Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Aim To explore the effects of NaAsO

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
Child ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Clinical Relevance ; Disease-Free Survival ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prednisone/therapeutic use* ; Prognosis ; Recurrence ; Immunoglobulin Light Chains, Surrogate/genetics*

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

To investigate the effects of sodium arsenite(NaAsO

OBJECTIVE: To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity. METHODS: Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed. RESULTS: The rats with TNBS- induced UC showed obvious weight loss (P < 0.01) and severe colon tissue injury with high pathological scores (P < 0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P < 0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P < 0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P < 0.05) ACE (P < 0.01)and Chao (P < 0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P < 0.01) and a lowered abundance of Burkholderiaceae (P < 0.05). Compared with the UC rats, the rats treated with E. faecium QH06 showed obvious body weight gain (P < 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P < 0.05), decreased protein expressions of IFN- γ, IL- 12, and TLR2 and mRNA expressions of IFN- γ and IL-12 (P < 0.01 or 0.05), and increased protein expressions of IL- 4 (P < 0.05). The Shannon index ACE (P < 0.05) and Chao (P < 0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P < 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae. CONCLUSION E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2.
Animals ; Colitis, Ulcerative/drug therapy* ; Colon/metabolism* ; Interleukin-10 ; Interleukin-12/therapeutic use* ; Male ; RNA, Messenger/metabolism* ; Rats ; Rats, Wistar ; Toll-Like Receptor 2/metabolism*

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial. RESULTS: The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P<0.05). There was no statistical difference in the urinary symptoms, quality of life, lecithin and other scores between two groups (P>0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial. CONCLUSION A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).