Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.

The incidence rate of abdominal trauma is increasing year by year in pediatric trauma， and traumatic pancreatic injury should be taken seriously by clinicians. The pancreas is located behind the peritoneum， and it is difficult to make an early diagnosis of pancreatic injury， especially in children with grade ‍Ⅰ‍/Ⅱ injury. Through a literature review， this article analyzes the application value of endocrine indices and abdominal ultrasound in the early diagnosis of pediatric pancreatic injury， so as to improve the rate of early diagnosis and avoid the onset of related complications. Changes of the endocrine indices such as serum insulin and C Peptide have certain advantages in diagnosing and evaluating the degree of pediatric pancreatic injury and can thus be used as early warning indices for pediatric pancreatic injury. Ultrasound elastography provides a new method for the diagnosis and differentiation of pancreatic injury； contrast-enhanced ultrasound， which has no radioactive damage， has relatively high specificity and sensitivity in identifying pediatric pancreatic injury， and therefore， it is expected to become an alternative to CT examination.

Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.
Biomarkers ; Biomarkers, Tumor/genetics* ; Carcinoma, Hepatocellular/diagnosis* ; Hepatitis B virus ; Humans ; Liver Neoplasms/diagnosis* ; RNA, Transfer/genetics*

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; C-Reactive Protein ; Caspase 3/metabolism* ; Interleukin-10 ; Interleukin-6/metabolism* ; Lactate Dehydrogenases/metabolism* ; Myeloblastin/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Network Pharmacology ; Procalcitonin/therapeutic use* ; Sepsis/genetics* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

OBJECTIVE The specificity of drug therapy in individuals and races has promoted the development and improvement of pharmacogenomics and precision medicine. While there is a few cognition on the minorities in China, especially in Lisu nationality from the Yunnan province. Therefore, we performed the research to improve the role of pharmacogenomics in the Lisu population from the Yunnan province of China. METHODS 54 variants of very important pharmacogenes selected from the PharmGKB database were genotyped in 199 unrelated and healthy Lisu adults from the Yunnan province of China, and then, genotyping data wtihχ2 test were analyzed. RESULTS We compared our data with those of other 26 populations from the 1000 Genomes Project, and acquired that the Lisu ethnicity is similar with the CDX (Chinese Dai in Xishuangbanna, China) and CHS (Southern Han Chinese, China). Furthermore, rs776746 (CYP3A5), rs1805123 (KCNH2), rs4291 (ACE), rs1051298 (SLC19A1) and rs1065852 (CYP2D6) were deemed as the most varying loci. The MAF of"G"at rs1805123 (KCNH2) in the Lisu population was the largest with the value of 51.0％. CONCLUSION There are significant differences in single nucleotide polymorphism loci, supplementing the phar?macogenomic information of the Lisu population in Yunnan province, China, and can provide a theoretical basis for indi?vidualized medication in the future.

OBJECTIVE Since the coronavirus disease 2019 (COVID-19) outbreak in December 2019, the search for a potential treatment for COVID-19 has been a constant focus. Therefore, we identified potential treatments for COVID-19 from Hippophae Fructus, a Tibetan medicine that may act on COVID-19, using a network pharmacology approach. METHODS We collected the chemical constituents and corresponding targets of Hippophae Fructus from traditional Chinese medicine system pharmacology (TCMSP). COVID-19 related genes were predicted in pubmed-Gene, OMIM and GeneCards databases. Then, protein-protein interactions (PPIs) of key genes were analyzed by STRING database. Compound-target-diseases network was constructed using Cytoscape software. The potential pathways were deter?mined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Additionally, molecular docking was used to verify the binding effect between the active component and the target. RESULTS A total of 33 components and 192 corresponding targets in Hippophae Fructus were found. 50 genes were obtained from the intersection of component targets and disease targets. These genes include IL-6, TNF, MAPK8 and PTGS2, which regu?late several pathways associated with COVID-19, involving Hepatitis B, Influenza A, TNF signaling pathway and Tuber?culosis. More importantly, high-node compounds such as quercetin and beta-sitosterol can well bind to key targets. CONCLUSION Some components in Hippophae Fructus can act on COVID-19 related genes and regulate multiple pathways. Perhaps Hippophae Fructus has the effect in treating COVID-19.

The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.

To investigate the value of head and neck CT angiography(CTA)in the evaluation of intraoperative hemorrhage of carotid body tumours. Head and neck CTA images of 36 patients with carotid body tumours confirmed by pathology were retrospectively analyzed.Patients were divided into two groups based on the intraoperative bleeding volume:<500 ml and≥500 ml groups.The patient's age,sex,Shamblin classification,size of the lesion,number of blood supply arteries,course of the disease,plain scan,and enhanced CT value between two groups were compared and analyzed.Logistics regression equation was established based on the CTA parameters with significant differences between the two intraoperative bleeding volume groups,and combined parameter was acquired.The receiver operating characteristic curve was established based on CTA single and combined parameters. The bleeding volume during the operation of carotid body tumors was significantly correlated with the age of patients(=0.019),the maximum diameter of tumours on axial images(=0.003),the maximum upper and lower diameters(=0.004),Shamblin classification(=0.012),and number of blood supply arteries(<0.001).The area under the receiver operating characteristic curve of the number of feeding arteries,the maximum diameter of axial images,maximum upper and lower diameters,Shamblin classification,and combined parameters were 0.865,0.781,0.806,0.766,and 0.927,respectively.When the optimal critical value was 0.408,the Youden index was 0.794,and the corresponding accuracy,sensitivity,and specificity were 0.919,0.909,and 0.923,respectively. Preoperative head and neck CTA can be used to evaluate the intraoperative blood loss.Combined parameters has the best diagnostic performance compared with single parameters.
Carotid Body Tumor ; diagnostic imaging ; Computed Tomography Angiography ; Head ; Humans ; Neck ; Retrospective Studies

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Aged ; Animals ; Bone Density ; Diabetes Mellitus, Experimental/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/etiology* ; Rats ; Receptor, IGF Type 1/physiology* ; Signal Transduction ; Streptozocin ; beta Catenin/physiology*

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.