Objective To discuss the effects of personality features on psychological status of patients with lung cancer in perioperative period.Methods Choosing 97 patients from the thoracic department of the second Xiangya Hospital of Central South University as the study objects.The general information,psychological status and personality features were investigated by using the self-made General Information Questionnaire,Eysenck Personality Questionnaire( EPQ),Self-rating Depression Scale (SDS),Self-rating Anxiety Scale(SAS) and Self-rating Symptom Scale(SCL-90).Results The scores of seven factors including total scores( 153.28±41.98),somatization ( 1.78 ± 0.42 ),compulsion ( 1.96 ± 0.52 ),depression ( 1.77 ± 0.67 ),anxiety ( 1.82 ± 0.56 ),hostility ( 1.68 ± 0.87 ),panic ( 1.44 ± 0.75 ) and psychosis ( 1.56 ± 0.51 ) in SCL-90 were higher than domestic norm (P ＜ 0.05 ).The score of EPQ-P(Psychoticism) ( 10.96 ± 2.65 ) were higher than the domestic norm ( 5.84 ± 3.27 )(P＜0.001 ),and EPQ-N(neuroticism) and EPQ-P were positively correlated with the scores of seven factors in SCL-90.Conclusion The mental status of patients with lung cancer in perioperative period is poor.Solitude and uncaring others are the features of personality,which is correlated with psychological status,and EPQ-E (introvertion-extroversion) and EPQ-N can predict the happening of negative psychology.

AIMTo search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized.

METHODSCoupling N-methyl-1,2, 3,6-tetrahydrapyridine ring system with 3,4-dibenzenesulfonyl-1,2,5-oxadiazole-2-oxide through esterification or amidation, a series of arecoline derivatives containing NO donors were designed and synthesised.

RESULTSA novel series of compounds structurally related to arecoline have been prepared, the proposed structures of eighteen new compounds were established by IR, 1H NMR, MS spectroscopy and elemental analysis. The effects of the target compounds on the vasodilation activity were tested in the isolated preparation of mice thoratic aorta.

CONCLUSIONThis preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.

Animals ; Aorta, Thoracic ; drug effects ; Arecoline ; analogs & derivatives ; chemical synthesis ; pharmacology ; In Vitro Techniques ; Nitric Oxide Donors ; chemistry ; pharmacology ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; pharmacology

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/genetics* ; Iridoids ; Kidney ; Male ; Mice ; Signal Transduction

OBJECTIVE To investigate the synergistic effect of triptolide （TPL） combined with epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） gefitinib on EGFR-mutated non-small cell lung cancer （NSCLC） cells and its potential mechanism. METHODS Human NSCLC cell lines H1975 （EGFR T790M/L858R mutated drug-resistant cell lines） and H1299 （EGFR wild-type non-drug-resistant cell lines） were cultured in vitro. MTT method was used to detect cell activity， and the effect of combined medication was evaluated by the combination index （CI）. The H1975 cells were divided into blank group， low- concentration and high-concentration groups of TPL （5 nmol/L or 15 nmol/L）， gefitinib group （2 μmol/L）， low-concentration and high-concentration groups of TPL+gefitinib （5 nmol/L TPL+2 μmol/L gefitinib， 15 nmol/L TPL+2 μmol/L gefitinib）. Flow cytometry was used to detect the apoptosis of H1975 cells and the distribution of the cell cycle. Molecular docking studies were used to predict the binding ability of TPL to EGFR. The expressions of phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） pathway and autophagy-related proteins [microtubule-associated protein 1 light chain 3α （MAP1LC3A）， MAP1LC3B] in H1975 cells were detected by flow cytometry. RESULTS TPL had a strong inhibitory effect on the proliferation of H1975 and H1299 cells in a time-dependent and dose-dependent manner. Forty-eight hours treatment of 5 or 15 nmol/L TPL combined with gefitinib had a synergistic inhibitory effect on the proliferation of H1975 cells （CI＜1）， while there was no synergistic inhibitory effect on H1299 cells （CI＞1）. Compared with the blank group， the apoptosis rate and the proportion of H1975 cells at G0/G1 phase were increased significantly in administration groups， while the proportions of cells at S phase and G2/M phase （except for several TPL groups） were decreased significantly， and the combination group had better effects （P＜0.05）. Molecular docking studies showed that the hydroxyl radical of TPL could form hydrogen bonds with the Thr854 residue of the product encoded by EGFR T790M/L858R mutation. Compared with the blank group， the expressions of pathway-related proteins were down-regulated significantly in administration groups， while those of autophagy-related proteins were up-regulated significantly， and the combination group had better effects （P＜0.05）. CONCLUSIONS TPL combined with gefitinib can synergically inhibit the proliferation activity of EGFR-mutated NSCLC cells， the mechanism of which may be related to the down-regulation of PI3K/Akt/ mTOR pathway and induction of autophagy.

OBJECTIVETo investigate the association of two single-nucleotide polymorphisms (SNPs) in IL1R1 gene (rs1558641 and rs949963) with the susceptibility to asthma in children from Central China.

METHODSA case-control study was performed in the asthma group and the control group, consisting of 208 children with asthma and 223 normal children from Central China, respectively. The genotypes of two SNPs in IL1R1 gene, rs1558641 and rs949963, were identified using polymerase chain reaction-restriction fragment length polymorphism. The serum level of IL1R1 was determined by enzyme-linked immunosorbent assay.

RESULTSThere were no significant differences in genotype and allele frequencies of rs1558641 between the asthma and control groups. In terms of rs949963, the frequencies of GG genotype and alleles were significantly higher in the asthma group than in the control group (P<0.05). The asthma group had a significantly higher serum level of IL1R1 than the control group (P=0.011). Moreover, the serum level of IL1R1 was significantly higher in patients with GG genotype than in those with AA or AG genotype for rs949963 (P=0.028).

CONCLUSIONSIL1R1 SNP rs949963 is associated with the susceptibility to asthma in children from Central China and may increase the serum expression of IL1R1.

Alleles ; Asthma ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-1 Type I ; genetics

Professor JIA Chunsheng believes that "Dongyuan's acupuncture therapy" proposed by GAO Wu could not entirely reflect LI Dongyuan's academic thought of acupuncture and moxibustion. Hence, we collected all of the academic works of LI Dongyuan and extracted the texts relevant with acupuncture-moxibustion therapy, titled as Dongyuan's acupuncture-moxibustion therapy. This process contributed to the deeper study on Dongyuan's acupuncture and moxibustion academic thought. By the influence of Dongyuan's acupuncture-moxibustion academic thought, in association with his clinical experience for dozens of years, Professor JIA Chunsheng proposed that acupuncture and moxibustion should pay attention to the regulation and tonification of spleen and kidney. In clinical practice, Zhongwan (CV 12), bilateral Tianshu (ST 25), Qihai (CV 6) and Guanyuan (CV 4) are commonly selected to consolidate the root, cultivate the primary and treat the spleen and kidney simultaneously. The locations of the above selected points are distributed like a star. This "star-like point selection method" points to the importance of the spleen and kidney (the primary qi). For many diseases, especially the disorders of internal injury, the star-like acupuncture therapy is commonly used and the relevant acupoints are supplemented. The good clinical efficacy has been achieved.
Acupuncture Points ; Acupuncture Therapy ; history ; methods ; China ; History, Ancient ; Humans ; Moxibustion ; history ; methods

Aim To explore the effect of GSK-3β (glycogen synthase kinase-3 beta) inhibitor TDZD-8 on the neuropathic pain induced by side effects of chemotherapeutic drug oxaliplatin and the underlying mechanism. Methods The rat model of oxaliplatin-induced neuropathic pain was established by intraperitoneal injection of oxaliplatin for five consecutive days; the anti-nociception effect was detected by intrathecal injection of TDZD-8. The spontaneous flinches and mechanical pain threshold were used to detect the changes of pain behavior of rats; immunofluorescence and Western blot analysis were used to detect the changes of spinal inflammation and protein levels of rats. Results Intrathecally injection of TDZD-8 significantly alleviated oxaliplatin induced hyperalgesia in rats. TDZD-8 injection obviously inhibited the activation spinal microglia and the inflammatory reaction. TDZD-8 administration significantly inhibited GSK-3β activation. Conclusion TDZD-8 blocks GSK-3β activation, decreases NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome mediated spinal inflammation and alleviates neuropathic pain.

Objective : To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway． Methods : Fifty female Wistar rats were randomly divided into Control group ，FA group，FA + MT 5 mg / kg group，FA + MT 10 mg / kg group and FA + MT 20 mg / kg group，with 10 rats in each group．Except for the Control group，all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model，and then treated with different MT doses for 14 d．The tainting was continued during the MT treatment．Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue，lung water content and lung coefficient were weighed and measured，glutathione ( GSH) ，superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ，and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ，in- terleukin (IL) -6，and IL-1 β concentrations，Western blot to detect the protein expression levels of Nrf2，heme ox- ygenase-1 (HO-1) ，nuclear factor-κB ( NF-κB) ，and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues，and quantitative polymerase chain reaction(qPCR) to detect the Nrf2，HO-1，and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels. Results : Compared with the control group，lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ，and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6，and IL-1 β levels were elevated (P＜0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P＜0. 05) ，and p-NF-κB protein expression levels were was ele- vated (P＜0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased，and the relative mRNA expression of Keap1 was elevated (P＜0. 05) ．Compared with the FA group，the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P＜0. 05) ，and the level of 8-OHdG was decreased (P＜0. 05) ; the levels of TNF-α , IL-6，and IL-1 β in the alveolar lavage fluid were de- creased (P＜0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P ＜0. 05) ．p-NF-κB protein expression level was decreased (P ＜0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P＜0. 05) ，and the relative mRNA expression level of Keap1 was decreased (P＜0. 05) in lung tissues，and all of them were in a dose-dependent manner． Conclusion MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.

OBJECTIVETo study the clinical effect of combination of kurarinone (KR) and interferon a-lb (IFNalpha-1b) in treating chronic hepatitis B.

METHODSOne hundred and forty-six patients with chronic hepatitis B were randomized into four groups. Under the basic conventional treatment, additional KR combined IFNa-lb was given to Group A, IFNa-lb to Group B and KR to Group C while none was given to Group D. The therapeutic course for them was 6 months and succeeded with 6 months of follow-up. Changes in liver histology, expression of transforming growth factor beta (TGF-beta) in liver tissue, and serum levels of TGF-beta, hyaluronic acid (HA), laminin (LN), collagen type IV (IVC), precollagen III (PCIII), as well as the negative conversion rate of HBeAg and HBV DNA, and normalization rate of alanine transaminase (ALT) before and after treatment were observed by immuno chemical method, RIA and ELISA.

RESULTSAfter treatment, in Group A, the scores of liver fibrosis and all the above-mentioned indexes significantly lowered, as compared with those in Group B and C, the difference was significant (P<0.05 or P<0.01). The negative conversion rate of TGF-beta in liver tissue was in accordance with the dynamic change of liver fibrosis. Comparison between Group B and C in those aspects showed insignificant difference (P >0.05).

CONCLUSIONKR combined with IFNalpha-1b shows better effect in treating chronic hepatitis B than that of using either of the two alone.

Adult ; DNA, Viral ; blood ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Flavonoids ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; isolation & purification ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Phytotherapy

Objective To investigate the keratin 9 gene mutation in epidermolytic palmoplantar keratoderma (EPPK) and its relationship with clinical manifestations. Methods Three Chinese pedigrees with EPPK were studied. Polymerase chain reaction (PCR) was performed to amplify the seven exons encoded by keratin 9. Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific PCR were used to reveal the sequence variation in the PCR products. Results An insertion-deletion mutation in the exon 1 of keratin 9 497delAinsGGCT, was revealed in all 3 EPPK families, resulting in the keratin 9 change from tyrosine166 to tryptophan and leucine (Y166delinsWL). Allele-specific PCR confirmed that the mutation was not a commonly seen polymorphism, but a novel mutation which has not been reported in The Human Intermediate Filament Mutation Database (http://www.interfil.org). Conclusions A new keratin 9 gene mutation, 497delAinsGGCT, is found in these Chinese EPPK pedigrees, which may be the genetic basis of EPPK.