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 therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.

BACKGROUND:The occurrence and development of various ophthalmic diseases are closely related to excessive oxidative stress,and the inhibition of oxidative stress response may produce preventive and therapeutic effects. OBJECTIVE:To explore the role of Pax6 gene expression on hydrogen peroxide-induced aging of mouse bone marrow mesenchymal stem cells(BM-MSCs). METHODS:Resuscitated BM-MSCs,Pax6/BM-MSCs,and shPax6/BM-MSCs were treated with hydrogen peroxide for 24 hours,and then β-galactosidase staining was performed.The proliferation index Ki67 expression and apoptosis were detected by flow cytometry.The expression of senescence-associated molecules(Wnt7a,p21,and p53)was detected by RT-PCR. RESULTS AND CONCLUSION:(1)After hydrogen peroxide treatment,the cells of the three groups showed senescence phenotype and β-galactosidase staining was positive.Compared with BM-MSCs group,the expression of positive cells in Pax6/BM-MSCs group was less and that in the shPax6/BM-MSCs group was more,and the difference was statistically significant(P<0.05).(2)The results of flow cytometry showed that compared with BM-MSCs group,the positive expression of Ki67 in the Pax6/BM-MSCs group increased and the level of apoptosis decreased,while the positive expression of Ki67 decreased and the level of apoptosis increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(3)RT-PCR showed that compared with the BM-MSCs group,the expression of Wnt7a,p53,and p21 decreased in the Pax6/BM-MSCs group,while the expression of Wnt7a,p53,and p21 increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(4)These findings indicate that overexpression of Pax6 can antagonize the aging progression of BM-MSCs induced by hydrogen peroxide,which may be related to Wnt signaling pathway.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
Calcium ; Acupuncture Therapy ; Acupuncture ; Acupuncture Analgesia/methods* ; Acupuncture Points ; Technology

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Background The monitoring of external radiation individual doses for radiation workers is a statutory task and serves as an important basis for the diagnosis of occupational diseases in this occupational group. Ensuring the accuracy and reliability of monitoring data is crucial for safeguarding the health of radiation workers. Objective To evaluate and compare the capabilities and levels of external radiation individual dose monitoring conducted by radiation hygiene service institutions in Shanghai, to standardize relevant workflows, and to improve the accuracy and reliability of the monitoring service. Methods From 2021 to 2023, annual intercomparisons of external radiation individual dose monitoring capabilities were organized for radiation hygiene service institutions in Shanghai. The study subjects were 19 to 21 radiation hygiene service institutions registered in Shanghai for each year and they all participated in the intercomparisons. The monitoring subjects included 16 district-level centers for disease control and prevention (CDCs) and 13 third-party testing agencies. Monitoring capabilities were analyzed based on single-group performance, comprehensive performance, and Q-value. In the intercomparison, a thermoluminescent dosimetry system was used to perform irradiation tests on thermoluminescence dosimeter [made of lithium fluoride (magnesium, copper, phosphorus), LiF (Mg, Cu, P)], and monitoring data for X-rays and γ-rays at different doses and radiation conditions were analyzed following a standard procedure specified by GBZ 207−2016. Statistical methods included t-test and Kolmogorov-Smirnov test, with statistical significance set at P<0.05. Results From 2021 to 2023, the number of participating institutions was 19, 21, and 19, respectively, with an overall pass rate of 94.9% (56/59). Two institutions failed in 2022 and one in 2023. The number of institutions meeting the excellent standard in single-group and comprehensive performance was 9, 12, and 13, respectively, and the number of institutions ultimately rated as excellent was 3, 7, and 8,respectively, with an overall excellence rate of 30.5% (18/59) and an excellence conversion rate of 52.9%. The pass rates for single-group and comprehensive performance were both 98.3%. The number of groups with negative deviation was 1.86 times that of groups with positive deviation for X-rays, and 1.10 times for γ-rays. For X-rays, there was a statistically significant deviation between doses of less than 1.0 mSv and more than 1.0 mSv (P=0.01), while there was no significant difference in the single-group performance deviation between X-rays and γ-rays at the same dose. There was a statistically significant difference between the reported and reference values for X-rays in 2021 and 2022 (P<0.05), but no significant difference in 2023 (P>0.05); there was no significant difference between the reported and reference values for γ-rays over the three years (P>0.05). Conclusion Over the past three years, the external radiation individual dose monitoring capability intercomparison results of radiation hygiene service institutions in Shanghai have shown that the pass rate remains at a high level, with the excellence rate increasing year by year. However, some institutions still need to improve their monitoring capabilities, and further cooperation among institutions and training for technical staff are needed to enhance the capabilities and standardization of external radiation individual dose monitoring in Shanghai.