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OBJECTIVE To study the ameliorative effect and potential mechanism of curcumin on diabetes model rats with depression based on cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway. METHODS The diabetes model rat with depression was established by high fat and high sugar diet+intraperitoneal injection of streptozotocin+chronic unpredictable stress-induced depression. The successfully modeled rats were randomly divided into model group， positive control group （0.18 g/kg metformin and 1.8 mg/kg fluoxetine， gavage）， curcumin low-dose and high-dose groups （30， 60 mg/kg， gavage） and curcumin high-dose+CREB inhibitor group [60 mg/kg curcumin （gavage）+5 mg/kg CREB inhibitor 666-15 （intraperitoneal injection）]， with 12 rats in each group. Another 12 healthy rats were selected as the normal group. Each group was given a corresponding intervention for 4 weeks， the fasting blood glucose level of rats was detected， and the depression of rats was assessed. The levels of corticosterone （CORT） and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin- 1β （IL-1β）， IL-6] in serum， and the levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT） in hippocampal tissue were determined. The pathological changes and neuronal apoptosis were observed in the hippocampal tissue of rats in each group； the expression levels of CREB， BDNF mRNA and protein in hippocampal tissue were detected. RESULTS Compared with the normal group， the hippocampal tissue of rats in the model group was severely damaged， and neurons were scattered， while the fasting blood glucose， the forced swimming immobility time， the tail suspension immobility time， serum levels of CORT， TNF-α， IL-1β and IL-6， and neuron apoptosis indexes were all increased or prolonged significantly （P＜0.05）. The levels of NE and 5-HT， the number of surviving neurons， and the expression levels of CREB and BDNF mRNA and protein in hippocampal tissue were decreased significantly （P＜0.05）. Compared with the 的model group， the damage to hippocampal tissue was relieved in the positive control group and curcumin groups， while the above indexes were improved significantly （P＜0.05）. The improvement effect of curcumin high-dose group was better than that of curcumin low-dose group （P＜0.05）. CREB inhibitor could significantly reverse the ameliorative effect of high-dose curcumin on the model rats （P＜0.05）. CONCLUSIONS Curcumin can improve the depression of diabetes model rats with depression， and relieve neuronal damage and inflammatory response， the mechanism of which may be associated with activating CREB/BDNF signaling pathway.
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We report a case of a long-term survivor of heart transplant who developed severe COVID-19 and was treated with a traditional Chinese medicine combined with conventional medicine. Throughout the treatment， the patient received active conventional medical treatment， and traditional Chinese medicine interventions included tonifying qi， invigorating the spleen and transforming phlegm， promoting yang and eliminating stagnation， resolving dampness and dissipating phlegm， and promoting blood circulation and eliminating stasis. The main therapeutic principles adopted were to recuperating depleted yang and rescuing the patient from collapse and to resolve phlegm and promote water. Pogezilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications was administered. In summary， it is crucial to the timely adjust the immunosuppressive regimen， combine use of various anti-infective agents with a focus on COVID-19， to protect of cardiac and renal function， and to integrate traditional Chinese medicine in the entire treatment process. As this case is rare， the diagnostic and therapeutic methods in traditional Chinese medicine， the use of immunosuppressive agents， and follow-up monitoring strategies can be a valuable reference.
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This paper reported a case of severe COVID-19 in the recovery stage with acute lymphoblastic leukemia treated by integrated traditional Chinese and western medicine， with the intention of shedding light on the clinical diagnosis and treatment of similar conditions. The patient， who had acute lymphoblastic leukemia， developed COVID-19 infection during the bone marrow suppression period after chemotherapy. Treatment with western medicine was mainly anti-infection， symptomatic management， and supportive care. During the recovery stage， considering the patient's chemotherapy history and disease progression， the overall syndrome was identified as deficiency of both qi and yin and binding of phlegm and blood. Based on the “state-target” combined treatment strategy， herbal prescriptions were selected and modified to address the “deficiency state”， “disease target”， and “symptom target”. In addition to western medicine， the patient was administered with Shengmai Powder （生脉散） and Compound Zhebei Granules （复方浙贝颗粒） in its modifications to boost qi， nourish yin， and reinforce healthy qi， nourish and cool the blood， ultimately achieving satisfactory therapeutic effects.
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This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.
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P2Y12 receptor antagonists and morphine are often recommended in patients with acute myocardial infarction.P2Y12 receptor antagonists can rapidly and potently reduce the platelet activity and prevent future thrombotic events.Meanwhile,combined morphine is used to relieve symptoms of angina.A number of studies have confirmed that morphine can decrease plasma concentrations of clopidogrel and impair its anti-platelet activity,which may lead to poor response in clopidogrel-treated patients with acute coronary syndrome.The randomized trials in healthy volunteers and patients with acute myocardial infarction also confirmed the similar drug-drug interaction between morphine and ticagrelor or prasugrel.Although the P2Y12 receptor antagonists combined with morphine are still used for myocardial infarction patients,there are few report on the objective evaluation of this drug interaction.This review,based on the findings of experimental as well as observational and randomized clinical studies,summarizes completely the drug interactions between oral P2Y12 receptor antagonists and morphine.
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Aim To investigate the effect of piperazinyl estrone(PE) on estrogen receptor expression and the transcriptional regulation of target genes.Methods Ovariectomized mice were given with PE in different doses (0.5 mg·kg~(-1),1 mg·kg~(-1),2 mg·kg~(-1))and estrone(0.71 mg·kg~(-1)) for 42 days,the protein expressions of Ers(Erαand Erβ)were shown by immunohistochemical method; To study transcriptional regulation of PE, PACT2-hERα and ERE2-TATA-LUC were co-transfected into MCF-7 cells by using Tfx 50 cationic liposome.Results Compared with ovx group, the groups with PE could up-regulate Ers of uteri in a dose-dependent manner,but its effect on Erα subtype was obvious.The classical ER signaling pathways could be activated by PE in co-transfected MCF-7 cells,but activation of PE was feebler than estrone with the same dose.Conclusion PE can up-regulate estrogen receptors in uteri. PE can transactivate ERE reportor gene through Erα and Erβ in MCF-7 cells, but its effect is feeble.