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Objective:To evaluate the effect of Qishi Tongguan Prescription on pregnancy outcomes after interventional recanalisation in patients with tubal infertility (TFI).Methods:This was a retrospective study based on real-world and propensity score matching. Totally 260 patients with TFI from January 2020 to October 2021 in Shuguang Hospital of Shanghai University of Traditional Chinese Medicine and Maternal and Child Health Hospital of Pudong New Area were selected as observation subjects, and were divided into 123 cases in the TCM combination group and 137 cases in the control group based on whether they were treated with Qishi Tongguan Prescription in combination with interventional revascularization. Propensity score matching (PSM) was used as a covariate to obtain a new sample of inter group covariate equilibrium, and confounding factors that may affect the pregnancy outcome of TFI patients undergoing interventional recanalization surgery were used as covariates. The intrauterine pregnancy rate, ectopic pregnancy rate, biochemical pregnancy rate, early abortion rate and adverse reactions of the two groups of patients within 12 months of follow-up were compared, and the influence of TFI intervention and recanalization combined with Qishi Tongguan Prescription on intrauterine pregnancy rate was evaluated.Results:Age, years of infertility, type of infertility, history of miscarriage, history of ectopic pregnancy, history of biochemical pregnancy, history of uterine surgery, history of pelvic laparotomy, and degree of tubal patency had an effect on whether intrauterine pregnancy was achieved after interventional reversal in patients with TFI ( P<0.05), with age [ OR (95% CI) was 0.843 (0.769, 0.926)], history of pelvic laparotomy [ OR (95% CI) was 0.477 (0.248, 0.920)] and the degree of tubal obstruction [ OR (95% CI) was 0.152 (0.046, 0.500)] were independent factors ( P<0.01 or P<0.05). 81 patients were seen in each of the 2 groups after PSM, of whom the intrauterine pregnancy rates in the combined herbal group at 9 and 12 months after recanalisation were 48.1% (39/81) and 58.0% (47/81) respectively, compared with 32.1% (26/81) and 35.8% (29/81) in the control group, with statistical significance between the 2 groups ( χ2 values of 4.34 and 8.03, respectively, P<0.01); there was no statistical significance in the ectopic pregnancy rate, biochemical pregnancy rate and early abortion rate between the 2 groups ( P>0.05). There were no significant adverse reactions during the treatment. Conclusion:Qishi Tongguan Prescription combined with interventional recanalization can effectively improve the intrauterine pregnancy rate and shorten the waiting time for pregnancy in patients with TFI with higher safety.
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Objective:To study the main active components and potential mechanism of the treatment of ovarian cancer by Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus based on network pharmacology and in vitro cell experiments.Methods:TCMSP and SwissTargetPrediction databases were used to retrieve and collect the active components and targets of Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus, and four databases including GeneCards, OMIM, DrugBank and DisGeNET were used to search the targets related to ovarian cancer. After screening the common potential targets of Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus and ovarian cancer, the STRING database was used to realize the construction of PPI network interacting with the proteins of the two common targets. DAVID database was used for GO and KEGG enrichment analysis. Cytoscape 3.9.0 software was used to construct the "active component-target-pathway" network. Finally, the key targets and pathways were validated in vitro. MTT method was used to detect the proliferation inhibition rate of human ovarian cancer SKOV3 cells with different concentrations of Quercetin and sitosterol. Human ovarian cancer SKOV3 cells were divided into control group, Quercetin group and sitosterol group according to the random number table method. After corresponding drug intervention for 48 hours, the effects of Quercetin and sitosterol on SKOV3 cell cloning ability were detected by clone formation experiment, the levels of Akt1, VEGFA, Caspase-3 mRNA in each group were detected by PCR, and the protein expressions of PI3K, Akt, p-Akt, Caspase-3, and VEGFA in cells were detected by Western blot.Results:Through screening, 29 effective chemical components in Scutellariae Barbatae Herba and 3 effective chemical components in Cremastrae Pseudobulbus Pleiones Pseudobulbus were obtained, including 2 components in total. 291 drug-related targets, 1969 potential targets of ovarian cancer were acquired. There were 137 common targets of "Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus" and the drug-disease intersection of ovarian cancer. Through GO functional analysis, 930 items were obtained, involving 722 biological processes, 76 cellular components and 132 molecular functions. KEGG enrichment analysis involved 169 signaling pathways, including tumor pathway, PI3K-Akt signaling pathway, P-53 signaling pathway, IL-17 signaling pathway, etc. In vitro experiment results showed that cell proliferation inhibition rate increased and cell cloning ability decreased in Quercetin and sitosterol groups; The levels of Akt1 and VEGFA mRNA in Quercetin group and sitosterol group decreased ( P<0.01 or P<0.05), the expression of Caspase-3 mRNA and protein increased ( P<0.01), and the expressions of PI3K, p-Akt and VEGFA protein decreased ( P<0.01). Conclusion:Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus inhibits the occurrence and development of ovarian cancer through multi target and multi pathway synergistic effects, and can induce SKOV3 cell apoptosis by regulating the expressions of key genes such as AKT1, VEGFA, Caspase-3, and PI3K/Akt pathway.
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BACKGROUND:Previous studies have demonstrated that cell transplantation has neuroprotective effect on intracerebral hemorrhage,and some researches have indicated that transplantation of bone marrow stromal cells(BMSCs)can promote neural function recovery after cerebral infarction.OBJECTIVE:To explore whether transplantation of BMSCs-modified by gtial cell line-dedved neurotrophic factor gene(GDNF)gene provides a better therapeutic effect than native BMSCs after stroke.METHODS:Totally 36 SD rats were induced intracerabral hemorrhage models by injecting autologous arterial blood,and then divided into 3 groups(n=6).each group was assigned into 2 sub-groups Rabbits in each group were stereotaxically grafted with 20 μL GDNF/BMSCs,BMSCs or saline respectively.The rats were executed at 1 and 2 weeks after operation,and immunohistochemistry was used to observe the expressions of synaptophysin(Syn)and growth associated protein-43(GAP-43)in the margin of the hemorrhagic focus.RESULTS AND CONCLUSlON:Compared with the BMSCs and control groups.both Syn-immunoreactive and GAP-43-immunoreactive products were significantly increased in the GDNF/BMSCs group(P＜0.05).Present results demonstrate that transplantation of GDNF gene-modified BMSCs provides better neuroprotection than native BMSCs delivery for stroke.
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BACKGROUND: There is few studies addressing the long-playing dynamic observation of cysteinyl aspartate specific protease 3 (Caspase-3) expression following cerebral ischemia/reperfusion.OBJECTIVE: To investigate the effect of transplantation of the neural stem cells (NSCs) modified with gene of glial cell line-derived neurotrophic factor (GDNF) on expression of Caspase-3 in adult Sprague Dawley rats with transient cerebral ischemia.DESING: Randomized controlled animal study.MATERIALS: Sixty Sprague Dawley rats were divided randomly into normal control group (N, n =5), ischemia/reperfusion group (IR, n=5), neural stem cell group (NSCs, n=25) and NSCs modified with gene of GDNF group (GDNF/NSCs, n =25). Several clean neonatal Sprague-Dawley rats were selected to harvest NSCs.METHODS: With the exception of normal control group, models of transient cerebral ischemia were created by modified suture method in other groups. At day 3 following reperfusion, 20 μL NSC suspension containing (4.0-5.0)×10~5 NSCs was infused into rats of the NSC group via right lateral ventricle. An equal volume of GDNF-modified NSC suspension was injected into rats of the GDNF/NSC group. 20 μL saline was infused into the rats of the ischemia/reperfusion group. Animals were anesthetized and sacrificed at week 1 following ischemia/reperfusion in the normal control and ischemia/reperfusion groups. Animals were anesthetized and sacrificed at weeks 1, 2, 3, 5, 7 following ischemia/reperfusion in the NSC and GDNF/NSC groups, 5 rats in each time point.MAIN OUTCOME MEASURES: The strept avidin-biotin immunostaining method was used to observe the distributive characteristics of Caspase-3 in the hippocampus and frontal parietal cortex.RESULTS: Immunohistochemical method (SP) showed that positive capase-3 products expressed in nucleus, cytoplasm and partial neurite. In hippocampus, number of Caspase-3-positive cells was decreased in NSC and GDNF/NSC groups. With the exception of at 1-week reperfusion, number of Caspase-3-positive cells was significantly lessened in the GDNF/NSC group compared with the NSC group at other time points (P < 0.05). In frontoparietal cortex, number of Caspase-3-positive cells was reduced in the NSC and GDNF/NSC groups over time. Except 1 and 2 weeks following ischemia/reperfusion, number of Caspase-3-positive cells was significantly lessened in the GDNF/NSC group compared with the NSC group (P < 0.05).CONCLUSION: Transplanting NSCs modified with gene of GDNF can improve remarkably neural function by deceasing Caspase-3 expression and reducing the nervous cell apoptosis. The transplantation of NSCs modified with gene of GDNF obtained better outcomes compared with NSC transplantation.
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Previous experiments has shown that Ginsenoside Rb1 (GRb1), which is one of the most important active ingredients in ginseng (Panax ginseng C.A. Meyer), reduced infarct and neurologic deficit followed by the transient cerebral ischemia in rats. The mechanism of this neuroprotective function is unclear. In this study, we tested whether the neuroprotective effect of GRb1 is achieved through preventing the neuronal apoptosis and modulating expression of neuronal apoptosis inhibitory protein (NAIP). Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in Wistar rats. GRb1 (40 mg/kg, i.p.) was administered immediately after the onset of reperfusion. The rats with neurological deficits were randomly divided into 2 groups: the ischemia and the GRb1 group. Each group was again divided into subgroups according to the various reperfusion time (3 h, 12 h, 1, 2, 3, 5, 10 days, n=4 per time point). Apoptotic cells were analyzed using TUNEL. Immunohistochemical method was used to assess expression of NAIP. This results showed that the number of apoptotic cells elevated at 3 h of reperfusion, and peaked at 24 h, then declined, but the number of apoptotic cells at 10 d after ischemia was significantly more than those of control groups (P＜0.01). Compared with ischemia group, the apoptotic cells decreased at all subgroups of GRb1; however, the significant differences were only found from 12 h to 3 d of reperfusion. In normal and sham groups, NAIP weak immunostaining was diffusely present in the neurons of parenchyma. The number of NAIP-positive cells started to increase in ischemic regions at 3 h after ischemia, peaked at 12 h and declined up to 5 d of reperfusion. At 5 d after ischemia, the number of NAIP-positive cells was less than that of control group (P＜0.05). A few astrocytes strongly expressed NAIP in the ischemic area. In the GRb1 group, the number of NAIP-positive cells from 12 h to 10 d after ischemia was evidently higher than in the ischemia group. Thus, these results suggest that GRb1 has potential ability to prevent apoptosis, the mechanism of which is related to induce expression of NAIP.
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BACKGROUND: In the central nervous system(CNS) of normal adults there are neural stem cells or neural progenitor cells, which are capable of self-renewing and multiple differentiating. In normal physiological conditions, intrinsic neural stem cells are in a resting state. What state will they be in during cerebral ischemia?OBJECTIVE: To observe the distribution, proliferation and differentiation of intrinsic neural stem cells in focal transient ischemia in rats.DESIGN: A randomized controlled exploratory trial based on the rats.SETTING: Neurobiological department, histological and embryological department of a medical college.MATERIALS: The experiment was conducted in the Neurobiological Department of Luzhou Medical College from July 2001 to July 2002. Altogether 41 healthy adult SD rats of either gender, weighting 250 g - 300 g, were selected.INTERVENTIONS: The focal ischemia model was made by blocking middle cerebral artery(MCA) and reperfusing for 0.5 hour, 3 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 5 days and 10 days. Sham-operation group was treated by the same method, but the filament was not long enough to block MCA, and normal rats served as control group. The rats were sacrificed at given time points, and their brains were made into cerebral slices. The single-and double-labeled immunohistochemical staining was employed to detect the proliferation, distribution and differentiation of intrinsic neural stem cells.MAIN OUTCOME MEASURES: The distribution, proliferation and differentiation of intrinsic neural stem cells.RESULTS: Immunoreactivity of proliferating cell nuclear antigen(PCNA)was present in most ependymal cells in ventricular zone(VZ), and PCNA-positive cells were sparsely distributed in the parenchyma in normal and sham-operation groups. At 3 hours of reperfusion, PCNA-labeled cells were first detected in rostral subventricular zone. At 12 hours of reperfusion and onward, PCNA-positive cells appeared in some choroid plexus cells in bilateral lateral VZ. At day 3 to day 10 of reperfusion, PCNA-labeled cells significantly increased in infarct boundary in preoptic area, striatum and deep layer of frontoparietal cortex. PCNA-labeled cells were first detected in subgranular zone of dentate gyrus 3 days after reperfusion, and increased with time. A very small number of double-positive cells expressed with PCNA and glial fibrillary acidic protein(GFAP) were first detected in infract boundary in preoptic area on day 3 and onward. No double-PCNA and NF-positive cells were detected within 10 days of reperfusion.CONCLUSION: Focal cerebral ischemia activates intrinsic neural stem cells, which proliferate and differentiate, and migrate toward ischemic striatum and frontoparietal cortex. This may help clarify the mechanism of functional recovery after ischemia.