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BACKGROUND: ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. METHODS: Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. RESULTS: Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. CONCLUSION: It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

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To explore the effect and underlying molecular mechanism of long non-coding RNA (lncRNA)-H19 on ovarian cancer (OC) cells, a total of 41 cases of OC and adjacent normal tissues were collected. H19 and microRNA (miR)-140 expressions in OC tissues and cells were detected using quantitative real-time polymerase chain reaction (qRT-RCR). The correlation between H19 expression and prognosis of OC patient was analyzed. siRNA (si)-H19 and si-negative control (NC) were transfected into OC cells. Cell proliferation was checked by cell counting kit-8 assay and colony formation assay, and cell migration and invasion were analyzed via Transwell assay. The targeted binding relationship between H19 and miR-140 was predicted and verified, miR-140 downstream gene was predicted and Wnt1 was screened out. The impact of in-miR-140 on the si-H19-induced decreased OC cell proliferation and migration was evaluated. H19 expression was upregulated in OC tissues and cells, and its overexpression was associated with a poor prognosis of OC. si-H19 remarkably reduced OC cell proliferation and migration. H19 upregulated Wnt1 expression through targeting miR-140 in OC cells. Altogether, miR-140 was notably downregulated in OC, and in-miR-140 partially inhibited the si-H19-induced decrease of OC cell proliferation and migration. H19 competitively bound to miR-140 to upregulate Wnt1, thereby promoting OC cell proliferation and migration.

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Cervical microbiota composition is associated with cervical HPV infection and CIN severity. Previous studies only assessed the total association between cervical microbiota and HPV infections or CINs, and yet no study reported the direct and indirect associations between cervical microbiota and CINs mediated by HPV infection, respectively. The aim of this study was to investigate the direct and indirect associations between microbiotas and CIN severity. Cervical microbiota of 126 women with CIN 1- (normal cytology and CIN 1) and 40 with CIN 2+ (CIN 2 and CIN 3) were analyzed using Illumina sequencing based on the 16S rRNA gene. HPV was detected using a highly sensitive PCR primer set (SPF1/GP6+). Indirect effects of Pseudomonas stutzeri, Bacteroides fragilis, Lactobacillus delbrueckii, Atopobium vaginae, and Streptococcus agalactiae mediated by HPV infection on CIN status were observed. The directions of the direct and the indirect associations between CIN status and Ps. stutzeri were opposite. The directions of the direct and the indirect associations between CIN status and A. vaginae were the same. B. fragilis, L. delbrueckii, and S. agalactiae only had indirect association with CIN status. In summary, our study provided suggestive evidence that some microbial populations could have direct or indirect effects mediated by affecting HPV infection on CIN progression. Besides HPV infection, microbial community composition possibly plays a role in cervical carcinogenesis.

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Human papillomavirus (HPV) types 16, 18 and 58 are ranked the top three high-risk HPV types for cervical intraepithelial neoplasia (CIN) and invasive carcinoma. We aimed to evaluate the diversity of HPV16, HPV18, and HPV58 genetic variants by HPV capture technology combined with next generation sequencing. 295, 73, and 148 variations were observed in 51 HPV16, 7 HPV18, and 11 HPV58 genomes, respectively. HPV16 isolates were predominantly of the A variant lineage, and sublineage A4 (Asian) was the most common. However, there were no significant differences in the distribution of HPV16 A1-3 and A4 variants between CIN1-, CIN2/3, and cervical cancer groups. The 7 HPV18 genomes were assigned to the A3/A4 and A1 sublineages. Of the 11 HPV58 genomes, the most predominant variant sublineages were A2, followed by A1 and B2. The majority of HPV16/18 samples containing contiguous genomic deletions were found to harbor HPV integration. Some T-cell epitope sequences in HPV16 E6 and E7 showed considerable divergence from the prototype NC_001526, suggesting their importance in immunotherapy of HPV-associated carcinomas. In conclusion, sequence diversity and phylogenies of HPV16, 18, and 58 provide the basis for future studies of discrete viral evolution, epidemiology, pathogenicity, and the differences in response to vaccines.

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HPV integration plays an important role in cervical carcinogenesis. HPV genotypes and the exact integration sites were investigated using HPV capture technology combined with next generation sequencing in 166 women. Three, one and six integration sites were verified in 7 HPV-positive 'normal cervical epithelium', 6 HPV-positive CIN2 and 15 HPV-positive CIN 3 samples, respectively. Of the 10 integrations, one and nine were involved with HPV33 and HPV16, respectively. Our study accurately evaluated HPV integration level in CINs and normal cervical tissues using high-throughput viral integration detection method providing basic evidence for HPV integration-driven cervical carcinogenesis.

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OBJECTIVE: The aim of this study was to compare the efficacy of low molecular weight heparin (LMWH) combined with graduated compression stockings (GCS) with GCS alone as prophylactic measures for venous thromboembolism (VTE) in post-operative patients with gynecologic cancer. METHODS: Patients diagnosed with gynecologic cancer undergoing primary major surgery between 2010 and 2011 in our institute were randomized to receive LMWH+GCS or GCS as VTE prophylaxis post-operatively. RESULTS: Altogether 247 patients were enrolled. The incidence of VTE in patients treated with LMWH + GCS was significantly lower than that in patients using GCS alone (0.8% Vs. 8.1%, P = 0.01). There were no severe bleeding complications in the patients with prophylactic use of LMWH and the occurrence rate of wound dehiscence was comparable between the two groups (P > 0.05). Multivariable logistic regression analysis revealed that age over 60 years (P = 0.015) , duration of operation over 3 hours (P = 0.04) and without prophylactic use of LMWH (P = 0.02) were independent risk factors for VTE. CONCLUSIONS: Dual prophylaxis with LMWH and GCS should be recommended for gynecologic cancer patients undergoing major surgery for its better efficacy than GCS. Prophylactic use of LMWH is safe and convenient. Patients with older age and prolonged operation time are at highest risk of developing VTE post-operatively.

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OBJECTIVE: To study the characteristics of HE4 expression in patients with epithelial ovarian cancer, and to evaluate whether the pre-treatment serum human epididymis protein 4 (HE4) level is an independent prognostic factor in the patients. METHODS: The clinicopathological characteristics and follow-up information of 112 patients with epithelial ovarian cancer were collected. The pre-treatment serum samples from these patients were measured for HE4 and CA125 expression. Serum HE4 levels were tested by a quantitative enzyme-linked immunosorbent assay (ELISA) and serum CA125 levels were tested using Elecsys kit. The correlation of HE4 and CA125 expressions with overall survival and other clinical data were analyzed. RESULTS: The median level of pre-treatment serum HE4 and CA125 in the 112 patients was 415.5 pmol/L (26.9-3253.5 pmol/L) and 699 U/ml (5-17 694 U/ml), respectively. Serum HE4 level before treatment was significantly related to grade (r = 0.21, P = 0.037), stage (r = 0.40, P = 0.001), amount of ascites (r = 0.39, P = 0.001), serum CA125 level (r = 0.53, P = 0.001) and residual disease after surgery (r = 0.22, P = 0.027), but was not related to menopausal stauts (P = 0.115), revealed by Spearman correlation test.However, logistic multivariate regression analysis indicated that residual tumor size was not significantly correlated with pre-operative HE4 level (P = 0.259). The mean survival of the 112 patients was 53 months. Log rank test indicated that the overall survival in patients with higher HE4 level was significantly shorter than those with lower HE4 level (P = 0.001). Multivariate Cox proportional hazard model analysis revealed that the pre-treatment serum HE4 level and residual tumor size were independent prognostic factors for overall survival (P = 0.044 and P = 0.048). CONCLUSION: Pre-treatment serum HE4 level is a valuable prognostic factor for the overall survival in patients with epithelial ovarian cancer.

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BACKGROUND: The female genital tract is an important bacterial habitat of the human body, and vaginal microbiota plays a crucial role in vaginal health. The alteration of vaginal microbiota affects millions of women annually, and is associated with numerous adverse health outcomes, including human papillomavirus (HPV) infection. However, previous studies have primarily focused on the association between bacterial vaginosis and HPV infection. Little is known about the composition of vaginal microbial communities involved in HPV acquisition. The present study was performed to investigate whether HPV infection was associated with the diversity and composition of vaginal microbiota. METHODS: A total of 70 healthy women (32 HPV-negative and 38 HPV-positive) with normal cervical cytology were enrolled in this study. Culture-independent polymerase chain reaction-denaturing gradient gel electrophoresis was used to measure the diversity and composition of vaginal microbiota of all subjects. RESULTS: We found significantly greater biological diversity in the vaginal microbiota of HPV-positive women (p < 0.001). Lactobacillus, including L. gallinarum, L. iners and L. gasseri, was the predominant genus and was detected in all women. No significant difference between HPV-positive and HPV-negative women was found for the frequency of detection of L. gallinarum (p = 0.775) or L. iners (p = 0.717), but L. gasseri was found at a significantly higher frequency in HPV-positive women (p = 0.005). Gardnerella vaginalis was also found at a significantly higher frequency in HPV-positive women (p = 0.031). Dendrograms revealed that vaginal microbiota from the two groups had different profiles. CONCLUSIONS: Our study is the first systematic evaluation of an association between vaginal microbiota and HPV infection, and we have demonstrated that compared with HPV-negative women, the bacterial diversity of HPV-positive women is more complex and the composition of vaginal microbiota is different.

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OBJECTIVE: To investigate the relationship between lymph vascular space invasion (LVSI) and various clinicopathologic factors in early-stage cervical squamous carcinoma; to explore the expression of P53, COX2 and CD44V6 in early stage squamous carcinoma of cervix and its relationship with prognosis. METHODS: A case-controlled study was conducted to compare LVSI positive group (n = 44) in early stage squamous carcinoma of cervix with LVSI negative group (n = 44). Expression of P53, COX2 and CD44V6 were evaluated by immunohistochemical method to analyze the relationship between LVSI, P53, COX2 and CD44V6 and various clinicopathologic factors and to investigate their prognostic influences. RESULTS: LVSI positive was correlated with lymph node metastasis and deep stromal invasion. The 5-year disease-free survival was 68.9% in LVSI positive group versus 94.7% in LVSI negative group (P < 0.01). And the 5-year overall survival was 70.2% in LVSI positive group versus 100% in LVSI negative group (P < 0.01) with a significant difference. COX2 was correlated with clinical stage and tumor volume while there was no correlation with P53, CD44V6 and clinical factors. The overall survival of P53, COX2 and CD44V6 positive cases were significantly shorter than that of negative ones, especially in constant positive cases of 3 markers (disease-free survival 60.0 months shorter than constant negative cases with an overall survival of 91.3 months, but there was no significant difference). CONCLUSION: LVSI is correlated with lymph node metastasis and deep stromal invasion in the early-stage squamous carcinoma of cervix while it is negatively correlated with disease-free survival and overall survival. COX2 is correlated with clinical stage and tumor volume. Furthermore P53 and CD44V6 are not correlated with clinical factors. The overall survival of P53, COX2 and CD44V6 positive cases are significantly shorter than that of negative ones.

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