Combination therapy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent leiomyomatosis peritonealis disseminata with endometriosis: A case report.

Background: Leiomyomatosis peritonealis disseminata (LPD) is a non-metastatic, homologous, multicentric benign disorder characterized by small leiomyomas scattered over the peritoneum and omentum. It is a rare and benign disease with invasive potential. LPD mainly attacks women of childbearing age but has also been reported in post-menopausal women, men, and young children. Non-specific clinical and imaging findings of LPD lead to difficult diagnoses and treatment. Case presentation: This study reports the case of a patient with recurrent LPD with endometriosis after multiple myomectomies and hysterectomy, who presented recurrent abdominal pain with progressive exacerbation. Imaging examinations showed irregular shadows in the pelvic cavity and multiple nodular changes in the peritoneum, which were considered malignant lesions. A solid mass sized 10 cm × 9 cm × 10 cm in the inferior pelvis and nodules scattered over the surface of pelvic and abdominal organs and the peritoneum were detected during the surgery. The patient was treated with cytoreductive surgery (CRS), peritonectomy, ovarian ablation, and hyperthermic intraperitoneal chemotherapy (HIPEC). The surgery was challenging, and the intraoperative bleeding reached 900 ml. However, the patient recovered well and achieved a tumor-free survival of 13 months. Conclusions: It was concluded that a combination of CRS, ovarectomy, and HIPEC might be one of the therapeutic strategies for recurrent LPD.

High salt intake combined with hypertension elevated the risk of primary liver cancer: a prospective cohort study.

Background: Hypertension and high-salt intake may act synergistically to increase the risk of primary liver cancer (PLC). We prospectively examined the joint effect of hypertension and salt intake on the risk of PLC incidence. Methods: A total of 92,978 participants were included in the final analyses. The study population was divided into 4 groups according to the presence or absence of hypertension and salt intake. Cox proportional hazards regression models were used to evaluate the association of hypertension and/or high-salt intake with the risk of incident cancers. The CAUSALMED procedure was used to perform the mediation analyses. Results: During a median follow-up of 12.69 years, a total of 418 incident cancer cases were identified. Hypertension was a risk factor for PLC in women but not in men. High salt intake was associated with an elevated risk of PLC in men. A significant interaction between salt intake and hypertension was found for the risk of PLC (P for interaction=0.045). Compared with Group 1 (hypertension-, high salt intake-), participants in Group 2 (hypertension-, high salt intake+) and Group 4 (hypertension+, high salt intake+) were associated with an elevated risk of PLC with the corresponding multivariate HRs (95%CIs) of 1.73(0.96,3.10) and 1.96(1.09,3.53) respectively. No significant mediation effect was found for the association between hypertension, salt intake and PLC risk. Conclusions: The combination of high salt intake and hypertension could significantly increase the risk of PLC. It may be reasonable to recommend a low-salt intake to prevent and control the prevalence of PLC and hypertension. Trial registration: Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August, 2011-Retrospectively registered, https://www.chictr.org.cn/showprojen.aspx?proj=8050.

The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis.

BACKGROUND: As a primarily N6-methyladenosine methyltransferase, methyltransferase 3 (METTL3) plays a crucial role in nonalcoholic fatty liver disease. However, its regulatory mechanism in steatosis remains unknown. METHODS: Alpha mouse liver 12 (AML12) cells were induced by free fatty acids (FFA). Triglycerides, lipid droplet assay, and Oil Red O staining were performed to evaluate steatosis. The expression of METTL3 and cytochrome P450 family 4 subfamily f polypeptide 40 (CYP4F40) was measured using Western blotting, real-time quantitative polymerase chain reaction, and dual-luciferase reporter assay. Triglycerides, total cholesterol, almandine aminotransferase, and aspartate aminotransferase were assayed after cinnamaldehyde treatment. Transcriptomics and metabolomics were performed to determine how METTL3 and cinnamaldehyde regulate steatosis. RESULTS: METTL3 protein level was reduced in FFA-induced steatosis in AML12 cells, and METTL3 knockdown aggravated the steatosis. Cinnamaldehyde alleviated steatosis by increasing METTL3 expression. A combined transcriptomics and metabolomics analysis revealed that METTL3 knockdown reduced CYP4F40 expression and reduced the level of capric acid, gamma-linolenic acid, arachidonic acid, and docosapentaenoic acid. Cinnamaldehyde promoted CYP4F40 expression by increasing METTL3 and increased the levels of capric acid, gamma-linolenic acid, arachidonic acid, and docosapentaenoic acid. Finally, the beneficial effects of cinnamaldehyde on steatosis were reversed after METTL3 knockdown. CONCLUSIONS: METTL3 knockdown aggravated steatosis in AML12 cells through CYP4F40-mediated fatty acid metabolism, and cinnamaldehyde alleviated steatosis via the METTL3-CYP4F40 pathway.

METTL3 promotes colorectal carcinoma progression by regulating the m6A-CRB3-Hippo axis.

BACKGROUND: Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. METHODS: Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. RESULTS: M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain-containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. CONCLUSIONS: M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway.

Case Report: Stage IIIc primary malignant mixed Müllerian tumor of the fallopian tube: A case of 5-year disease-free survival after cytoreductive surgery combined with peritoneal resection and adjuvant chemotherapy with paclitaxel plus carboplatin.

Malignant mixed Müllerian tumor (MMMT) of the fallopian tube is rare and has a poor prognosis. For the patient with fallopian tube MMMT, complete resection of the tumor invading the viscera and the peritoneum is a prerequisite for long-term survival. We report a case of stage IIIc MMMT of the fallopian tube treated by cytoreductive surgery (CRS), peritoneal resection, and adjuvant chemotherapy (paclitaxel plus carboplatin), with 5-year tumor-free survival. Postoperative chemotherapy combining platinum and paclitaxel is the most potent adjuvant therapy.

Jiangzhi Granule attenuates non-alcoholic steatohepatitis by suppressing TNF/NFκB signaling pathway-a study based on network pharmacology.

Jiangzhi Granule is a commonly used traditional Chinese medicine for treating non-alcoholic fatty liver disease. However, its key ingredients and underlying mechanisms for attenuating nonalcoholic steatohepatitis (NASH) remain unclear. To address this issue, UPLC-TOF-MS based chemical profiling, network pharmacology and animal experimental validation were employed. First, a total of 56 main ingredients of Jiangzhi Granule and 38 ingredients in the blood and liver (after oral administration) were identified. Then, 170 potential targets of the absorbed ingredients and 50 targets of NASH were identified, and 10 overlapped genes were identified as candidate targets of Jiangzhi Granule for NASH treatment. A Jiangzhi Granule-ingredients-targets-disease network was constructed using Cytoscape software, which included eight main ingredients (such as emodin, resveratrol and quercetin) and 10 candidate targets (such as TNF, IL6 and CCL2). Functional enrichment indicated that the candidate targets were enriched in multiple pathways (such as the TNF signaling pathway). Furthermore, a NASH mice model was constructed and intervened with Jiangzhi Granule. The results revealed that Jiangzhi Granule could ameliorate NASH characteristics, such as histopathological changes and liver cholesterol level. Meanwhile, Jiangzhi Granule significantly decreased the mRNA and protein expression of TNFα in NASH mice liver, suppressed NFκB activation, and inhibited the expression of macrophage activation marker F4/80 and M1-type polarization marker CD11b/CD11c. ELISA assay indicated that Jiangzhi Granule reduced pro-inflammatory cytokines (including TNFα, IL-1ß and IL-6) in the liver. Collectively, our results suggested that Jiangzhi Granule could attenuate NASH by suppressing TNF/NFκB signaling mediated macrophage M1-type polarization.

CircRNA_0084927 promotes colorectal cancer progression by regulating miRNA-20b-3p/glutathione S-transferase mu 5 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. The 5-year survival rate of patients with early-stage CRC could reach 90%, but it is very low in patients with advanced-stage CRC. Recent studies have shown that circular RNAs play important roles in regulating the migration and invasion of CRC cells. AIM: To elucidate the role of circRNA_0084927 (circ_0084927) in the migration and invasion of CRC cells and its underlying mechanism. METHODS: Clinical tissue samples and cells were collected, and the expression of circ_0084927 was detected by quantitative polymerase chain reaction (qPCR). The diagnostic performance of circ_0084927 was assessed by receiver operating characteristic curve analysis. The role of circ_0084927 in CRC cell proliferation, migration, and invasion was determined using cell counting kit-8 assay, wound healing assay, and transwell assay, respectively. The regulatory relationship among circ_0084927, miRNA-20b-3p (miR-20b-3p), and glutathione S-transferase mu 5 (GSTM5) was identified using databases, luciferase reporter assay, qPCR, and Western blot analysis. AKT-mTOR signaling was also verified after circ_0084927 knockdown or miR-20b-3p mimic treatment. RESULTS: The expression of circ_0084927 was significantly increased in CRC tissues and cells, and it was higher in advanced-stage CRC compared with early-stage CRC. The area under the curve (AUC) of circ_0084927 was 0.806 [95% confidence interval (CI): 0.683-0.896]. In addition, the AUC was 0.874 (95%CI: 0.738-0.956) in patients with advanced-stage CRC and 0.713 (95%CI: 0.555-0.840) in those with early-stage CRC. Knockdown of circ_0084927 inhibited the migration and invasion of HCT116 cells. Moreover, circ_0084927 was found to act as a sponge of miR-20b-3p. MiR-20b-3p activation reduced the circ_0084927 level, whereas miR-20b-3p inhibition increased the circ_0084927 level. But the effect was not found after circ_0084927 mutation. In addition, miR-20b-3p expression in CRC patients was also reduced and negatively correlated with circ_0084927 expression. The function of circ_0084927 in HCT116 cells with circ_0084927 knockdown was rescued by miR-20b-3p. Moreover, GSTM5 expression was significantly decreased after overexpressing miR-20b-3p or inhibiting circ_0084927, but its expression was rescued when circ_0084927 and miR-20b-3p were both inhibited. Finally, AKT-mTOR signaling was markedly regulated by circ_0084927 and miR-20b-3p. CONCLUSION: The expression of circ_0084927 is significantly increased in CRC and higher in advanced-stage CRC than in early-stage CRC. Moreover, circ_0084927 potentially regulates CRC cell migration and invasion via the miR-20b-3p/GSTM5/ AKT/mTOR pathway.

Upregulated RACK1 attenuates gastric cancer cell growth and epithelial-mesenchymal transition via suppressing Wnt/ß-catenin signaling.

Purpose: As there have been few studies on the effects of the receptor for activated C kinase 1 (RACK1) on gastric cancer (GC), we aimed to explore such effects and the mechanism that may be involved. Patients and methods: Normal gastric epithelial cells and six GC cell lines were used to detect the mRNA expression of RACK1. Overexpressing RACK1 was transfected in HGC27 and MGC803 cells. The effects of overexpressing RACK1 on cell viability, migration, and invasion were determined by cell counting kit-8, wound scratch, and Transwell assay, respectively. The expressions of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling related genes were detected using quantitative real-time PCR or Western blot. Wnt pathway agonist LiCl was added into RACK1 overexpressing GC cells, and then cell viability, migration, and invasion were also detected. Results: RACK1 was downregulated in GC cell lines. Under the circumstance that overexpressing RACK1 was successfully transfected in the two lowest RACK1-expressing GC cells, significant inhibition of cell viability, migration, and invasion, promotion to the mRNA and protein expression of E-cadherin, as well as a decrease in the N-cadherin and Snail expressions could be observed. Overexpressing RACK1 also enhanced the protein level of phosphorylation-ß-catenin/ß-catenin and attenuated c-Jun protein expression. Additionally, LiCl could partially reverse the inhibitory effects of cell viability, migration and invasion by overexpressing RACK. Conclusion: We found RACK1 possibly inhibited epithelial-mesenchymal transition of GC cells through limitation of the Wnt/ß-catenin pathway, thereby suppressing cell migration and invasion; RACK1 could also suppress cell growth.

Clinical Efficacy of Modified Yanghe Decoction in Ankylosing Spondylitis: A Randomized Controlled Trial.

BACKGROUND This study evaluated the effects of Modified Yanghe Decoction on pain, disease activity, and functional capacity, and its safety in subjects with ankylosing spondylitis (AS). MATERIAL AND METHODS A randomized, controlled study of subjects with AS was conducted over 8 weeks to compare the efficacy of the Modified Yanghe Decoction to celecoxib-sulfasalazine therapy. Subjects were evaluated at visit 1, and at weeks 4 and 8 of the trial. The Bath ankylosing spondylitis disease activity index (BASDAI), nocturnal back pain (NBP), total back pain (TBP), patient global disease activity (PGDA), the Bath ankylosing spondylitis functional index (BASFI), and the Bath ankylosing spondylitis metrology index (BASMI) were measured at each time point. Safety was monitored throughout the study through blood, urine, and stool samples, along with heart, liver, and kidney function tests. The ASAS 20 improvement criteria were used as efficacy criteria. RESULTS A total of 80 subjects were included. Both treatment groups were effective: 32 subjects (80%) in the Modified Yanghe Decoction group and 34 (85%) in celecoxib-sulfasalazine group met ASAS 20 improvement criteria; no statistically significant difference between groups was observed (P>0.05). Two subjects in the Modified Yanghe Decoction group reported mild diarrhea during the trial. In the celecoxib-sulfasalazine group, 8 subjects experienced upper-abdominal pain; in 3 subjects this was combined with lowered white blood cell count and in 1 subject it was combined with mild proteinuria. This represents a statistically significant difference in safety (P<0.05) between the 2 treatments. CONCLUSIONS This study demonstrates the efficacy and safety of the Modified Yanghe Decoction in AS treatment, especially for patients who have poor clinical responses, severe adverse reactions, or for patients unable to afford the standard clinical options.