OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

AIM: To investigate the potential causal relationship between gut microbiota(GM)and primary open-angle glaucoma(POAG)based on a two-sample Mendelian randomization(MR)analysis.METHODS: The exposure data was derived from the Genome-Wide Association Studies(GWAS)of GM at the University of Bristol, while the outcome data for POAG was sourced from the MRC Integrative Epidemiology Unit(IEU)Open GWAS database. In this study, inverse variance weighted(IVW), MR Egger, weighted median(WM), Simple Mode, and Weighted Mode were analyzed to investigate the potential causal relationships between GM and POAG. IVW was used as the primary method for this study, and sensitivity analysis was conducted to assess the reliability of the MR analysis.RESULTS: The IVW analysis revealed that Butyrivibrio(OR=1.170, 95%CI: 1.057-1.295, P=0.002), Howardella(OR=1.188, 95%CI: 1.043-1.355, P=0.010), and LachnospiraceaeUCG001(OR=1.229, 95%CI: 1.016-1.485, P=0.033)were correlated with the risk of POAG. Conversely, Candidatus Soleaferrea(OR=0.810, 95%CI: 0.670-0.981, P=0.031), Ruminococcustorquesgroup(OR=0.656, 95%CI: 0.453-0.950, P=0.026), and RuminococcaceaeUCG013(OR=0.770, 95%CI: 0.598-0.990, P=0.041)were protective factors for POAG. Sensitivity analysis showed that there were no heterogeneity and pleiotropy among the instrumental variables.CONCLUSION: The MR study indicated a causal relationship between GM and POAG. Given the sight-threatening characteristic of POAG, early identification and intervention in the relative factors was significant for the prognosis of POAG.

Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.

Objective:To analyze the clinical characteristics of Chlamydia psittaci pneumonia in the elderly, and factor related to the disease severity. Methods:Clinical data of 32 elderly patients with Chlamydia pneumoniae pneumonia admitted in the First People′s Hospital of Xiaoshan District from January 2019 to January 2021 were retrospectively analyzed. The patients were diagnosed by the second generation sequencing using bronchoalveolar lavage fluid (BALF) samples. There were 17 patients in moderate group and 15 patients in severe group; the liver function, muscle enzymes, imaging and lymphocyte subsets of the two groups were compared. Results:There were no significant differences in the age, gender and basic diseases, bird contact history, flaccid fever and dry cough symptoms between two groups, while there were significant differences in mental symptoms and gastrointestinal symptoms between the two groups ( P=0.032, 0.018). There were significant differences in ALT , AST, LDH , CK , CK-MB, CRP, BNP , troponin-T and PCT between the two groups (all P<0.001). The increase of leukocytes was not significant in both groups. The moderate group was dominated by single lobe involvement, while the severe group was dominated by multi lobe involvement and pleural effusion ( P=0.043, 0.015, 0.023). The total lymphocytes, T lymphocytes, CD4 + T cells, CD8 + T cells, CD4 +/CD8 + ratio, NK cells, B cells, CD4 +CD8 + double positive T cells decreased in both groups, while those in the severe group decrease more markedly ( P<0.05). CD4 -CD8 - double negative T cells were higher in the severe group than those in the moderate group ( P<0.001). CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells were correlated with severity index PSI and CURB-65 ( P<0.05). Conclusions:The liver function, muscle enzyme, lymphocyte immune function in patients with Chlamydia psittaci pneumonia are impaired, which were more markedly in severe patients. The multileaf infiltration and increased procalcitonin may indicate the severe pneumonia. CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells are correlated with the severity of pneumonia.

Objective:To understand the molecular characteristics of Escherichia coli producing Shiga toxin 2e subtype isolated from different sources in China. Methods:Three human-derived, 13 animal-derived and eight food-derived stx2e-positive Escherichia coli strains which were isolated during 2012 to 2018 were analyzed by antimicrobial susceptibility testing and whole genome sequencing. The stx subtype, serotype, multi-locus sequence type, virulence genes and antimicrobial resistance genes of each strain were determined by whole genome sequences. The phylogenetic relationship and genetic composition of Shiga-toxin prophage were explored. Results:Twenty-four stx2e-STEC strains were typed into 19 O∶H serotypes and 19 sequence types (STs). Each strain carried at least one kind of antimicrobial resistance gene and 19 out of 24 strains were resistant to at least one kind of antimicrobials. Three human-derived strains were heterogenous in serotypes and STs, but there were several animal and food-derived strains shared the same serotype or ST with human strains and showed close relationship in the phylogenetic analysis. The sequences of stx2e among all strains were highly conserved (similarity >99.7%), but there were significant differences in the size and the gene composition of Shiga toxin prophage genome. Conclusions:This is report about the characteristics of rare human-derived Stx2e-STEC strains in China. Comparing human isolates with animal-and food-derived strains, it indicates that Stx2e-STEC strains are highly genetic diversity and have the potential to infect humans.

Objective:To evaluate the antimicrobial resistance of non-O157 Shiga toxin-producing Escherichia coli (STEC) isolated from human cases. Methods:From 2011 to 2019, 33 non-O157 STEC strains recovered from diarrheal patients from 7 provinces/cities were collected, including Qinghai (1 isolate), Heilongjiang (1 isolate), Guangxi (2 isolates), Shandong (2 isolates), Guangdong (4 isolates), Henan (11 isolates), and Shanghai (12 isolates). Minimum inhibitory concentration (MIC) of 19 antimicrobials were tested by broth microdilution method; O∶H serotypes, Multi-locus sequence typing (MLST) and antimicrobial resistance genes were determined by whole genome sequencing.Results:A total of 33 non-O157 STEC strains were typed into 19 O∶H serotypes and 17 sequence types (STs), respectively. Ten strains were resistant to one or more antibiotics,of which five were multiple drug-resistant (MDR). The resistance rate of tetracycline was 30.3% (10 isolates), and azithromycin resistant strains were detected (12.12%, 4 isolates), but all strains were susceptible to carbapenems. All strains carried the blaEC gene, and the Extended-Spectrum β-Lactamase (ESBL) genotype blaCTX-M-15 were detected (3.0%, 1 isolates). The fosA7 gene was firstly detected in non-O157 STEC strains. Conclusion:MDR, azithromycin resistance, and multiple drug resistance genes were detected in human-derived non-O157 STECs in many regions in China, but they were all susceptible to carbapenems. Our results might guide the clinical treatment of STEC infections.

Objective:To evaluate the antimicrobial resistance of non-O157 Shiga toxin-producing Escherichia coli (STEC) isolated from human cases. Methods:From 2011 to 2019, 33 non-O157 STEC strains recovered from diarrheal patients from 7 provinces/cities were collected, including Qinghai (1 isolate), Heilongjiang (1 isolate), Guangxi (2 isolates), Shandong (2 isolates), Guangdong (4 isolates), Henan (11 isolates), and Shanghai (12 isolates). Minimum inhibitory concentration (MIC) of 19 antimicrobials were tested by broth microdilution method; O∶H serotypes, Multi-locus sequence typing (MLST) and antimicrobial resistance genes were determined by whole genome sequencing.Results:A total of 33 non-O157 STEC strains were typed into 19 O∶H serotypes and 17 sequence types (STs), respectively. Ten strains were resistant to one or more antibiotics,of which five were multiple drug-resistant (MDR). The resistance rate of tetracycline was 30.3% (10 isolates), and azithromycin resistant strains were detected (12.12%, 4 isolates), but all strains were susceptible to carbapenems. All strains carried the blaEC gene, and the Extended-Spectrum β-Lactamase (ESBL) genotype blaCTX-M-15 were detected (3.0%, 1 isolates). The fosA7 gene was firstly detected in non-O157 STEC strains. Conclusion:MDR, azithromycin resistance, and multiple drug resistance genes were detected in human-derived non-O157 STECs in many regions in China, but they were all susceptible to carbapenems. Our results might guide the clinical treatment of STEC infections.

Objective:To investigate the prevalence and molecular characteristics of Escherichia coli ( E. coli) producing a novel Shiga toxin 2k subtype in goat in Lanling county, Shandong province. Methods:In November 2019, 512 goat fecal samples were collected from different households in Lanling county, Shandong province. After enriched with EC broth, stx-positive samples were detected by PCR and inoculated in CHROMagar? ECC agar and CHROMagar? STEC agar. The whole genomes of stx-positive strains were sequenced. Based on the genomic senquences, the stx subtype, serotype, multi-locus sequence type and virulence genes of each strain were analyzed. Results:Eighty-six strains of Shiga toxin-producing E. coli (STEC) were isolated from 512 goat fecal samples. Five stx subtypes were identified and 37 strains were positive for stx2k. The 86 STEC strains belonged to 20 O∶H serotypes and 18 different sequence types (STs). Conclusions:STEC strains circulating in goats in Lanling county, Shandong province were heterogeneous in stx subtypes, serotypes and virulence gene profiles, and a certain proportion of strains producing a novel Shiga toxin 2k subtype were detected.

For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases.
Behavior ; China ; epidemiology ; Climate ; Communicable Diseases ; classification ; epidemiology ; Communicable Diseases, Emerging ; epidemiology ; Disease Outbreaks ; Ecology ; Forecasting ; Humans ; Incidence