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.

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.

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 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

Objective To investigate the pathogenic mutations of BRCA1 and BRCA2 in patients with early-onset breast cancer(≤35 years) and explore the relationships between BRCA1/2 mutations and clinical features.Methods Seventy-four patients with early-onset breast cancer were enrolled,who were treated in Hospital 307 between September 2014 and June 2016.High-throughput sequencing was used to test the 49 exon sequences and adjacent sequences of BRCA1 and BRCA2.χ2 test was used to analyze the distribution of BRCA1/2 pathogenic mutations in each group that was set up according to clinical features.Results Fifteen mutations(20.27%) were identified,including 5(6.76%) in BRCA1 and 10(13.51%) in BRCA2.Eleven new pathogenic mutations were discovered,and BRCA1:c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutations in the group with a family history of breast cancer or ovarian cancer was higher than in the group without a family history (40.91% vs 11.54%) (χ2=6.534,P=0.011).Conclusion BRCA1/2 pathogenic mutation is significant for early-onset breast cancer,especially for those with a family history of breast or ovarian cancer.The new mutations may be specific to Chinese people.BRCA1:c.5470_5477delTGCCCAAT may be the ancestor mutation among the Chinese.

Objective To explore the methods for constructing the digital three-dimensional model of fetal heart. Methods Original two-dimensional CT image data sets were collected from 4 abortion fetuses with fetal malformations but not heart malformation or chromosomal abnormalities. The three-dimensional fetal heart model was reconstructed using Mimics14.0 software. Results In the reconstructed three-dimensional fetal heart, the left atrium, left ventricle, right atrium, right ventricle, the ascending aorta, the main pulmonary and their branches, the superior cava and inferior vena cava were marked with different colors, and these structures could be displayed individually or with other structures. This model also allowed three-dimensional arbitrary scaling, shifting or rotation at any angle, and the diameter of the each vessel could be measured with the software. Conclusion The fetal heart model can be successfully reconstructed from the CT datasets using three-dimensional reconstruction software to facilitate clinical and anatomical teaching.