Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82％and 9.76％,without statistically significant difference(P＞0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).
Adult ; Humans ; Network Pharmacology ; RNA-Seq ; Coronary Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Biomarkers ; Syndrome ; Tablets ; Molecular Docking Simulation

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.

Objective To investigate the expression and clinicopathological significance of Bcl-2 and Bax genes in colorectal cancer (CRC) patients complicated with schistosomiasis. Methods The CRC patients receiving surgical treatment in the First Affiliated Hospital of Dali University from June 2016 to June 2020 were recruited as the study subjects, and 30 subjects were randomly sampled from the CRC patients complicated with schistosomiasis (CRC-S group) and 30 subjects were randomly sampled from the CRC patients without schistosomiasis (CRC group) using a random number table method. The cancer specimens were sampled from subjects in the CRC-S and CRC groups, and the peri-cancer specimens were sampled from subjects in the CRC group. The Bcl-2 and Bax expression was quantified in cancer and peri-cancer specimens using a real-time fluorescent quantitative PCR (qPCR) assay and immunohistochemistry at transcriptional and translational levels, and the cell apoptosis was detected in cancer specimens using HE staining. Results A total of 60 subjects were enrolled, including 30 cases in the CRC group and 30 cases in the CRC-S group. There were no significant differences between the two groups in terms of gender distribution (χ² = 0.271, P > 0.05), mean age (t = -0.596, P > 0.05), tumor growth pattern (χ² = 0.275, P > 0.05), tumor location (χ² = 4.008, P > 0.05), tumor invasion depth (χ² = 0.608, P > 0.05), degree of tumor differentiation (χ² = 0.364, P > 0.05), or presence of vascular metastasis (χ² = 1.111, P > 0.05), while significant differences were seen between the two groups in terms of histological type, presence of lymph node metastasis and TMN staging (χ² = 5.963, 8.297 and 5.711, all P values < 0.05). qPCR assay and immunohistochemistry quantified significantly higher Bcl-2 and Bax expression in cancer specimens from the CRC and CRC-S groups than in the peri-cancer specimens from the CRC group at both translational and transcriptional levels (all P values < 0.05), and higher Bcl-2 and lower Bax expression were seen in the cancer specimens from the CSC-S group than that from the CRC group (all P values < 0.05). In addition, the cell apoptotic rate was significantly greater in the cancer specimens in the CRC group than in the CRC-S group (42.00% vs. 23.35%; χ² = 41.500, P = 0.000). Conclusion Schistosomiasis may be involved in the development and progression of CRC through affecting Bcl-2 and Bax gene expression in the apoptosis signaling pathway.

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.
Animals ; Gastric Mucosa ; Methylnitronitrosoguanidine/toxicity* ; Precancerous Conditions/chemically induced* ; Rats ; Stomach Neoplasms/drug therapy*

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, CONCLUSIONS Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.
Beijing/epidemiology* ; Breast Feeding ; China/epidemiology* ; Communicable Diseases/epidemiology* ; Female ; Hospitalization ; Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy