This study aims to investigate the effects and mechanisms of the effective-compounds of Jinshui Huanxian formula (ECC-JHF) in improving pulmonary fibrosis. Animal experiments were approved by the Ethics Committee of the Animal Experiment Center of Henan University of Chinese Medicine (approval number: IACUC-202306012). The mouse model of pulmonary fibrosis was induced using bleomycin (BLM). Hematoxylin-eosin (H&E) staining was used to detect the histopathological changes of lung tissues. Masson staining was used to assess the degree of fibrosis in lung tissues. Immunofluorescence (IF) and real-time quantitative PCR (qPCR) were performed to measure the expression of collagen type I (COL I), α-smooth muscle actin (α-SMA), fibronectin (FN), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) in lung tissues. Flow cytometry (FCM) was employed to detect the proportion of M1 and M2 macrophages in the bronchoalveolar lavage fluid (BALF) of mice. IF and qPCR were also used to detect the expression of lipase family member N (LIPN) in lung tissues. Free fatty acid assay kit was used to detect the level of free fatty acids in lung tissue. Bone marrow-derived macrophages (BMDMs) were treated with interleukin-4 (IL-4) to induce M2 polarization. FCM was used to measure the proportion of CD206⁺ M2 macrophages. IF was utilized to detect LIPN expression and lipid droplet decomposition. The results showed that in BLM-induced pulmonary fibrosis mice, ECC-JHF significantly attenuated BLM-induced alveolar inflammation and collagen deposition, inhibited fibroblast activation in lung tissues, and decreased the proportion of M2 macrophages in BALF. It also significantly suppressed LIPN expression and free fatty acid level in lung tissues. In the IL-4 induced BMDMs M2 polarization model, ECC-JHF significantly inhibited the proportion of CD206⁺ M2 macrophages, down-regulated the expression of LIPN, and blocked lipid droplet catabolism. These results suggest that ECC-JHF may alleviate bleomycin-induced pulmonary fibrosis by inhibiting lipid droplet decomposition and M2 macrophage polarization.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective To investigate the molecular mechanism of sulforaphane(Sul)promoting bone marrow stem cells(BMSCs)differentiating into osteoblasts.Methods BMSCs were divided into the control group(without any treatment),induction group(induction of osteogenic differentiation),and induction+Sul group(induction of osteogenic differentiation with the addition of 40 μmol/L of Sul).The adenovirus-shRNA-Mock,-shRNA-TET1,-shRNA-TET2,and-shRNA-TET3 were transfected into BMSCs as the shRNA-Mock group,shRNA-TET1 group,shRNA-TET2 group,and shRNA-TET3 group.BMSCs were cultured in cell culture medium containing osteogenic differentiation induction medium and 40 μmol/L of Sul,and then transfected with adenovirus-shRNA-TET1,-shRNA-TET2,-shRNA-TET3,and-shRNA-Mock as the induction+Sul+shRNA-TET1 group,induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,and induction +Sul+shRNA-Mock group.The mRNA and protein expression levels of Runx2 after BMSCs differentiated into osteoblasts were determined by qPCR and Western blot.The DNA content of Runx2 promoter region bound to Histone H3 after BMSCs differentiated into osteoblasts was determined by chromatin immunocoprecipitation(ChIP).The methylation level of Runx2 promoter region of BMSCs differentiated into osteoblasts was determined by HpaⅡenzyme and MspⅠenzyme digestion combined with qPCR.The degree of BMSCs differentiated into osteoblasts was determined by alizarin red staining.Results Compared with the induction group,the mRNA and protein expression levels of Runx2 in the induction+Sul group were significantly increased(P<0.05);the content of DNA in the Runx2 promoter region bound to Histone H3 was increased(P<0.05),the methylation level of Runx2 promoter region was reduced(P<0.05),and the alizarin red staining score was elevated(P<0.05).Compared with the induction+Sul group,the content of DNA in the Runx2 promoter region bound to Histone H3 in the induction+Sul+shRNA-TET1 group was decreased(P<0.05),the methylation level of Runx2 promoter region was increased(P<0.05),and the alizarin red staining score was decreased(P<0.05).While there was no significant change among the induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,induction+Sul+shRNA-Mock group(P>0.05).Conclusion Sul can promote the differentiation of BMSCs into osteoblasts through promoting DNA demethylation of Runx2 promoter region by TET1.

Air Pollution/analysis* ; Environmental Exposure/analysis* ; China/epidemiology* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Monitoring

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective To analyze the effects and mechanisms of a disintegrin and metalloproteinase with thrombospondin motifs 14(ADAMTS14)gene in gastric cancer associated with Helicobacter pylori(Hp)infection and explore the potential of ADAMTS14 as a novel target for biological therapy of gastric cancer.Methods The Caner Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were utilized to analyze differentially expressed genes in gastric cancer tissues and Hp-positive gastric mucosa,and to screen potential targets.For the selected target ADAMTS14,its expression pattern in gastric cancer and Hp-positive gastric mucosa was analyzed.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis was performed on the genes co-expressed with ADAMTS14 in gastric cancer.Kaplan-Meier Plotter database was used to analyze the correlation between high-and low-ADAMTS14 expression and prognosis of gastric cancer patients.The expression of ADAMTS14 and its relationship with clinicopathological features in 30 patients with gastric cancer were analyzed using real-time fluorescent quantitative PCR(RT-qPCR)and immunohistochemistry.The relationship between Hp infection and ADAMTS14 expression was analyzed using GEO database,and confirmed by cell line infection experiment.ADAMTS14 expression in gastric cancer cell line NCI-N87 was silenced by small interfering RNA to analyze its effect on the function of gastric cancer cells;The effect of ADAMTS14 knockdown on downstream target genes of Hippo signaling pathway was analyzed by RT-qPCR and Western blotting.Results A total of 16 genes closely related to Hp infection and gastric cancer were identified by analyzing the TCGA and GEO databases.According to TCGA database,the ADAMTS14 expression in gastric cancer tissues was higher than that in healthy gastric mucosa(P<0.0001).RT-qPCR and immunohistochemistry results also showed higher ADAMTS14 expression in gastric cancer tissues compared to adjacent tissues(P<0.01).Survival analysis demonstrated poor prognosis in patients with high ADAMTS14 expression(P<0.001).Data from GSE60427 showed that ADAMTS14 expression was upregulated in Hp-infected gastric mucosa and cell lines(P<0.001).After Hp P12 infection,the ADAMTS14 expression in NCI-N87 cells was higher than that in uninfected group.ADAMTS14 knockdown significantly inhibited the proliferation and migration of NCI-N87 cells(P<0.05),and it also significantly inhibited the expression of Hippo signaling pathway target genes,including BMP7,BMPR2,FZD4,PARD3 and SAV1(P<0.05).Conclusion ADAMTS14 is highly expressed in Hp-positive gastric mucosa and gastric cancer tissues,which may accelerate gastric cancer progression by regulating Hippo signaling pathway,and holds potential as a new marker and therapeutic target for Hp infective gastric cancer.

Objective To investigate the effect of exosomal miR-146a-5p expression on gray matter volume in patients with major depressive disorder(MDD).Methods A total of 113 MDD patients(MDD group)and 107 healthy controls(HC)(HC group)were selected.Peripheral blood was collected and exosomes were isolated to quantify miR-146a-5p expression.Brain high-resolution T1 WI images of MDD and HC were obtained via MR,and gray matter volume was computed via SPM12 software.The interaction effect of"Depression×miR-146a-5p expression"on gray matter volume was analyzed using SPM's Flexible factorial design,and the between-group difference was assessed by extracting the mean value,thus to analyze whether MDD-related gray matter volume abnormalities were dependent on miR-146a-5p expression.Results Exosomal miR-146a-5p expression was significantly elevated in MDD group compared to HC group.Voxel-based factorial analysis revealed a relationship between high miR-146a-5p expression in MDD group and reduced gray matter volume in the anterior and posterior cingulate cortices(independent voxel threshold P＜0.001,AlphaSim corrected),and a significantly reduced gray matter volume as compared with HC group was detected in the two regions.Conclusion The exosomal miR-146a-5p is overexpressed in patients with MDD and may be associated with specific cortical atrophy in patients with MDD.

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]

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

Objective To investigate the effect of Shenqi Dihuang decoction combined with recombinant erythropoietin and L-carnitine on renal function in patients with end-stage renal disease and the regulation of Janus activated kinase/signal transducer and activator of transcriptions(JAK/STAT)pathway.Methods A total of 144 patients with end-stage renal disease who were treated in the Second Affiliated Hospital of Xingtai Medical College from October 2019 to October 2021 were selected as the study objects.Patients were divided into Shenqi Dihuang decoction treatment group and conventional treatment group according to random number table method,72 cases in each group.Maintenance hemodialysis was performed in both groups.The conventional treatment group received recombinant erythropoietin and L-carnitine,while the Shenqi Dihuang decoction treatment group had Shenqi Dihuang decoction(prescription composition:30 g each of raw Astragalus,Parasitic loranthus,Eclipta,Polyporus,Poria bark,Raw coix seed,Salvia miltiorrhiza,and Pyrrosia,15 g each of Codonopsis pilosula,Dogwood,Herba lycopi,and Common yam rhizome,10 g each of raw Rehmannia glutinosa,Litchi core,Silkworm sand and Curcuma zedoary,6 g Cassia seed),once a day for 3 months.The clinical efficacy,renal function,microinflammatory status and serum JAK/STAT pathway related protein levels were observed after treatment in two groups of patients with different treatment modalities,and the occurrence of adverse reactions was recorded.Results The total effective rate of Shenqi Dihuang decoction was higher than that of conventional treatment group[90.28%(64/72)vs.77.78%(55/72),P<0.05].After treatment,the residual renal function(RRF),24-hour urine protein,blood urea nitrogen(BUN),blood creatinine(SCr)and inflammatory factors[hypersensitive C-reactive protein(hs-CRP),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)]were lower than before treatment,the post-treatment RRF of the Shenqi Dihuang decoction treatment group was higher than that of the conventional treatment group(mL/min:4.82±1.18 vs.3.96±1.05),while 24 hours urine protein(mg:62.26±12.16 vs.97.71±16.28),BUN(mmol/L:16.25±3.64 vs.20.65±4.13),SCr(μmol/L:242.25±25.62 vs.280.62±26.63),hs-CRP(mg/L:5.86±1.15 vs.7.78±1.32),IL-6(ng/L:3.26±0.64 vs.4.62±1.13)and TNF-α(μg/L:29.23±5.64 vs.32.66±6.13)were significantly lower than those in the conventional treatment group(all P<0.05).After treatment,JAK and STAT in Shenqi Dihuang decoction group were increased compared with before treatment,phosphorylated JAK(p-JAK)and phosphorylated STAT(p-STAT)were decreased compared with before treatment(both P<0.05),while the serum JAK/STAT pathway related protein levels in conventional treatment group were not significantly changed(all P>0.05).Therefore,JAK and STAT in the Shenqi Dihuang decoction treatment group after treatment were significantly higher than those in the conventional treatment group[JAK(μg/L):1.46±0.28 vs.1.26±0.26,STAT(μg/L):1.37±0.25 vs.0.99±0.24,both P<0.05],p-JAK and p-STAT were significantly lower than those in the conventional treatment group[p-JAK(μg/L):0.45±0.08 vs.0.65±0.13,p-STAT(μg/L):0.66±0.13 vs.0.82±0.28,both P<0.05].There was no statistically significant difference in the incidence of adverse reactions between the two groups[13.88%(10/72)vs.9.72%(7/72),P>0.05].Conclusion Taking Shenqi Dihuang decoction based on recombinant erythropoietin and L-carnitine treatment can effectively inhibit the JAK/STAT signaling pathway,and improve renal function and micro-inflammatory status in patients with end-stage renal disease,thereby improving the therapeutic effect.