Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To explore the influence of intravenous injection of cis-atracurium during anesthesia induction on QT interval(QTc),hemodynamics and oxidative stress level in patients undergoing hysteroscopic surgery.Methods Patients undergoing hysteroscopic surgery were classified into control group and treatment group.The treatment group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+0.15 mg·kg-1 of cis-atracurium besylate for injection,while the control group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+the same amount of 0.9％NaCl as treatment group.Laryngeal mask was placed in the two groups after 3 min,and laryngeal mask ventilation was given for general anesthesia.QTc value and hemodynamics[mean arterial pressure(MAP)]were detected before entering the room(T0),after 1 min of propofol+fentanyl intravenous injection(T1),after 1 min of cis-atracurium besylate for injection/0.9％NaCl(T2),immediately after laryngeal mask insertion(T3)and after 3 min of laryngeal mask insertion(T4).The anesthetic effect,postoperative dynamic pain visual analogue scale(VAS)score and sore throat were counted.The levels of serum oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)]at T0 and at the end of surgery(T5)were detected,and the safety was assessed.Results Fifty-two cases in treatment group and forty-four cases in control group were included.There was no statistical difference in QTc value between treatment group and control group at T0-T4(all P＞0.05).The MAP values in treatment group and control group at T3 were(84.22±5.96)and(86.78±6.11)mmHg,respectively,with a statistical difference(P＜0.05).The laryngeal mask insertion times in treatment group and control group were(17.02±2.47)and(19.52±2.34)s;the spontaneous breathing recovery times were(8.51±1.84)and(6.18±1.15)min;the eye opening time were(10.49±2.42)and(9.53±2.17)min;the laryngeal mask removal time were(11.16±2.16)and(10.21±2.34)min;the incidence rates of postoperative sore throat were 13.46％and 31.82％,and the differences were statistically significant(all P＜0.05).The levels of SOD in treatment group and control group at T5 were(36.63±4.17)and(33.26±4.86)nU·mL-1;the levels of MDA were(7.42±2.14)and(8.59±2.83)mmol·L-1(all P＜0.05).The adverse drug reactions in treatment group were mainly nausea and vomiting,respiratory depression and hypotension,and the adverse drug reactions in control group were mainly nausea and vomiting and respiratory depression.The incidence rates of adverse reactions in treatment group and control group were 13.46％and 11.36％,respectively(P＞0.05).Conclusion Cis-atracurium intravenous injection during anesthesia induction has no influence on QTc in patients undergoing hysteroscopic surgery,and has advantages in stabilizing intraoperative hemodynamics,reducing postoperative sore throat and improving serum oxidative stress indicators.

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]

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Purpose::Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods::Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.Results::Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. Conclusion::This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*

The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

Aim To observe cellular damage and astrocyte activation at different time points of cerebral ischemia and reperfusion. Methods The middle cerebral artery of male SpragueDawley rats was occluded for 90 min followed by different time points of reperfusion. Eighty-five SPF male SD rats were randomly divided into control group (Sham), IR3, 6, 12, 24 and IR48h (MCAO followed by 48 h of reperfusion) group. Cerebral ischemia and reperfusion injury was observed by HE staining, and the structure of astrocytes was estimated with transmission electron microscopy (TEM). GFAP expression was detected by immunofluorescence staining and Western blot. Results Cerebral ischemia following by different time points of reperfusion led to different degrees of cellular damage, which was the most serious at 24 h of reperfusion. TEM showed destruction of astrocytes structure, swollen organelles and broken mitochondrial ridge. After cerebral ischemia-reperfusion, the expression levels of GFAP were significant up-regulated in the ischemic penumbra cortex and the highest was at 48 h of reperfusion, indicating astrocytes were activated. In addition, the results showed the gradual decrease in GFAP expression in the infarct core. Conclusions After cerebral ischemia-reperfusion, cellular damage is aggravated, and astrocytes are gradually activated in the ischemic penumbra. With the extension of reperfusion time, the boundaries of infarct area and ischemic area are gradually clear, and scarring may occur.