Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

Objective To investigate the relationship between body composition and serum lipids and uric acid among adults in Maonan, and to analyze the effect of body composition changes on blood lipid and uric acid. Methods Totally 584 Maonan adult volunteers in Maonan village of Maonan Autonomous County in Guangxi, the age from 20 to 80 were recruited. The height was measured by the personal height tester; the body composition was measured by the ANITAMC-180 instrument; and the blood lipids and blood uric acid were measured by the Hitachi 7600 instrument. The obtained data were statistically analyzed by SPSS 20. 0. Results The age,height, weight, free fat mass, muscle mass, presumptive bone mass, body water, proptein,extracellular water, intracellular water, and waist-to-hip ratio were greater in Maonan men than in women (P<0. 05). However, whereas male fat content, body fat rate, and subcutaneous fat content were smaller than those of female (P < 0. 01). The total prevalence of hyperuricemia and hyperlipidemia in Maonan nationality was 13. 9% and 28. 4%, respectively. The prevalence of hyperuricemia and hyperlipidemia in males was higher than in females. In males, the body mass, body mass index, free fat mass, fat mass, muscle mass, presumptive bone mass, protein, extracellular water, body fat rate, visceral fat content, subcutaneous fat content and waist-hip ratio of the hyperlipidemia group were higher than the normal group (P<0. 05); and in females, the age, body mass index, fat mass, body fat rate, visceral fat content and waist-hip ratio of the hyperlipidemia group were higher than the normal group. In male, The body mass, free fat mass, presumptive bone mass, body water, extracellular water of the hyperuricemia group were higher than the normal group (P<0. 05); In females, the age, body mass, body mass index, fat mass, extracellular water, body fat ratio, muscle mass, visceral fat content, subcutaneous fat content, and waist-hip ratio of the hyperuricemia group were higher than the normal group. Conclusion The detection rate of hyperlipidemia and hyperuricemia in males of Guangxi Maonan nationality is all higher than that in females. The body composition is significant differences between the normal adults and the patients with hyperlipidemia and hyperuricemia of Maonan nationality in Guangxi.

The Lewis lung carcinoma (LLC) metastatic mouse model was used to investigate the effects of gefitinib and Sijunzi Tang (SJZ) on pre-metastatic niche. The experimental protocol was approved by the Ethics Committee which belongs to Cancer Hospital, Chinese Academy of Medical Sciences. To generate spontaneous lung metastatic models, 1×10⁶ luciferase-labeled LLC cells were injected subcutaneously in the shaved right flank of mice. One day after LLC inoculation, the mice were randomly divided into model (saline), gefitinib (50 mg·kg^-1) treatment, SJZ treatment (25.74 g·kg^-1), and co-treatment gefitinib with SJZ groups, with intragastrical administration. After 14 days of continuous administration, tumor size was detected by IVIS^® Spectrum system. The number of monocytes and neutrophils and the expression levels of chemokine receptors (CXCR1, CCR2) and carcinogenic gene (c-Kit), in peripheral blood, spleen and lung tissues of mice were determined by flow cytometry. The contents of interleukin-IL-1α (IL-1α) and interleukin-6 (IL-6) were detected by the enzyme linked immunosorbent assay (ELISA). After 21 days of treatment, tumors were surgically removed, weighed and the tumor volume was measured with vernier caliper and the antitumor effect of co-administration was evaluated. After 45 days of administration, the survival of mice was recorded. The results of flow cytometry showed that the percentage of neutrophils in gefitinib group, SJZ group, and co-treatment group was significantly decreased in the lung tissue compared to the model group (P<0.05 or P<0.01), but there was no significant difference between three treatment groups (P>0.05). In the mouse peripheral blood and lung tissue, compared with the model group, the expression levels of CXCR1, CCR2 and c-Kit on the surface of neutrophils and monocytes in SJZ group and co-treatment group decreased or decreased significantly (P<0.01 or P<0.05). However, there was a significant increase in the expression level of c-Kit on the surface of monocytes (P<0.05). In the mouse spleen tissue, the expression levels of CXCR1, CCR2 and c-Kit in the gefitinib group increased significantly (P<0.05), while decreased significantly in SJZ or co-treatment group (P<0.05). The results of ELISA showed that the content of IL-1α in SJZ group decreased significantly in the plasma of the mice compared with the model group (P<0.01) and the content of IL-6 in co-treatment group decreased significantly (P<0.05). Compared with the gefitinib group, the content of IL-1 in the co-treatment group decreased significantly (P<0.05). In the tumor tissues of mice, compared with the model group, the content of IL-1α in the co-treatment group decreased significantly (P<0.05). Furthermore, the content of IL-1α in co-administrated group and IL-6 in SJZ or co-treatment group decreased significantly compared with the gefitinib group (P<0.05). After 21 days of continuous administration, the tumor inhibition rates of gefitinib group, SJZ group and co-administrated group were 45.7%, 38.4%, and 84.8%, respectively. After 45 days of administration, the survival rate of the model group was 0%, whereas the gefitinib, SJZ or co-treatment group has a survival rate of 40%, 60%, or 60%, respectively. In summary, our study illustrated that Sijunzi Tang could improve the anti-tumor effect of gefitinib by regulating pre-metastatic niche.

To analyze the medication features and regularity of prescriptions of traditional Chinese medicines in treating patients with coronary heart disease angina pectoris based on the launched Chinese patent medicines. In the article,we collected all of the launched Chinese patent medicines for treating coronary heart disease and angina pectoris from the Chinese patent medicine value assessment information database,and set up a medical record normalized database,then carried out the classification of syndromes. The medication features and prescription rules for angina pectoris were analyzed by frequency statistics and association rules(IBM SPSS Modeler 14. 1 Premiums software,Apriori algorithm). Finally,a total of 170 prescriptions were selected,and 197 Chinese herbs were included,involving to totally 11 syndrome types,in which blood stasis syndrome,Qi stagnation and blood stasis syndrome,Qi deficiency and blood stasis syndrome,Qi-Yin deficiency and blood stasis syndrome were the main syndrome types. The frequency of single-herb medicines for the four main syndrome types,the combination of commonly used medicines,and the core prescriptions were summarized. After comparing the core prescriptions of the four syndrome types,we could analyze the medication features and prescription rules. In conclusion,the therapeutic principle is blood-activating and stasis-dissolving,and consideration was also given to promoting Qi,invigorating Qi and resuscitation and invigorating Qi-Yin. The main medicines include Danshen(Salvia Miltiorrhizae Radix et Rhizoma) and Chuan-xiong(Chuanxiong Rhizoma). According to different types of syndromes,Chinese herbal medicines are added,such as Jiangxiang(Dalbergiae Odoriferae Lignum), Chishao(Paeoniaeradix Rubra), Sanqi(Notoginseng Radix et Rhizoma), Honghua(Carthami Flos),Bingpian(Borneolum Syntheticum),Renshen(Ginseng Radix et Rhizoma). Frequency statistics and association rules are combined to explore the medication features and core prescriptions,which provide ideas for the treatment of angina pectoris and the development of new drugs.
Angina Pectoris ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; therapeutic use

Objective To analysis the effects on the growth of rats by repeated restraint in dermal exposure test. Methods SD rats in the restraint group was bound for 6 hours per day for 91 days according the way by dermal exposure, while SD rats in the control group didn't receive the treatment. Clinical signs, body weight and food consumption changes were observed for 91 days. When the study was terminated, hematology, clinical biochemistry, urinalyses, gross necropsy, and histopathology were carried out. Statistical methods such as the generalized estimating equation were used to compare the differences between two groups. Results The statistical results of generalized estimating equation showed that there was an interaction between the group and test time for male and female rats in body weight changes (P<0.05), and the body weight of male rats in the restraint group was lower than the control group (P<0.05) . Further analysis showed that for male rats there was significant difference between groups since the forth week (P<0.05), and the interaction was found between groups and test time (P<0.05) . For female rats, the interaction was found since the eighth week between the group and test time (P <0.05) .There was no significant differences in other parameters between two groups (P>0.05) . Conclusion Repeated restraint during dermal exposure affected the body weight gain of rats, and the sensitivity of male rats was higher than that of female rats.

Health self-management group adopts the mode of chronic disease self-management and offers a series of courses for community residents in order to help them carry out health self-management. For healthy people, the program aims at disease prevention by means of improving health literacy, acquiring health knowledge and skills, and developing a healthy lifestyle.While for patients, the program aims to prevent or slow the progression of diseases by means of helping them deal with their condition, achieving disease self-management. By nearly ten years of exploration and practice in Shanghai communities, with the program a working system had been established which was dominated by patriotic health campaign committee office at the levels of city and district, and technologically supported by centers for disease control and prevention with support and cooperation of the town government.The program was implemented by community health service centers and neighborhood ( village ) committee.A large-scale and whole-society promotion had been really achieved in community residents with health self-management. By the end of 2015, health self-management groups had covered all of the city's streets ( town ) and neighborhood ( village ) committee, 26 thousand groups set up and nearly 440 thousand community residents participated in group activities.

OBJECTIVETo study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism.

METHODH202-induced lens oxidative injury in vitro rat model was establish to observe the impact of gigantol combined with syringic acid on lens transparency under a dissecting microscope. D-galactose-induced cataract rat model was established to observe the impact of gigantol combined with syringic acid on lens transparency under a slit-lamp. UV spectrophotometry was adopted to detect the inhibitory activity of gigantol combined with syringic acid against AR. Molecular docking method was used to detect binding sites, binding types and pharmacophores of gigantol combined with syringic acid in prohibiting aldose reductase.

RESULTBoth in vitro and in vivo experiments showed a good anti-sugar cataract activity in the combination of gigantol and syringic acid and a better collaborative effect than single component-gigantol and syringic acid and positive control drug Catalin. Molecular docking and dynamic simulation showed their collaborative AR-inhibiting amino acid residue was Asn160 and the major acting force was Van der Waals' force, which formed common pharmacophores.

CONCLUSIONGigantol combined with syringic acid shows good anti-cataract, their action mechanism is reflected in their good collaborative inhibitory effect on AR.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Bibenzyls ; Cataract ; drug therapy ; enzymology ; Drug Synergism ; Female ; Gallic Acid ; analogs & derivatives ; pharmacology ; Guaiacol ; analogs & derivatives ; pharmacology ; Humans ; In Vitro Techniques ; Lens, Crystalline ; drug effects ; enzymology ; Male ; Rats ; Rats, Wistar

BACKGROUNDThe induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.

METHODSIslet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.

RESULTSIslets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher.

CONCLUSIONSThe HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.

Animals ; Blotting, Western ; Graft Survival ; Heme Oxygenase-1 ; genetics ; metabolism ; Interleukin-10 ; blood ; Islets of Langerhans ; enzymology ; metabolism ; Islets of Langerhans Transplantation ; Male ; Mice ; Mice, Inbred BALB C ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous

Objective To investigate the expression level of lipoprotein lipase (LPL) mRNA in chronic lymphocytic leukemia (CLL) patients and evaluate the prognostic value of LPL in CLL Methods Quantitative real-time RT-PCR (qRT-PCR) was performed in 62 CLL patients, 10 normal controls using Taqman probe system. Association between LPL and other known prognostic factors, such as IgVH mutation status, ZAP-70 and CD38 expression, was determined using the Spearman correlation analysis. ROC curve was used to determine the cut-off value of LPL expression level, the positive and negative predictive value of IgVH mutation status. Results The correlation coefficients of the standard curves in qRT-PCR were not less than 0.990. The coefficients of variation (CV) of interrun assay and intramn assay were < 5%, and the sensitivity can reached 102 copies/μg RNA. The median LPL mRNA expression level was 0.006 0 (0-0.737 0) in 62 CLL patients, whereas in 10 normal controls LPL mRNA expression level was extremely low with the median level of 0 (0-0.000 4). The expression levels of LPL in three CLL samples after miniMACS-sorted CD19 positive B cells were 0.036 0, 0.075 0 and 0.197 0, which were similar to the levels before miniMACS-sorted (0.024 0, 0.074 0 and 0.225 0). LFL expression was significantly associated with IgVH mutation status (r=0.45, P<0.05) . LPL expression level in IgVH unmutated patients [0.006 0 (0.000 7-0.110 0)] was significantly higher than the level in IgVH mutated patients [0.002 0(0.000 2-0.027 0)] (U=96.5, P<0.05). LPL expression was also significantly associated with ZAP-70 (r=0.38, P<0.05), CD38 expressions (r=0.43, P<0.05). According to ROC curve, the cut-off of LPL mRNA expression level was 0.036, with a 66.7% specificity, a 72.4% sensitivity, a 51.8% positive predictive value (IgVH unmutated), and a 83.3% negative predictive value (IgVH mutated) for IgVH mutation status. Conclusions The qRT-PCR assay is reliable and sensitive. LPL mRNA expression significantly correlates with IgVH mutation status, ZAP-70 and CD38 expression, and could be a predictive marker of IgVH mutation status. Our data confirms a role for LPL as a novel prognostic indicator in CLL.