Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Aim To investigate the preventive and therapeutic effects of the mfat-1 gene therapy on exper-imental autoimmune encephalomyelitis in mice.Meth-ods mfat-1 gene therapy was used to render the host endogenous capability of producing ω-3 PUFAs,con-comitantly reduce the levels of ω-6 PUFAs,and change the proportion of ω-3/ω-6 PUFAs.Then,the levels of PUFAs in blood were analyzed by gas chromatography.The neurological deficits in mice were evaluated by neurological dysfunction score.HE staining and LFB staining of mouse spinal cord slices were used to ob-serve central nervous system inflammation infiltration and demyelinating lesions.Flow cytometry microsphere microarray technology was used to detect the content of cytokines in serum.Results The mfat-1 gene therapy could significantly raise the proportion of ω-3/ω-6 PU-FAs(P＜0.05),markedly delay the incubation period and peak period and reduce neurological dysfunction scores(P＜0.05),and improve inflammation and de-myelination of spinal cords(P＜0.05).It could also greatly increase the levels of IL-2,IFN-γ,IL-4 and IL-17 in serum(P＜0.05).Conclusion The pro-portion of ω-3/ω-6 PUFAs in blood circulation en-hanced by mfat-1 gene therapy can effectively prevent and treat experimental autoimmune encephalomyelitis in mice.

Transcatheter aortic valve replacement(TAVR)has emerged as a promising therapeutic alternative for addressing aortic valve-related pathologies.However,the occurrence of rapid arrhythmias linked to TAVR procedures is progressively drawing scrutiny.Presently,pharmacologic interventions constitute the mainstay of managing atrial arrhythmias related to TAVR,while the potential of ablation as a viable treatment modality remains undefined.Notably,in cases where the arrhythmia's genesis is presumed to be intricately linked to the prosthetic valve,the practicality and safety of ablation procedures remain unverified.Our institution has successfully ventured into radiofrequency ablation for a distinctive patient presenting with this intricate condition,thereby tentatively affirming the efficacy and safety of catheter ablation administered on the surface of prosthetic valves.

Objective:To analyze the effects of highdose methotrexate(HD-MTX)and lenalidomide as central nervous system(CNS)prophylaxis strategies in patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively.The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies.Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement.The CNS relapse-free survival(CRFS)rate,adverse effects,and the effects of different prophylaxis strategies on overall survival(OS)rate and progression-free survival(PFS)rate were evaluated in different groups and subgroups.Results:There were 200 patients enrolled in this study,80 cases in lenalidomide group and 120 cases in HD-MTX group.According to the delivery timing of prophylactic HD-MTX,the patients in HD-MTX group were further divided into two groups:80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval.At a median follow-up of 48(14-133)months,the 4-year CRFS rate,4-year PFS rate,and 4-year OS rate of the HD-MTX group was 93.6％,57.2％,and 68.8％,respectively,while that of the lenalidomide group was 90.4％,69.4％and 75.6％.There were no significant differences in 4-year CRFS rate,4-year PFS rate,and 4-year OS rate between HD-MTX group and lenalidomide group(all P＞0.05),but lenalidomide group showed a trend of improvement in PFS.Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups(91.7％vs 83.4％,P＞0.05),while 4-year PFS rate showed difference(49.5％vs 64.2％,P＜0.05).A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group,and 25 cycles occurred neutropenia accompanied with infection(10.1％),while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection(8.3％).Both the two groups had no treatment-related deaths.Conclusion:Compared with HD-MTX,lenalidomide combined with immunochemotherapy can prevent CNS relapse,at the same time,improve prognosis,which is a safe and well tolerated central prophylaxis strategy.

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]

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals

OBJECTIVE: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. METHODS: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. RESULTS: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. CONCLUSION Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans ; Child ; Nutritional Status ; Cross-Sectional Studies ; Iodine ; Sodium Chloride, Dietary/analysis* ; China ; Water

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male ; Humans ; Androgens/therapeutic use* ; Receptors, Androgen/genetics* ; Prognosis ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Cell Line, Tumor ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Gene Expression Regulation, Neoplastic