ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

Backgrounds Insomnia is frequent in schizophrenia and is found to be negatively affected by stressful life events,psychotic symptoms and depressive disorder,while the relationship among the four remains understudied in community-dwelling patients with schizophrenia.Objective To analyze the effect of stressful life events on insomnia in community-dwelling patients with schizophrenia,and to explore the mediation effect of psychotic symptoms and depression,so as to provide references for the intervention of insomnia in community-dwelling patients with schizophrenia.Methods From April to June 2023,a sample of 1 105 patients with schizophrenia attending 48 community health centers in Chengdu,Sichuan province and fulfilling the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria were included.All subjects were assessed using Stressful Life Event Scale(SLEs),Athens Insomnia Scale(AIS),Psychosis Screening Questionnaire(PSQ),and Patient Health Questionnaire Depression Scale(PHQ-9).Spearman correlation analysis was used to determine the correlation among the scales.Then the mediation model was constructed using Smart PLS 4.0,and tested with partial least squares algorithm and Bootstrap techniques.Results 332 patients(30.05%)with community schizophrenia were found to have insomnia.AIS scores in patients with schizophrenia were positively correlated with the scores on SLEs,PSQ and PHQ-9(r=0.165,0.322,0.554,P<0.01).Stressful life events indirectly contributed to insomnia through both separate mediation path and chained mediation path of psychotic symptoms and depressive disorder,and the indirect effect size of 0.102,0.372 and 0.190 was obtained,accounting for 10.46%,38.15%and 19.49%,respectively.Conclusion The stressful life events not only directly exert an impact on insomnia,but also indirectly contribute to insomnia through both the separate and chained mediation effect of psychotic symptoms and depressive disorder.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

Objective To explore the therapeutic effect and mechanism of pressing and rubbing method on myofascial pain syndrome(MPS)rats.Methods A total of 12 rats were randomly selected from 60 rats as the normal group,and the remaining rats were used to construct the MPS model by blunt strike combined with centrifugal exercise.Then 48 successfully modeled rats were randomly divided into model group,pressing and rubbing method group,pressing and rubbing method + Dantrolene[ryanodine receptor(RyR)inhibitor]group,pressing and rubbing method + normal saline group,with 12 rats in each group.The mechanical pain threshold was measured by von-Frey method.Detection of soft tissue tension,electromyography was performed;the ultrastructure of the pain point tissue was observed by transmission electron microscopy.The content of calcium ion(Ca2+)in the tissue of trigger point was detected by colorimetry.The protein expressions of dihydropyridine receptor(DHPR)α1,RyR and acetylcholinesterase(AChE)in the pain points of rats were detected by Western Blot.Results Compared with the normal group,the mechanical pain threshold,soft tissue tension in trigger point and the protein expressions of DHPRα1,RyR and AChE in the model group were decreased and the Ca2+ + content was increased(all P＜0.05),and the peak potential with higher amplitude was observed in the electromyogram.The ultrastructure of the trigger point tissue was damaged.Compared with the model group,the mechanical pain threshold,soft tissue tension of trigger point and the protein expressions of DHPRα1,RyR and AChE in the trigger point tissue of the rats in the pressing and rubbing method group and the pressing and rubbing method + normal saline group were increased,and the Ca2+ content was decreased(all P＜0.05),the electromyography was restored to be stable,the ultrastructural damage of the trigger point tissue was alleviated.Compared with the pressing and rubbing method group,the mechanical pain threshold,soft tissue tension of trigger point and protein the expressions of DHPRα1,RyR and AChE in the trigger point tissue of the rats in the pressing and rubbing method + Dantrolene group were decreased,and the Ca2+ content was increased(all P＜0.05),the electromyogram showed electrical activity changes,the ultrastructure of the trigger point tissue was damaged.Conclusion The pressing and rubbing method may improve MPS in rats by activating the DHPR/RyR signaling pathway.

A boy,aged 14 years,was admitted due to recurrent cough and expectoration for more than 1 month,with aggravation and fever for 2 days. After admission,he presented with tachypnea and a significant reduction in transcutaneous oxygen saturation,and emergency chest CT examination showed large patchy exudation and consolidation of both lungs. The boy was given tracheal intubation and invasive mechanical ventilation immediately,and his condition was improved after active symptomatic treatment. On the 10th day of hospitalization,the boy experienced fever again,and the laboratory tests showed positive results for Epstein-Barr virus and Mycoplasma antibody IgM,along with pancytopenia,elevated triglycerides,decreased fibrinogen,and increased levels of ferritin and soluble CD25. The boy was diagnosed with hemophagocytic lymphohistiocytosis. Bone marrow biopsy showed the presence of atypical lymphocytes,and aggressive natural killer cell leukemia was considered according to clinical manifestations and flow cytometry immunophenotype. Therefore,the possibility of hemophagocytic lymphohistiocytosis should be suspected in case of severe infection with pancytopenia and rapid disease progression,and hematological malignancies should also be ruled out. Bone marrow biopsy should be performed as early as possible to make a confirmed diagnosis and perform timely treatment.

Objective:To investigate the molecular mechanism by which exosomes secreted from human bone marrow mesenchymal stem cells (BMSCs) regulate pancreatic cancer (PC) cells.Methods:The exosomes secreted by BMSCs were extracted and identified. Human PC cell lines (PANC-1 and AsPC-1) were then divided into 3 groups: simple cell group, exosome group and inhibitor group. For inhibitor group, PI3K/AKT Signaling Pathway inhibitor LY294002 was added, followed by exosomes. Subsequently, the protein expression of phosphatidylinositol 3-kinase (PI3K) protein kinase B(AKT) and their phosphorylated types was detected by Western-blot, and the contents of PC cell markers B7-H4 and CA199 were detected by ELISA kit. The CCK-8 experiment was mainly conducted to detect the proliferation ability of cells, the flow cytometry to detect apoptosis, and the Transwell experiment to detect the migration and invasion ability of cells.Results:The exosomes secreted by BMSCs were extracted successfully. The expression of PC cell markers B7-H4 and CA199, the proliferation rate, and the invasion and migration ability of cancer cells were all decreased for both PANC-1 and AsPC-1, while the apoptosis rate increased, all of which had statistical significance ( P<0.001). There were no significant differences for the above parameter in inhibitor group compared with the simple cell group ( P>0.05). The p-PI3K and p-Akt of PANC-1 cells in simple cell group were (5.81±1.87), (5.30±1.21), while up-regulated to (12.74±3.28), (11.22±2.35) with statistically significant differences ( P<0.001) after exosomes were added. Meanwhile, the above 2 kinds of protein expression of AsPC-1 cells in simple cell group were (4.75±0.87), (4.15±1.32), while increased to (10.83±3.19), (9.28±2.33) in exosome group with statistically significant differences ( P<0.001). On the other hand, there was no significant differences for the protein expression of P-PI3K and P-AKT in inhibitor group ( P>0.05) compared with the simple cell group. Conclusion:Exosomes secreted by BMSCS can inhibit the proliferation of PC cells and its migration and invasion ability by activating PI3K/AKT signaling pathway, thus playing a role in antitumor effect.

Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD & antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.
Rats ; Animals ; RNA, Circular/genetics* ; Transcriptome ; RNA, Long Noncoding/genetics* ; Anticonvulsants ; MicroRNAs/genetics* ; RNA, Messenger ; Carbamazepine ; Amino Acids ; Gene Regulatory Networks

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
NF-kappa B/metabolism* ; Interleukin-18/metabolism* ; Proliferating Cell Nuclear Antigen/genetics* ; Cyclin D1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Muscle, Smooth, Vascular ; Cell Proliferation ; Signal Transduction ; Cytokines/metabolism* ; Glucose/metabolism*

China ; History of Medicine ; Medicine/standards*