Objective　To investigate the level of pertussis antibody in 344 healthy population in Hebei Province in 2023, and to understand the infection status and estimate the potential infection of pertussis. Methods　A total of 344 healthy people of all ages from 7 cities (counties) in Hebei Province in 2023 were stratified by random sampling method. The demographic characteristics, vaccination history and pertussis history of the subjects were collected. Serum IgG antibody against pertussis toxin (PT-IgG) were determined by enzyme-linked immunosorbent assay (ELISA). Results　The geometric mean concentration (GMC) of PT-IgG in 344 healthy people was 5.28 IU/mL, and the antibody positive rate (PT-IgG concentration ≥ 40 IU/mL) was 6.10% (21/344). There was no significant difference in proportion of antibody levels and antibody concentration ≥40 IU/mL between males and females. The top three regions with the highest antibody positive rate were Xinhe County in Xingtai (20.00%), Lianchi District in Baoding (11.43%), and Shijiazhuang (9.37%). There was a significant difference in pertussis antibody levels among different regions (P=0.007), but no significant difference in pertussis antibody concentration ≥40 IU/mL among different regions (P=0.100). The GMC of antibody was the highest in the 1~<3 years old group (11.45 IU/mL), followed by the <1 year old group (8.15 IU/mL). There was a significant difference in the pertussis antibody levels among different age groups (P=0.001). The proportion of antibody concentration ≥40 IU/mL was the highest in the 1~<3 years old group (20.83%), followed by the <1 year old group (12.77%). There was a significant difference in the proportion of antibody concentration ≥40 IU/mL among different age groups (P=0.028). And 303 (88.08%) cases of the 344 healthy people had a history of DTaP , 4.62%, 46.86% and 48.52% of healthy people had completed 1-2 , 3 and 4 doses of DTaP, respectively. Among the healthy people who had completed 1-2 doses of DTaP, there was no significant difference in the level of pertussis antibody among different age groups (P=0.47). Among the healthy people who had completed 3 doses of basic immunization and 4 doses of complete immunization, there was a significant difference in the level of pertussis antibody among different age groups (P=0.04, P=0.01). There was no significant difference in the proportion of PT-IgG concentration ≥40 IU/mL among different age groups and different immunization doses (P=0.72). Conclusion　The overall antibody level and proportion of PT-IgG concentration ≥40 IU/mL in the healthy population of Hebei Province in 2023 were both low, indicating the inadequacy of the protective effect of the current immunization program for children, although vaccinated people could still infect with pertussis disease, we need to further monitoring and optimization of immune strategies indicating.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.

Objective:To investigate the carriage status of Neisseria meningitidis ( Nm) among the healthy population in Hebei Province for the prevention and control of meningitis. Methods:From 2015 to 2022, throat swabs were collected from health people, which were selected by cluster random sampling in 11 cities of Hebei.The positive rate of Nm was detected by bacterial culture. The serogroups of isolated strains were identified.The laboratory detection results of Nm strains, combined with epidemiological survey data, were synthetically analyzed. Results:A total of 20 245 people were investigated; 249 strains of Nm were isolated; the overall Nm carriage rate was 1.23%. The carriage rate was significantly higher in men than in women(χ 2=28.831, P<0.05). The positive rates of Nm in different age groups were significantly different(χ 2=428.018, P<0.05), with the highest rates in the 15-19 year-old group(4.90%, 149/3 042). The positive rates of Nm were significantly different in different regions(χ 2=177.512, P<0.05), with the highest positive rate of Nm in Xingtai, Shijiazhuang, Chengde and Baoding city in sequence. Among the isolated Nm strains, ungroupable serogroups, serogroup B, serogroup C, and serogroup W accounted for 71.49%(178/249), 13.65%(34/249), 6.83%(17/249) and 4.42%(11/249), respectively. Conclusions:The carriage rate of Nm among healthy population is generally low in Hebei Province. It is recommended to continue to strengthen monitoring, pay attention to the changes and distribution characteristics of Nm, and formulate scientific and targeted prevention and control measures of meningococcal disease.

Background: and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. Results: We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. Conclusions These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

Abstract: Objective To evaluate the impact of meningococcal vaccine immunization on the incidence of meningococcal meningitis, aiming to refine the local immunization strategies and programs. Methods Data on the reported incidence of meningococcal meningitis in Hebei province for 1970-2023 were collected, and interrupted time-series( ITS) analysis was used to quantitatively analyze the levels and slope change of the incidence of meningococcal meningitis before and after vaccine immunization and before and after inclusion in the Expanded Program on Immunization (EPI). Results The annual average reported incidences of meningococcal meningitis in Hebei province before vaccination (1970-1979), before (1980-2007) and after (2008-2023) the inclusion of the vaccine in the EPI were respectively 20.79 per 100 000, 1.66 per 100 000, and 0.018 per 100 000. The interrupted time-series analysis from 1970 to 2023 showed an initial meningitis incidence rate of 24.12 per 100 000 (t=9.86, P<0.05), with an average annual decrease of 1.07 per 100 000 (t=-2.42, P<0.05). After the introduction of the meningococcal vaccine in 1980, the incidence of meningococcal meningitis decreased quickly with an annual average decline of 18.39 per 100 000, showing a significant short-term intervention effect (t=-2.70, P<0.05); however, the rate of decrease slowed over the long term to 0.13 per 100 000, with the long-term intervention effect not being significant (P>0.05). And the incidence was significantly increased due to the outbreak (t=7.80, P<0.05). From 1980 to 2023, the initial level of incidence was 5.13 per 100 000 (t=8.70, P<0.05), and decreased by 0.23/100 000 per year on average (t=-6.42, P<0.05). After the inclusion of the vaccine in the EPI in 2008, the rate of decrease further slowed down to an average of 0.008 per 100,000 per year, with the long-term intervention effect being significant (t=2.50, P<0.05); the impact of epidemic outbreaks on incidence during this period was not statistically significant (P>0.05). Conclusions Meningococcal meningitis vaccination has led to a general downward trend in the incidence of meningitis in Hebei Province, and has flattened the trend of increased incidence caused by outbreaks. Therefore, long-term maintenance in immunization programs on the meningococcal meningitis is necessary. In addition, it is important to strengthen the monitoring of the distribution of epidemic serogroups in patients and healthy carriers, and to adjust immunization strategies timely based on changes in bacterial populations, selecting and promoting vaccines accordingly for the prevalent strains.

Abstract: Objective To analyze the epidemiological characteristics of human brucellosis in Hebei Province, and to explore strategies and measures for its prevention and control. Methods Data on brucellosis cases reported in Hebei Province were collected from the National Notifiable Infectious Disease Reporting Information System. The total situation of brucellosis was described, and the epidemiological characteristics of brucellosis in Hebei Province were analyzed. The spatial autocorrelation analysis method was used to explore the spatial distribution characteristics of brucellosis incidence at the county level in Hebei Province. Results From 2018 to 2023, a total of 21 718 cases of brucellosis were reported in Hebei Province, with 1 death (in 2021). The annual incidence rate fluctuated between 3.91/100 000 to 6.26/100 000, with an average annual reported incidence rate of 4.84/100 000. The epidemic peak was from April to July, showing obvious seasonal characteristics. The incidence in males was higher than in females, with a male-to-female ratio of 2.81∶1. The incidence age was concentrated 30-<70 years, accounting for 85.33% of the total cases. The primary occupational group affected was farmers, accounting for 88.59%. The top three cities with the highest average annual incidence rate were Zhangjiakou, Chengde, and Hengshui, which reported a total of 7 801 cases, representing 35.92% of the total cases in the province. From the perspective of spatial distribution: the global spatial autocorrelation analysis showed clustering distribution in Hebei Province from 2018 to 2023, and there were hot spots in local spatial autocorrelation analysis. The high-incidence areas of brucellosis were mainly concentrated in Zhangjiakou (13.651 3/100 000) and Chengde (13.116 7/100 000) in the north of Hebei Province during the past six years. The "low-low" clustering areas were mainly distributed in Tangshan, Shijiazhuang, and Handan. The "low-high" clustering areas were mainly located around the "high-high" cluster areas, in some counties of Zhangjiakou and Chengde. Conclusions The situation of human brucellosis prevention and control in Hebei Province remains challenging. It is recommended to strengthen the management of infection sources, enhance the surveillance of human brucellosis, focus on health education and behavior intervention in high-risk groups, and intensify prevention and control efforts in the hotspot areas.

Objective To construct a comorbidity network for medical expenses by analyzing the rele-vant medical records,and to construct a deep learning prediction model by combining with the disease net-works and long short-term memory neural networks in order to improve the accuracy of individual medical ex-pense prediction and provide the assistance for optimizing the medical policies and enhancing the patient health management level.Methods Based on the medical records of Taiwan,China Health Insurance Research Data-base during 2000-2013,the data of 5.84 million visits from 9 963 patients were analyzed,and a comorbidity network of medical expenses for 104 common diseases was constructed.The network structure was analyzed and the potential comorbidity was predicted,and the deep learning model of individual medical cost was con-structed by combining the input of patient's gender,age,medical history and other information.Results The constructed medical cost comorbidity network consists of 104 nodes,3 390 edges and 6 modules,and is a high-ly connected network with nodes,indicating that the medical costs possesses the high correlation between dis-eases.The constructed deep learning prediction model significantly improves the prediction accuracy compared to the traditional regression models and deep learning models that do not fully consider the comorbidity infor-mation.Conclusion The constructed model provides a new theoretical perspective for understanding the co-morbidity of diseases,as well as an effective tool for accurately predicting medical costs,optimizing medical re-source allocation and achieving the personalized medical services.

Objective:To evaluate the value of conventional ultrasound, shear wave elastic parameters and immunohistochemistry in predicting axillary lymph node metastasis of breast cancer.Methods:The ultrasonographic features and pathological results of 172 masses in 152 breast cancer patients who underwent surgery in the First Affiliated Hospital of Shihezi University Medical College from May to October 2020 were analyzed retrospectively. The patients were divided into metastatic group and non-metastatic group according to the status of axillary lymph nodes. The conventional ultrasound characteristics, shear wave velocity (SWV) and immunohistochemical indexes (ER, PR, HER-2, Ki-67) of 2 groups of breast cancer masses were analyzed. Finally, the parameters with statistically significant difference between groups were selected and the Logistic regression model was established.Results:There were significant differences in the aspect ratio, calcification, SWVmean and HER-2 expression between metastatic group and non-metastatic group (all P<0.05). A prediction model was constructed with aspect ratio >1, calcification, high SWVmean and HER-2(+ ). The area under receiver operating characteristic curve (AUC) of the subjects was 0.891, which was larger than the single parameter (all P<0.05), and was in good agreement with pathological results (Kappa=0.731). Conclusions:The joint prediction model can be used to predict the status of lymph nodes, and the axillary lymph node metastasis is more likely to occur in breast cancer with the aspect ratio >1, calcification, high SWVmean and HER-2(+ ).