Research progress of nano delivery system in mRNA tumor vaccines / 药学学报

Tumor vaccine is one of the most promising therapeutic strategies in tumor immunotherapy. It promotes the antigen presentation process by delivering tumor antigen and then activates the anti-tumor immune response. As a new class of vaccines, messenger RNA (mRNA) vaccines can activate the immune system to achieve the purpose of immunotherapy by delivering the mRNA sequence of a specific antigen into the body and expressing the corresponding antigen protein. Compared with traditional vaccines, mRNA vaccines have the advantages of a short production cycle, high effectiveness, and strong immunogenicity. In recent years, the application of mRNA vaccines in tumor immunotherapy has attracted widespread attention, but the instability and low delivery efficiency of mRNA limit its application. Nano delivery system can effectively solve the problem of mRNA vaccine delivery, greatly promote the research process and clinical application of mRNA tumor vaccines, and has become a hot spot in the research of mRNA vaccines. In this review, we introduced the mRNA tumor vaccines, focusing on the application of nano delivery system in mRNA tumor vaccines, in order to provide new ideas and new methods for the efficient delivery of mRNA tumor vaccines and tumor immunotherapy.

Effects of PCIA with esketamine on postpartum depression in puerpera undergoing cesarean section / 中华麻醉学杂志

Objective:To evaluate the effects of patient-controlled intravenous analgesia (PCIA) with esketamine on postpartum depression (PPD) in puerpera undergoing cesarean section.Methods:A total of 300 American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 25-35 yr, with body mass index≤35 kg/m 2, scheduled for elective cesarean section under spinal anesthesia, were divided into 2 groups ( n=150 each) by a random number table method: control group (group C) and esketamine group (group E). PCIA was performed at the end of surgery.In group C, the PCIA solution contained sufentanil citrate 50 μg, butorphanol tartrate 12 mg and metoclopramide injection 20 mg in 200 ml of 0.9% normal saline.In group E, the PCIA solution contained esketamine 1 mg/kg, sufentanil citrate 50 μg, butorphanol tartrate 12 mg and metoclopramide injection 20 mg in 200 ml of 0.9% normal saline.The PCA pump was set to deliver a background infusion of 4 ml/h and a bolus dose of 4 ml at 30 min lockout interval.The analgesia lasted for 48 h after surgery, and the visual analog scale (VAS) score was maintained<4 points.Acetaminophen 0.5 g was administered orally as a rescue analgesic when VAS score≥4 points and pain was still unrelieved after PCA pump was pressed twice in a row.The Edinburgh Postnatal Depression Scale (EPDS) was performed at 1 day before and at 3, 7 and 42 days after surgery.Depression was classified on EPDS as mild (score≥10) and severe (score≥13). The patients with preoperative depression were excluded from the study.The occurrence and degree of depression were recorded.The requirement for rescue analgesia within 0-6 h, 6-12 h, 12-24 h and 24-48 h after surgery and development of adverse effects within 3 days after surgery were recorded. Results:Compared with group C, the incidence of PPD was significantly decreased and degree was reduced at 3 and 7 days after surgery, incidence of rescue analgesia was decreased in different time periods ( P<0.05), and no significant change was found in the incidence of adverse effects in group E ( P>0.05). Conclusion:Esketamine can not only provide good postoperative analgesia but also improve PPD in puerpera when it is used for PCIA after cesarean section.

Preventive use of antiemetic drugs on the incidence of nausea and vomiting after cesarean section under multi-mode analgesia / 中国医师杂志

Objective:To investigate the effect of preventive use of antiemetic drugs on postoperative nausea and vomiting (PONV) in patients with cesarean section(CS) under multi-mode analgesia.Methods:The clinical data of 5530 patients with cesarean section in the University of Hong Kong-Shenzhen Hospital (HKU-SZH) from February 1, 2016 to January 31, 2020 were retrospectively collected and divided into four groups: Ondansetron 4 mg group (group A, n=2 712), Dexamethasone 5 mg group (group B, n=39), Ondansetron 4 mg combined with Dexamethasone 5 mg group (Group C, n=413), and blank group (Group D, n=2 366). All drugs were given before the end of theoperation. The prophylactic effectiveness with different antiemetic prescription has been compared in this study. Results:There were no significant differences in height, weight, age, the ratio of NRs≥6 at 24 h and oxycodone usage among the four groups ( P>0.05). The incidence of postoperative nausea and vomiting was 2.29%(62/2 712), 0(0/39), 1.45%(6/413) and 1.90%(45/2 366), respectively. There was no significant difference between the four groups ( P=0.463). Conclusions:Prophylaxis antiemetic administration seems do not reduce the incidence of PONV after CS under this strategy of multi-mode analgesia.

Effect of Longxuetongluo capsule in protecting vascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced apoptosis / 中国中药杂志

Focal cerebral ischemia reperfusion is an essential process during ischemic stroke. The apoptosis of vascular endothelial cells induced by ischemia/reperfusion (I/R) injury is an important cause for brain injury after focal cerebral ischemia. Longxuetongluo capsule (LTC) has been used for the treatment of ischemic stroke in clinic. However, its underlying action mechanism is still unclear. This study aimed to verify the protective effect and mechanisms of LTC on HUVEC cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through MTT, LDH, flow cytometry, AO/EB staining and western blot assays. As a result, OGD/R significantly decreased the viability of HUVEC cells, which was significantly improved by LTC. LDH release assay showed that OGD/R significantly increased the lactate dehydrogenase (LDH) release, and LTC dramatically reduced the OGD/R-induced LDH release. Further mechanism study indicated that LTC dose-dependently inhibited the cleavage of PARP, caspase 3, and caspase 9 induced by OGD/R, suggesting that LTC could inhibit the activation of caspase 3/9 apoptosis pathway in the OGD/R-induced apoptosis of HUVEC cells. In conclusion, LTC could protect HUVEC cells against OGD/R injury by inhibiting the activation of mitochondria-related caspase 3/9 apoptosis pathway.

Efficacy and mechanism of puerin Ⅰ in improving disorder of glycolipid metabolism in ApoE-/-mice / 中国中药杂志

Pu-erh tea is a unique post-fermented tea processed from tender leaves of Camellia assamica. Characteristic component puerins were produced during the microbial fermentation process.This study focuses on the therapeutic effect and mechanism of puerinⅠ(P1) in Pu-erh tea on ApoE-/- mice with dyslipidemia and diabetes. It was found that P1 could significantly decreased total cholesterol (TC), triglyceride (TG) and fast blood glucose (FBG), and markedly improved impaired glucose tolerance (IPGTT) and insulin sensitivity (ITT) in hyperlipidemic and hyperglycemic ApoE-/- mice. Further experiments proved that P1 reduced FBG and plasma TG levels by inhibiting intestinal α-glycosidase enzymes activity and by activating low-density lipoprotein receptor respectively. This study confirmed the therapeutic effect and mechanism of P1 on ApoE-/- mice with diabetes and hyperlipidemia. Based on the good efficacy of this compound, P1 could be used as a new drug to treat the disorder of glycolipid metabolism.

Study on the expression of epidermal growth factor receptor protein during benzo(a)pyrene induced carcinogenesis / 中华预防医学杂志

Objective@#To explore the expression of epidermal growth factor receptor(EGFR) protein during benzo(a)pyrene (BaP) induced carcinogenesis.@*Methods@#This study, we firstly utilized immunofluorescence assay and Western-blot to examine EGFR expression of the BaP which was constructed previously by project team induced malignant transformation human bronchial epithelial cell (BTC) and the control (16HBE cell). Then, we selected 36 healthy SD rats, divided into two groups according to simple random method, 18 rats each group. The constructed rat lung neoplasm model induced by pulmonary injection of BaP (10 mg/ml of BaP solution in 0.2 ml corn oil), contrast group use 0.2 ml corn oil, lung tissue was collected and the EGFR expression of lung tissue was detected by immunofluorescence assay and Western blot. T analysis was used to test the different of EGFR between two groups.@*Results@#Immunofluorescence analysis showed that the EGFR expression in BTC was significantly higher than 16HBE cell. Meanwhile, Western blot also was used to confirmed this result, the relative expression of EGFR protein in the rats of the model group the control group were 1.04±0.13 and 2.32±0.12, respectively, and the difference was statistically significance (t=12.39, P<0.001). In vivo, well-defined tumor was found in the rat with pulmonary injection of BaP, and the lung showed diffuse alveolar septal thickening, alveolar wall destruction and pulmonary alveoli fusion, which suggested that the rat lung neoplasm model was constructive successfully. Furthermore, we found the EGFR expression of lung was increased dramatically in the rat lung neoplasm model by immunofluorescence detection and Western blot. The relative expression of EGFR protein in the rats of the model group the control group were 0.21±0.03 and 1.30±0.07, respectively, and the difference was statistically significance (t=12.84, P<0.001).@*Conclusion@#Expression of EGFR protein was increased during BaP carcinogenesis, and EGFR may play an important role in the carcinogenesis of BaP.

Progress in research for pharmacological effects of Pu-erh tea / 中国中药杂志

Pu-erh tea has gradually aroused general concern with social development and people's enhanced awareness of health. Pu-erh tea is rich in multiple active constitute such as flavonoids, catechins, phenolic acids, flavanols polymer, purine alkaloids, and hydrolysable tannin as a microbial-fermented tea.It is reported that Pu-erh tea have a variety of pharmacologically activities, such as anti-hyperlipidemic, anti-diabetic, anti-oxidative, anti-tumor, anti-bacterial, anti-inflammatory, and anti-viral effects. In this paper, the main pharmacological effects of Pu-erh tea are reviewed. We wish this work will provide some references and clues for further research of Pu-erh tea.

Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets / 中国天然药物

An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid (CGA) and taurocholic acid (TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L(-1) of ammonium acetate buffer solution containing 0.5% of formic acid - acetonitrile as mobile phase at a flow rate of 300 μL·min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1-10 ng·mL(-1) for CGA and 2-150 ng·mL(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets (SBTs). In the single-dose study, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2) of CGA were (0.763 8 ± 0.542 0) ng·mL(-1), (1.0 ± 0.5) h, and (1.3 ± 0.6) h, respectively. In the multiple-dose study, the Cmax, Tmax and t1/2 of CGA were (0.663 7 ± 0.583 3) ng·mL(-1), (1.1 ± 0.5) h, and (1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.

Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

Adolescent mixed epithelial and stromal tumor of the kidney：one case report and literature review / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features of adolescent mixed epithelial and stromal tumor of the kidney ( MESTK) and improve recognization of this rare disease. Methods Clinicopathological and immunohistochemical characteristics of MESTK occured in 17-year-old girl were studied. Reviewed the related literatures, clinical and pathological characteristics of adoles-cent MESTK were analysed comprehensively. Results Congenital perineal spill was the main clinical manifestations. Microscopically, the tumor showed nodules and was composed of a mixture of epithelial and stromal elements. Glands were lined with columnar or cilia-ted columnar cells. Stromal cells surrounding glands seemed like ovaries and away from glands seemed like the differentiation of smooth muscle. Immunohistochemical staining revealed that the epithelial cells were positive for CK7 and vimentin. Stromal cells expressed desmin, smooth muscle actin ( SMA) , ER and PR. It was noteworthy that stromal cells away from glands expressed desmin. Conclu-sions As a kind of rare benign neoplasm of kidney, MESTK often occurs in perimenopausal women. But MESTK can also occur in ad-olescence, and has nothing to do with the use of hormone. Therefore, the renal tumor occurred in teenagers with biphasic differentiation should be differentiated from MESTK.

Effect of Wnt signaling suppression on gefitinib in non small cell lung cancer cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.</p><p><b>METHODS</b>PC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.</p><p><b>RESULTS</b>Treating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.</p><p><b>CONCLUSION</b>Suppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.</p>

The study on content analysis of iPhone Apps for smoking cessation / 重庆医学

Objective To examine the content of the 69 iPhone applications(Apps) for smoking cessation that were distributed through the online iTunes store and explore Apps′level of adherence to the U .S .Public Health Service′s 2008 Clinical Practice Guideline for Treating Tobacco Use and Dependence (called guidelines) for the purpose of developing high quality Apps ,as of De-cember 29 ,2012 .Methods All Apps was categorized into 5 types based on National Tobacco Cessation Collaborative .In order to get the Apps′level of adherence to guidelines ,the content of every application was compared with guidelines respectively .Results Apps identified for smoking cessation were found to have low levels of adherence to key guidelines .Conclusion It is necessary that current and future Apps should be developed around evidence-based practices and guidelines to get reliable Apps for smoking cessa-tion .