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 effect of stress-induced protein Sestrin2 (SESN2) on necroptosis of mouse dendritic cell (DC) induced by lipopolysaccharide (LPS) combined with zVAD, a panaspartate-specific cysteine protease (caspase) inhibitor.Methods:The DC2.4 cell line derived from the bone marrow of mouse in the 3rd to 10th generations was cultured. The cells were stimulated with LPS for 0 hour, 6 hours, 12 hours, and 24 hours, and grouped according to the stimulation time points. Western blotting was performed to determine the protein expression of SESN2 in each group. Overexpression empty lentivirus (NC), SESN2 gene overexpression RNA sequence lentivirus (SESN2 LV-RNA), small interfering empty lentivirus (NS), and SESN2 gene small interfering RNA sequence lentivirus (SESN2 siRNA) were transfected into DC2.4 cells. After 72 hours of transfection, cell fluorescence expression was observed under the inverted fluorescence microscope. Cells in each transfection group were stimulated with LPS for 24 hours. The blank control groups were set up and cultured with phosphate buffered saline (PBS) for 24 hours. Western blotting was performed to measure SESN2 protein expression. In the same groups as above, cells were stimulated with LPS+zVAD for 24 hours. The blank control groups were set up and cultured with PBS for 24 hours. Western blotting was used to determine the expression of mixed lineage kinase domain-like protein (MLKL) and phosphorylated-MLKL (p-MLKL). The p-MLKL levels and the number of positive cells were observed using laser scanning confocal microscopy. The necroptotic cell ratios were assessed by both flow cytometry and Hoechst staining.Results:Compared to the LPS 0 hour group, the expression of SESN2 in the LPS 24 hours group showed a significant increase. Therefore, 24 hours was chosen as the subsequent stimulation time point. After successful lentivirus transduction and 24 hours of cultivation, the MLKL phosphorylation level in the SESN2 siRNA+LPS+zVAD group was significantly higher than that in the NS+LPS+zVAD group. The MLKL phosphorylation in the SESN2 LV-RNA+LPS+zVAD group was significantly lower than that in the NC+LPS+zVAD group. The MLKL phosphorylation levels in both the NS+LPS+zVAD group and the NC+LPS+zVAD group were obviously higher than those in the NS+PBS group and the NC+PBS group, respectively. Laser scanning confocal microscopy showed that the trends in quantity and fluorescence intensity of p-MLKL protein expressions were consistent with the above results. The results from flow cytometry analysis and Hoechst staining showed that the rates of cell necrotic apoptosis in SESN2 siRNA+LPS+zVAD group were significantly higher than those in NS+LPS+zVAD group [flow cytometry analysis: (30.800±1.153)% vs. (20.800±1.114)%, Hoechst staining: (75.267±0.451)% vs. (46.267±3.371)%, both P < 0.05], indicating that knocking down SESN2 further exacerbated the occurrence of necroptosis. The necrotic apoptosis rates in SESN2 LV-RNA+LPS+zVAD group were significantly lower than those in NC+LPS+zVAD group [flow cytometry analysis: (7.160±0.669)% vs. (19.240±2.322)%, Hoechst staining: (32.433±3.113)% vs. (48.567±4.128)%, both P < 0.05], indicating that overexpressing SESN2 reversed such response and markedly reduced the proportion of necroptotic cells compared to the corresponding empty vector group. Conclusion:SESN2 exhibits an inhibitory effect on necroptosis of DC in sepsis. Targeted SESN2 expression may regulate the process of DC-mediated immune response in sepsis.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective To investigate the effects of methionine restriction(MR)on macrophages in lipopolysaccharide(LPS)-induced acute lung injury(ALI)and to explore the underlying mechanism.Methods According to the random number table method,36 male C57BL/6J mice(6～8 weeks old,23±2 g)were divided into 3 groups with 12 mice in each group:the sham group,the LPS group and the LPS+MR group.HE staining and pathological scoring of lung injury were performed in lung tissues.The expression of LPS-binding protein(LBP)and Toll-like receptor-4(TLR4)was detected by RT-qPCR and Western blotting.Macrophage-colony stimulating factor(M-CSF),granulocyte-macrophage-colony stimulating factor(GM-CSF)and chemokine C-C motif ligand 3(CCL3)which are all macrophage-associated chemokines were analyzed by immunohistochemistry.Results Compared with the sham group,the pathological score of lung injury in the LPS group was significantly increased(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased;The number of positive cells of CD11b,F4/80,M-CSF,GM-CSF and CCL3 were significantly increased(P＜0.01).MR significantly improved LPS-induced ALI,and decreased the pathological score of lung injury(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were decreased;Compared with the LPS group,the number of positive cells of CD11 b,F4/80,M-CSF,GM-CSF and CCL3 were reduced in the LPS+MR group(P＜0.01).Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.

【Objective】 To analyze the effects of different fortified feeding methods on nutritional metabolism and growth rate of preterm very low birth weight infants (VLBWI), in order to provide new clues for improving the prognosis of the preterm infants. 【Methods】 A total of 115 cases of premature VLBWI admitted to Department of Neonatology, The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020 were included in this study, and were divided into fortified breastfeeding group (HFM group), mixed feeding group, and premature formula feeding group (PF group) based on their feeding methods. The effects of different feeding methods on the nutritional metabolism and growth rate of premature VLBWI were analyzed. 【Results】 1) The hospitalization time of infants in the HFM group was shorter than that in PF group and mixed feeding group (t=7.185, 6.924, P<0.05). 2) The proportion of necrotizing enterocolitis (NEC) in the HFM group during hospitalization was lower than that in the PF group (P<0.05); the proportions of late onset septicemia(LOS) and extra uterine growth restriction(EUGR) in the HFM group during hospitalization were lower than those in the PF group (χ²=5.030, 4.147, P<0.05); the proportion of LOS was lower than that of the mixed feeding group(χ²=6.589, P<0.05). 3) During hospitalization, the proportions of abdominal distension, bloody stools and increased eosinophils in the HFM group were lower than those in the PF group (P<0.05), which in mixed feeding group was lower than those in PF group (Fisher exact test, P<0.05). 4) At discharge, the weight and length growth rate of the HFM group were higher than those of the mixed feeding group (t=3.722, 0.425, P<0.001) and the PF group (t =6.015, 0.496, P< 0.001). 【Conclusion】 Fortified breastfeeding can more effectively increase the growth rate of VLBWI in premature infants, improve nutritional metabolism, reduce complications and adverse feeding reactions related to premature infants, and is safer and more effective.

Objective:To explore the genetic etiology of a Chinese pedigree affected with Branchio-oculo-facial syndrome (BOFS) and summarize the prenatal phenotype of BOFS patients.Methods:A pedigree with BOFS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in December 2021 was selected as the study subject. Clinical data of the pedigree was collected. The fetus was subjected to routine prenatal ultrasound scan. Trio-whole exome sequencing (trio-WES) was carried out for the fetus and its parents, and candidate variant was verified by Sanger sequencing. Relevant literature was searched from the database to summarize the prenatal phenotype of BOFS patients. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Ultrasound exam suggested the fetus had cleft lip and palate. Its father had presented with high palatal arch, prematurely grayed hair, occult cleft lip, congenital preauricular fistula, red-green color blindness and unilateral renal agenesis. Its grandfather also had high palatal arch, prematurely gray hair, protruding ears, congenital preauricular fistula and hearing disorders. Trio-WES revealed that the fetus and its father had both harbored a heterozygous c. 890-1G>A variant of the TFAP2A gene. The same variant was not found in its mother. Sanger sequencing confirmed that its grandfather had also harbored the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PVS1+ PM2_Supporting). Combined with 36 similar cases retrieved from the literature, the prenatal phenotypes of BOFS patients had included growth restriction (25/37), renal abnormalities (10/37), cleft lip and palate (5/37) and oligohydramnios (5/37). Conclusion:The c. 890-1G>A variant of the TFAP2A gene probably underlay the pathogenesis of BOFS in this pedigree. Discovery of the novel variant has enriched the mutational spectrum of the TFAP2A gene. The common prenatal phenotypes of BOFS have included growth restriction, renal abnormalities, cleft lip and palate and oligohydramnios. Delineation of the intrauterine phenotype of BOFS may facilitate its prenatal diagnosis, clinical diagnosis, treatment and genetic counseling.

Objective To investigate the impact and mechanism of efaproxiral (RSR13),a hemoglobin allosteric agent,on lung injury in rats caused by explosion-induced shock waves in plateau areas. Methods Eighty-two healthy male SD rats (8-week-old,transferred from an altitude of 2 880 m to 4700 m within 6 h)were randomly divided into blast injury group and RSR13+blast injury group (intraperitoneal injection of 150 mg/kg RSR132 h before explosion).Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group (n=30)and 5-m RSR13+blast injury group (n=30). Additionally,16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group (n=8)and 6-m RSR13+blast injury group (n=8).The left 6 rats served as control (n=6).Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period.HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion,along with arterial blood gas analysis.The contents of glutathione (GSH),malondialdehyde (MDA ) and superoxide dismutase (SOD ) in the lung tissues were determined by colorimetry.Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue.Results RSR13 pretreatment increased the survival rate immediately after explosion (93.3％ vs 46.7％,P<0.01 )and at 1 h after explosion (86.7％ vs 46.7％,P<0.01 )in plateau areas of 5 m from the explosion source.At high altitude,RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source (8.27±0.93 vs 13.70±0.78,P<0.01 ),but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury (P>0.05 ).In addition,RSR13 pretreatment also increased GSH content (40.27±12.47 vs 22.62±10.88 μg/g,P<0.05),but showed no obvious effect on MDA content and SOD activity (P>0.05 ),decreased the protein level of cleaved caspase-3 (P<0.01 )and increased that of occludin (P<0.05 )in the lung tissues.Conclusion RSR13 exerts significant protective effect on lung injury in rats caused by explosion-induced shock waves in high-altitude environment,which may be related to its increasing antioxidant capacity,reducing cell apoptosis and decreasing barrier permeability of lung ventilation.

A new Schiff base fluorescence probe (E)-3-(4-(E)-((4-hydroxyphenyl) imino) methyl) phenyl)-1-(6-methoxynaphthal-2-yl) isopropyl-2-en-1-one (DFFH) was synthesized by using 6-methoxy-2-acetylnaphthalene as raw material. The probe was characterized by nuclear magnetic resonance (1H NMR,13C NMR) and high-resolution mass spectroscopy (HRMS),etc. In the EtOH-H2O (1:4,V/V) system,the 4-hydroxyaniline portion of probe DFFH complexed with Fe3+to form a 1:1 metal complex,resulting in a significant decrease in fluorescence at 386 nm. In the DMSO-H2O (9:1,V/V,pH=5) system,N2H4 reacted with α,β-unsaturated carbonyl group and underwent cyclization addition reaction,and at the same time,the cleavage of the imine bond released aldehyde group from the probe,showing a ratio type fluorescence recognition characteristices. The luminescence intensity of the probe solution decreased slightly upon the additon of Fe3+,and the probe solution changed from colourless to yellowish-brown with the addition of different concentrations of N2H4. Whereas the detection of Fe3+and N2H4 did not interfere with each other. The experimental results showed that probe DFFH had high sensitivity and selectivity toward Fe3+and N2H4,with detection limit of 34.0 nmol/L for Fe3+and 30.0 nmol/L for N2H4,respectively. Moreover,probe DFFH was applied to detection of the contents of Fe3+and N2H4 in actual water samples with satisfactory results,and the spiking recoveries were 96.5％～102.3％and 98.1％～103.0％,respectively.

Objective To investigate the expression of long non-coding RNA(lncRNA)small nucleolar RNA host gene(SNHG)25 and microRNA(miR)-497-5p in glioma tissues and their relationship with clinical features and prognosis.Methods A total of 157 glioma patients admitted to the hospital from January 2019 to January 2020 were selected as the glioma group,and 100 patients who underwent surgical treatment due to craniocerebral injury in the same hospital during the same period were selected as the control group.The ex-pression levels of lncRNA SNHG25 and miR-497-5p were detected in glioma tissues and normal brain tissues resected during operation.The patients were followed up for 3 years.The correlation between the expression levels of lncRNA SNHG25 and miR-497-5p was analyzed,and the relationship between the expression level of lncRNA SNHG25 and miR-497-5p and the clinical characteristics and prognosis of patients were analyzed.Re-sults Compared with the control group,the expression level of lncRNA SNHG25 in the glioma group was in-creased(P＜0.05),and the expression level of miR-497-5p was decreased(P＜0.05).Compared with the maximum diameter of tumors＜4 cm,World Health Organization(WHO)central nervous system tumor grade Ⅰ-Ⅱ,the expression level of lncRNA SNHG25 was increased and the expression level of miR-497-5p was decreased in glioma tissues with the maximum diameter of tumors ≥4 cm and WHO central nervous sys-tem tumor grade Ⅲ-Ⅳ(P＜0.05).The expression level of lncRNA SNHG25 in glioma patients was nega-tively correlated with miR-497-5p(r=-0.370,P＜0.05).The cumulative survival rate of lncRNA SNHG25 high expression group was lower than that of lncRNA SNHG25 low expression group(P＜0.05),and the cu-mulative survival rate of miR-497-5p low expression group was lower than that of miR-497-5p high expression group(P＜0.05).Grade Ⅲ-Ⅳ of WHO central nervous system tumor grade and high expression of lncRNA SNHG25 were risk factors for poor prognosis of glioma patients(P＜0.05),while high expression of miR-497-5p was a protective factor(P＜0.05).Conclusion The expression of lncRNA SNHG25 is increased and the expression of miR-497-5p is decreased in glioma tissues,which is related to the maximum diameter of tumor and high WHO central nervous system tumor grade,and can lead to poor prognosis of glioma patients.

Objective To observe the effect of pressure-controlled ventilation volume-guaranteed(PCV-VG)mode on respiratory mechanics,lung injury markers and postoperative pulmonary complications(PPCs)in thoracoscopic patients.Methods Fifty-nine patients undergoing elective thoracoscopic lobecto-my,29 males and 30 females,aged 18-64 years,BMI 18.5-26.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using a random number table method:the PCV-VG mode group(group P,n=29)and the volume-controlled ventilation(VCV)mode group(group V,n=30).The PCV-VG mode was used for one-lung ventilation(OLV)in group P,and the VCV mode was used in group V.Anesthesia in-duction and maintenance medications were consistent in all patients.PaO2 was recorded before induction of anesthesia,5 minutes after intubation,15 minutes after OLV,30 minutes after OLV,and 3 days postopera-tively,and oxygenation index(OI)and intrapulmonary shunt rate(Qs/Qt)were calculated.Peak airway pressure(Ppeak),pulmonary dynamic compliance(Cdyn),and driving pressure(DP)were recorded 5 minutes after intubation,15 minutes after OLV,and 30 minutes after OLV.Clara cell secretory protein-16(CC-16)and interleukin-6(IL-6)concentration were measured before induction of anesthesia and after ex-tubation.Recording the occurrence of PPCs within 1 week after surgery.Results Compared with group V,Ppeak and DP were significantly reduced,Cdyn was increased significantly in group P 15 minutes and 30 minutes after OLV(P＜0.05),PaO2 and OI were significantly increased in group P 3 days postoperatively(P＜0.05),CC-16 and IL-6 concentrations were significantly reduced in group P after extubation(P＜0.05).Compared with group V,the incidence of PPCs was significantly reduced in group P(P＜0.05).Conclusion During one-lung ventilation for thoracoscopic surgery,the pressure-controlled ventilation vol-ume-guaranteed mode reduces peak airway pressure and driving pressure,improves pulmonary dynamic compliance and improves oxygenation,reduces the incidence of PPCs.