OBJECTIVETo show the involvement of lymphocyte-derived catecholamines in the pathogenesis of rheumatoid arthritis (RA), we investigated the change in expression of tyrosine hydroxylase (TH), a rate-limiting enzyme of catecholamine synthesis, by CD4+ T lymphocytes in lymphoid tissues of DBA/1 mice with collagen-induced arthritis (CIA).

METHODSCIA model was induced by chicken type II collagen in DBA/1 mice. The joints of the mice were observed for clinical score of swelling on and after the 22nd day of primary immunization. Pathological changes of ankles were examined by staining of tissue sections with hematoxylin and eosin on the 35th and 55th day following primary immunization. Immunofluorescent histochemistry was used to identify the number of TH-positive, CD4-positive, and double-labeled cells in the mesenteric lymph nodes and the spleen.

RESULTSPaw-swelling onset was on days 29 - 32 after the first immunization in DBA/1 mice. Clinical score for swelling of the paws reached peak on day 46 after the first immunization. Compared with the ankles of intact or vehicle mice, the joints of CIA mice had these characteristics: increased inflammatory cells in the synovial tissues, proliferated synoviocytes in the multilayers, narrowed articular space, and destructed articular cartilages. Simultaneously, the number of TH-positive, CD4-positive, and double-labeled cells in the mesenteric lymph nodes and the spleen was significantly increased on days 35 and 55 following the first immunization. Between day 35 and day 55 post-immunization, there was no significant difference in the number of these positive cells.

CONCLUSIONCD4+ T lymphocytes up-regulate TH expression in the process of CIA and therefore, it is suggested that endogenous catecholamines of lymphocytes involve in the pathogenesis of RA.

Animals ; Arthritis, Experimental ; metabolism ; Arthritis, Rheumatoid ; CD4-Positive T-Lymphocytes ; metabolism ; Lymphoid Tissue ; metabolism ; Male ; Mice ; Mice, Inbred DBA ; Tyrosine 3-Monooxygenase ; metabolism

BACKGROUNDBevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients.

METHODSStandard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mgxm(-2)xd(-1)), one patient irinotecan (125 mg/m(2) every 2 weeks) and one patient topotecan (1.2 mgxm(-2)xd(-1)). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment.

RESULTSFive of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages < 50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature.

CONCLUSIONSBevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.

Adolescent ; Adult ; Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Camptothecin ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioma ; drug therapy ; metabolism ; mortality ; pathology ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Young Adult

OBJECTIVETo observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI).

METHODSFifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope.

RESULTSCompared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group.

CONCLUSIONSThe SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Acute Disease ; Animals ; Blood Urea Nitrogen ; Cell Adhesion Molecules ; metabolism ; Chromatography, Liquid ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluorescent Antibody Technique ; Immunoblotting ; Kidney Function Tests ; Kidney Tubules ; blood supply ; drug effects ; enzymology ; pathology ; Low Density Lipoprotein Receptor-Related Protein-2 ; metabolism ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; enzymology ; pathology ; Saponins ; analysis ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Staining and Labeling ; Tablets

For constructing pcDNA-ORF5, pcDNA-ORF5-ORF6, pcDNA-ORF5/6, the ORF5 and ORF6 of porcine reproductive and respiratory syndrome virus (PRRSV) were amplified by RT-PCR, and transiently transfected into 293T cells by calciumphosphate co-precipitation. After 48 h, 293T cells were collected and surveyed by flow cytometry examination. The result indicated that the expression level of the E protein that mediated by the M protein was higher than that of the E protein expressed independently. Then pcDNA-ORF5, pcDNA-ORF5-ORF6, pcDNA-ORF5/6 were respectivly co-transfected into 293T cells with pHIT60 (include MuLV structural genes,namely gag and pol) and pHIT111 (retroviral genome, containing LacZ as a reporter). The supernatants were harvested 48 h post-transfection,and the analysis of the characteristic of the pseudotyping virions was performed by Western blot and infection test. The result indicated that the E proteins were expressed on the virions, and incorporated into the retroviral virions. Infection test were performed on Marc-145 and PAM, all the cells infected were Lac Z positive. These results indicated the pseudotype virions of MuLV-E and MuLV-E/M were infectious, and higher infectivity was achieved by MuLV-E/M.
Flow Cytometry ; Leukemia Virus, Murine ; genetics ; Plasmids ; Porcine respiratory and reproductive syndrome virus ; genetics ; Viral Envelope Proteins ; genetics ; physiology ; Viral Matrix Proteins ; genetics ; physiology ; Virion ; genetics

OBJECTIVETo study the impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma.

METHODSData collected from 120 patients with locally advanced mid-low rectal cancer (T2-4 and/or N1-2M0) treated from January 2005 to June 2008 was investigated. The patients were divided into two groups: the study group (n=54) was treated with neoadjuvant therapy (preoperative radiation with a total dosage of 50 Gy and synchronous 5-Fu-based chemotherapy) followed by radical tumor resection 4-6 weeks after;the control group (n=66) underwent primary surgery without neoadjuvant therapy. The clinical stage was evaluated before and after neoadjuvant therapy. The total lymph nodes yields, as well as the tumor-positive lymph nodes of each resected specimen was compared between the two groups statistically.

RESULTSClinical downstage was achieved in 30 cases (56%) in study group after neoadjuvant therapy. The number of total lymph nodes and positive lymph nodes harvested from each resected specimen in the control group were 14+/-7 and 2.2+/-3.7, meanwhile those were 9+/-6 and 0.7+/-2.4 in study group, which were all significantly lower than those in control group (P<0.01).

CONCLUSIONSPreoperative radiotherapy combined with chemotherapy can downstage the tumor and reduce the retrieval rate of total lymph nodes and positive lymph nodes in locally advanced rectal cancer. It is necessary to retrieve as many lymph nodes as possible for it has some prognostic significance for the patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Nodes ; pathology ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; pathology ; surgery ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To investigate and analyze the reasons for the omission of adjuvant radiotherapy after breast-conserving surgery (BCS) in patients with breast cancer.Methods The clinicopathologial characteristics and socioeconomic data of 55 breast cancer patients undergoing BCS without postoperative adjuvant radiotherapy in our hospital from 2012 to 2016 were retrospectively analyzed.Results Among the 55 patients who did not receive radiotherapy,25 patients were due to low local recurrence risk,12 patients were due to economic or family reasons,12 patients were due to fear of adverse reactions of radiotherapy,and 5 patients were not recommended by primary physicians for radiotherapy.In addition,3 cases with multiple distant metastases and 3 cases with concomitant thyroid cancer didn't received radiotherapy.Conclnsions Low risk local recurrence is the main reason for the omission of adjuvant radiotherapy,followed by the fear of radiation-induced toxicity and poor financial support.Patient education and medical insurance may improve the adjuvant radiotherapy compliance.

Objective To observe the clinical efficacy of TCM foot bath in adjuvant treatment for early diabetic lower-extremity peripheral arterial disease (LEPAD). Methods Totally 90 cases with early diabetic LEPAD were divided into treatment group and control group by random number table method, with 45 cases in each group. Control group was given routine treatment, including health education, diet control, proper exercise, control of blood sugar, blood pressure and blood lipids, nutritional nerves, dilation of blood vessels. On the basis of control group, the treatment group was given TCM foot bath, soaking the lower limbs for 30 minutes each time, once a day, for 12 weeks. The clinical efficacy of the two groups was evaluated. The TCM syndrome score, maximum painless walking distance, temperature of the toe skin, diameter of the lower extremity arterial blood vessels, lower extremity arterial blood flow, ankle brachial index (ABI), blood pressure (BP), FBG, HbA1c, serum adiponectin, IL-6 and TNF-α were detected. The blood routine, liver and kidney function were detected and adverse reactions were recorded. Results The total effective rate was 82.22% (37/45) in the treatment group and 68.89% (31/45) in the control group. The treatment group was significantly better than the control group (Z=-2.099, P=0.036). Compared with before treatment, the levels of TCM syndromes, BP, FBG, HbA1c, serum IL-6 and TNF-α were significantly lower in both groups after treatment (P<0.05); serum adiponectin level increased after treatment (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial blood vessels, the lower extremity arterial blood flow and ABI were significantly improved. Compared with the control group, the scores of TCM syndromes in the treatment group were significantly lower (P<0.05); the levels of IL-6 and TNF-α in the treatment group were significantly lower than those in the control group (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial vessels, the lower extremity arterial blood flow and ABI, serum adiponectin level in the treatment group were significantly higher than those of the control group (P<0.05). Conclusion TCM foot bath in adjuvant treatment for early diabetic LEPAD is with obvious efficacy, and the mechanism may be related to improving the level of serum inflammatory cytokines to inhibit the inflammatory injury of blood vessels.

OBJECTIVE: This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD. METHODS: We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation. RESULTS: The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression. CONCLUSION This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.
Humans ; Depressive Disorder, Major/genetics* ; Depression ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Risk Factors ; Serotonin Plasma Membrane Transport Proteins

This study investigated the anti-ascites effect of the total saponins of Phytolaccae Radix(PRTS) and the mechanism.H22 cell suspension was used(ip) to induce ascites in ICR male mice, and the model mice were randomized into model group, positive drug group(furosemide, 6 mg·kg~(-1)), total extract of Phytolaccae Radix(PRTE) group, and PRTS(1.29 g·kg~(-1)).Another 10 male mice were selected as the blank group.Mice in the blank group and model group were given(ig) normal saline containing 0.5% CMC-Na, and those in the positive drug group, PRTE group, and PRTS group received(ig) corresponding doses of drugs, once a day, for 8 consecutive days.The ascites volume, urine volume, and fecal water content in mice with ascites, serum levels of antidiure-tic hormone(ADH), renin in renin-angiotensin-aldosterone system(RAAS), angiotensin Ⅱ(AngⅡ), and aldosterone(ALD), expression of aquaporin(AQP)1-AQP4 in kidney, expression of AQP1, AQP3 in colon, and expression of phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt) pathway-related proteins were detected to explore the anti-ascites mechanism of PRTS.The results showed that the PRTS can increase the urine volume and fecal water content and decrease the ascites volume of ascites mice.Moreover, PRTS significantly reduced the expression of AQP1-AQP4 in kidney and AQP1, AQP3 in colon, serum levels of renin, AngⅡ, ALD, and ADH, and the expression of p-PI3 K and p-Akt in the kidney of ascites mice.PRTS exerts anti-ascites effect by promoting urination and defecation.The mechanism is that it inhibits the activities of RAAS and ADH and suppresses the phosphorylation of PI3 K/Akt signaling pathway, thereby restricting the expression of AQPs in the kidney and colon.
Animals ; Aquaporin 1 ; Ascites/metabolism* ; Male ; Mice ; Mice, Inbred ICR ; Proto-Oncogene Proteins c-akt/metabolism* ; Renin/metabolism* ; Saponins/pharmacology* ; Water/metabolism*

BACKGROUND: Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy. METHODS: A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). RESULTS: We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05). CONCLUSION Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.
Chemoradiotherapy ; Disease-Free Survival ; Female ; Humans ; Neoplasm Staging ; Prospective Studies ; Retrospective Studies ; Th17 Cells ; Treatment Outcome ; Uterine Cervical Neoplasms/therapy*