OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Objective:To observe the effect of metformin on intestinal metabolites and its protective effect on lung injury in an elderly sepsis rat.Methods:SD rats were fed at the Animal Laboratory Center of Zhengzhou University, fourteen elderly SD rats were randomly divided into three groups: sham surgery (age-Sham, AgS group, n=4), cecal ligation and perforation induced sepsis (age-Cecal ligation and puncture, AgCLP group, n=5), and oral administration of metformin (100 mg/kg) after 1 h of CLP treatment (age-Metformin, AgMET group, n=5). Collected rat feces 24 h after modeling, and analyzed the composition and inter group differences of metabolites in the feces using liquid chromatography tandem mass spectrometry non targeted metabolomics. Collected rat lung tissues and detected the expression levels of inflammation related genes and pathological changes in the tissue. The visualization of metabolic changes between groups were presented using orthogonal partial least squares discriminant analysis, heatmaps, and unsupervised principal component analysis, respectively. MetaboAnalyst 3.0 was used to evaluate the Pathway analysis of metabolites, and this software was based on the KEGG database and the human metabolome database. Results:The expressions of CCL4 ( F=203.00, P<0.001), CXCL1( F=65.69, P<0.001), IL-6 ( F=38.94, P<0.002), TNF-α ( F=14.85, P=0.005) between two groups of rats were significantly different (all P<0.05). However, there was no significant difference in CCL2 expression between AgCLP group and AgMET group. Furthermore, compared with the AgS group, the relative intensities of 17 metabolites such as 7-methylxanthine, N-Arachidonylglycine and Manolide in AgCLP group were significantly increased, whereas the 9 metabolites such as Phenazone, Gly-Phe and Valyproline were significantly decreased, and metformin treatment could reverse these changes of the above metabolites. Correlation analysis showed that the IL-6 and TNF-α levels were positively correlated with the relative strength of 7-Methylxanthine, N-Arachidonylglycine and other metabolites, but negatively correlated with the Phenazone and Gly-Phe. CCL4 and CXCL1 were positively correlated with Manolide, but negatively correlated with Valyproline. Conclusion:The results of this study showed that metformin improved sepsis induced acute lung injury and regulates the host intestinal metabolites, which might provide a potential and effective treatment for elderly sepsis induced acute lung injury.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.

ObjectiveTo conduct a systematic review of the susceptibility gene polymorphism sites of primary knee osteoarthritis (PKO). MethodsThe literature on genetic susceptibility and gene polymorphisms of PKO were retrieved from PubMed, Web of Science, CNKI, Wanfang Data, and China Biomedical Literature Database from establishment of the library to December, 2020, and systematically reviewed. ResultsA total of 42 papers on the polymorphism sites of human PKO susceptibility genes were included, involving cellular signaling pathways related to PKO pathogenesis, including inflammatory response, receptor signaling pathway, transcription factor signaling pathway, bone-related signaling pathway, etc. Multiple gene polymorphism sites located in inflammatory factor genes, chemokine genes, Toll-like receptor genes, transcription factor genes, obesity-related genes, and bone-related genes. ConclusionInflammatory factor genes and bone-associated allele polymorphisms are likely to be related to PKO susceptibility.

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.