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.

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*

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

To analyze the disease group structure and its trends in key departments of large public hospitals using diagnosis related group (DRG) data, explore the key points of intervention and optimization of disease groups in departments, and further promote the rational allocation of department resources.

Objective To observe the effect of postoperative local injection of platelet-rich plasma(PRP)on patients'early inflammatory response and functional recovery in ankle fractures with lower tibiofibular injuries.Methods Fifty ankle fracture patients with lower tibiofibular injuries admitted to our hospital from January 2017 to December 2022 with postoperative local injection of PRP were selected as the PRP group,and 50 ankle fracture patients with lower tibiofibular injuries undergoing surgical treatment with ligament repair protocols in the same time period with their matched gender and age were selected as the conventional group.We compared the postoperative conditions,postoperative 3 d swelling,postoperative pain visual analogue(VAS)scores and levels of platelet-derived growth factor(PDGF),transforming growth factor β1(TGF-β1),and inflammatory mediators in the two groups,and counted the 24-week postoperative good rate,ankle plantarflexion-dorsiflexion mobility,the quality of the restoration,and the complications in the two groups.Results The swelling grading in the PRP group was lower than that in the conventional group(28 cases of grade Ⅰ,20 cases of grade Ⅱ,and 2 cases of gradeⅢ)in the 3 d postoperative period(15 cases of grade Ⅰ,23 cases of grade Ⅱ,and 12 cases of gradeⅢ),and the VAS scores in the 3 d and 7 d postoperative period[(3.24±0.61)and(2.40±0.42)points]were lower than those in the conventional group[(3.78±0.74)and(2.96±0.55)],and the lower limb weight-bearing activity time(4.01±0.65)weeks,fracture healing time(3.05±0.42)months,and postoperative return to normal work time(3.17±0.47)months were shorter than those in the conventional group[weight-bearing activity time of lower limbs(4.29±0.74)weeks,fracture healing time(3.23±0.48)months,and postoperative return to normal work time(3.40±0.59)months].While the operation time(106.53±19.77)min,number of intraoperative fluoroscopies(14.47±3.23)times,and intraoperative blood loss(84.07±25.60)ml were not statistically different from those of the conventional group[operation time(108.20±18.41)min,number of intraoperative fluoroscopies(14.53±3.06)times,and intraoperative blood loss(86.23±22.17)ml]were not statistically different when compared(P＞0.05).There was no statistical difference in the comparison of preoperative inflammatory mediators,PDGF,and TGF-β1 between the two groups(P＞0.05).In both groups,PDGF was higher and interleukin-6(IL-6),TGF-β1,C-reactive protein(CRP),and tumour necrosis factor-α(TNF-α)were lower at 12 weeks postoperatively compared with the preoperative period(P＜0.05).In the PRP group,the postoperative PDGF was higher than that of the conventional group,and the inflammatory mediators and TGF-β1 were lower than those of the conventional group at 12 weeks postoperatively(P＜0.05).In the PRP group,the postoperative 24 week good rate and ankle plantarflexion-dorsiflexion mobility were higher than that of the conventional group,and the inferior tibiofibular coalition anterior spacing(ITFACS)and inferior tibiofibular coalition posterior spacing(ITFPCS)were lower than that of the conventional group,and there was no statistically significant difference in the rate of complications when comparing the rate with that of the conventional group(P＞0.05).Conclusion Local PRP injection combined with ligament repair protocol for treatment of ankle fractures with lower tibial fibula injuries accelerates patients'early functional recovery and improves the quality of anatomical repositioning,which may be related to the inhibition of inflammatory mediator release and the promotion of bone repair.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

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]