Upregulation of lysine-specific demethylase 6B aggravates inflammatory pain through H3K27me3 demethylation-dependent production of TNF-α in the dorsal root ganglia and spinal dorsal horn in rats.

AIMS: Lysine-specific demethylase 6B (KDM6B) serves as a key mediator of gene transcription. It regulates expression of proinflammatory cytokines and chemokines in variety of diseases. Herein, the role and the underlying mechanisms of KDM6B in inflammatory pain were studied. METHODS: The inflammatory pain was conducted by intraplantar injection of complete Freund's adjuvant (CFA) in rats. Immunofluorescence, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR were performed to investigate the underlying mechanisms. RESULTS: CFA injection led to upregulation of KDM6B and decrease in the level of H3K27me3 in the dorsal root ganglia (DRG) and spinal dorsal horn. The mechanical allodynia and thermal hyperalgesia following CFA were alleviated by the treatment of intrathecal injection of GSK-J4, and by microinjection of AAV-EGFP-KDM6B shRNA in the sciatic nerve or in lumbar 5 dorsal horn. The increased production of tumor necrosis factor-α (TNF-α) following CFA in the DRGs and dorsal horn was inhibited by these treatments. ChIP-PCR showed that CFA-induced increased binding of nuclear factor κB with TNF-α promoter was repressed by the treatment of microinjection of AAV-EGFP-KDM6B shRNA. CONCLUSIONS: These results suggest that upregulated KDM6B via facilitating TNF-α expression in the DRG and spinal dorsal horn aggravates inflammatory pain.

Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection.

BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.

Integrative Comparison of mRNA Expression Patterns in Breast Cancers from Caucasian and Asian Americans with Implications for Precision Medicine.

Asian Americans (AS) have significantly lower incidence and mortality rates of breast cancer than Caucasian Americans (CA). Although this racial disparity has been documented, the underlying pathogenetic factors explaining it are obscure. We addressed this issue by an integrative genomics approach to compare mRNA expression between AS and CA cases of breast cancer. RNA-seq data from the Cancer Genome Atlas showed that mRNA expression revealed significant differences at gene and pathway levels. Increased susceptibility and severity in CA patients were likely the result of synergistic environmental and genetic risk factors, with arachidonic acid metabolism and PPAR signaling pathways implicated in linking environmental and genetic factors. An analysis that also added eQTL data from the Genotype-Tissue Expression Project and SNP data from the 1,000 Genomes Project identified several SNPs associated with differentially expressed genes. Overall, the associations we identified may enable a more focused study of genotypic differences that may help explain the disparity in breast cancer incidence and mortality rates in CA and AS populations and inform precision medicine. Cancer Res; 77(2); 423-33. ©2016 AACR.

Sleep quality in Chinese patients with rheumatoid arthritis: contributing factors and effects on health-related quality of life.

BACKGROUND: Poor sleep quality is common in rheumatoid arthritis (RA) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). The increasing prevalence of poor sleep in RA patients is associated with adverse demographic, clinical, and psychological characteristics. However, there are currently no known reported studies related to the effects of sleep quality on HRQoL in RA patients from China. This cross-sectional study aims to evaluate the contributors of poor sleep and the effects of sleep quality on HRQoL in Chinese RA patients. METHODS: A self-report survey was administered to 131 RA patients and 104 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. RA patients completed the Hospital Anxiety and Depression Scale for anxiety and depression, the 28-joint Disease Activity Score for disease activity, the 10 cm Visual Analog Scale for pain, the Health Assessment Questionnaire-Disability Index for functional capacity and the Short Form 36 health survey for HRQoL. Blood samples were taken to gain some biochemical indicators (e.g., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide). Independent samples t-tests, Chi square analysis, logistic regression modeling and linear regression were used to analyze these data. RESULTS: Our results found that the prevalence of poor sleep (PSQI ≥ 5) was 78.6% and the mean global score of PSQI was 7.93 (SD 3.98) in patients, which were significantly higher than the controls (18.7% and 3.88 (SD 1.89), respectively). There were significant correlations among synthetic disease-modifying antirheumatic drugs, erythrocyte sedimentation rate, pain, disease activity, functional capacity, anxiety/depression and sleep quality in RA patients. Meanwhile, logistic regression models identified disease activity and depression as predictors of poor sleep quality. Poor RA sleepers had impaired HRQoL than good RA sleepers, and sleep quality was independently and significantly associated with social function and mental components summary. CONCLUSIONS: The majority of Chinese RA patients suffered from poor sleep, which significantly impairs their HRQoL. The data suggested the need for holistic assessment and management of RA patients and the importance of objective interventions to improve their sleep quality and finally to improve their HRQoL.

[Prognostic analysis of 443 cases of stage II colorectal cancer and the value of adjuvant chemotherapy].

BACKGROUND AND OBJECTIVE: Prognosis of stage II colorectal cancer varies. Whether or not to perform adjuvant chemotherapy on patients with stage II colorectal cancer is controversial. This study was to explore the prognostic factors for the patients with stage II colorectal cancer and evaluate the effect and the necessity of adjuvant chemotherapy. METHODS: Between January 2000 and January 2005, 443 patients with stage II colorectal cancer receiving radical surgery at Sun Yat-sen University Cancer Center were retrospectively analyzed. The overall survival rate and survival curve were analyzed using the Kaplan-Meier method and the log-rank test. The univariate and multivariate prognostic analyses were performed by the Cox regression model. Patients with or without chemotherapy (Xelox/Folfox regimen) with high-risk factors were analyzed respectively. RESULTS: The median follow-up time was 59 months, and the 3-and 5-year survival rates were 88.4% and 82.5%, respectively. Univariate analysis showed that intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 were poor prognostic factors. Patients with intestinal obstruction or perforation, the number of sampled nodes < 9 achieved higher 5-year survival (80% and 86%) undergoing adjuvant chemotherapy than those receiving surgery alone (67% and 64%). CONCLUSIONS: The prognosis of colorectal cancer patients with intestinal obstruction or perforation, diabetes mellitus, inadequate surgical margin, and the number of sampled nodes < 9 are relatively poor. Adjuvant chemotherapy is recommended to patients with intestinal obstruction, perforation or sampled nodes < 9.

[Clinical analyses of 70 cases of multiple primary colorectal carcinoma].

BACKGROUND & OBJECTIVE: Multiple primary colorectal carcinoma (MPCC) is not rarely seen, but it possesses a unique biological characters. This study was to investigate the clinical characteristics, diagnosis, therapeutic principle and prognosis of MPCC. METHODS: Data of 70 MPCC patients, treated by operation from 1997 to 2003, were analyzed. Of the 70 patients, 61 had synchronous carcinoma (SC) and 9 had metachronous carcinoma (MC). RESULTS: Fifty-five patients were diagnosed by colonoscopy, barium enema or CT scan pre-operationally, while 15 were diagnosed intra-operationally due to the oversized tumor at the distal end of the colon. Thirty-three patients had colorectal carcinoma accompanying with adenoma and multiple polyps. All the patients underwent surgical resection except 3, who received short-circuit operation because of unresectable lesions. Fifty-two patients received radical resection, while 15 received palliative resection due to hepatic or peritoneal metastasis. The overall 3-and 5-year survival rates were 65.7% and 45.7%. In the patients who received radical resection, the 3-and 5-year survival rates were 78.1% and 59.3%. CONCLUSIONS: The occurrence of MPCC is largely related with adenomas and polyps. The extent of resection should be individually determined by the lesion location, range, the distance of lesions as well as the general condition of the patients. Prognosis of MPCC is relatively good. The patients accompanying with adenoma and multiple polyps should be followed up intensively.

[Preparation and in vitro evaluations of topically applied capsaicin transfersomes].

OBJECTIVE: Capsaicin transfersomes were prepared and its quality specifications were evaluated. METHOD: Capsaicin transfersomes were prepared by high shear dispersing machine and evaluated on the entrapment efficiency, drugs release rate and in vitro skin permeation. RESULT: Capsaicin transfersomes is composed of single unilamellar vesicles, with average size of 150.6 nm. Capsaicin entrapment efficiency achieved 96.7% while concentration of lecithin used was 8%. cumulative release amount of capsaicin was in direct proportion to the ethanol concentration in the medium. The in vitro rate cumulative penetration rate of capsaicin was higher in transfersomes than in cream and suspension in rats. Adomen skin cumulative penetration rate in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way,cumulative penetration rate in vitro of capsaicin transfersomes through abdomen skin epidermal membrance was significantly higher than that with derma and full skin in men. CONCLUSION: Entrapment efficiency of capsaicin transfersomes reached 96.7%, meeting the criterion of China pharmacopia( > 80%), skin penetration of capsaicin was enhanced by a capsaicin transfersomes preparation and was affected by diverse characters and levels of skin.

[Comparing the effect of adjuvant chemotherapy by portal vein infusion with intraluminal chemotherapy for colorectal cancer].

OBJECTIVE: To compare the effect of 5-fluorouracil (5-FU) portal vein infusion (PVI) for 7 days after radical resection, with intraluminal chemotherapy during operation for eliminating liver metastasis and elevating long-term prognosis in colorectal cancer. METHODS: 162 colorectal cancer patients with radical resection were divided into portal vein chemotherapy group (group A, 82 cases) and intraluminal chemotherapy group (group B, 80 cases) randomly. In group A, 5-fluorouracil were infused with 1g per day constantly for 7 days after operation through portal vein catheters, which placed into greater omental vein and fixed on the abdominal wall. In group B, intraluminal chemotherapy was given and 5-fluorouracil 0.5 g was injected into the greater omental vein during operation. RESULTS: The short-term complications and long-term effect in the two groups were compared by statistical software SPSS 8.0. Group A had more operative complications, and no statistical differences was found in hospital time and survival rate of the two groups. The 5-year survival rate is 76.7% (group A: 74.3%, group B: 79.2%), and the liver metastasis rate is 19.8%. There is no significant difference between the two group-survival curves. Multiple variable analysis suggested that Dukes' stage was the prognosis factor (P < 0.05). CONCLUSIONS: The present study demonstrated that the two chemotherapy methods play an important role in preventing liver metastasis and improving the survival rate, and the intraluminal chemotherapy would be easier and simpler. The result should be further improved by using combined chemotherapy.