ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Objective To investigate the changes of serum cathepsin L(CTSL)in patients with acute exacerbation of chronic heart failure(CHF)and its relationship with lipid metabolism and severity of the disease.Methods A prospective study was conducted on 186 elderly patients with acute exacerbation of CHF admitted to our hospital from February 2021 to October 2024.Their serum levels of CTSL and lipid metabolism indicators were measured at admission.According to the quartile of CTSL,they were divided into groups A(CTSL≤3.31 μg/L,47 cases),B(3.31μg/L＜CTSL≤3.70 μg/L,46 cases),C(3.70 μg/L＜CTSL＜4.41 μg/L,47 cases),and D(CTSL≥4.41 μg/L,46 cases).The general clinical data,blood lipid metabolism and severity of disease were compared among the four groups.Pearson correlation analysis was used to analyze the correlation between CTSL and blood lipid metabolism indicators,and ordinal regression model and restricted cubic spline analysis was employed to examine the relationship between serum CTSL and the se-verity of acute exacerbation of CHF.Results There were significant differences in total cholester-ol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipopro-tein cholesterol(LDL-C)among the four groups of patients(P＜0.05,P＜0.01).Pearson correla-tion analysis showed that serum CTSL level was positively correlated with TC,TG and LDL-C levels(r=0.203,P=0.005;r=0.178,P=0.015;r=0.184,P=0.012),and negatively with HDLC(r=—0.344,P=0.000).Ordinal regression analysis indicated that serum CTSL level was an inde-pendent risk factor affecting the severity of CHF in patients with acute exacerbation(P＜0.05).Restricted cubic spline analysis revealed that serum CTSL level was in a linear relationship with the severity of acute exacerbation of CHF(x2=3.140,P=0.371).When serum CTSL＞3.73μg/L,the severity of the condition was increased significantly.Conclusion Serum CTSL level is closely associated with lipid metabolism in elderly patients with acute exacerbation of CHF,and is an independent risk factor for the severity of disease.

Objective To investigate the changes of serum cathepsin L(CTSL)in patients with acute exacerbation of chronic heart failure(CHF)and its relationship with lipid metabolism and severity of the disease.Methods A prospective study was conducted on 186 elderly patients with acute exacerbation of CHF admitted to our hospital from February 2021 to October 2024.Their serum levels of CTSL and lipid metabolism indicators were measured at admission.According to the quartile of CTSL,they were divided into groups A(CTSL≤3.31 μg/L,47 cases),B(3.31μg/L＜CTSL≤3.70 μg/L,46 cases),C(3.70 μg/L＜CTSL＜4.41 μg/L,47 cases),and D(CTSL≥4.41 μg/L,46 cases).The general clinical data,blood lipid metabolism and severity of disease were compared among the four groups.Pearson correlation analysis was used to analyze the correlation between CTSL and blood lipid metabolism indicators,and ordinal regression model and restricted cubic spline analysis was employed to examine the relationship between serum CTSL and the se-verity of acute exacerbation of CHF.Results There were significant differences in total cholester-ol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipopro-tein cholesterol(LDL-C)among the four groups of patients(P＜0.05,P＜0.01).Pearson correla-tion analysis showed that serum CTSL level was positively correlated with TC,TG and LDL-C levels(r=0.203,P=0.005;r=0.178,P=0.015;r=0.184,P=0.012),and negatively with HDLC(r=—0.344,P=0.000).Ordinal regression analysis indicated that serum CTSL level was an inde-pendent risk factor affecting the severity of CHF in patients with acute exacerbation(P＜0.05).Restricted cubic spline analysis revealed that serum CTSL level was in a linear relationship with the severity of acute exacerbation of CHF(x2=3.140,P=0.371).When serum CTSL＞3.73μg/L,the severity of the condition was increased significantly.Conclusion Serum CTSL level is closely associated with lipid metabolism in elderly patients with acute exacerbation of CHF,and is an independent risk factor for the severity of disease.

ObjectiveAcute myocardial infarction (AMI) is a highly prevalent and deadly disease globally, with its incidence continuing to rise in recent years. Timely reperfusion therapy is crucial for improving the prognosis of AMI patients. However, myocardial reperfusion can lead to irreversible myocardial ischemia/reperfusion (MI/R) injury, which is associated with adverse cardiovascular outcomes following AMI. Studies have shown that microRNAs (miRNAs) are abnormally expressed during MI/R injury and play an important role in the fate of cardiomyocytes. Effective preventive and therapeutic strategies against MI/R injury remain lacking in clinical practice, necessitating elucidation of the molecular mechanisms underlying MI/R onset and progression. This study investigated the role of microRNA-878 (miR-878) in the regulation of mitochondria-mediated apoptosis in MI/R injury. MethodsThe H9c2 cells were flushed with a gas mixture containing 1% O₂, 5% CO₂ and 94% N₂ for 3 h. Then the cells were incubated in complete culture medium under 5% CO₂ and 95% air for 6 h to mimic in vivo hypoxia/reoxygenation (H/R) injury. Cell viability were detected by CCK-8 assay. The concentrations of lactate dehydrogenase (LDH) were then measured.The level of apoptosis was analyzed by flow cytometry. The morphology of mitochondria was analyzed by immunofluorescence and laser confocal microscopy. The levels of mitochondrial reactive oxygen species (mtROS) were detected by immunofluorescence. Dual luciferase reporter gene assay was used to study the binding site of miR-878 and Pim1. RNA immunoprecipitation (RIP) assay was used to verify the binding relationship between miR-878 and Pim1. The gene expression levels were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot. ResultsThe study found that compared with the control group, the expression of miR-878 in H/R-treated H9c2 cells was significantly increased ((1.00±0.25) vs (9.70±2.63), P<0.01). In H/R-induced cells, transfection of miR-878 inhibitor significantly increased cell viability ((46.67±3.00) vs (74.62±4.08), P<0.000 1), and decreased LDH release ((358.58±41.71) vs (179.09±15.59), P<0.000 1) and cell apoptosis rate ((43.41±0.72) vs (27.42±4.48), P<0.01). At the same time, downregulation of miR-878 expression significantly inhibited DRP1-mediated mitochondrial overdivision and mtROS production ((6.60±0.57) vs (4.32±0.91), P<0.000 1). The mechanism study showed that miR-878 could target and bind Pim1 and inhibit the expression level of Pim1 ((1.00±0.13) vs (0.38±0.03), P<0.01). Rescue experiments confirmed that down-regulation of Pim1 expression significantly reversed the anti-injury effect of miR-878 inhibitor in H9c2 cells (P<0.01), promoted mitochondrial overdivision and mtROS production ((1.00±0.12) vs (2.41±0.12), P<0.01), and decreased the expression level of p-DRP1 ((1.00±0.15) vs (0.59±0.06), P<0.05). ConclusionThe present study demonstrates that miR-878 expression is upregulated in H9c2 cardiomyocytes subjected to H/R injury. Inhibition of miR-878 expression alleviates H/R-induced cardiomyocyte damage. Notably, downregulation of miR-878 significantly inhibits DRP1-mediated mitochondrial fission and mitigates mtROS production. Mechanistically, miR-878 targets and binds to the 3'-UTR of the Pim1 gene, thereby suppressing Pim1 protein expression. Collectively, these findings suggest that under H/R conditions, miR-878 promotes excessive mitochondrial fragmentation through DRP1 activation by targeting Pim1, ultimately contributing to cardiomyocyte injury. Modulation of the miR-878/Pim1 axis may represent a potential therapeutic strategy for mitigating MI/R-induced cardiac damage.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

AIM To establish a two reference substances for determination of multiple components(TRSDMC)method for the simultaneous content determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A,isochlorogenic acid C,deoxyelephantopin,isodeoxyelephantopin,isoscabertopin and scabertopin in Elephantopus scabre L..METHODS The analysis was performed on a 35℃thermostatic Waters Symmetry C18,Phenomenex C18,Agilent ZORBAX Eclipse Plus C18 columns(4.6 mm×250 mm,5.0 μm),with the mobile phase comprising of acetonitrile and 0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,326 nm.Chlorogenic acid was used as an internal standard to calculate the relative correction factors of neochlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A and isochlorogenic acid C,while isodeoxyelephantopin was used as an internal standard to calculate the relative correction factors of deoxyelephantopin,scabertopin and isoscabertopin,after which the content determination was made.Subsequently,cluster analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were conducted.RESULTS Eleven constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 95.3%-103.4%with the RSDs of 0.32%-3.45%.The result obtained by TRSDMC approximated those obtained by external standard method.Isochlorogenic acid A,isochlorogenic acid C,isochlorogenic acid B,chlorogenic acid,luteolin-7-O-glucuronide and cryptochlorogenic acid were taken as quality differential constituents.CONCLUSION This reliable and stable method can be used for the quality control of E.scabre.

Objective To investigate the value of the human chorionic gonadotropin(hCG)stimulation test in the diagnosis of disorder of sexual development(DSD)in children.Methods A retrospective analysis was conducted on 132 children with DSD.According to the karyotype,they were divided into three groups:46,XX group(n=10),46,XY group(n=87),and sex chromosome abnormality group(n=35).The above groups were compared in terms of sex hormone levels before and after hCG stimulation test,and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed.Results There was no significant difference in the multiple increase of testosterone after stimulation among the three groups(P>0.05).In the 46,XY group,the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes.Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue(P<0.05).Conclusions The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD,and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.[Chinese Journal of Contemporary Pediatrics,2024,26(2):158-163]