Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

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]

Objective To establish an evaluation system of pathogen detection rate of hospitalized patients before antimicrobial treatment based on process and outcome indicators,and study its application effect.Methods Hospi-talized patients with therapeutic antimicrobial treatment in a tertiary first-class hospital from July 2022 to June 2023 were selected as the study objects.Difference in process and outcome indicators were compared between before(Ju-ly-December 2022,control group)and after(January-June 2023,intervention group)the implementation of inter-vention in the evaluation system for pathogen detection rate of hospitalized patients before antimicrobial treatment.Results 41 577 and 27 052 hospitalized patients received therapeutic antimicrobial agents were included in the inter-vention group and control group,respectively.Pathogen detection rate and the accurate pathogen detection rate in the intervention group were both higher than those in the control group(74.2％vs 62.8％and 90.3％vs 82.5％,respectively),both with statistically significant differences(both P＜0.001).The goal achievement rate and im-provement rate for pathogen detection rate were 237.5％and 18.2％respectively,the goal achievement rate and im-provement rate for accurate pathogen detection rate were 104.0％and 9.5％respectively.For the process indica-tors,the conformity rate of detection and diagnosis,accurate collection rate,timely transfer rate,acceptance rate of pathogen specimens in the intervention group were all higher than those in the control group,differences were all statistically significant(all P＜0.001).For the outcome indicators,detection rates of targeted indicators and blood culture specimens,pathogen detection rate before treatment of restricted and special grade antimicrobial agent,as well as detection rate of sterile body fluid specimens in the intervention group were all higher than those in the con-trol group,with statistical significance(all P＜0.05).In addition,the positive rate of blood culture specimens in-creased from 18.5％before intervention to 21.7％after intervention,with statistically significant difference(P＜0.05).Conclusion The establishment of indicator evaluation system can improve the detection rate and accurate detection rate of pathogens before antimicrobial treatment,as well as the management quality and connotation of indicators.

Humans ; Anti-Bacterial Agents/therapeutic use*

Anti-Bacterial Agents/therapeutic use* ; Child ; Humans

Cholesterol Ester Storage Disease/genetics* ; Humans ; Mutation ; Sterol Esterase/genetics*

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring.Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation.Meanwhile,abnormal expression of Toll-like receptor 2 (TLR2) and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies.IL-6 and IL-10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders.To investigate whether murine CMV (MCMV) infection causes alterations in placental IL-6/10 and TLR2/4 levels,we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection.Mouse model of acute MCMV infection during pregnancy was created,and pre-pregnant MCMV infected,lipopolysaccharide (LPS)-treated and uninfected mice were used as controls.At E13.5,E14.5 and E18.5,placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed.The results showed that after acute MCMV infection,the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5,accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights.However,LPS 50 μg/kg could decrease the IL-6 expression at E13.5 and E14.5.This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more proinflammatory cytokine IL-6.High dose of LPS stimulation (50 tg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage.Imbalance ofIL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

BackgroundAs a major complication after orthotopic liver transplantation (OLT), the occurrence of acute kidney injury (AKI) is frequently defined by serum creatinine (Cr); however, the accuracy of commonly used blood urea nitrogen (BUN), uric acid (UA), and β-microglobulin (β-MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.

MethodsPatients who underwent OLT in three centers between July 2003 and December 2013 were enrolled. The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and classified by stage. Measurement data were analyzed using the t-test or Wilcoxon rank-sum test; enumerated data were analyzed using the Chi-square test or Fisher's exact test. Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic (ROC) curve analysis.

ResultsThis study excluded 976 cases and analyzed 697 patients (578 men and 119 women); the post-OLT AKI incidence was 0.409. Compared with the no-AKI group, the AKI group showed very significant differences in Model for End-stage Liver Disease score (14.74 ± 9.91 vs. 11.07 ± 9.54, Z = 5.404; P < 0.001), hepatic encephalopathy (45 [15.8%] vs. 30 [7.3%], χ = 12.699; P < 0.001), hemofiltration (28 [9.8%] vs. 0 [0.0%], χ = 42.171; P < 0.001), and 28-day mortality (23 [8.1%] vs. 9 [2.2%], χ = 13.323; P <0.001). Moreover, mean values of Cr, BUN, UA, and β-MG in the AKI group differed significantly at postoperative days 1, 3, and 7 (all P < 0.001). ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 (sensitivity 80.1%, specificity 75.7%, cutoff value 88.23 μmol/L), 0.916 for Stage 2 (sensitivity 87.6%, specificity 82.6%, cutoff value 99.9 μmol/L), and 0.972 for Stage 3 (sensitivity 94.1%, specificity 88.2%, cutoff value 122.90 μmol/L).

ConclusionThe sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.

Acute Kidney Injury ; blood ; Adult ; Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Retrospective Studies ; Uric Acid ; blood ; beta 2-Microglobulin ; blood

Objective:To investigate the role of pro-inflammatory cytokine IL-17 involved in the pathogenesis of cytomegalovirus hepatitis in vivo.Methods:First of all,disseminated infection model was established.Then,mice were randomly divided into 4 groups:normal control group,MCMV-infected control group,IL-17 blockade group,and isotype control group.Mice were sacrificed on day 7 after infection.The levels of IL-17 protein were detected by Western blot.Hematoxylin eosin (HE) staining was performed to evaluate the pathologic change of the liver.Serum ALT levels were detected by a Roche DPPI biochemical analyzer.The level of serum IL-17 was measured by double antibody sandwich ELISA.The expressions of mRNA of IL-17R,IFN-γand IL-10 in liver were detected by RT-PCR.Results:Compared with MCMV-infected mice and isotype control,the blockade of IL-17 inhibited the expression of IL-17 protein in liver (P＜0.05).The degree of liver damage reduced obviously.The serum ALT was significantly lower [(146±15)vs (102±11)vs (37±12),P＜0.05].The level of serum IL-17 was relatively reduced[(719.76±6.06)vs (722.1±4.62) vs (707.53 ±8.58),P＜0.05].The expression of IFN-γmRNA [(0.56± 0.06)vs (0.55±0.13)vs (0.96±0.2),P＜0.05] and IL-10 mRNA[(0.55±0.073) vs (0.51 ±0.07) vs (0.903 ±0.18),P＜0.05] increased significantly,while that of IL-17R did not change apparently[(0.81±0.16)vs (0.89±0.38) vs (0.87±0.23),P＞0.05].Conclusion:The increased expression of pro-inflammatory cytokine IL-17 is involved in the pathogenesis of immune injury in cytomegalovirus hepatitis.The blockade of IL-17 is helpful to relieve the liver damage and improve the liver function.