Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Overexpression of LncRNA SLC25A25-AS1 Inhibits Proliferation‚ Migration‚ and Invasion of HeLa Cells / 中国生物化学与分子生物学报

Long non-coding RNA SLC25A25-AS1 has a tumor inhibition effect in the development of colorectal cancer. However‚ the mechanism of SLC25A25-AS1 in cervical cancer needs further study. We studied the abnormal expression of SLC25A25-AS1 in the serum of the patients with cervical cancer and the patients with cervical intraepithelial neoplasia (CIN) and explored the mechanism of SLC25A25-AS1 in the development of cervical cancer. The expression levels of SLC25A25-AS1 in the serum of normal controls‚ patients with cervical cancer‚ and patients with CIN were detected by RT-qPCR. The important role of SLC25A25-AS1 in HeLa cells was analyzed in vitro and in vivo experiments. Compared with the normal group‚ the expression level of serum SLC25A25-AS1 was decreased in patients with cervical cancer. In vitro‚ overexpression of SLC25A25-AS1 inhibited cell proliferation‚ migration‚ and invasion of HeLa cells. Tumor formation in nude mice assay showed that the subcutaneous tumor weight and volume of nude mice injected with SLC25A25-AS1-overexpressed HeLa cells were significantly smaller than that of nude mice injected with control cells (P<0. 05). SLC25A25-AS1 may play an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Application and thinking of working-process based CBL teaching method for undergraduate practice teaching in clinical laboratory of hematology / 中华医学教育探索杂志

Clinical laboratory of hematology is highly professionalized, with abstract concepts, and a variety of laboratory techniques. The working-process based CBL teaching method may help clinical laboratory interns better understand the clinical significance and the mutual relationship of laboratory tests, improve the comprehensive ability and cultivate the general clinical thinking ability.

Effect of Shugan Jianpi Jiedu Prescription Medicated Serum on Proliferation， Migration and Invasion of Triple-negative Breast Cancer MDA-MB-231 Cells Based on PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

Objective:To study the efficacy and mechanism of Shugan Jianpi Jiedu prescription （SJJ） in the treatment of triple-negative breast cancer through <italic>in vitro</italic> cell experiments. Method:The following groups were set up in this study： a normal serum group，a pirarubicin group，and low-，medium-， and high-dose SJJ-medicated serum groups. Twenty SD rats were randomly divided into four groups and administered with SJJ solution （16.8，8.2，4.05 g·kg^-1） and normal saline （equal volume） according to the body surface area to prepare serum. MDA-MB-231 cells were treated separately. The proliferation， migration and invasion of MDA-MB-231 cells were detected by the cell counting kit-8（CCK-8），wound healing assay and transwell cell invasion assay. The phosphoinositide 3-kinase （PI3K），protein kinase B （Akt）， and mechanistic target of rapamycin （mTOR） protein expression levels in MDA-MB-231 cells were tested by the Western blot. Result:The cell proliferation in the three different doses of medicated serum groups and the pirarubicin positive control group was significantly inhibited as compared with that in the normal serum group（<italic>P</italic><0.01），and there was no statistical difference for this between the medium/high dose medicated serum group and the pirarubicin positive control group.The wound healing in the SJJ-medicated serum groups and the pirarubicin group was slowed down as compared with that in the normal serum group （<italic>P</italic><0.01），and the effect in the SJJ-medicated serum groups was weaker than that in the pirarubicin group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The number of cells invading the lower transwell chamber was decreased as compared with that in the normal serum group （<italic>P</italic><0.01），and there was no statistical difference between the medium-/high-dose SJJ-medicated serum groups and the pirarubicin group. Western blot results showed that 48 h after treatment，the PI3K，Akt， and mTOR expression levels in the cells of SJJ-medicated serum groups and the pirarubicin group were lower than those of the normal serum group（<italic>P</italic><0.01）. Conclusion:The SJJ-medicated serum could inhibit the proliferation， migration and invasion of MDA-MB-231 cells presumedly by down-regulating the protein expression levels in the PI3K/Akt/mTOR signaling pathway.

Efficacy of Modified Qufeng Runmian Powder () on Acne Vulgaris with Syndromes of Dampness and Blood Stasis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of a Chinese medicine (CM) Modified Qufeng Runmian Powder (, MQFRMP) for the treatment of acne vulgaris with CM syndromes of dampness and blood stasis.@*METHODS@#In this multicenter, randomized, double-blind, placebo-controlled clinical trial, 220 acne vulgaris patients with CM syndrome of dampness and blood stasis were included and randomly assigned using a central area group random design to receive either MQFRMP or the placebo, with 110 cases in each group. MQFRMP or a placebo at 145 g/bag were administered once daily for 4 weeks, respectively. The primary index of efficacy was the effective rate according to the acne severity score (ASS). The secondary indices of efficacy included the changes in the dermatology life quality index (DLQI) score, VISIA scores (spots, pores, brown spots, porphyrins and red areas) and skin assessment (skin pH, sebum amount and hydration) according to a SOFT skin multianalyzer.@*RESULTS@#(1) Follow-up: a total of 204 patients completed the follow-up, with 103 in the treatment group and 101 in the control group. (2) Effective rate: the total effective rate of the treatment group was significantly higher than the control group [83.5% (86/103) vs. 31.7% (32/101), P0.05). (6) Safety: two cases of mild drug allergy were observed in the treatment group.@*CONCLUSION@#MQFRMP was effective and safe for the treatment of acne vulgaris with syndromes of dampness and blood stasis. (No. ChiCTR1900020479).

Acupuncture combined with cranial electrotherapy stimulation on generalized anxiety disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of acupuncture combined with cranial electrotherapy stimulation (CES) on generalized anxiety disorder (GAD).@*METHODS@#A total of 200 patients with GAD were randomized into an acupuncture+CES group, an acupuncture group, a CES group and a medication group, 50 cases in each one. In the medication group, patients were treated with tandospirone citrate tablet orally, 10 mg after breakfast, lunch and dinner respectively. In the CES group, CES was adopted by SCS brain electromedical instrument, 60 min each time, once a day. In the acupuncture group, acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 29), Shenting (GV 24), etc., 30 min each time, once a day. In the acupuncture+CES group, CES was adopted before acupuncture. Treatment of sixty days was required in the 4 groups. Before and after treatment, the scores of Hamilton anxiety scale (HAMA), World Health Organization's quality of life questionnaire-brief version (WHOQOL-BREF) and treatment emergent symptom scale (TESS) were observed, the clinical effect was evaluated, and the relapse of anxiety during follow-up of 1 year after treatment was recorded in the 4 groups.@*RESULTS@#Compared before treatment, the scores of HAMA after treatment were decreased (@*CONCLUSION@#Acupuncture combined with CES can effectively relieve the symptoms in patients with GAD, improve the quality of life, reduce the occurrence of adverse reactions and the relapse rate, and its clinical effect is obviously superior to the western medication, the simple application of acupuncture or CES.

The clinicopathologic parameters and prognostic analysis of vulvar squamous cell carcinoma / 中华肿瘤杂志

Objective@#To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva.@*Methods@#We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma.@*Results@#The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression-free survival was 90.0 months. The 5-year progression-free survival rate of the total patients was 55.5%, while the 10-year progression-free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode (all P<0.001). Multivariate analysis showed that number of metastatic lymph nodes (P<0.05) was an independent prognostic factor for progression-free survival.@*Conclusion@#The study illustrates that number of metastatic lymph nodes represents important independent factor for progression-free survival of patients with vulvar squamous cell carcinoma.

Protective Effect of Dihuang Yinzi on Cerebral Ischemia-reperfusion Injury in Rats and Its Mechanism / 中国实验方剂学杂志

Objective: To explore the protective effect and the preliminary mechanism of Dihuang Yinzi on cerebral ischemia-reperfusion injury in rats. Method: The middle cerebral artery occlusion (MCAO) model was established. Totally 90 SD rats were randomly divided into 6 groups:sham operation group, model group, nimodipine group (0.01 g·kg-1) and high, medium, low-dose Dihuang Yinzi groups (38.80, 19.40, 9.70 g·kg-1), with 20 rats in each group.The modified neurological severity score (mNSS) was assayed at the 7th, 14th, 28th days after operation, and the volume of cerebral infarction, pathological changes of brain tissue, the BrdU positive cells and mRNA levels of Notch1, Jagged1 and Hes1 in subventricular zone(SVZ)were observed respectively by triphenyl tetrazolium chloride(TTC) stain, htorylin eastin(HE) stain, immunofluorescence technique and reverse transcriphase polymerase chain reaction(Real-time PCR) methods at the 28th day after the operation. Result: The mNSS on the 7th, 14th, 28th days of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly lower than that of model group(PPth day, the percentage of cerebral infarction volume in brain tissue volume of high, medium-dose Dihuang Yinzi groups and nimodipine group were smaller than that of model group(Pth day, the BrdU positive cells in SVZ of the above 3 groups were significantly higher than model group(PPPth day, the mRNA levels of Notch1, Jagged1 and Hes1 of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly higher than those of model group(PPPPConclusion: Dihuang Yinzi can improve the nerve function defect of MCAO rat model, and reduce the volume of cerebral infarction and the pathological changes of brain tissue, thus playing a protective role in cerebral ischemia-reperfusion injury rats. Its mechanism may be related to the activation of the Notch signaling pathway, and the up-regulation of expressions of Notch1, Jagged1 and Hes1 mRNA, thus promoting the proliferation of NSCs.

Autophagy induced synergistic inhibitory effect of cetuximab in combination with triptolide on proliferation and metastasis of colorectal SW480 cells / 中国药理学通报

Aim: To investigate the effect of triptolide combined with epidermal growth factor receptor monoclonal antibody cetuximab on the biological behavior of human colorectal cancer cell line SW480. Methods: MTT assay was used for estimating the survival rates of SW480 cells exposed to different concentrations and different durations of triptolid and cetuximab. Colony formation assay was used for showing the proliferation and wound healing assay was performed to assess the effects of drugs on cell migration, Western blot was used for testing the expression of LC3-II, p62, E-cadherin, Vimentin, mTOR, Snail, and Twist. Results: The SW480 growth of cells was inhibited by triptolide in a dose- and time-dependent manner and cetuximab was only in a dose-dependent manner. The combination regimen of cetuximab and triptolide exerted a synergistic effect. Triptolide could decrease expression of p62 increase expression of LC3-II and induce autophagic apoptosis. Triptolide monotherapy group and combination group could significantly inhibit EMT in SW480 cells, and the E-cadherin protein was up-regulated, Vimentin protein was down-regulated, and key molecules Snail and Twist were down-regulated. Conclusion: Triptolide combined with cetuximab has a synergistic effect on the inhibition of proliferation and metastasis of SW480 cells. Triptolide induces autophagic apoptosis by inhibiting the mTOR pathway. Autophagy mediated by triptolide can inhibit EMT of SW480 cells and may be a mechanism to reverse the resistance of cetuximab.

Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)

The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.

Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity

To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly β-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-keto-acid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other K(ATP) channel openers.

Corrigendum to: Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity

The affiliation of the second author, Lei Sen Han, should be corrected.

Effect of Comprehensive Therapy based on Chinese Medicine Patterns on Self-Efficacy and Effectiveness Satisfaction in Chronic Obstructive Pulmonary Disease Patients / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of comprehensive therapy based on Chinese medicine (CM) patterns on self-efficacy and satisfaction with its effectiveness in patients with chronic obstructive pulmonary disease (COPD).@*METHODS@#A total of 216 patients were randomly divided into the trial group (n =108) and the control group (n=108) based on the stratified and block randomization design. Patients in the trial group were treated with conventional Western medicine combined with Bufei Jianpi Granules (), Bufei Yishen Granules (), and Yiqi Zishen Granules () according to the CM patterns respectively, and patients in the control group were treated with conventional Western medicine. The COPD Self-Efficacy Scale (CSES) and the Effectiveness Satisfaction Questionnaire for COPD (ESQ-COPD) were employed in a 6-month treatment and in further 6 month follow-up visit.@*RESULTS@#Among the 216 patients, 191 patients (97 in the trial group and 94 in the control group) fully completed the study. After 12-month treatment and follow-up, the mean scores of the trial group all continued to increase over time, which were significantly higher than those of the control group (P <0.05), and the improvement in the following trial group domain: negative affect domain (12.13%), intense emotional arousal domain (12.21%), physical exertion domain (11.72%), weather/environmental domain (13.77%), behavioral risk domain (7.67%) and total score (10.65%). The trial group also exhibited significantly higher mean scores in the ESQ-COPD (P <0.05) and the improvement in the following domain: capacity for life and work domain (30.59%), clinical symptoms domain (53.52%), effect of therapy domain (35.95%), convenience of therapy domain (35.54%), and whole effect domain (52.47%).@*CONCLUSIONS@#Bufei Jianpi Granules, Bufei Yishen Granules and Yiqi Zishen Granules can improve the self-efficacy and satisfaction of COPD patients.

Whether Fire-needle Therapy Benefits Plaque Psoriasis: A Multicenter, Randomized, and Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To observe the clinical effectiveness and safety of fire-needle therapy, an external approach of Chinese medicine in treating plaque psoriasis.@*METHODS@#This study was a two-parallel-arm randomized controlled trial. A total of 151 participants with plaque psoriasis were randomly assigned to the fire-needle therapy group (treatment group, 76 cases) or the control group (75 cases) at a 1:1 allocation ratio using SAS software. All participants received Oral Huoxue Jiedu Decoction (, HXJDD) and applied externally vaseline cream twice a day. Participants in the treatment group received fire-needle therapy once weekly for 4 weeks plus HXJDD and vaseline cream applied the same as the control group. The primary outcome measure was Psoriasis Area and Severity Index (PASI) score, and the secondary outcomes were Dermatology Life Quality Index (DLQL), and Hamilton Anxiety Rating Scale (HAMA), as well as Chinese medicine (CM) syndrome score and photos of target lesions. The indices were evaluated before and after treatment.@*RESULTS@#Sixty-eight patients in each group completed the study. The treatment group has not yet achieved significant improvement in PASI score (P>0.05) compared to the control group. However, significant differences were found between the two groups in relieving CM syndrome (P<0.05) and improving quality of life (P<0.05).@*CONCLUSION@#Fire-needle appears to be safe and may have benefit for psoriasis, the short-term treatment and small sample size limit the conclusions of this study. Further rigorous randomized controlled trials with longer treatment are recommended.

Role of different nicotinic acetylcholine receptor subtypes in skeletal muscles in sepsis-related nerve-muscle dysfunction in septic rats: neuroelectrophysiology / 中华麻醉学杂志

Objective To evaluate the role of different nicotinic acetylcholine receptor ( nAChR) subtypes in skeletal muscles in sepsis-related nerve-muscle dysfunction in septic rats by neuroelectrophysiol-ogy. Methods SPF adult male Sprague-Dawley rats, weighing 200-220 g, aged 2-3 months, were stud-ied. Sepsis was induced by cecal ligation and puncture in chloral hydrate-anesthetized rats. Twelve portions of sciatic nerve-tibialis anterior muscles taken at day 3 after successful establishment of the sepsis modelserved as group S. Another 12 portions of sciatic nerve-tibialis anterior muscles of normal rats served as group C. The endplate potential ( EPP ) was monitored by intracellular microelectrode recording. Six por-tions of nerve-muscle samples were incubated with the adult nAChR (ε-nAChR ) specific antagonist wa-glerin-1 at a concentration of 1 μmol∕L, the fetal nAChR (γ-nAChR) specific antagonist αA-OIVA at a concentration of 250 nmol∕L and neuronal nAChR (α7-nAChR) antagonist methyllycaconitine ( MLA) at a final concentration of 6 nmol∕L. The amplitude of EPP was recorded at 15 min of incubation, and the differ-ence in the amplitude of EPP (ΔEPP) and changing rate of EPP (ΔEPP％) were calculated. Another 6 portions of samples were incubated for 15 min with the Kreb mixture of waglerin-1 and 250 nmol∕LαA-OIVA at a final concentration of 1 μmol∕L, the Kreb mixture of waglerin-1 and 6 nmol∕L MLA at a final concen-tration of 1 μmol∕L, and the Kreb mixture of αA-OIVA and 6 nmol∕L MLA at a final concentration of 250 nmol∕L, and then the amplitude of EPP was recorded. Washout was performed with antagonist free Kreb so-lution for 15 min between treatments with different blockers. Results Compared with group C, ΔEPP andΔEPP％ were significantly decreased after antagonizing ε-nAChR, ΔEPP％ was decreased after antagoni-zing γ-nAChR, ΔEPP and ΔEPP％ were increased after antagonizing α7-nAChR, the amplitude of EPP was increased after antagonizingε-nAChR+γ-nAChR andε-nAChR+α7-nAChR, and the amplitude of EPP was decreased after antagonizing γ-nAChR+α7-nAChR (P<0. 05). ΔEPP and ΔEPP％ were significantly higher after antagonizing α7-nAChR than after antagonizingγ-nAChR in group S ( P<0. 05) . The EPP was significantly lower after antagonizingε-nAChR+α7-nAChR than after antagonizingε-nAChR+γ-nAChR ( P<0. 05) . Conclusion Weakened function of ε-nAChR and enhanced function of α7-nAChR in the mem-brane of the end-plate in skeletal muscle are the main reasons for sepsis-related nerve-muscle dysfunction in septic rats, and the role is comparable between them.

Prognostic analysis of stageⅠb2 andⅡa2 cervical squamous cancer without high risk factors treated with neo-adjuvant chemotherapy and radical hysterectomy / 中华妇产科杂志

Objective To analyze the prognosis ofⅠb2 andⅡa2 cervical squamous cancer without high risk factors treated with neo-adjuvant chemotherapy(NACT)and radical hysterectomy. Methods This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO)stageⅠb2 andⅡa2 cervical squamous cancer without high risk factors who underwent platinum-based NACT followed by radical surgery from January 2008 to January 2015.The responses of NACT were observed and compared in their effect on postoperative pathologic risk factors. Kaplan-Meier method and Cox regression analysis were performed to analyze survival status. Results This study was recruited 282 patients with the average age of(44.4±6.7)years old.After NACT,42 patients achieved complete response [CR,14.9%(42/282)],while 138 patients achieved partial response[PR,48.9%(138/282)]and 102 stable disease [SD, 36.2%(102/282)]. The rate of pathologic diameter ≥4 cm, deep stromal invasion(DSI) positive and lymph-vascular space invasion(LVSI)positive rate decreased significantly in CR and PR group compared with SD group(P<0.05). The number of postoperative risk factors in CR, PR and SD groups varied significantly(χ 2=64.869, P=0.000). Besides,the rate of multiple intermediate risk factors was respectively 0 vs 13.8% vs 45.1%(χ2=7.107, P=0.008). The disease relapsed in 23 patients, and 12 died. On the whole series, 5-year overall survival rate was 91.7%, and 5-year recurrence-free survival rate was 88.9%. The rate of recurrence(P=0.002)and mortality(P=0.036)were higher in LVSI positive patients compared with LVSI negative. And the rate of recurrence was higher in patients with multiple intermediate risk factors,compared with no or one intermediate risk factors(P=0.002).Univariate analysis revealed that LVSI positive and multiple intermediate risk factors were the factors predicted recurrence and mortality(P<0.05), and no significance in age, stage, tumor grade, tumor diameter before or after NACT, response to NACT,or DSI positive factors(all P>0.05).The multivariate analysis showed that,the factor of primary tumor diameter≥6 cm(P=0.022)and multiple intermediate risk factors(P=0.001)were independent prognostic variables for recurrent-free survival.Besides,multiple intermediate risk factors was independent prognostic variable for overall survival(P=0.034). After surgery, 107 patients did not receive adjuvant therapy,while 175 patients received adjuvant therapy with 26 radiotherapy,46 chemotherapy and 103 concurrent radiochemotherapy.On survival analysis of postoperative adjuvant treatment,5-year recurrence-free survival rate of radiotherapy group was significantly lower in patients with the factor of SD response to NACT(P=0.011)and multiple intermediate risk factors(P=0.008), while overall no significance in overall survival rate(P>0.05).Conclusions NACT may be play beneficial role in relieving the status of intermediate risk factors for stage Ⅰb2 andⅡa2 cervical squamous cancer without high risk factors. The status of multiple intermediate risk factors is independent prognostic factors for recurrence and mortality. For patients with multiple intermediate risk factors, postoperative adjuvant chemotherapy or concurrent radiochemotherapy might be the better choice to prevent relapse.

Research on Current Situation and Development Strategies of TCM Cultural Tourism in Jiangsu Province / 中国中医药信息杂志

At present, the tourism industry has risen into a national strategic pillar industry. The development of the TCM industry has been included in the national strategy. The integration of the two major industries, TCM culture and tourism, is of great significance in promoting the development of the tourism industry and structural transformation. Jiangsu Province has a wealth of TCM cultural tourism resources, with unique industrial development advantages. Based on the analysis of the advantages and current situation of TCM cultural tourism in Jiangsu Province, this article put forward some suggestions for the development of TCM cultural tourism in order to provide a reference for promoting the integration and development of TCM culture and tourism industry.

Mechanism of RNA interference HOXB7 gene expression in colon cancer on pro-liferation and apoptosis of cancer cells / 中国免疫学杂志

Objective:To investigate the effect of inhibiting of HOXB7 gene expression on proliferation and apoptosis of colon cancer cells.Methods:The synthetic negative control siRNA (negative control group) and HOXB7-siRNA (HOXB7 transfection group) were transfected into human colon cancer SW480 cells by LipofectamineTM2000 liposome mediated method,untreated cells as blank group.RT-PCR and Western blot were used to detect the mRNA and protein expression of HOXB7 after transfected 48 h respectively;cell proliferation was detected by CCK8 assay after transfected 24,48,72,96 h;cells apoptosis was detected by flow cytometry after transfected 48 h;the expression of apoptosis related proteins Bcl-2,Bax and Notch1 signaling pathway Notch1 and Hes1 were detected by Western blot.Results:The mRNA and protein expression of HOXB7 in HOXB7 transfected group was significantly lower than that in blank group(P<0.05);OD value was no statistical significance in the three groups after transfected 24 h(P>0.05), while after transfected 48,72,96 h,compared with the control group,OD value in HOXB7 group was significantly decreased(P<0.05);compared with the blank group,the apoptosis rate in HOXB7 transfection group increased significantly,and the expression of Bcl-2, Notch1 and Hes 1 proteins was down regulated,and the expression of Bax protein was up-regulated(P<0.05).Conclusion:RNA inter-ference in the expression of HOXB7 gene in colon cancer can inhibit the proliferation of cancer cells and induce apoptosis by inhibiting of the Notch1 signaling pathway.

Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells / 中华医学杂志(英文版)

<p><b>Background</b>Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells.</p><p><b>Methods</b>Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 μmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 μmol/L) for 1 h before the addition of ox-LDL (100 μg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P < 0.05 was considered statistically significant.</p><p><b>Results</b>Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 μmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 μmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment.</p><p><b>Conclusions</b>This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.</p>

Effect of exercise on adiponectin in aged obese rats / 中国应用生理学杂志

OBJECTIVE@#To explore effects of exercise on the expression of adiponectin mRNA and protein in visceral adipose tissue, plasma adiponectin concentration, and insulin resistance of aged obese rats.@*METHODS@#Male SD rats age to 21 days old were fed with high-fat diet (fat percentage was 36.3% to 40.0%) for three stages of adolescence, maturity and old age to establish elderly obesity rats model. When the rats aged to 60 weeks old, natural growing elderly rats were randomly divided into control group (C) and aged exercise group (AE), =6; elderly obesity rats were randomly divided into obesity control group (OC) and obesity exercise group (OE), =6. The treadmill grade was 0°, the exercise speed and time were 15 m/min×15 min, 4 groups each time, between consecutive groups the rats had 5 minutes rest, the rats were exercised for 60 minutes every day, five days a week, continuous exercise for 8 weeks. Then, the expressions of adiponectin mRNA and protein in visceral adipose tissue were determined. The concentrations of blood glucose, plasma adiponectin and insulin were measured. Insulin resistance was calculated.@*RESULTS@#Comparison with control group, the expressions of adiponectin mRNA and protein were obviously decreased, the concentration of blood glucose and insulin resistance were significantly increased in obesity control group, while the expressions of adiponectin mRNA and protein were obviously increased. Comparison with obesity control group, the expressions of adiponectin mRNA and protein, the concentration of plasma adiponectin were obviously increased, the concentration of blood glucose and insulin resistance were significantly decreased in obesity exercise group.@*CONCLUSIONS@#Adiponectin mRNA and protein expression in visceral adipose tissue is decreased and accompanied by high blood glucose and insulin resistance in elderly obesity rats. Exercise can increase the adiponectin mRNA and protein expression in visceral adipose tissue, elevate levels of plasma adiponectin, and decrease the level of blood glucose and insulin resistance in elderly obesity rats.