The Impact of Traditional Chinese Medicine QingreHuoxue Treatment and the Combination of Methotrexate and Hydroxychloroquine on the Radiological Progression of Active Rheumatoid Arthritis: A 52-Week Follow-Up of a Randomized Controlled Clinical Study.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.

Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis: A Multicenter, Double-Blind, Randomized Controlled Trial.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA-albeit to a lesser degree than csDMARDs-with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.

The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer.

Paclitaxel is widely used as a first-line chemotherapeutic drug for patients with ovarian cancer and other solid cancers, but drug resistance occurs frequently, resulting in ovarian cancer still presenting as the highest lethality among all gynecological tumors. Here, using DIGE quantitative proteomics, we identified UBC13 as down-regulated in paclitaxel-resistant ovarian cancer cells, and it was further revealed by immunohistochemical staining that UBC13 low-expression was associated with poorer prognosis and shorter survival of the patients. Through gene function experiments, we found that paclitaxel exposure induced UBC13 down-regulation, and the enforced change in UBC13 expression altered the sensitivity to paclitaxel. Meanwhile, the reduction of UBC13 increased DNMT1 levels by attenuating its ubiquitination, and the up-regulated DNMT1 enhanced the CHFR promoter DNA methylation levels, leading to a reduction of CHFR expression, and an increased in the levels of Aurora A. Our findings revealed a novel function for UBC13 in regulating paclitaxel sensitivity through a DNMT1-CHFR-Aurora A pathway in ovarian cancer cells. UBC13 could potentially be employed as a therapeutic molecular drug for reversing paclitaxel resistance in ovarian cancer patients.

Endostar combined with irinotecan/calcium folinate/5-fluorouracil (FOLFIRI) for treating advanced colorectal cancer: A clinical study.

PURPOSE: The current study aimed to evaluate the short-term efficacy and safety of endostar plus irinotecan/calcium folinate/5-fluorouracil (FOLFIRI) in treatment of advanced colorectal cancer (CRC). METHODS: Forty patients with advanced CRC were enrolled in this study and randomly assigned to two groups. The control group (n = 18) and tested group (n = 22) were received FOLFIRI alone and FOLFIRI plus endostar, respectively. The end points were overall response rate, progression-free survival (PFS) and toxicity. RESULTS: A total of 38 patients (17 in control group and 21 in tested group) completed two cycles of treatment and were deemed assessable for response. Patients treated with FOLFIRI plus endostar experienced a obviously higher overall response rate (42.9%) compared with patients who received FOLFIRI alone (29.4%) and a statistically significant improvement in median PFS (14.5 vs. 11.0  months). The toxicity of FOLFIRI/endostar was comparative to that of FOLFIRI with regard to gastrointestinal reactions, haematologic toxicity, peripheral neuropathy and cholinergic syndrome. Cardiovascular adverse reactions including electrocardiogram abnormality and hypertension, which might be ascribed to endostar treatment, were reversible and manageable. CONCLUSION: The addition of endostar to FOLFIRI resulted in a higher overall response rate and longer PFS and did not increase unacceptable adverse responses in patients with advanced CRC. Future randomised controlled clinical trials with a larger group of patients are warranted to further investigate the value of FOLFIRI plus endostar in CRC treatment.

Alternative splicing of the androgen receptor in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS.

TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.

Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients. Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1 expression, increase of autophagosome formation, and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17 inhibition by siRNA or enforced overexpression by a pcDNA3.1(+)-TXNDC17 plasmid correspondingly decreased or increased the autophagy response and paclitaxel resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17 overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17, through participation of BECN1, induces autophagy and consequently results in paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or target in ovarian cancer therapeutics.

[Expression of suppressor of cytokine signaling-3 and caspase-3 in endometriosis and their correlation].

OBJECTIVE: To investigate the expression of suppressor of cytokine signaling(SOCS)-3 and caspase-3 and their correlative significance in endometriosis. METHODS: Immunohistochemical EnVision method was used to detect the SOCS-3 and caspase-3 protein expression in ectopic and eutopic endometrium (n = 32) of patients with endometriosis, as well as normal endometrium (n = 30) of women without endometriosis. RESULTS: SOCS-3 and caspase-3 proteins were expressed in all three groups and not affected by the menstrual cycles. The expression of SOCS-3 in ectopic endometrium (5.54 ± 2.12) was significantly lower than that in eutopic (7.39 ± 1.09, P = 0.001) and control group (7.48 ± 1.26, P < 0.01), but without difference between the eutopic and control group (P = 0.756). SOCS-3 expression in ectopic and eutopic endometrium was significantly lower in III/IV stages than that in I/II stages of endometriosis (P < 0.05). Significantly lower expression of caspase-3 protein was found in ectopic (3.20 ± 1.24) and eutopic endometrium (3.88 ± 1.93) as compared with the control group (6.49 ± 1.85, P < 0.01), however ectopic and eutopic endometrium showed no significant difference (t = 1.66, P = 0.10). There was no significant difference of the expression of caspase-3 in ectopic and eutopic endometrium at different disease stages (P > 0.05). Positive correlation was found between the expression of SOCS-3 and caspase-3 proteins in ectopic endometrium (r = 0.655, P < 0.01). CONCLUSION: SOCS-3 may be involved in the development of endometriosis through inhibition of apoptosis of ectopic endometrial cells.

Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation.

BACKGROUND: The aim of this study was to investigate the mechanism by which low-dose mifepristone serves as an antiimplantation contraceptive drug. A human endometrial explant system was used to study the effects of low-dose mifepristone (65 nmol/L and 200 nmol/L) on expression of the water channel family aquaporins, aquaporin-1 and aquaporin-2 (AQP1/AQP2), at the time of implantation. STUDY DESIGN: Endometrial samples from 17 normally cycling patients at the "window of implantation" were treated with different concentrations of mifepristone. The protein and mRNA expression of AQP1/AQP2 in the endometrium was examined using immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: The IHC and RT-PCR analyses demonstrated that expression of AQP1/AQP2 was increased by mifepristone in a dose-dependent manner, with the highest AQP1/AQP2 expression levels detected in subjects treated with 200-nmol/L mifepristone. CONCLUSION: Low-dose mifepristone may negatively regulate implantation by increasing AQP1/AQP2 protein and mRNA expression. The findings from this study provide further evidence to support the potential contraceptive activity of low-dose mifepristone.

[Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation].

OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS) patients, and to verify the clinical utility of AS syndrome differentiation and treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS) and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types, Shen invigorating blood activating method (SIBAM) and heat clearing dampness resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354 AS patients of SDISOS and DHOS were randomly assigned to the treatment group and the control group using a multi-center randomized, positive drug parallel-controlled clinical trail. Patients in treatment group were treated by BQD or QQD according to syndrome typing, while those in the control group took Sulfasalazine enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was 86.75% in the treatment group, and the total effective rate of Chinese medical syndrome was 85.47%. They could significantly reduce patients' integrals of Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.

[Treatment of rheumatoid arthritis arthralgia by xiaoyan zhitong paste: a clinical observation].

OBJECTIVE: To formulate a comprehensive treatment program for rheumatoid arthritis arthralgia by clinical observing the efficacy of Xiaoyan Zhitong Paste (XZP). METHODS: Adopted was stratified, block randomized, double-blinded, placebo parallel controlled method. Subjects were assigned to the treatment group and the placebo group. Those in the treatment group were treated by external application of XZP, one to two pastes each time, covering the painful area, exchange once per 24 h, with one-day interval during a 7-day consecutive medication, two 7-days of treatment consisting of one therapeutic course. XZP placebos were applied for those in the placebo group in the same medication way. Joint pain and VAS were taken as main indices for observing the clinical efficacy of XZP. RESULTS: The improvement of the analgesic effect and the Chinese medical syndrome efficacy of XZP were superior to that of the placebo. CONCLUSION: XZP showed obvious effect in treating rheumatoid arthritis arthralgia with no obvious adverse reaction.

[Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease].

OBJECTIVE: To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. METHODS: The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation), 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of EnVision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. RESULTS: LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6.79±2.38, 5.26±2.63 and 3.10±1.65, all P<0.01), while there were no difference compared with gestational trophoblastic neoplasms (6.42±2.68, P=0.113). The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6.30±2.98, 4.93±2.50, 4.43±2.04 and 3.33±2.06, all P<0.01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P<0.05). While, there was no correlation between the expressions of the two proteins (P>0.05). CONCLUSIONS: High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.

Value of P16 expression in the triage of liquid-based cervical cytology with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.

BACKGROUND: The management of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL) is still controversial and it is advisable to make a triage for these two cytological abnormalities. P16(INK4) (P16) has been shown to be a potential biomarker for predicting high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. The aim of the study was to determine the value of P16 expression by immunostaining method compared with high-risk human papillomavirus (HR-HPV) DNA test in the triage of ASCUS/LSIL women. METHODS: Totally 86 eligible residual liquid-based cytological specimens with ASCUS and 45 with LSIL were obtained. All specimens were submitted to HR-HPV DNA test (HC2) and P16 immunocytochemical staining simultaneously. And all women underwent colposcopy and biopsy after cytology. RESULTS: The positive rate of P16 staining was 32.6% in ASCUS and 42.2% in LSIL, which was significantly lower than that of HR-HPV test in both ASCUS (P < 0.05) and LSIL (P < 0.05). Moreover, the positive rate of P16 staining was 12.7% in normal histology, 61.5% in CIN 1, 87.0% in CIN 2-3, and 100.0% in cancer, in which P16 positive rate was significantly lower than HR-HPV positive rate in normal group. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of P16 staining for predicting CIN 2 or more were 87.5%, 68.6%, 38.9%, 96.0%, and 72.1%, respectively in the ASCUS; while 90.0%, 71.4%, 47.4%, 96.2% and 54.7%, respectively in the LSIL, in which the specificity and accuracy of P16 staining were significantly higher than those of HR-HPV test in both ASCUS and LSIL (P < 0.05). CONCLUSION: P16 immunostaining had significantly higher specificity and accuracy than HR-HPV DNA test for predicting for high-grade CIN and cervical cancer in ASCUS and LSIL and can be used for the triage of women with ASCUS/LSIL cytological abnormality.

Reduced miR-100 expression in cervical cancer and precursors and its carcinogenic effect through targeting PLK1 protein.

AIM: Although aberrant miRNAs expression has been documented, altered miR-100 expression in cervical cancer and precursor tissues and its carcinogenic effect and mechanism remain unexplored. The aim of our study was to investigate the role of miR-100 alteration in cervical carcinogenesis. METHODS: The expression of miR-100 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in 125 cervical tissues including normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and cervical cancer, as well as in five cervical cell lines. Through modulating miR-100 expression using miR-100 inhibitor or mimic in vitro, cell growth, cycle and apoptosis were tested separately by MTT or flow cytometry and meanwhile Polo-like kinase1 (PLK1) mRNA and protein expressions were detected by qRT-PCR and immunoblotting. The expression of PLK1 in 125 cervical tissues was also examined by immunohistochemical staining and the correlation between miR-100 and PLK1 expression in the same tissues was analysed. Finally, HPV-16 E6/E7 expression was modulated by gene transfection and subsequently the level of miR-100 was examined by qRT-PCR. RESULTS: The miR-100 expression showed a significantly and gradually reduced tendency from low-grade CIN, high-grade CIN to cervical cancer tissues and a significant decrease in HPV positive cervical cancer cell lines. The modulation of miR-100 expression remarkably influenced cell proliferation, cycle and apoptosis, as well as the level of PLK1 protein, but not mRNA, in vitro experiments. PLK1 expression was negatively correlated with miR-100 expression in CIN3 and cervical cancer tissues. The modulation of HR-HPV E6/E7 expression did not change miR-100 level. CONCLUSIONS: The reduced miR-100 expression participates in the development of cervical cancer at least partly through loss of inhibition to target gene PLK1, which probably occurs in a relative late phase of carcinogenesis. HR-HPV E6/E7 may not directly regulate miR-100 expression in cervical cells.

[Preliminary study on the relationship between tubal intraepithelial carcinoma of the fimbria and pelvic high-grade serous carcinoma].

OBJECTIVE: To explore the relationship between tubal intraepithelial carcinoma (TIC) of the fimbria and pelvic high-grade serous carcinoma. METHODS: All 34 cases of pelvic high-grade serous carcinoma with clear fimbria were evaluated from January 2009 to June 2010, including ovarian carcinoma (n = 26), tubal carcinoma (n = 7) and peritoneal carcinoma (n = 1). Among of these ovarian carcinomas, 12 cases were surface deposits and the other 14 cases within ovarian parenchyma. All 42 cases of non high-grade serous carcinoma in this period including 13 endometrioid ovary carcinomas, 11 clear cell ovary carcinomas, 11 mucinous ovary carcinomas, 6 low-grade serous ovary carcinomas, 1 low-grade serous tubal carcinoma, were also collected as a reference. The presence of tubal intraepithelial carcinomas was assessed. Based on the presence of TIC, high-grade serous ovary carcinomas were divided into TIC positive(+) and TIC negative(-) groups, and the clinical and pathological features of them were also evaluated. RESULTS: Fifteen cases (44%) were identified TIC in 34 high-grade pelvic serous carcinomas, and all of them were in the fimbria only, while none of TIC was found in control cases. There were significant difference between the two groups (χ(2) = 23.086, P = 0.000). Eleven cases (42%) were identified TIC in all 26 high-grade ovarian serous carcinomas, in which 8 cases with unilateral ovary carcinomas were associated with ipsilateral TIC, 2 cases with bilateral ovary carcinomas associated with unilateral TIC and one case with bilateral ovary carcinoma was associated with bilateral TIC. Four TIC (4/7) were identified in 7 cases with high-grade tubal serous carcinomas, and there was no presence of TIC in the 1 high-grade serous peritoneal carcinoma. Of all 26 high-grade ovarian serous carcinomas, 6/11 cases were surface deposits, and 5/11 were parenchyma tumors in TIC(+) group while 6/15 cases were surface deposits and 9/15 were parenchyma tumors in TIC(-) group, in which there were correlated in distribution of TIC between the two groups (P > 0.05). The average diameter of ovarian cancer were 6.9 and 6.5 cm between the two groups with no significant differences (t = 0.409, P = 0.690). CONCLUSION: TIC is specific to high-grade serous carcinomas and maybe have something to do with the pathogenesis of pelvic serous carcinomas.

Expression of octamer-4 in serous and mucinous ovarian carcinoma.

BACKGROUND: Octamer-4 (Oct4) is a well known regulator of self-renewal in embryonic stem cells; it has been detected in several human cancers and may play a critical role in carcinogenesis. AIMS: To assess the expression of Oct4 in epithelial ovarian tumours. METHODS: Expression of Oct4 was evaluated by immunohistochemistry in 460 cases of various epithelial ovarian lesions as well as 35 cases of normal fallopian tube epithelium. The association between Oct4 expression and various clinical pathological parameters was analysed. RESULTS: Oct4 expression was significantly increased from normal epithelium (both ovarian epithelium and fallopian tube epithelium) to benign and borderline cystadenoma to carcinoma in the serous lesion subgroup. Oct4 overexpression was associated with more advanced FIGO stage and higher histological grade in serous adenocarcinoma. Conversely, Oct4 expression did not differ among mucinous lesions or correlate with clinicopathological parameters in patients with mucinous adenocarcinoma. CONCLUSION: Results suggest that Oct4 expression may contribute to the initiation, promotion and progression of serous ovarian carcinoma; it might be a useful biomarker for the diagnosis and outcome prediction of serous ovarian carcinoma.

[Protein gene product 9.5-immunoactive nerve fibers and its clinical significance in endometriotic peritoneal lesions].

OBJECTIVE: To investigate the association between distribution of protein gene product (PGP) 9.5-immunoactive nerve fibers in peritoneal endometriotic lesions and disease-associated pain symptoms. METHODS: Thirty two peritoneal endometriotic lesions from patients with endometriosis (16 cases with pain and 16 cases without pain) and matched with 20 peritoneal tissues from patients with uterine leiomyoma without endometriosis were stained immunohistochemically for PGP9.5-immunoactive nerve fibers. RESULTS: The positive rate and density of PGP9.5-immunoreactive nerve fibers in peritoneal endometriotic leision were 62% (10/16) and (3.8+/-1.7)/mm2 in endometriosis patients with pain, which were significantly higher than 19% (3/16) and (1.7+/-0.5)/mm2 in endometriosis patients without pain (P<0.05) and 25% (5/20) and (1.3+/-0.6)/mm2 in peritoneal tissues in women without endometriosis (P<0.05). However, no differences were found between endometriosis patients without pain and women without endometriosis (P>0.05). Moreover, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions in endometriosis patients with pain was positively correlated with the severity of pain (r=0.855, P<0.05). In addition, the density of PGP9.5-immunoreactive nerve fibers in peritoneal lesions was statistically higher in endometriosis patients with chronic pelvic pain and (or) dysmenorrhea than those in endometriosis patients with other type of pain (P<0.05), which was not associated with active lesion, site and staging (P>0.05). CONCLUSION: It suggested that PGP9.5-immunoreactive nerve fibers might confer the mechanism of pelvic pain with endometriosis.

[Clinical study on active rheumatoid arthritis treated with simiao xiaobi decoction].

OBJECTIVE: To observe the clinical efficacy and safety of Simiao Xiaobi Decoction (SXD) in treating active rheumatoid arthritis (RA) of humid pyretic toxic Bi-Zheng (HPTB) syndrome type. METHODS: One hundred and twenty RA patients were randomly assigned to 2 groups, 60 in the treatment group receiving SXD, and 60 in the control group receiving methotrexate, all were treated for 12 weeks. Clinical efficacy in patients was evaluated, referring to the criteria recommended by European League Against Rheumatoism (EULAR), in terms of effective rate, main symptoms, signs, scoring on symptom/sign by Chinese medicine scale and DAS28, physical and chemical indices, long-term outcome of patients and the average therapeutic effect initiating time. Meantime, the adverse reaction was recorded. RESULTS: The study was completed in 103 patients, 52 in the treated group and 51 in the control group. According to a per-protocol analysis, the effective rate was better in the treatment group than in the control group with marked difference in terms of Chinese and Western medicine respectively (92.3% vs 70.6% and 86.5% vs 62.7%, P<0.05). Superiorities in the treatment group were also seen in the improvements of main symptoms and signs, symptom/sign scores, DAS28 scores, and long-term outcome. Moreover, the average therapeutic effect initiating time was shorter (5.31 +/- 0.36 weeks vs 8.28 +/- 0.45 weeks), while the incidence of adverse reaction was less in the treatment group than in the control group (6.7% vs 43.3%, P<0.05). CONCLUSION: SXD can improve the joint symptoms and general condition of RA patients of HPTB type with shorter initiating time and less adverse reaction.

Identification of glia maturation factor beta as an independent prognostic predictor for serous ovarian cancer.

Serous ovarian carcinoma (SOC) is the most common subtype of epithelial ovarian cancer which remains the leading cause of death from gynaecologic malignancy. Further knowledge of the proteins involved in serous ovarian cancer may lead to new treatment targets, new markers for early detection or prognosis prediction. In this study, we applied proteomic techniques to analyse the protein expression profiles of SOC and normal ovarian epithelium tissues. Totally 54 aberrantly expressed proteins were identified using 2-DE combined with MALDI-TOF/TOF. Six of these proteins were validated by western blot. Corresponding gene expression analysis of these proteins was also performed using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Additionally, we analysed glia maturation factor beta (GMFB) protein expression by immunohistochemistry in 246 patients with various degrees of ovarian epithelial lesions. GMFB expression in SOC was found to be significantly enhanced than that in normal epithelium, benign serous adenoma and borderline serous adenoma tissues, and was positively correlated with FIGO stage (P=0.012). High GMFB expression was associated with poor disease-free survival (P=0.010) and overall survival (P=0.003), while multivariate analysis revealed GMFB to be an independent prognostic factor for disease-free survival (P=0.026) and overall survival (P=0.006) in patients with SOC. We therefore propose that proteins identified here may be involved in the development or progression of SOC, and GMFB can be considered as a prognostic predictor for SOC patients.

Phosphatase of regenerating liver-3: a novel and promising marker in human endometriosis.

OBJECTIVE: To investigate the expression of phosphatase of regenerating liver-3 (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship with endometriosis. DESIGN: A clinical retrospective and molecular study. SETTING: Department of obstetrics, gynecology, and reproductive medicine. PATIENT(S): One hundred and five women with histopathologically confirmed endometriosis, and 50 women with histopathologically assessed normal endometria. INTERVENTION(S): Immunohistochemical staining and Western blot analysis. MAIN OUTCOME MEASURE(S): Expression of PRL-3 protein. RESULT(S): As shown by the immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and membrane. The cells that tested positive for PRL-3 were detected in endometriotic tissues that did not occur in eutopic and normal endometria. Statistical analysis indicated that the expression of PRL-3 was closely associated with the clinical stages and recurrence of endometriosis. CONCLUSION(S): Expression of PRL-3 is related to the clinical stages and recurrence of endometriosis, which provides use with a novel marker and promising target in the treatment of human endometriosis.