Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective To evaluate the baseline characteristics and short-term safety of lecanemab in treatment of Alzheimer's disease(AD)in Chinese patients in a real-world study.Methods A mul-ticenter,retrospective,observational study was conducted on 646 AD patients who were continu-ously recruited and receved of lecanemab therapy in 84 medical centers from June 26,2024 to March 1,2025.Their clinical data,including baseline Mini-mental state examination(MMSE)score and clinical dementia rating(CDR)score before and after treatment,were collected,and the CDR-global score(CDR-GS)and CDR-sum of box score were calculated.The incidences of infu-sion-related reactions(IRR)and amyloid-related imaging abnormalities(ARIA),including ARIA with edema and effusion(ARIA-E)and ARIA with hemosiderin deposit(ARIA-H)within 3 months of treatment were observed and recorded.Apolipoprotein E(ApoE)genetic test was per-formed on 454 patients.Baseline characteristics and short-term safety of the patients were ana-lyzed.Results There were 301 patients(46.59％)having a baseline CDR-GS score of 0.5 and 345(53.41％)patients had a CDR score of 1.In the 454 patients receiving genetic test,the ApoEε4 carriers accounted for 31.27％(202 cases),including 17 cases of ApoEε4 homozygous carriers(8.42％).The incidence of IRR was 4.95％(32/646),which mainly occurred during the first infu-sion(90.63％,29/32),and there were 96.88％(31/32)of mild and 3.13％(1/32)of moderate IRR,with main manifestations of fever,dizziness,vomiting,etc.Sixteen patients(2.48％)experienced ARIA,including 5(31.25％)ARIA-E,10(62.50％)ARIA-H,and 1(6.25％)ARIA-E and ARIA-H.For the 5 patients with ARIA-E,2 were symptomatic,and in terms of radiographic severity,3 cases were mild and 2 cases were moderate ARIA-E.In the 10 patients with ARIA-H,all of them had no clinical symptoms,and in terms of radiographic severity,6 had mild and 4 had moderate ARIA-H.Among the 17 ApoEε4 homozygous patients,only one patient(5.88％)experi-enced ARIA-H with a moderate radiographic severity.Multivariate analysis showed that age in-creased the trend of ARIA risk,but no statistical difference was observed(P=0.056).Conclusion In this real-world study in China,AD patients receiving lecanemab treatment have the characteris-tics of being younger in age but higher disease severity.Short-term follow-up data suggest that lecanemab has good safety.

Objective To evaluate the baseline characteristics and short-term safety of lecanemab in treatment of Alzheimer's disease(AD)in Chinese patients in a real-world study.Methods A mul-ticenter,retrospective,observational study was conducted on 646 AD patients who were continu-ously recruited and receved of lecanemab therapy in 84 medical centers from June 26,2024 to March 1,2025.Their clinical data,including baseline Mini-mental state examination(MMSE)score and clinical dementia rating(CDR)score before and after treatment,were collected,and the CDR-global score(CDR-GS)and CDR-sum of box score were calculated.The incidences of infu-sion-related reactions(IRR)and amyloid-related imaging abnormalities(ARIA),including ARIA with edema and effusion(ARIA-E)and ARIA with hemosiderin deposit(ARIA-H)within 3 months of treatment were observed and recorded.Apolipoprotein E(ApoE)genetic test was per-formed on 454 patients.Baseline characteristics and short-term safety of the patients were ana-lyzed.Results There were 301 patients(46.59％)having a baseline CDR-GS score of 0.5 and 345(53.41％)patients had a CDR score of 1.In the 454 patients receiving genetic test,the ApoEε4 carriers accounted for 31.27％(202 cases),including 17 cases of ApoEε4 homozygous carriers(8.42％).The incidence of IRR was 4.95％(32/646),which mainly occurred during the first infu-sion(90.63％,29/32),and there were 96.88％(31/32)of mild and 3.13％(1/32)of moderate IRR,with main manifestations of fever,dizziness,vomiting,etc.Sixteen patients(2.48％)experienced ARIA,including 5(31.25％)ARIA-E,10(62.50％)ARIA-H,and 1(6.25％)ARIA-E and ARIA-H.For the 5 patients with ARIA-E,2 were symptomatic,and in terms of radiographic severity,3 cases were mild and 2 cases were moderate ARIA-E.In the 10 patients with ARIA-H,all of them had no clinical symptoms,and in terms of radiographic severity,6 had mild and 4 had moderate ARIA-H.Among the 17 ApoEε4 homozygous patients,only one patient(5.88％)experi-enced ARIA-H with a moderate radiographic severity.Multivariate analysis showed that age in-creased the trend of ARIA risk,but no statistical difference was observed(P=0.056).Conclusion In this real-world study in China,AD patients receiving lecanemab treatment have the characteris-tics of being younger in age but higher disease severity.Short-term follow-up data suggest that lecanemab has good safety.

Objective To observe the expression of pro-inflammatory factors including interleukin(IL)-1a,IL-1β,IL-6 and IL-8 after silencing and over-expressing of tumor necrosis factor receptor-associated factor 6(TRAF6)in vitro,explore the effect of TRAF6 on pro-inflammatory factors after Kaposi's sarcoma-associated herpesvirus(KSHV)infection,and provide new ideas for the study of the pathogenesis of KSHV.Methods The silence and over-expression TRAF6 models were established using KSHV(+)iSLK cell line,and the transfection level was de-tected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).After 48 and 72 hours of cultiva-tion of cells,the expression levels of pro-inflammatory factors after silencing and over-expressing TRAF6 were de-tected by enzyme-linked immunosorbent assay(ELISA)and compared.Results TRAF6-silence(siTRAF6)and TRAF6-over-expression(TRAF6-OE)cell models were established successfully.ELISA results showed that pro-inflammatory factors IL-1α,IL-1β,IL-6,and IL-8 increased in varying degrees after silencing TRAF6,while these pro-inflammatory factors decreased in varying degrees after TRAF6 over-expression,IL-6 and IL-8 levels changed remarkablely,suggesting that TRAF6 had a certain inhibitory effect on pro-inflammatory factors and played an im-portant role in the signaling pathway of pro-inflammatory effects after KSHV infection.Conclusion TRAF6 has a certain inhibitory effect on pro-inflammatory factors and is expected to serve as a potential target to inhibit the pro-gression of Kaposi's sarcoma.

Objective To observe the expression of pro-inflammatory factors including interleukin(IL)-1a,IL-1β,IL-6 and IL-8 after silencing and over-expressing of tumor necrosis factor receptor-associated factor 6(TRAF6)in vitro,explore the effect of TRAF6 on pro-inflammatory factors after Kaposi's sarcoma-associated herpesvirus(KSHV)infection,and provide new ideas for the study of the pathogenesis of KSHV.Methods The silence and over-expression TRAF6 models were established using KSHV(+)iSLK cell line,and the transfection level was de-tected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).After 48 and 72 hours of cultiva-tion of cells,the expression levels of pro-inflammatory factors after silencing and over-expressing TRAF6 were de-tected by enzyme-linked immunosorbent assay(ELISA)and compared.Results TRAF6-silence(siTRAF6)and TRAF6-over-expression(TRAF6-OE)cell models were established successfully.ELISA results showed that pro-inflammatory factors IL-1α,IL-1β,IL-6,and IL-8 increased in varying degrees after silencing TRAF6,while these pro-inflammatory factors decreased in varying degrees after TRAF6 over-expression,IL-6 and IL-8 levels changed remarkablely,suggesting that TRAF6 had a certain inhibitory effect on pro-inflammatory factors and played an im-portant role in the signaling pathway of pro-inflammatory effects after KSHV infection.Conclusion TRAF6 has a certain inhibitory effect on pro-inflammatory factors and is expected to serve as a potential target to inhibit the pro-gression of Kaposi's sarcoma.

The prevalence of Lyme disease in endogenous populations in Urumqi,Xinjiang was investigated.In total,795 serum samples were collected from residents of three townships in the surrounding area of Urumqi City from 2022 to 2023,which included 383 from Lucaogou Town,145 from Shuixigou Town,and,267 from Tori Township.Serum levels of IgG and IgM antibodies were screened with an enzyme linked immunosorbent assay(ELISA)and confirmed by western blot(WB)analysis.Clinical data of WB-positive indi-viduals were collected and comprehensive analysis was con-ducted for case diagnosis.The chi square test was used for statistical analysis of the results and the P＜0.05 was consid-ered statistically significant.In total,110(13.84％)of 795 samples were positive.The positivity rates was higher in females than males[16.26％(73/449)vs.10.69％(37/346),x2=5.076,P=0.024],while there was no significant difference among age groups(x2=2.569,P=0.766).The positivity rates for serum antibodies in Shuixigou Town,Lucaogou Town,and Tuoli Township were 17.98％(48/267),14.48％(21/145),and 10.70％(41/383),respectively,with a significantly higher rate in Tuoli Township than Lucaogou Town(x2=7.041,P=0.008).Of 110 individuals who were initially positive for IgG and IgM antibodies with the ELISA,82(10.31％)were con-firmed positive by WB analysis.In total,20(2.52％)patients were diagnosed with Lyme disease based on clinical manifesta-tions.Lyme disease is epidemic among the population in Urumqi,as the infection rate is higher than the national average.Hence,continued surveillance is recommended for prevention of Lyme disease.

Purpose/Significance To expound the development status,difficulties and challenges of smart hospital in China,so as to pro-vide references for the subsequent related research.Method/Process By using the methods of bibliometrics and literature review,the definition of smart hospital is summarized and feasible suggestions on the construction of smart hospital are put forward.Result/Conclusion Smart hospital in China has initially established a"trinity"structural framework of smart healthcare,smart service and smart management,playing a positive role in improving patient satisfaction and promoting high-quality development of hospitals.It is necessary for the government,hospitals,social capital and other multi-party cooperation to jointly promote the construction of smart hospital in China and better protect people's health.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the factors influencing the occurrence of small for gestational age(SGA)at different degrees and provide a basis for early identification of severe SGA cases.Methods Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital.The neonates were divided into three groups:severe SGA group(birth weight below the 3rd percentile for gestational age and sex),mild SGA group(birth weight ≥3rd percentile and＜10th percentile),and non-SGA group(birth weight ≥10th percentile).An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees.Results A total of 14 821 neonates were included,including 258 cases(1.74％)in the severe SGA group,902 cases(6.09％)in the mild SGA group,and 13 661 cases(92.17％)in the non-SGA group.The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups(P＜0.0125).The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group(P＜0.0125).Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight(OR=1.838),maternal pre-pregnancy obesity(OR=3.024),in vitro fertilization-embryo transfer(OR=2.649),preeclampsia(OR=1.743),connective tissue disease during pregnancy(OR=1.795),nuchal cord(OR=1.213),oligohydramnios(OR=1.848),and intrauterine growth restriction(OR=27.691)were all associated with a higher risk of severe SGA(P＜0.05).Maternal parity as a multipara(OR=0.457)was associated with a lower likelihood of severe SGA(P＜0.05).Conclusions Maternal pre-pregnancy underweight,maternal pre-pregnancy obesity,in vitro fertilization-embryo transfer,preeclampsia,connective tissue disease during pregnancy,oligohydramnios,nuchal cord,and intrauterine growth restriction are closely related to the occurrence of more severe SGA.Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.[Chinese Journal of Contemporary Pediatrics,2024,26(3):262-268]