OBJECTIVETo study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

METHODSThe 3rd passage subcutaneous transplantation tumor was taken as the origin of the model by using MKN-45 human gastric cancer cell lines. MKN-45 human gastric cancer nude mouse model was established using OB glue adhesive method. Then 30 nude mice were divided into the model group, the XSR group, and the chemotherapy group. Mice in the XSR group were intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No intervention was given to mice in the model group. After 6 weeks of medication, the tumor weight was measured, and the tumor inhibition rate calculated. The size, the peak height, and the peak area of 5 microsatellite instability sites were detected.

RESULTSThe tumor inhibition rate was 40. 84% in the XSR group. The tumor weight was significantly lower in the XSR group than in the model group (P < 0.01), showing no statistical difference when compared with the chemotherapy group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the model group was 70%, and the incidence of low microsatellite instability (MSI-L) was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR treatment.

CONCLUSIONXSR showed inhibition on microsatellite instable orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Mice ; Mice, Nude ; Microsatellite Instability ; drug effects ; Neoplasm Transplantation ; Stomach Neoplasms

OBJECTIVETo observe the effect of activation of aldehyde dehydrogenase 2 (ALDH2) by ethanol on the expression of c-Jun N-terminal kinase (JNK) in the kidney of diabetic rats.

METHODSEightheen healthy male SD rats were randomly divided into 3 groups (n = 6): normal control group, diabetes group and ethanol + diabetes group. After 8 weeks, 24 h urine samples from rats were collected to detect urinary protein content. The kidney was isolated and the ratio of kidney weight/body weight (index of kidney weight) was detected. The levels of fasting blood glucose, glycosylated hemoglobin serum urea nitrogen and serum creatinine were measured. Morphological changes of renal tissue were observed by optical microscope. The protein expressions of ALDH2 and JNK in renal tissue were detected by Western blot.

RESULTSCompared with the normal control rats, the levels of fasting blood glucose, glycosylated hemoglobin, serum urea nitrogen, serum creatinine and the index of kidney weight were increased markedly in diabetic rats. The expression of ALDH2 protein was decreased, while p-JNK, JNK protein expressions and the ratio of p-JNK/JNK were increased. The morphological observation was shown that the amount of glomerular mesangial matrix were increased, basement membrane were thickened and capillary lumen were narrowed. However,in ethanol + diabetes group, renal function was improved and the damage of renal structure was attenuated. The expression of ALDH2 protein was increased, while p-JNK, JNK and the ratio of p-JNK/JNK were decreased.

CONCLUSIONEnhanced ALDH2 expression can protect kidney in diabetic rats, which may be relevant with inhibitting the activity of JNK pathway.

Aldehyde Dehydrogenase ; metabolism ; physiology ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; enzymology ; Ethanol ; pharmacology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Kidney ; enzymology ; Male ; Mitochondrial Proteins ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.

METHODSAn MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.

RESULTSThere were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.

CONCLUSIONSTIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".

Animals ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cyclooxygenase 2 ; genetics ; metabolism ; Extracellular Fluid ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Stomach Neoplasms ; metabolism ; secondary ; Telomerase ; genetics ; metabolism ; Tumor Microenvironment ; physiology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/ R) injury in diabetic rats.

METHODSDiabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups (n = 8). After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glycosylated hemoglobin (HbA1c) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.

RESULTSIn contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/- dp/dtmax) and left ventricular work (RPP) were decreased, left ventricular end diastolic pressure (LVEDP) and LDH release were increased, and ALDH2 mRNA and protein expressions were decreased; compared with I/R in diabetic rat, ALDH2 agonist ethanol significantly promoted the recovery of LVDP, +/- dp/dtmax, RPP, reduced HbA1c level, LVEDP and LDH released, ALDH2 mRNA and protein expressions were increased.

CONCLUSIONIn diabetic rat, the expression of ALDH2 was decreased when heart was subjected to I/R. Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/R) injury in diabetic rats.

METHODSNormal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bcl-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR.

RESULTSIn diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bcl-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bcl-2/Bax mRNA expression.

CONCLUSIONIn diabetic rats, enhanced ALDH2 expression can offer mycardial protection possibly in relation to suppress cell apoptosis.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; enzymology ; Ethanol ; pharmacology ; Male ; Mitochondrial Proteins ; agonists ; metabolism ; Myocardial Ischemia ; enzymology ; etiology ; Myocardial Reperfusion Injury ; enzymology ; pathology ; prevention & control ; Myocardium ; enzymology ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDWork-related musculoskeletal disorders (WMSDs) have high prevalence in sewing machine operators employed in the garment industry. Long work duration, sustained low level work and precise hand work are the main risk factors of neck-shoulder disorders for sewing machine operators. Surface electromyogram (sEMG) offers a valuable tool to determine muscle activity (internal exposure) and quantify muscular load (external exposure). During sustained and/or repetitive muscle contractions, typical changes of muscle fatigue in sEMG, as an increase in amplitude or a decrease as a shift in spectrum towards lower frequencies, can be observed. In this paper, we measured and quantified the muscle load and muscular activity patterns of neck-shoulder muscles in female sewing machine operators during sustained sewing machine operating tasks using sEMG.

METHODSA total of 18 healthy women sewing machine operators volunteered to participate in this study. Before their daily sewing machine operating task, we measured the maximal voluntary contractions (MVC) and 20%MVC of bilateral cervical erector spinae (CES) and upper trapezius (UT) respectively, then the sEMG signals of bilateral UT and CES were monitored and recorded continuously during 200 minutes of sustained sewing machine operating simultaneously which equals to 20 time windows with 10 minutes as one time window. After 200 minutes' work, we retest 20%MVC of four neck-shoulder muscles and recorded the sEMG signals. Linear analysis, including amplitude probability distribution frequency (APDF), amplitude analysis parameters such as roof mean square (RMS) and spectrum analysis parameter as median frequency (MF), were used to calculate and indicate muscle load and muscular activity of bilateral CES and UT.

RESULTSDuring 200 minutes of sewing machine operating, the median load for the left cervical erector spinae (LCES), right cervical erector spinae (RCES), left upper trapezius (LUT) and right upper trapezius (RUT) were 6.78%MVE, 6.94%MVE, 6.47%MVE and 5.68%MVE, respectively. Work load of right muscles are significantly higher than that of the left muscles (P < 0.05); sEMG signal analysis of isometric contractions indicated that the amplitude value before operating was significantly higher than that of after work (P < 0.01), and the spectrum value of bilateral CES and UT were significantly lower than those of after work (P < 0.01); according to the sEMG signal data of 20 time windows, with operating time pass by, the muscle activity patterns of bilateral CES and UT showed dynamic changes, the maximal amplitude of LCES, RCES, LUT occurred at the 20th time window, RUT at 16th time window, spectrum analysis showed that the lower value happened at 7th, 16th, 20th time windows.

CONCLUSIONSFemale sewing machine operators were exposed to high sustained static load on bilateral neck-shoulder muscles; left neck and shoulder muscles were held in more static positions; the 7th, 16th, and 20th time windows were muscle fatigue period that ergonomics intervention can protocol at these periods.

Adult ; Electromyography ; methods ; Female ; Humans ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; physiology ; Neck Muscles ; physiology ; Shoulder ; physiology ; Textile Industry ; Workload ; Young Adult

OBJECTIVETo explore a method of extracting tumor interstitial fluid (TIF) which is similar to muddy phlegm in Chinese medicine (CM), interleukin-8 (IL-8) in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on tumor recurrence.

METHODSTumor tissue was ground, centrifuged, and filtered for intercellular substances. Tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline (NS) and a blank control on tumor recurrence.

RESULTSThe content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different (P>0.05). Postoperative tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups (60%, 12/20 vs. 20%, 4/20. vs. 15%, 3/20, χ(2) =11.058, P<0.01). Tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group.

CONCLUSIONSTIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative tumor recurrence, which provided preliminary experimental basis for hypothesis of "tumor-phlegm microenvironment".

Animals ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid ; Interleukin-8 ; analysis ; Mice ; Neoplasms, Experimental ; pathology ; Postoperative Period ; Recurrence

Objective To investigate clinical efficacy of Xiaotan Tongluo Gel combined with mecobalamin tablets in treating chemotherapy-induced peripheral neuropathy (CIPN). Methods Totally 67 cases of CIPN were divided into the treatment group (36 cases) and the control group (31 cases). Both groups were given mecobalamin tablets, 0.5 mg each time, three times a day, orally. Patients in the treatment group were treated with Xiaotan Tongluo Gel for external use at the same time. The patients in control group were treated with placebo gel for external use, 1 mL/cm2, rubbed on the skin 1 cm more than sensory obstruction in diameter. The treatment for both groups lasted for 14 d as a treatment course, and the treatment lasted for 2 courses. The changes of peripheral nerve toxicity, TCM syndrome scores and the nerve conduction velocity were observed in the two groups. Results On the 14th and 28th days of treatment, the total effective rates of peripheral nerve toxicity were 75.00% and 91.67% in the treatment group, and 38.71% and 67.74% in the control group, and the treatment group was significantly better than those of the control group (P=0.002, P=0.005); On the 14th and 28th days of treatment, the total effective rate of TCM efficacy in the treatment group was 75.00% and 94.44% respectively, and that in the control group was 45.16% and 64.52% respectively, and the treatment group was significantly better than the control group (P=0.018, P=0.005). Compared with before treatment, the TCM syndrome scores in both groups were significantly reduced on the 14th and 28th days (P＜0.01); The TCM syndrome scores in the treatment group were significantly lower than those in the control group at the same time points after treatment (P＜0.01). Compared with before treatment, the sensory and motor nerve conduction speeds of the peroneal and median nerves in the two groups at 14th and 28th days were significantly increased (P＜0.01); Comparing the two groups at the same time point after treatment, the sensory and motor nerve conduction velocity of the peroneal and median nerves in the treatment group was significantly better than that in the control group (P＜0.05, P＜0.01). Conclusion Xiaotan Tongluo Gel combined with mecobalamin tablets can effectively improve the peripheral neurotoxicity induced by chemotherapy, TCM syndrome scores, and the nerve conduction velocity.

OBJECTIVETo evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients.

METHODSThis randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores.

RESULTSUsing time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01).

CONCLUSIONAdditional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Middle Aged ; Placebos ; Quality of Life ; Stomach Neoplasms ; drug therapy ; physiopathology ; Young Adult

[Abstract] Objective: To explore the mRNA molecular targets for diagnosis of hepatic carcionoma and to investigate their functional roles in proliferation and cell cycle of hepatic cancer cells. Methods: Based on the statistical analysis of miRNA expression data from 377 hepatic carcionoma samples and 37 adjacent non-cancerous samples in TCGAdatabase, a group of 33 differentially expressed miRNAs were identified.A further screen of these differentially expressed miRNAs was performed using the receiver operating characteristic curve (ROC curve) and Kaplan-Meier survival analysis; and with referring to the current publications, miR-451 was screened as the study subject. HepG2 cells were transfected with pLVX-shRNA2-miR-451 to over-express miR-451. The effect of miR-451 over-expression on the proliferation of HepG2 cell was determined by CCK-8 assay; while the effect on cell cycles was detected by flow cytometry. Results: The expression of miR-451 in the adjacent non-cancerous tissues was significantly lower than that in cancer tissues ([473.40±390.24] vs [1 990.47±2 118.04], P<0.05). MiR-451 could be used as an early diagnostic biomarker of hepatic carcionoma, with a high ROC value of 0.91 (sensitivity 0.89, specificity 0.87). The results of in vitro experiments showed that the proliferation of HepG2 cells was significantly decreased after miR-451 over-expression (48 h: [0.69±0.04] vs [1.08±0.05]; 72 h: [0.76±0.07] vs [1.52± 0.02]; all P<0.01), and a large number of cells were blocked in S phase(P<0.05). Conclusion: miR-451 has the potential to be used as a biomarker for hepatic carcionoma diagnosis and prognosis; moreover, it also exhibits the inhibitory effect on proliferation of hepatic cancer cells.