OBJECTIVETo study the effects of two specific cyclooxygenase inhibitors (SCI), rofecoxib and celecoxib, combined with chemotherapeutic drugs 5-Fu, DDP and VP-16 on gastric cancer cell line BGC-823, and to evaluate whether specific cyclooxygenase inhibitors can be used as a synergetic agent in chemotherapy.

METHODSThe gastric cancer cell line BGC-823 cells were incubated for 48 hours with rofecoxib and celecoxib, 5-Fu, DDP and VP-16 (concentration gradient of 5-Fu, DDP and VP-16:1 microg/ml, 10 microg/ml and 100 microg/ml), or in combination, respectively. MTT working solution was added to each culture and calculated the survival rates of gastric cancer cells. Median-effect principle and Professor Jin's evaluation methods were applied to detect the interaction between the specific cyclooxygenase inhibitors and chemotherapeutic agents.

RESULTSThe inhibition rates of gastric cancer cells were 42.63% +/- 1.26% and 50.67% +/- 2.35% by treatment with 0.1 micromol/L rofecoxib and 50 micromol/L celecoxib, respectively. The inhibition rates of gastric cancer cells by treatment with 5-Fu, DDP and VP-16 at different concentrations (1 microg/ml, 10 microg/ml and 100 microg/ml) were 39.75% +/- 3.14%, 49.96% +/- 2.08%, 87.93% +/- 3.66%; 48.28% +/- 2.08%, 59.46% +/- 1.69%, 88.23% +/- 4.81%; and 29.23% +/- 3.27%, 49.34% +/- 3.75%, 79.24% +/- 2.44%, respectively. However, the inhibition rates showed a synergetic role while combined the two SCI (0.1 micromol/L rofecoxib and 50 micromol/L celecoxib) with chemotherapeutic agent at different concentrations (P <0.05).

CONCLUSIONBoth rofecoxib and celecoxib have an ability to suppress gastric cancer cells in vitro, and the synergetic role becomes evident when rofecoxib and celecoxib are combined with chemotherapeutic agents at different concentrations, which indicate that the two specific cyclooxygenase inhibitors may be used as a chemotherapeutic sensitizer.

Adenocarcinoma ; pathology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Celecoxib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Cyclooxygenase Inhibitors ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Etoposide ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Lactones ; pharmacology ; Pyrazoles ; pharmacology ; Stomach Neoplasms ; pathology ; Sulfonamides ; pharmacology ; Sulfones ; pharmacology

OBJECTIVETo study the mechanism of action of Tougu Xiaotong Capsule (透骨消痛胶囊, TGXTC) ex vivo in suppressing chondrocyte (CD) apoptosis induced by sodium nitroprussiate (SNP).

METHODSThirty New Zealand rabbits, 2 months old, were randomized by lottery into five groups, six in each: the blank group treated with saline, the positive control group treated with Zhuanggu Guanjie Pill (壮骨关节丸, 70 mg/kg), and the three experimental groups, EGA, EGB, and EGC, treated with low dose (35 mg/kg), moderate dose (70 mg/kg), and high dose (140 mg/kg) of TGXTC, respectively. All treatments were administered via gastrogavage twice a day for 3 days. Arterial blood was collected from the abdominal aorta and drug or drug metabolites-containing serum was prepared. CDs obtained from knee joints of 16 four-week-old New Zealand rabbits were cultured to the third passage and confirmed by toluidine blue staining. SNP of various final concentrations (0, 0.5, 1.0, and 2.0 mmol/L) was used to induce CD apoptosis, and the dosage-effect relationship of SNP in inducing CD apoptosis was determined. Serum samples from the blank, control, and three dosages of TGXTC-treated rabbits were tested in the CD culture in the presence of SNP. Cell apoptosis was determined by Hoechst 33342 staining, viability of CDs was quantified by MTT, CD apoptosis rate was determined by annexin V-FITC/PI staining, levels of p53 and Bcl-2 mRNA expression in CDs were determined with RT-PCR, and contents of caspase-3 and caspase-9 proteins were determined by colorimetry.

RESULTSCD apoptosis was induced by SNP at all concentrations tested and in a dose-dependent manner. The SNP concentration of 1 mmol/L and treatment duration of 24 h appeared to be optimal and were selected for the study. Serum samples from the positive control rabbits and from the two higher doses of TGXTC-treated rabbits showed reduction of SNP-induced CD apoptosis, decrease in p53 mRNA expression, inhibition of catalytic activities of caspase-3 and caspase-9, and increase in Bcl-2 mRNA expression when compared with the serum from the blank group (P<0.05).

CONCLUSIONTGXTC-containing sera antagonized SNP-induced CD apoptosis and the molecular basis for the action was associated with up-regulation of Bcl-2, down-regulation of p53 expression, and inhibition of caspase-3 and caspase-9 catalytic activities.

Animals ; Apoptosis ; drug effects ; Biocatalysis ; drug effects ; Capsules ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Chondrocytes ; drug effects ; enzymology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Male ; Models, Biological ; Nitroprusside ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Rabbits ; Reproducibility of Results ; Serum ; chemistry ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVETo compare the efficacy of preemptive epidural analgesia combined with postoperative epidural analgesia, postoperative epidural analgesia alone and intravenous analgesia for postoperative pain relief and their effects on plasma interleukin-6 (IL-6) concentration following radical surgery for gastric carcinoma.

METHODSSixty-six patients with gastric carcinoma scheduled for gastrectomy were randomly divided into 3 groups, namely group P (n=22), group E (n=22) and group V (n=22), to receive preemptive epidural analgesia combined with postoperative epidural analgesia, exclusive postoperative epidural analgesia, and exclusive postoperative intravenous analgesia, respectively. Hemodynamic data were recorded for all the patients during the operation, and visual analogue scale (VAS) was used to assess the pain intensity at 4, 8, 16, 24, 48 and 72 h after surgery. Plasma IL-6 concentration was determined before surgery and at 24, 48, 72 h after surgery.

RESULTSNo significant changes occurred in the hemodynamics during the preoperative periods. VAS and IL-6 were lower in group P than in group E and V, and group E had lower measurement than group V (P<0.05).

CONCLUSIONPreemptive epidural analgesia combined with postoperative epidural analgesia provides more satisfactory pain relief and more effectively prevents IL-6 increment than exclusive epidural analgesia or intravenous analgesia after gastrectomy for gastric carcinoma.

Adult ; Amides ; administration & dosage ; Analgesia, Epidural ; methods ; Analgesics ; administration & dosage ; Female ; Fentanyl ; administration & dosage ; Gastrectomy ; methods ; Humans ; Infusions, Intravenous ; Interleukin-6 ; blood ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; Stomach Neoplasms ; blood ; surgery ; Treatment Outcome

The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.
Angiotensinogen ; genetics ; metabolism ; Animals ; Aorta, Abdominal ; pathology ; physiopathology ; Carotid Artery, Common ; pathology ; physiopathology ; Hindlimb Suspension ; Male ; Muscle, Smooth, Vascular ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Renin-Angiotensin System ; physiology ; Weightlessness Simulation

BACKGROUNDAccurate assessment of intra- as well as extra-cardiac malformations and radiation dosage concerns are especially crucial to infants and children with interrupted aortic arch (IAA). The purpose of this study is to investigate the value of prospective electrocardiogram (ECG)-triggered dual-source computed tomography (DSCT) angiography with low-dosage techniques in the diagnosis of IAA.

METHODSThirteen patients with suspected IAA underwent prospective ECG-triggered DSCT scan and transthoracic echocardiography (TTE). Surgery was performed on all the patients. A five-point scale was used to assess image quality. The diagnostic accuracy of DSCT angiography and TTE was compared with the surgical findings as the reference standard. A nonparametric Chi-square test was used for comparative analysis. P <0.05 was considered as a significant difference. The mean effective radiation dose (ED) was calculated.

RESULTSDiagnostic DSCT images were obtained for all the patients. Thirteen IAA cases with 60 separate cardiovascular anomalies were confirmed by surgical findings. The diagnostic accuracy of TTE and DSCT for total cardiovascular malformations was 93.7% and 97.9% (P > 0.05), and that for extra-cardiac vascular malformations was 92.3% and 99.0% (P < 0.05), respectively. The mean score of image quality was 3.77 ± 0.83. The mean ED was 0.30 ± 0.04 mSv (range from 0.23 mSv to 0.39 mSv).

CONCLUSIONSIn infants and children with IAA, prospective ECG-triggered DSCT with low radiation exposure and high diagnostic efficiency has higher accuracy compared to TTE in detection of extra-cardiac vascular anomalies.

Aorta, Thoracic ; diagnostic imaging ; pathology ; Coronary Angiography ; methods ; Electrocardiography ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Radiation Dosage

Apoptosis ; Human Umbilical Vein Endothelial Cells ; Humans ; Lipoproteins, LDL/adverse effects* ; MicroRNAs/genetics* ; Molecular Chaperones/genetics*

OBJECTIVE: To evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism. METHODS: A total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44). RESULTS: BBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01). CONCLUSIONS BBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.
Animals ; Male ; Mice ; Antineoplastic Agents/therapeutic use* ; beta Catenin/metabolism* ; Diarrhea/drug therapy* ; Fluorouracil/pharmacology* ; Intestinal Mucosa ; Mucositis/metabolism* ; Pentobarbital/therapeutic use* ; Proliferating Cell Nuclear Antigen/metabolism* ; Saline Solution

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method