Objective To identify the potential core genes affecting the prognosis of sepsis based on bioinformatics.Methods The Gene Expression Omnibus(GEO)database was used to screen the gene expression datasets GSE54514 and GSE65682 from septic pa-tients.Key genes related to the prognosis of sepsis were screened by weighted gene co-expression network analysis(WGCNA)and Venn analysis.the Metascape database,the RcisTarget package,and the CIBERSORT algorithm were used to perform gene function enrichment analysis,transcription factor enrichment analysis,and immune infiltration analysis.The dataset GSE5772 was selected for validation to screen core genes associated with the prognosis of sepsis,and the survival analysis was performed by the Kaplan-Meier method.Results Co-expression network analysis was performed on the datasets GSE54514 and GSE65682,respectively,and the"green"and"brown"modules with the highest prognostic correlation to sepsis were selected.The intersection of genes in the two modules was taken,and 20 key genes were obtained by Venn analysis.These key genes were mainly enriched into the regulation of cell morphology,monocyte migration,and other pathways.Enrichment analysis of the transcription factor showed that the transcription factor ZNF148 might be one of the main regulators of the gene set.Further verification of data set GSE5772 revealed that the genes FGD3,MBP,MSN,RNF130 and SETD1B were significantly low expressed in septic patients(P＜0.05).Immune infiltration analysis showed that these five core genes were closely related to the content of immune cells.The expressions of FGD3,MSN and RNF130 were correlated with the survival rate of septic pa-tients(P＜0.05).Conclusion Five core genes associated with the prognosis of sepsis were screened via bioinformatics methods,which are closely related to immune cells.The genes FGD3,MSN and RNF130 may be important predictors for the prognosis of sepsis.

OBJECTIVE To clarify the weight index and optimize the technology of compound Mingmu Yijing pills. METHODS Water content, dissolution time limit and bolus-forming pass rate were included as evaluation indexes. The analytic hierarchy process(AHP) and the criterion importance through inter-criteria correlation(CRITIC) method based on the objectivity of indicators were adopted, AHP-CRITIC mixed weighting method. In this way, the relative coefficients of each index were calculated for weight distribution and comprehensive score, and the molding process was optimized and verified by Box-Behnken response surface test. RESULTS Compared with the single weighting method, the AHP-CRITIC mixed weighting method was more reasonable and stable. This method finally optimized the forming process conditions of Mingmu Yijing pills as follows: adding water amount of 0.8 times, the damp mass infiltration for 0.5 h, drying temperature of 60 ℃, drying time of 8 h. The mean comprehensive score of validation experiment was 88.21, RSD was 0.29%. CONCLUSION AHP-CRITIC method scientifically determines the weight of multiple indicators, and the verification test confirms that the optimized molding process is stable and feasible, which can be used in practical large-scale production.

Mirabilis jalapa L. is a plant of the family of Miraceae, native to tropical America and introduced to China during the Ming Dynasty. Its main medicinal part is the root. After sorting, it was found that the research on the medicinal properties of the Mirabilis Radixis incomplete, and the records of medicinal properties do not fully match the current application, and there is a situation of "the raw and processed for different treatments". This study further explored its medicinal properties. The Mirabilis Radix is bitter, pungent, and slight cold; belonging to the bladder, liver, and stomach meridians; it has the functions of clearing heat and dampness, detoxifying and reducing swelling, promoting blood circulation and regulating menstruation, dispelling wind and dampness, and nourishing yin. It was taken orally, with decoction, and adults should take 15-30 g, not in the form of original powder. People with spleen and stomach deficiency and cold should take it with caution, and pregnant women should not take it; for external use, an appropriate amount of fresh products should be applied and mashed. Processed Mirabilis Radix, recorded by Tujiazu medicine and Uyghur medicine, after boiling or steaming, the medicinal properties change and the nourishing effect is enhanced, but there is a lack of relevant research. Further exploration of the medicinal properties of the Mirabilis Radix can provide reference for clinical application, standard improvement, and product development.

Wastewater-based epidemiology(WBE)can effectively assess population health status,but it is lack of analytical methods which can simultaneously analyze a number of pharmaceuticals and biomarkers in wastewater.In this work,a method including sample pretreatment and instrumental detection for quantifying 83 kinds of pharmaceuticals and biomarkers in the influent of wastewater treatment plants(WWTPs)was established by sing solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS).The water sample(200 mL)with 83 kinds of target compounds was divided into two aliquots,which were then enriched and purified using HLB columns at pH=6.7 and pH=2 respectively,followed by elution with 6 mL of methanol and 6 mL of methanol containing 2%(V/V)formic acid,respectively,and then dried by nitrogen blown,concentrated,and finally redissolved to 0.5 mL,filtered through a nylon filter(0.22 μm).The target compounds in the samples were determined using UPLC-MS/MS in electrospray ionization under both positive and negative ion multiple reaction monitoring modes,with quantification using the internal standard method.The method exhibited good linearity(r>0.996)for the 83 kinds of target compounds in the concentration range of 0.1-500 ng/mL,and intra-day and inter-day precisions were 1.2%-16.5%.The recoveries of target substances in pure water and influent samples from a WWTP were 51.6%-166.6%and 56.4%-150.1%,respectively,with relative standard deviations of 0.2%-31.9%and 0.3%-20.9%,respectively.The method detection limits of target compounds were 0.02-7.72 ng/L.This method was applied to determine pharmaceuticals and biomarkers in the influent samples of a WWTP in Guangzhou,and 54 kinds of pharmaceuticals and 4 kinds of biomarkers were detected.The concentrations of acetaminophen and erythromycin were the highest among the pharmaceuticals,1.6-3.4 μg/L and 0.6-1.1 μg/L,respectively.The concentration of caffeine was the highest among the biomarkers,i.e.,33.3-43.9 μg/L.This method had high sensitivity,good stability and accuracy,and was suitable for detection of pharmaceuticals and biomarkers in the influent of WWTP,which could provide analytical method support for conducting studies on WBE.

Objective:To explore the clinical and genetic characteristics of three children with Hyperekplexia.Methods:Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis.Results:The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c. 1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment. Conclusion:Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.

Objective:To explore the expression levels and significance of programmed death factor 1 (PD-1)/programmed death factor ligand 1 (PDL-1) in T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs) in patients with unexplained recurrent spontaneous abortion (URSA).Methods:Forty-two URSA patients (as patient group), 34 healthy pregnant women (as normal pregnancy group) and 30 unpregnant healthy examination patients (as control group) were collected for retrospective analysis,all study subjects were from patients who were treated in Taizhou Hospital affiliated to Wenzhou Medical University from February 2020 to February 2022. Flow cytometry was used to detect the expression level of PD-1/PDL-1 in Treg cells, Breg cells and [T cells, B cells and natural killer cells (TBNK)] lymphocyte subsets, as well as the expression level of serum Th1 (IFN-γ, TNF-α)/Th2 (IL-4, IL-6, IL-10)/Th17 (IL-17) cytokine expression. The patients were treated with lymphocyte immunotherapy, the changes of PD-1/PDL-1 levels were detected at the end of treatment, and the pregnancy outcome was recorded during follow-up. Comparisons between multiple groups were performed by ANOVA, comparisons before and after treatment in URSA patients were performed by paired T-test, and correlation of each test index by bivariate correlation analysis.Results:The expression levels of PD-1/PDL-1 in Treg, Breg cells and T lymphocyte subsets in peripheral blood of patients with URSA was significantly lower than that of healthy pregnant women(all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was negatively correlated with the expression of serum Th1 cytokines Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) (The r values were -0.44, -0.85, -0.33, and -0.94, respectively, all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was positively correlated with the expression of serum Th2 cytokines interleukin 4(IL-4), interleukin 6(IL-6) and interleukin 10(IL-10)(The r values were 0.55, 0.47, 0.41, 0.33, 0.46, and 0.69, respectively,all P<0.01). The proportion of Breg cells and Treg cells were positively correlated with the level of serum IL-10 expression(The r values were 0.97, and 0.95 respectively, all P<0.01). The proportion of Treg cells was negatively correlated with the expression of IL-17( r=?0.95, P<0.01). The expression of PD-1/PDL-1 in Breg cells and Treg cells was positively correlated with the expression of serum IL-10(The r values were 0.95, 0.36, 0.96, and 0.95, respectively, all P<0.01). There was a negative correlation between serum IL-10 expression level and IL-17 expression level( r=?0.58, P<0.01). After URSA treatment, pregnancy was successful in 23 cases and failed in 19 cases. The expression of PD-1/PD-L1 on CD4, CD8, Tregs cells and Bregs cells in USRA treatment group was significantly higher than that before treatment( P<0.01), but there was no significant change in treatment failure group( P>0.05). Conclusion:The low expression of PD-1/PD-L1 in Treg cells, Breg cells and T cell subsets in peripheral blood of patients with URSA results in the immune imbalance of Th1/Th2 and Tregs/Th17, and the damage of maternal-fetal immune tolerance leads to pregnancy failure, which may be a potential therapeutic target.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

Humans ; Nerve Tissue Proteins ; Epithelial-Mesenchymal Transition/genetics* ; Constriction, Pathologic ; Receptors, Immunologic ; Epithelial Cells/metabolism* ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Lewy bodies formed by abnormal deposition of α-synuclein (α-syn) in neurons and glial cells are diagnostic markers of α-synucleinopathies. However, the early diagnosis of α-synucleinopathies is delayed due to the difficulty of brain biopsy at present. Because that α-syn can produce prion-like replication and spread to the periphery under pathological conditions, the ultramicro detection of pathologic α-syn in extracranial tissues by real-time quaking-induced conversion (RT-QuIC) technique can provide a basis for early diagnosis of α-synucleinopathies. In this paper, we review RT-QuIC technique in detecting α-syn seeding activity in different tissues of patients with α-synucleinopathies to summarize the potential value of RT-QuIC technique in early diagnosis or differential diagnosis of α-synucleinopathies.