Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

The influence of gut microbiota on membranous nephropathy: A two-sample Mendelian randomization study.

BACKGROUND: Therapeutic approaches that target the gut microbiota may be helpful in the potential prevention and treatment of membranous nephropathy (MN). Several studies demonstrated a correlation between gut microbiota and MN. However, the confounding evidence cannot prove a causal relationship between gut microbiota and MN. MATERIALS AND METHODS: The aim of our study is to assess genome-wide association study data for a causal relationship between gut microbiota and MN using a two-sample Mendelian randomization (MR) approach. Inverse variance weighted (IVW) was used as the primary technique to determine the association of genetic variants from gut microbiota and MN patients. Besides, sensitivity analyses confirmed the accuracy of the results. Finally, we applied false discovery rate (FDR) correction to results with IVW < 0.05 during multiple hypothesis testing. RESULTS: The results from IVW estimates indicated that Bacillales exhibited a significant association with MN, acting as a risk factor (OR = 1.52, 95% CI: 1.14 - 2.02, p = 0.005). In addition, our univariable MR results showed that 7 bacterial taxa (Melainabacteria, Butyricicoccus, Catenibacterium, Ruminiclostridium5, RuminococcaceaeUCG003, RuminococcaceaeUCG013, and Gastranaerophilales) had suggestive associations with MN. The sensitivity analysis did not reveal any significant heterogeneity in the instrumental variables or horizontal pleiotropy. CONCLUSION: Our findings provided causal evidence for the effect of gut microbiota on MN patients and broadened the spectrum of bacterial taxa that might be involved in the pathogenesis of MN. These selected bacterial taxa hold promise as new biomarkers, which may aid in designing targeted therapeutic modalities for MN, improving our comprehension of the gut-kidney axis.

Efficacy and Cost-Effectiveness Analysis of Internet-Based Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and chronic mental illness with a high rate of disability. Internet-based cognitive behavioral therapy (ICBT) makes online treatment available to patients and has been shown to be effective. However, 3-arm trials on ICBT, face-to-face cognitive behavioral group therapy (CBGT), and only medication are still lacking. OBJECTIVE: This study is a randomized, controlled, assessor-blinded trial of 3 groups for OCD: ICBT combined with medication, CBGT combined with medication, and conventional medical treatment (ie, treatment as usual [TAU]). The study aims to investigate the efficacy and cost-effectiveness of ICBT related to CBGT and TAU for adults with OCD in China. METHODS: In total, 99 patients with OCD were selected and randomly assigned to the ICBT, CBGT, and TAU groups for treatment for 6 weeks. The primary outcomes were the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the self-rating Florida Obsessive-Compulsive Inventory (FOCI), compared at baseline, during treatment (3 weeks), and after treatment (6 weeks), to analyze efficacy. The secondary outcome was the EuroQol Visual Analogue Scale (EQ-VAS) scores of the EuroQol 5D Questionnaire (EQ-5D). The cost questionnaires were recorded to analyze cost-effectiveness. RESULTS: Repeated-measures ANOVA was used for data analysis, and the final effective sample size was 93 (ICBT: n=32, 34.4%; CBGT: n=28, 30.1%; TAU: n=33, 35.5%). After 6-week treatment, the YBOCS scores of the 3 groups significantly decreased (P<.001), and there were no significant differences among groups. The FOCI score of the ICBT (P=.001) and CBGT (P=.035) groups was significantly lower than that of the TAU group after treatment. The total cost of the CBGT group (renminbi [RMB] 6678.45, 95% CI 4460.88-8896.01 [US $1010.36, 95% CI 678.87-1345.84]) was significantly higher than that of the ICBT group (RMB 3308.81, 95% CI 2476.89-4140.73[US $500.58, 95% CI 374.72-626.43], P<.001) and the TAU group (RMB 2259.61, 95% CI 2074.16-2445.05 [US $341.85, 95% CI 313.79-369.90], P<.001) after treatment. The ICBT group spent RMB 303.19 (US $45.97) less than the CBGT group and RMB 11.57 (US $1.75) less than the TAU group for each unit reduction in the YBOCS score. CONCLUSIONS: Therapist-guided ICBT combined with medication is as effective as face-to-face CBGT combined with medication for OCD. ICBT combined with medication is more cost-effective than CBGT combined with medication and conventional medical treatment. It is expected to become an efficacious and economic alternative for adults with OCD when face-to-face CBGT is not available. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023840; https://www.chictr.org.cn/showproj.html?proj=39294.

[A new antiviral isoquinoline alkaloid from Thalictrum glandulosissimum].

A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.

Association Studies on Gut and Lung Microbiomes in Patients with Lung Adenocarcinoma.

Lung adenocarcinoma (LADC) is a prevalent type of lung cancer that is associated with lung and gut microbiota. However, the interactions between these microbiota and cancer development remain unclear. In this study, a microbiome study was performed on paired fecal and bronchoalveolar lavage fluid (BALF) samples from 42 patients with LADC and 64 healthy controls using 16S rRNA gene amplicon and shotgun metagenome sequencing, aiming to correlate the lung and gut microbiota with LADC. Patients with LADC had reduced α-diversity in the gut microbiome and altered ß-diversity compared with healthy controls, and the abundances of Flavonifractor, Eggerthella, and Clostridium were higher in the gut microbiome of LADC patients. The increased abundance of microbial species, such as Flavonifractor plautii, was associated with advanced-stage LADC and a higher metastasis rate. Phylogenetically, Haemophilus parainfluenzae was the most frequently shared taxon in the lung and gut microbiota of LADC patients. Gut microbiome functional pathways involving leucine, propanoate, and fatty acids were associated with LADC progression. In conclusion, the low diversity of the gut microbiota and the presence of H. parainfluenzae in gut and lung microbiota were linked to LADC development, while an increased abundance of F. plautii and the enriched metabolic pathways could be associated with the progression of LADC.

Stigma toward mental disorders and associated factors among community mental health workers in Wuhan, China.

BACKGROUND: Stigma toward mental disorders (STMD) is a significant barrier to mental health service delivery. To improve the provision of mental health services for community-dwelling residents in China, this study investigated STMD and its associated factors in community mental health workers (CMHWs) in Wuhan, China. METHODS: In this cross-sectional study, a total of 3869 CMHWs (22.9% men and 37.1 ± 8.4 years old) were randomly selected through multistage sampling and invited to participate in this survey. The perceived devaluation-discrimination scale (PDD) and the National Mental Health Literacy Questionnaire (NMHLQ) were used to assess STMD and mental health knowledge, respectively. The presence of STMD was indicated by a mean item score of 3.0 or higher on the PDD. Multiple logistic regression was used to identify factors associated with STMD. RESULTS: Of the CMHWs, 41.9% had poor mental health knowledge (NMHLQ score < 80), and 18.5% exhibited STMD. In multiple regression analysis, factors significantly associated with STMD were social workers (vs. primary care physicians, OR = 1.44, p < .001), poor self-rated capacity to handle common mental health problems (vs. good, OR = 1.57, p < .001), and poor mental health knowledge (vs. NMHLQ score ≥ 80, OR = 1.46, p < .001). CONCLUSION: STMD is common among Chinese CMHWs. To reduce STMD among CMHWs, training programs in mental health care skills and mental health education may be necessary.

Genomic analysis of almost 8,000 Salmonella genomes reveals drivers and landscape of antimicrobial resistance in China.

IMPORTANCE: We established the largest Salmonella genome database from China and presented the landscape and spatiotemporal dynamics of antimicrobial resistance genes. We also found that economic, climatic, and social factors can drive the rise of antimicrobial resistance. The Chinese local Salmonella genome database version 2 was released as an open-access database (https://nmdc.cn/clsgdbv2) and thus can assist surveillance studies across the globe. This database will help inform interventions for AMR, food safety, and public health.

The temporal dynamics of antimicrobial-resistant Salmonella enterica and predominant serovars in China.

Salmonella enterica is one of the most common bacterial pathogens in humans and animals. Systematic studies on the trends and geographical distribution of antimicrobial-resistant Salmonella and dominant serovars have been well studied in European and American countries while not in China. Here, taking the One-Health strategy, we used >35 000 Salmonella enterica isolates to explore the temporal and spatial dynamics of dominant serovars in China. We found that Salmonella Typhimurium was the dominant serovar causing human infection in China, which was consistent with Australia but inconsistent with North American and European countries. The proportion of Salmonella serovars Typhimurium, London, Rissen, Corvallis, Meleagridis, Kentucky, and Goldcoast showed an increasing trend during 2006-2019. We randomly selected 1962 isolates for comparative genomics and antimicrobial resistance studies and found that the number of antibiotic resistance genes (ARGs) per isolate increased 1.84 and 2.69 times of human and non-human origins, respectively, spanning 14 years. The proportion of antimicrobial-resistant Salmonella isolates had an increasing trend during 2006-2019, especially beta-lactam, quinolone, tetracycline, and rifampicin resistance. Moreover, we found that higher diversity of sequence types (STs) in S. Typhimurium than in other serovars, ST34 from pig and ST19 from chicken origin, were mainly associated with isolates causing child and adult gastro-infection, respectively. Our results fill in the data gap on the trends of dominant serovars and antimicrobial resistance of Salmonella enterica in China. These data provide useful information for public health decision-makers prioritizing interventions for foodborne diseases and food safety.

[Comparative analysis of different fecal DNA extraction methods].

The community structure and diversity of the gut microbiota are associated with human diseases. However, the analysis of different community structure might be influenced by experimental approaches such as the quality of DNA extraction. Therefore, evaluating the efficiency of different DNA extraction methods for specific intestinal species is a guideline for obtaining a comprehensive human gut microbial profile, which may assist the in-depth investigation into the structure of the gut microbial community. The aim of this study was to perform a comparative analysis of five different DNA extraction methods. With the aid of qPCR, the efficiency of five DNA extraction kits was evaluated in terms of the purity of the extracted DNA, the DNA concentration, and the abundance of genomic DNA extracted from specific intestinal species. The results showed that the kit Q gave the best extraction results, especially for Gram-positive bacteria such as Lactobacillus and Bifidobacterium. The average DNA concentration of the N kit was lower than that of the Q kit, but there was no significant difference between the two in terms of the purity. Compared to the other three commercial kits (M, PSP, TG), the efficiency of the N kit in extracting the genomic DNA of the specified microorganisms were the least different from those of the Q kit. In contrast, the DNA extracted by the M kit was of higher quality but of lower concentration, and was not very efficient for Gram-positive bacteria. The DNA extracted by the TG and PSP kits was inferior to the other validated kits in terms of the concentration, quality and bacterial abundance. These results provide a basis for the selection of genomic DNA extraction methods in microecological research experiments.

Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer (CRC), which has attracted broad attention. However, the mechanism by which it is involved in CRC development is not fully understood. AIM: To explore its potential causative role in CRC development, we evaluated the colon pathology, mucosa barrier, colon microbiota and host transcriptome profile after F. nucleatum infection in an azoxymethane/dextran sulfate sodium salt (AOM/DSS) mouse model. METHODS: Three groups of mice were compared to reveal the differences, i.e., the control, AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups. RESULTS: Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group, and AOM/DSS mice with F. nucleatum infection showed the highest tumor formation ratio among the three groups. Moreover, the colon pathology was the most serious in the AOM/DSS-FUSO group. We found that the structure of the colon microbiota changed considerably after F. nucleatum infection; striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups, and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO group. By comparing intestinal transcriptomics data from AOM vs AOM/DSS-FUSO mice, we showed that transcriptional activity was strongly affected by dysbiosis of the gut microbiota. The most microbiota-sensitive genes were oncogenes in the intestine, and the cyclic adenosine monophosphate signaling pathway, neuroactive ligand-receptor interaction, PPAR signaling pathway, retinol metabolism, mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO group. Additionally, we showed that microbial dysbiosis driven by F. nucleatum infection enriched eight taxa belonging to Proteobacteria, which correlates with increased expression of oncogenic genes. CONCLUSION: Our study demonstrated that F. nucleatum infection altered the colon mucosal microbiota by enriching pathogens related to the development of CRC, providing new insights into the role of F. nucleatum in the oncogenic microbial environment of the colon.

Effect of the "Art Coloring" Online Coloring Game on Subjective Well-Being Increase and Anxiety Reduction During the COVID-19 Pandemic: Development and Evaluation.

BACKGROUND: COVID-19 has spread worldwide and generated tremendous stress on human beings. Unfortunately, it is often hard for distressed individuals to access mental health services under conditions of restricted movement or even lockdown. OBJECTIVE: The study first aims to develop an online digital intervention package based on a commercially released coloring game. The second aim is to test the effectiveness of difference intervention packages for players to increase subjective well-being (SWB) and reduce anxiety during the pandemic. METHODS: An evidence-based coloring intervention package was developed and uploaded to an online coloring game covering almost 1.5 million players worldwide in January 2021. Players worldwide participated to color either 4 rounds of images characterized by awe, pink, nature, and blue or 4 rounds of irrelevant images. Participants' SWB and anxiety and the perceived effectiveness of the game in reducing anxiety (subjective effectiveness [SE]) were assessed 1 week before the intervention (T1), after the participants completed pictures in each round (T2-T5), and after the intervention (T6). Independent 2-tailed t tests were conducted to examine the general intervention (GI) effect and the intervention effect of each round. Univariate analysis was used to examine whether these outcome variables were influenced by the number of rounds completed. RESULTS: In total, 1390 players worldwide responded and completed at least 1 assessment. Overall, the GI group showed a statistical significantly greater increase in SWB than the general control (GC) group (N=164, t162=3.59, Cohen d=0.59, 95% CI 0.36-1.24, P<.001). Compared to the control group, the best effectiveness of the intervention group was seen in the awe round, in which the increase in SWB was significant (N=171, t169=2.51, Cohen d=0.39, 95% CI 0.10-0.82, P=.01), and players who colored all 4 pictures had nearly significant improvements in SWB (N=171, F4,170=2.34, partial ŋ2=0.053, P=.06) and a significant decrease in anxiety (N=171, F4,170=3.39, partial ŋ2=0.075, P=.01). CONCLUSIONS: These data indicate the effectiveness of online psychological interventions, such as coloring games, for mental health in the specific period. They also show the feasibility of applying existing commercial games embedded with scientific psychological interventions that can fill the gap in mental crises and services for a wider group of people during the pandemic. The results would inspire innovations to prevent the psychological problems caused by public emergencies and encourage more games, especially the most popular ones, to take more positive action for the common crises of humankind.

Correction: Effect of the "Art Coloring" Online Coloring Game on Subjective Well-Being Increase and Anxiety Reduction During the COVID-19 Pandemic: Development and Evaluation.

[This corrects the article DOI: 10.2196/37026.].

[Effect of rhTPO to the Proliferation and Apoptosis of Acute Myeloid Leukemia Cell Lines].

OBJECTIVE: To investigate the effects of recombinant human thrombopoietin (rhTPO) to proliferation and apoptosis of acute myeloid leukemia (AML) cell lines. METHODS: After the treatment of different concentrations of rhTPO (0, 50, 100 ng/ml) for different time (24,48,72 h)，the cell proliferation rates of the AML cell lines (Kasumi-1, Skno-1, HEL, HL-60, THP-1) were determined by CCK-8 method. Apoptosis rate of each cell line cocultured with rhTPO was detected by Annexin V/PI method. The relative expression of TPO receptor c-MPL (myeloproliferative clonal antibody) mRNA in AML cell lines was detected by Q-PCR. The expression of c-MPL protein in each cell line was detected by Western blot. The expression of c-MPL antigen in HL-60 cells treated by different concentrations of rhTPO was detected by Flow cytometry. RESULTS: RhTPO showed no promotion to the proliferation of Kasumi-1, Skno-1, HEL, HL-60, THP-1 cell lines，however，it showed inhibitory effect to cell proliferation (72 h 0 ng/ml vs 100 ng/ml, P= 0.029) and pro-apoptotic (48 h 0 ng/ml vs 50 ng/ml, P=0.0143) in HL-60 cells. In Kasumi-1, Skno-1, HEL and THP-1 cells, there showed no statistically significant differences in apoptosis rate among each groups treated by different concentrations of rhTPO. Each AML cell line showed different levels of c-MPL gene and c-MPL protein expression, but HEL cells showed the highest expression in both of them. After HL-60 cells were treated by different concentrations of rhTPO for 48 hours, there showed no statistical difference in c-MPL antigen expression among each groups. CONCLUSION: RhTPO can not promote the proliferation of Kasumi-1, Skno-1, HEL, HL-60 and THP-1 leukemia cell lines. On the contrary, rhTPO can inhibit HL-60 cell proliferation and promote its apoptosis, and this effect is not related to c-MPL gene expression or protein expression.

Gut Mycobiota Dysbiosis in Pulmonary Tuberculosis Patients Undergoing Anti-Tuberculosis Treatment.

Patients with pulmonary tuberculosis (TB) undergoing anti-tuberculosis (anti-TB) treatment were previously reported to present gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been reported. Here, we conducted a follow-up study of 29 naive TB patients who received first-line anti-TB drug treatment; we collected their fecal samples at different time points, as well as 22 fecal samples from healthy subjects. Fungal ITS2 and bacterial 16S rRNA amplicon sequencing were used to analyze the effects of active TB and anti-TB treatment on the gut microbiota. We found that naive TB patients had bacterial and fungal dysbiosis with altered community composition and a decreased density of the transkingdom correlation network. Anti-TB drug treatment significantly decreased the diversity of bacteria and fungi with altered composition. Notably, we observed that the abundance of Purpureocillium lilacinum tended to decrease and Nakaseomyces spp. tended to increase in the anti-TB treatment, and all of them had increased proportions in the three TB groups compared with healthy subjects. We found that the fungal-bacterial transkingdom network was severely altered in TB patients after 2 months of treatment, and new fungal-enriched connections that were not observed in other groups after 6 months of treatment. This study provides the first detailed analysis of dysbiosis of the gut mycobiota due to active TB and anti-TB treatment. The results suggest that fungi play an important role in the balance of the gut microbiota and may be associated with the progression of TB, influencing the microbiota and immunity homeostasis in those receiving anti-TB treatment. IMPORTANCE Numerous studies have shown that the gut bacterial microbiota is altered in active TB patients and that anti-TB drugs have profound and long-term impacts. However, as an integral part of the microbiota, fungi have rarely been studied. The need to investigate both the bacterial and fungal microbiota, as well as the relationship between them is apparent. The significance of our study is in our examination of the changes in the bacterial and fungal microbiota simultaneously in both active TB and patients receiving anti-TB treatment. We found that fungi play an important role in the bacterial-fungal transkingdom network, especially during the anti-TB therapy. These findings underscore the importance of fungi in gut microbiota dysbiosis during active TB and anti-TB treatment processes. In addition, our findings suggest it is meaningful to research potential adjunctive therapies that reduce fungal expansion and increase commensal bacterial abundance after anti-TB treatment, which would help the recovery of TB patients.

Genomic Characterization of Salmonella enterica Isolates From Retail Meat in Beijing, China.

Salmonella enterica remains one of the leading causes of foodborne bacterial disease. Retail meat is a major source of human salmonellosis. However, comparative genomic analyses of S. enterica isolates from retail meat from different sources in China are lacking. A total of 341 S. enterica strains were isolated from retail meat in sixteen districts of Beijing, China, at three different time points (January 1st, May 1st, and October 1st) in 2017. Comparative genomics was performed to investigate the genetic diversity, virulence and antimicrobial resistance gene (ARG) profiles of these isolates. The most common serotype was S. Enteritidis (203/341, 59.5%), which dominated among isolates from three different time points during the year. Laboratory retesting confirmed the accuracy of the serotyping results predicted by the Salmonella In Silico Typing Resource (SISTR) (96.5%). The pangenome of the 341 S. enterica isolates contained 13,931 genes, and the core genome contained 3,635 genes. Higher Salmonella phage 118970 sal3 (219/341, 64.2%) and Gifsy-2 (206/341, 60.4%) prevalence contributed to the diversity of the accessory genes, especially those with unknown functions. IncFII(S), IncX1, and IncFIB(S) plasmid replicons were more common in these isolates and were major sources of horizontally acquired foreign genes. The virulence gene profile showed fewer virulence genes associated with type III secretion systems in certain isolates from chicken. A total of 88 different ARGs were found in the 341 isolates. Three beta-lactamases, namely, bla CTX - M - 55 (n = 15), bla CTX - M - 14 (n = 11), and bla CTX - M - 65 (n = 11), were more prevalent in retail meats. The emergence of qnrE1 and bla CTX - M - 123 indicated a potential increase in the prevalence of retail meats. After the prohibition of colistin in China, three and four isolates were positive for the colistin resistance genes mcr-1.1 and mcr-9, respectively. Thus, we explored the evolution and genomic features of S. enterica isolates from retail meats in Beijing, China. The diverse ARGs of these isolates compromise food security and are a clinical threat.

More diversified antibiotic resistance genes in chickens and workers of the live poultry markets.

BACKGROUND: Poultry farms and LPMs are a reservoir of antimicrobial resistant bacteria and resistance genes from feces. The LPM is an important interface between humans, farm animals, and environments in a typical urban environment, and it is considered a reservoir for ARGs and viruses. However, the antibiotic resistomes shared between chicken farms and LPMs, and that of LPM workers and people who have no contact with the LPMs remains unknown. METHODS: We characterized the resistome and bacterial microbiome of farm chickens and LPMs and LPM workers and control subjects. The mobile ARGs identified in chickens and the distribution of the mcr-family genes in publicly bacterial genomes and chicken gut metagenomes was analyzed, respectively. In addition, the prevalence of mcr-1 in LPMs following the ban on colistin-positive additives in China was explored. RESULTS: By profiling the microbiomes and resistomes in chicken farms, LPMs, LPM workers, and LPM environments, we found that the bacterial community composition and resistomes were significantly different between the farms and the LPMs, and the LPM samples possessed more diversified ARGs (59 types) than the farms. Some mobile ARGs, such as mcr-1 and tet(X3), identified in chicken farms, LPMs, LPM workers, and LPM environments were also harbored by human clinical pathogens. Moreover, we found that the resistomes were significantly different between the LPM workers and those who have no contact with the LPMs, and more diversified ARGs (188 types) were observed in the LPM workers. It is also worth noting that mcr-10 was identified in both human (5.2%, 96/1,859) and chicken (1.5%, 14/910) gut microbiomes. Although mcr-1 prevalence decreased significantly in the LPMs across the eight provinces in China, from 190/333 (57.1%) samples in September 2016-March 2017 to 208/544 (38.2%) samples in August 2018-May 2019, it is widespread and continuous in the LPMs. CONCLUSION: Live poultry trade has a significant effect on the diversity of ARGs in LPM workers, chickens, and environments in China, driven by human selection with the live poultry trade. Our findings highlight the live poultry trade as ARG disseminators into LPMs, which serve as an interface of LPM environments even LPM workers, and that could urge Government to have better control of LPMs in China. Further studies on the factors that promote antibiotic resistance exchange between LPM environments, human commensals, and pathogens, are warranted.

[Molecular Features and Clinical Significance of Acute Myeloid Leukemia in Elderly Patients].

OBJECTIVE: To study the molecular characteristics and clinical significance of elderly patients with acute myeloid leukemia (AML). METHODS: Dideoxy sequencing was used to analyze the mutation spectrum and clinical significance of 51 hematopathy-related genes in 52 patients with newly diagnosed elderly AML. The efficacy of 39 patients receiving DCAG chemotherapy was also analyzed. RESULTS: The mutational frequency was high in elderly AML patients (98.1%, 51/52), and there were some coexistence or mutual exclusion between different mutations. Both the number of mutations and the incidence of epigenetic mutations DNMT3A, TET2 (P<0.01), as well as FLT3-ITD (P<0.05) increased with age. c-KIT mutations were most common in favorable-risk AML (P<0.01), while NPM1 and DNMT3A were common in intermediate-risk AML (P<0.05), especially in AML with normal karyotype. The complete remission rate of elderly AML patients receiving DCAG chemotherapy was 71.8% (28/39). CONCLUSION: Elderly AML patients have specific molecular characteristics, and the incidence of methylation-related gene mutations is very high, showing a certain significance for clinical diagnosis and treatment.

Composition of fecal microbiota in low-set rectal cancer patients treated with FOLFOX.

BACKGROUND: FOLFOX treatment is a method used widely to reduce tumor size in low-set rectal cancer, with variable clinical results. FOLFOX agents comprise a mixture of oxaliplatin and 5-fluorouracil, the efficacy of which might be modulated by the gut microbiome in humans. This study aimed to determine whether the bowel microbiota is a factor that influences FOLFOX treatment. METHODS: To investigate the role of gut microbiota during FOLFOX treatment, we carried out comprehensive metagenomic and metabolomic analyses on 62 fecal samples collected from 37 low-set rectal cancer patients. A set of 31 samples was collected before the patients underwent treatment; another 31 samples were obtained after the treatment was completed. Among these samples, 50 were paired samples collected before and after FOLFOX treatment. The patients were divided into responder and nonresponder groups according to the treatment outcome. Metagenomic sequencing was performed on these fecal samples. Diverse bacterial taxa were identified by MetaGeneMark, Soapaligner, and DIAMOND; microbiotal data analyses were carried out in the R environment. Differences in microbial taxa and metagenomic linkage groups were observed in multiple comparative analyses. RESULTS: The gut microbiota was altered after treatment. Compared with before treatment, the changes in bacterial diversity and microbiotal composition after treatment were more apparent in the responder group than in the nonresponder group. Bacterial species analysis revealed a group of gut bacteria in multiple comparisons, with a group of eight specific species being associated with the outcome of FOLFOX treatment. Responders and nonresponders before treatment were clearly separated based on this bacterial subset. Finally, the metagenomic linkage group network and metabolomic analyses based on the genomic data confirmed a more significant change in the gut microbiota during FOLFOX treatment in the responder group than in the nonresponder group. CONCLUSIONS: Overall, our results describe a dynamic process of gut microbiotal changes from the start to the end of FOLFOX treatment, and verified a close relationship between microbiota and treatment outcome. Recognition of the significance of microbiotal intervention before FOLFOX treatment for low-set rectal cancer may improve the effects of these agents.

Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine.

Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.

An examination of data from the American Gut Project reveals that the dominance of the genus Bifidobacterium is associated with the diversity and robustness of the gut microbiota.

Bifidobacterium and Lactobacillus are beneficial for human health, and many strains of these two genera are widely used as probiotics. We used two large datasets published by the American Gut Project (AGP) and a gut metagenomic dataset (NBT) to analyze the relationship between these two genera and the community structure of the gut microbiota. The meta-analysis showed that Bifidobacterium, but not Lactobacillus, is among the dominant genera in the human gut microbiota. The relative abundance of Bifidobacterium was elevated when Lactobacillus was present. Moreover, these two genera showed a positive correlation with some butyrate producers among the dominant genera, and both were associated with alpha diversity, beta diversity, and the robustness of the gut microbiota. Additionally, samples harboring Bifidobacterium present but no Lactobacillus showed higher alpha diversity and were more robust than those only carrying Lactobacillus. Further comparisons with other genera validated the important role of Bifidobacterium in the gut microbiota robustness. Multivariate analysis of 11,744 samples from the AGP dataset suggested Bifidobacterium to be associated with demographic features, lifestyle, and disease. In summary, Bifidobacterium members, which are promoted by dairy and whole-grain consumption, are more important than Lactobacillus in maintaining the diversity and robustness of the gut microbiota.