Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.

Objective:To investigate the expression of Neurexophilin 4(NXPH4)in hepatocellular carcinoma(HCC)and its clinical significance and function.Methods:Retrieved LIHC project data(mRNA expression profiles and clinical records)from TCGA,analyzed differential NXPH4 expression in HCC versus adjacent non-tumor tissues,and investi-gated correlations between NXPH4 expression and clinicopathological characteristics/prognostic outcomes in HCC.Using GOEA and GSEA to investigate potential biological functions of NXPH4 in hepatocellular carcinoma.Results:NXPH4 exhibited significant upregulation in 23 cancer types(P<0.05),with significant associations to advanced HCC progression markers including TNM stage(P<0.05),histologic grade(P<0.05),and vascular invasion(P<0.05).Clinically,elevated NXPH4 expression correlated with reduced OS(HR=1.64,95%CI:1.15-2.33,P=0.006)and DSS(HR=1.88,95%CI:1.19-2.96,P=0.007).The immune infiltration results showed that NXPH4 expression was significantly correlated with Th2 cells and Th17 cells(all P values<0.05).Furthermore,NXPH4 expression was positively correlated with the levels of several immune checkpoint markers:TIGIT(r=0.265),PD-1(r=0.297),CTLA-4(r=0.302),and LAG-3(r=0.179,all P<0.001).Gene enrichment analysis revealed NXPH4 was significantly enriched in:pattern specification process(P<0.001);receptor ligand activity(P<0.001);collagen formation(P=0.009);activation of matrix metalloproteinases(P<0.001);neuro-active ligand receptor interactions(P<0.001);and ALK2 signaling(P=0.039).Conclusion:NXPH4 is associated with clinical pathological staging and poor prognosis in HCC patients;NXPH4 is associated with oncogenic pathways and im-mune infiltration,and has high value in predicting patient prognosis and immunotherapy.

Objective To study the impact of a subject's testing state on residual noise level and ABR wave V amplitude during non-sedated ABR testing using Kalman-weighted averaging(KWA).Methods Twenty-one adults(18～34 years old,42 ears)with normal hearing were enrolled for non-sedated ABR testing under three different states(lying,sitting,and writing)in a quiet room using a new Kalman-weighted averaging ABR system(vivosonic integrity system).The residual noise level and the amplitude of wave V for click ABR(cABR)of each subject were recorded.The traditional ABR test system(interacoustics,IA)was also used to record ABR with the residual noise level and the amplitude of wave V measured at the same time.Results ① There was no significant difference in am-plitude of wave V between traditional ABR and non-sedated ABR in three different testing states(P＞0.05).②The residual noise levels in the lying and sitting states of KWA ABR were lower than those of traditional ABR,but there was no statistically difference(P＜0.05).The residual noise level of the KWA ABR system in writing state was significantly higher than that of the other three conditions(P＜0.05).③ There was no significant difference between the left and right ears in the residual noise level and amplitude of wave V for non-sedated ABR in writing state(P＞0.05).Conclusion Compared with traditional ABR,the non-sedated KWA ABR system in uriting state was significantly higher than that of the other three conolitions.Haw ever,the residual noise level in lying and sit-ting states had no significant difference with conditional ABR,and different states of the subject had impact on the residual noise level in the ABR testing to sone extent.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q₁, Q₃) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.
Adolescent ; Adult ; Body Mass Index ; Humans ; Male ; Middle Aged ; Obesity/complications* ; Obesity, Metabolically Benign/epidemiology* ; Risk Factors ; Stroke/epidemiology*

Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.

BACKGROUNDErythromycin-resistant Streptococcus pneumoniae isolates that causing invasive pneumococcal diseases (IPD) in Chinese children remain uncharacterized. This study aims to identify the resistance genes associated with erythromycin resistance and to determine the genetic relationships of IPD isolates in Chinese children.

METHODSA total of 171 S. pneumoniae strains were isolated from 11 medical centers in China from 2006 to 2008. All the isolates were characterized via serotyping and antibiotic susceptibility determination. The erythromycin-resistant isolates were further characterized via ermB and mefA gene detection, multi-locus sequence typing analysis, and pulsed-field gel electrophoresis.

RESULTSA total of 164 (95.9%) isolates showed resistance to erythromycin, of which 162 strains with high high-level resistance (MIC ≥ 256 µg/ml). A total of 104 (63.4%) isolates carry the ermB gene alone, whereas 59 (36.0%) harbor both ermB and mefA genes. Of the 59 strains, 54 were of serotypes 19A and 19F and were identified as highly clonal and related to the Taiwan(19F)-14 clone.

CONCLUSIONSThe erythromycin resistance rate in IPD isolates is significantly high and is predominantly mediated by the ermB gene. Isolates that carry both ermB and mefA genes are predominantly of serotypes 19A and 19F.

Adolescent ; Anti-Bacterial Agents ; pharmacology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Erythromycin ; pharmacology ; Humans ; Infant ; Multilocus Sequence Typing ; Pneumococcal Infections ; microbiology ; Serotyping ; Streptococcus pneumoniae ; classification ; drug effects ; genetics ; isolation & purification

OBJECTIVETo research the bacteriostatic effects of Qingkailing Injection Extract (QKLIE) and combination therapy of Qingkailing Injection (QKLI) and antibiotics on bacteria carrying New Delhi metallo-3-lactamase 1 (NDM-1) blaNDM-1 resistance gene, and to determine their minimal inhibitory concentrations (MIC).

METHODSThe antimicrobial experiments of QKLIE (Radix Isatidis, baicalin, gardenia, honeysuckle) and combination therapy of QKLI and antibiotics were performed by using the agar dilution method and K-B method. The MIC was determined from each extract.

RESULTSThere were different degrees of inhibitory effects on resistant bacteria carrying blaNDM-1 by extracts from main components of QKLI. Of them, the inhibitory effect of baicalin was the best and the MIC of the resistant bacteria was 0.015 g/mL to WD, 0.020 g/mL to WX, 0. 005 g/mL to WJ, and more than 0.020 g/mL to pGEX-4T-NDM-1/DH5alpha (GST-NDM-1), respectively. The MIC value of each extract was sequenced from high to low as baicalin, honeysuckle, gardenia, and Radix Isatidis. Furthermore, combination therapy of QKLI and antibiotics greatly enhanced the antimicrobial activity of each antibiotics when used alone, showing very obvious antibacterial effects on multidrug resistant bacteria carrying blaNDM-1 gene. Of them, the optimal effects were obtained when combined with penicillins (penicillin G, mezlocillin, piperacillin/ tazobactam, ampicillin/sulbactam), with the antibacterial effects improved by 10 folds. The antibacterial effects of other kinds of antibiotics were improved to some extent. Conclusions QKLIE and combination therapy of QKLI and antibiotics showed better bacteriostatic effects on resistant bacteria carrying blaNDM-1 gene. This study provided theoretical bases for drug development, medication and treatment for super-resistant bacteria carrying blaNDM-1.

Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; genetics ; Drug Resistance, Multiple, Bacterial ; drug effects ; genetics ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; beta-Lactamases ; genetics

Objective To analyze the prevalence of metabolic syndrome (MS) in Kazakh population, using the NCEP-ATP Ⅲ, CDS, IDF MS standards. Methods Questionnaire-based survey,physical examination and blood testing were conducted according to cluster random samplings in Kazakh residents in Xinjiang. 2745 samples were collected and diagnosed by NCEP-ATP Ⅲ, CDS,IDF standards to analyze the prevalence, with the distribution of its main components of MS, among the Kazakhs population. Results The prevalence rates of MS diagnosed by NCEP-ATP Ⅲ, CDS,IDF standards were 18.5%, 14.2% and 26.6%, while they became 14.2%, 10.9% and 20.1% after standardized by age. The prevalence of MS diagnosed by NCEP-ATP Ⅲ and IDF standard in males were higher than in females, while CDS was in the opposite situtation. The prevalence of MS by these three standards increased with age. Among all the main components of MS diagnosed after these three standardization process, the prevalence of obesity, blood pressure rising and the abnormity of HDL-C were rather high. The prevalence of MS main components ≥1, ≥2, ≥3, ≥4, 5 ranked the highest compared to the lowest as to the IDF, ATP Ⅲ ' and CDS diagnostic. standards Conclusion The prevalence rates and gender distribution of MS diagnosed by different standards among Kazakhs were different. The prevalence of IDF standard was the highest, with the IDF standard better than the others in early identifying the risk factors of cardiovascular disease.

OBJECTIVETo investigate the influence of baicalin on the IL-1beta induced pro-MMP-1 in HGF and the effects of baicalin on MMP-3 expression in periodontal ligament cells (PDLCs).

METHODSThe amount of secreted pro-MMP-1 and MMP-3 expression was detected by ELISA and cell immunochemistry.

RESULTS(1) The amount of secreted pro-MMP-1 (3.333 +/- 0.123) microg/L increased significantly following 1 microg/L of IL-1beta, compared with control group (1.960 +/- 0.180) microg/L. Addition of baicalin to cell culture medium for 1 hour following IL-1beta decreased pro-MMP-1 secretion in a dose-dependent manner in the range of 10 approximately 1,000 microg/L. (2) 1 microg/L IL-1beta could significantly stimulate the synthesis and secretion of MMP-3 in PDLCs. (3) The baicalin could not interfere the synthesis of MMP-3, but could inhibit the release of MMP-3 from PDLCs.

CONCLUSIONSBaicalin could inhibit the secretion of pro-MMP-1 and MMP-3 expression in IL-1beta induced HGF and PDLCs, which suggests that baicalin may play an important role in preventing and treating periodontal disease.

Collagenases ; biosynthesis ; genetics ; Enzyme Precursors ; biosynthesis ; genetics ; Fibroblasts ; enzymology ; pathology ; Flavonoids ; pharmacology ; Gingiva ; enzymology ; pathology ; Humans ; Interleukin-1 ; pharmacology ; Interleukin-1beta ; Matrix Metalloproteinase 1 ; Metalloendopeptidases ; biosynthesis ; genetics ; Peptide Fragments ; pharmacology ; Periodontal Ligament ; enzymology ; pathology ; Periodontitis ; enzymology ; pathology ; Scutellaria ; chemistry