Objective To analyze the trends in the disease burden of pertussis in China from 1990 to 2021, and to provide a basis for the development of effective prevention and control strategies. Methods Using the 2021 Global Burden of Disease Study (GBD) database, the incidence, mortality, and disability-adjusted life years (DALYs), as well as the age-standardized rates of pertussis in China from 1990 to 2021 were analyzed. Descriptive statistical methods were employed to analyze the characteristics of the pertussis disease burden, and the Joinpoint regression model was used to analyze the trends in pertussis disease burden. Results From 1990 to 2021, the incidence, mortality, and DALYs of pertussis in China decreased from 1 503 800 cases, 10 951 deaths, and 954 900 person-years to 65 400 cases, 548 deaths, and 46 500 person-years, representing a decrease of 95.65%, 95.00%, and 95.13%, respectively. The corresponding age-standardized rates also decreased by 93.58%, 92.47%, and 92.53%, respectively. The Joinpoint regression model revealed a significant downward trend in the age-standardized incidence, mortality, and DALYs rates for pertussis (AAPCs were -8.32%, -9.65%, and -9.58%, respectively, P<0.001). The disease burden was slightly higher in females than in males, with the majority of cases occurring in children under 10 years old, particularly in infants under 1 year old, where the burden was the heaviest. As age increased, the disease burden decreased. Conclusion Between 1990 and 2021, the overall disease burden of pertussis in China showed a significant downward trend, with gender and age differences. Special attention should be given on the prevention and control of pertussis in children under 10 years old, especially in infants under 1 year old.

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Objective To explore the core genes related to the diagnosis and prognosis of gastric cancer(GC)based on Gene Expression Omnibus(GEO)database and screen the molecular targets involved in the occurrence and development of GC.Methods GC microarray data GSE118916,GSE54129 and GSE79973 were downloaded from GEO database,and the differentially expressed genes(DEGs)were screened.Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks(PPI)were constructed to identify the hub genes,whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA.The expression levels of these core genes were also detected in different GC cell lines using qRT-PCR.Results Seventy-seven DEGs were identified,which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand,involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion.Nine hub genes were obtained,among which SPARC,TIMP1,THBS2,COL6A3 and THY1 were significantly up-regulated and TFF1,GKN1,TFF2 and PGC were significantly down-regulated in GC.The abnormal expressions of SPARC,TIMP1,THBS2,COL6A3,TFF2 and THY1 were significantly correlated with the survival time of GC patients.ROC curve analysis showed that aberrant expression of TIMP1,SPARC,THY1 and THBS2 had high diagnostic value for GC.High expressions of SPARC,TIMP1,THBS2 and COL6A3 were detected in GC tissues.In the GC cell lines,qRT-PCR revealed different expression patterns of these hub genes,but their expressions were largely consistent with those found in bioinformatics analyses.Conclusion SPARC,TIMP1,THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Objective To explore the core genes related to the diagnosis and prognosis of gastric cancer(GC)based on Gene Expression Omnibus(GEO)database and screen the molecular targets involved in the occurrence and development of GC.Methods GC microarray data GSE118916,GSE54129 and GSE79973 were downloaded from GEO database,and the differentially expressed genes(DEGs)were screened.Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks(PPI)were constructed to identify the hub genes,whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA.The expression levels of these core genes were also detected in different GC cell lines using qRT-PCR.Results Seventy-seven DEGs were identified,which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand,involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion.Nine hub genes were obtained,among which SPARC,TIMP1,THBS2,COL6A3 and THY1 were significantly up-regulated and TFF1,GKN1,TFF2 and PGC were significantly down-regulated in GC.The abnormal expressions of SPARC,TIMP1,THBS2,COL6A3,TFF2 and THY1 were significantly correlated with the survival time of GC patients.ROC curve analysis showed that aberrant expression of TIMP1,SPARC,THY1 and THBS2 had high diagnostic value for GC.High expressions of SPARC,TIMP1,THBS2 and COL6A3 were detected in GC tissues.In the GC cell lines,qRT-PCR revealed different expression patterns of these hub genes,but their expressions were largely consistent with those found in bioinformatics analyses.Conclusion SPARC,TIMP1,THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective　To perform the pathogenic and genomics analyses on isolates of Streptococcus suis (Ss) from three human infections in Shenzhen, aiming to provide a basis for the prevention and control of Ss outbreaks. Methods　The suspected bacterial strains from three blood plate cultures of three critically ill patients in three hospitals were subjected to biochemical identification, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and real-time fluorescent PCR identification, resulting in the identification of three strains positive for Streptococcus suis serotype 2(SS2). Pure positive cultures were taken for an antimicrobial susceptibility test and extracted nucleic acids for whole-genome sequencing and analysis. The whole-genome sequencing and analysis included species identification, antibiotic resistance genes alignment, multilocus sequence typing (MLST), virulence genes alignment, and coregene-based phylogenetic tree analysis. Results　The blood agar isolates from three patients were all identified as Ss, the VITEK 2 identified them as SS2, and MALDI-TOF-MS identified them as Ss. Real-time PCR results for the universal gene gdh and serotype 2 cps2 gene of Ss were both positive. The antimicrobial susceptibility test results showed that all three strains were resistant to erythromycin and clindamycin, with variable sensitivity to tetracycline. Whole-genome sequencing results showed that all three strains were identified as Ss, including one ST7 strain and two ST1 strains. The virulence gene prediction results based on the VFDB database showed that all three strains were positive for mrp, sly, and cps, indicating high virulence gene characteristics. The analysis of the phylogenetic tree based on coregene showed that the three strains were in different evolutionary branches, with two ST1 strains having a closer evolutionary distance. Conclusions　The pathogens responsible for these three critically ill patients were SS2, and all three strains were resistant to erythromycin and clindamycin. Genetically, they all carried virulence genes that are found in highly virulent strains, while showed differences in MLST typing and phylogenetic tree analysis, indicating the presence of different genotypes of high pathogenicity SS2 in Shenzhen area and had caused sporadic cases, which requires high attention.

Objective:To assess the differences in multidimensional clinical manifestations between patients with irritable bowel syndrome (IBS) matching the Rome Ⅲ criteria but not matching Rome Ⅳ and IBS patients matching the Rome Ⅳ criteria, among patients diagnosed with IBS according to Rome Ⅲ criteria.Methods:From November 2016 to October 2017, a total of 472 IBS patients admitted to six hospitals were selected, which included Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (139 cases), Sir Run Run Shaw Hospital, School of Medicine of Zhejiang University (95 cases), the First Affiliated Hospital of Dalian Medical University (96 cases), the Affiliated Hospital of Guizhou Medical University (90 cases), the People′s Hospital of Guangxi Zhuang Autonomous Region (20 cases), and the Second Affiliated Hospital of Xi′an Jiaotong University (32 cases). The 472 IBS patients were divided into the group that matching the Rome Ⅳ criteria (Rome Ⅳ group), and the group that matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria (Rome Ⅲ group). The basic characteristics (IBS course, post-infectious IBS, history of smoking or drinking, etc.), abdominal symptoms, and defecation-related symptoms of two groups were compared and analyzed by face-to-face questionnaires. Multi-dimensional clinical manifestations assessment was completed by questionnaires, which included gastrointestinal symptom rating scale (GSRS), irritable bowel syndrome-severity scoring system (IBS-SSS), irritable bowel syndrome-quality of life (IBS-QOL), and hospital anxiety and depression scale (HADS). Independent sample t-test, rank sum test, and chi-square test were used for statistical analysis. Results:There were 344 patients (72.9%) in Rome Ⅳ group and 128 patients (27.1%) in Rome Ⅲ group. The IBS course of patients in Rome Ⅳ group was longer than that in Rome Ⅲ group (3.0 years (7.0 years) vs. 2.0 years (5.7 years)), and the difference was statistically significant ( Z=-2.73, P=0.006). The GSRS scores of loose stools and abdominal pain of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group, and the GSRS scores of increased exhaust and abdominal distension of IBS patients in Rome Ⅳ group were lower than those in Rome Ⅲ group (3.0(2.0) vs. 2.0(4.0), 3.0(2.0) vs.1.0(2.0), 1.5(3.0) vs. 2.0(3.0), 1.0 (3.0) vs. 2.0(3.0)), and the differences were statistically significant ( Z=-2.48, -9.90, -2.11 and -2.06, P=0.013, <0.001, =0.035 and =0.040). The proportions of fatigue and dizziness of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (58.4% (201/344) vs. 43.0% (55/128), 30.8% (106/344) vs. 29.7% (38/128)), and the differences were statistically significant ( χ2=8.37 and 12.36, P=0.004 and <0.001). The scores of anxiety and depression subscales of the HADS of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (6.5 (6.8) vs. 6.0 (6.0), 5.0 (6.0) vs. 3.0 (5.0)), and the differences were statistically significant ( Z=-2.58 and -2.40, P=0.010 and 0.017). The scores of IBS-SSS scale, abdominal pain severity, abdominal pain frequency, and impact on quality of life of IBS patients in Rome Ⅳ group were all higher than those in Rome Ⅲ group (249.5 (108.0) vs. 177.0 (111.8), 50.0 (25.0) vs. 20.0 (30.0), 50.0 (70.0) vs. 10.0 (30.0), 66.0 (42.0) vs. 42.5 (34.0)), and the differences were statistically significant ( Z=-7.79, -9.64, -10.65 and -2.48, P<0.001, <0.001, <0.001 and =0.013). The score of IBS-QOL for behavioral disorder of IBS patients in Rome Ⅳ group was lower than that in Rome Ⅲ group (74.5±21.6 vs. 79.2±17.7), and the difference was statistically significant ( t=-2.22, P=0.027). Conclusion:The clinical symptoms of patients mathching the Rome Ⅳ criteria are more typical and severe, as compared with those of IBS patients matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria.

Objective To measure and analyze biological characteristics and aging phenotype of SHJH^hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. MethodsWith ICR mice of the same age as control group, the body mass growth data of SHJH^hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH^hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH^hr mice were measured. The venous blood of 8-week-old SHJH^hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH^hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. ResultsCompared with ICR mice, the female and male body mass of SHJH^hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH^hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. ConclusionSHJH^hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

Objective:To observe the clinical characteristics of esophageal reflux after total gastrectomy (ERATG), and to explore the mechanism of occurrence.Methods:Fourteen gastric cancer patients who underwent total gastrectomy were prospectively enrolled in this study. The postoperative symptoms were observed and recorded and 24 h MII-pH with pH monitoring was performed to investigate the characteristics of postoperative reflux.Results:After total gastrectomy patients were with different degrees of ERATG as heartburn, appetite loss, chest tightness and belching. The overall nature of ERATG is mainly weak acid, with a pH between 4 and 7. ERATG involved esophageal-jejunal anastomosis and a length of esophagus 7 cm above the anastomosis. Patients with typical reflux symptoms had a lower pH minimum in the upright position than those without typical symptoms[(4.76±0.71) vs.(5.68±0.37), t=2.866, P<0.05]. Patients with typical reflux symptoms had a higher frequency of reflux of mixed liquid and liquid-air reflux than those without typical symptoms[liquid(31.25±29.76) vs.(4.50±9.14), t=0.011, P<0.05; liquid-air(19.50±12.99) vs.(2.00±2.61), t=0.004, P<0.05]. Conclusion:ERATG is mainly a upward reflux of weakly acidic gas, with typical symptoms of heartburn, appetite loss, chest tightness and belching. Patients with typical symptoms usually have lower pH in the upright position.

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