine learning to predict the probability of breast cancer developing bone metastasis.Methods:Data of breast cancer patients diagnosed between 2010 and 2015 were extracted from The Surveillance,Epidemiology,and End Results(SEER)database.The variables were screened by least absolute shrinkage and selection operator(LASSO)regression,univariate and multivariate logistic regression analysis,and statistically significant risk factors were included to build a prediction model.In this study,nine machine learning algorithms,including decision tree,elastic network,K-nearest neighbor,lightweight gradient elevator,logistic regression,neural network,random forest,support vector machine and limit gradient lifting,were used to adjust the model hyperparameters through random search and 5x cross-validation to build a breast cancer bone metastasis prediction model.The area under the receiver operating characteristic(ROC)curve,calibration curve and decision curve were used to evaluate the model,the optimal model was obtained,and the importance of variables was analyzed based on the optimal model.Finally,a network calculator for predicting the risk of bone metastasis of breast cancer was established using the optimal model.Results:The study included 10 106 patients with breast cancer,7 073 patients in the training set,and 3 033 patients in the validation set.We found that 4 494(63.5%)patients in the training set and 1 927(63.5%)patients in the validation set developed bone metastases,respectively.Race,pathologic grade,estrogen receptor(ER)status,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER2)status,N stage,lung metastasis,radiotherapy,chemotherapy and surgery were independent predictors of bone metastasis.The training set and verification set were used to verify the model,and the limit gradient lifting algorithm was superior to other machine learning algorithms by integrating the evaluation indexes such as the area under the ROC curve,calibration curve and decision curve.Finally,we used limit gradient algorithm to build network calculator for prediction of breast cancer bone metastases(https://bcbm.shinyapps.io/DynNomapp/).Conclusion:This study developed a predictive model based on machine learning to predict the probability of bone metastases in breast cancer patients,hoping to help clinicians make more rational treatment decisions.

Objective To propose an evaluation and screening indicator for the reliability of emergency ventilators.Methods Firstly,a regression model was used to clean the data and remove noise to ensure the accuracy of regression analysis.Then,four groups of highly correlated data combinations,including inspiratory tidal volume-minute expiratory volume,peak airway pressure-minute expiratory volume,peak airway pressure-inspiratory tidal volume and positive end-expiratory pressure(PEEP)-mean airway pressure,were determined with the methods of curve fitting and transfer function,and the difference between the theoretical output and the actual output of the data combinations was regarded as an indicator to judge whether the ventilator functioned well or not;finally,the indicator proposed was applied to single and multiple ventilators,and the feasibility of the indicator was determined by the proportion of the ventilators functioning well.Results The evaluation results with a single ventilator showed the four groups of data combinations had the actual output fitted well with the theoretical output,and all the differences between the theoretical output and the actual output were lower than the threshold;the results with multiple ventilators indicated there were 71.49％ventilators functioning well,which was very close to the actual result that 72％ventilators behaved well.Conclusion The evaluation and screening indicator for emergency ventilators has high feasibility,and theoretical support is provided for reliability assessment and selection of series of emergency treatment equipment.[Chinese Medical Equipment Journal,2024,45(7):8-16]

Objective To analyze the medication rules of national patented Chinese herbal compounds for the treatment of diabetic peripheral neuropathy(DPN)by data mining method,and to provide reference for clinical medication.Methods The patents of Chinese medicine compound for the treatment of DPN were retrieved from the website of the China National Intellectual Property Administration(CNIPA).Excel 2021 was used for frequency statistics.RAW Graphs 2.0 was used to make a Sankey diagram of the efficacy of high-frequency Chinese medicinals.SPSS Statistics 25.0 software was used for hierarchical cluster analysis of the medicines,and the core prescriptions were mined based on Cytoscape 3.9.1.Results A total of 101 patented prescription were included,involving 243 herbs.The top three Chinese medicines in the descending order of occurrence frequency were Salviae Miltiorrhizae Radix et Rhizoma,Astragali Radix,and Paeoniae Radix Alba.Most of the medicines of patented Chinese medicine compounds for the treatment of DPN were warm and mild in nature,sweet,bitter and pungent in flavor,and had the meridian tropism of liver,heart and spleen meridians.According to the therapeutic actions,the medicine can be divided into tonic drugs,blood-activating and stasis-removing drugs,exterior-releasing drugs,liver-calming and wind-extinguishing drugs,heat-clearing drugs,bleeding-arresting drugs,mind-calming drugs,and urination-promoting and dampness-percolating drugs.The association rule analysis revealed the drug combination of Astragali Radix and Angelicae Sinensis Radix with the highest support.After hierarchical cluster analysis,the top 31 Chinese medicinals were classified into 7 groups.The core prescription which was composed of 7 medicines,namely Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix was finally mined out.Conclusion The treatment of DPN with patented Chinese herbal compounds is based on the therapies of supplementing deficiency,activating blood and removing stasis,and warming and unblocking meridians and collaterals.Meanwhile,consolidating the acquired foundation by strengthening spleen and soothing liver is also stressed.Clinically,the herbal pairs of Astragali Radix-Angelicae Sinensis Radix,Paeoniae Radix Alba-Salviae Miltiorrhizae Radix et Rhizoma are the optional drugs,and the core prescription composed of Astragali Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix,Cinnamomi Ramulus and Angelicae Sinensis Radix can be used for the whole course of DPN.

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 screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.