Surgical outcomes and survival for T4 gastric cancer extending to the transverse colon.

BACKGROUND: For the treatment of locally advanced (T4) gastric cancer, extended multi-organ resection remains controversial. This study aimed to evaluate the surgical outcomes and survival of patients with T4 gastric cancer extending to the transverse colon. METHODS: A total of 2,652 gastric cancer patients underwent surgery between December 2011 and December 2015. Data from 40 of these patients who underwent curative resection for T4 gastric cancer extending to the transverse colon were obtained. Patient characteristics, related complications, long-term survival, and prognostic factors for T4 gastric cancer were analyzed. RESULTS: Postoperative morbidity occurred in 5 (12.5%) patients. All of the patients were cured with conservative treatment. No procedure-related mortality occurred. The 1-, 3-, and 5-year overall survival (OS) rates were 75.0%, 49.2%, and 36.9%, respectively, with a median survival time of 24 months. Univariate analysis revealed tumor size (P=0.049), advanced T stage (P=0.013), and lymph node metastasis (P=0.006) to be poor prognostic factors of OS. Advanced T stage and lymph node metastasis were identified by multivariate analysis as being independent prognostic factors. Further, it was observed that lymph node metastasis grade was associated with poorer OS. CONCLUSIONS: Patients with T4 gastric cancer extending to the transverse colon might benefit from curative resection with acceptable morbidity and mortality.

USP28 contributes to the proliferation and metastasis of gastric cancer.

USP28, a member of the deubiquitinating enzymes family, plays a vital role in the physiological process of cell proliferation, differentiation and apoptosis, DNA repair, immune response, and stress response. USP28 has been reported to be overexpressed in bladder cancer, colon cancer, breast carcinomas, and so on. Nevertheless, the role of USP28 in gastric cancer has not yet been investigated. In our study, we examined the USP28 expression in 87 paired samples of gastric cancer and normal gastric tissues. We found that USP28 was overexpressed in gastric cancer compared with normal gastric tissues (P < 0.01), and its overexpression was related to the degree of differentiation and metastases. Inhibiting USP28 expression in vitro suppressed the proliferation and invasion of gastric cancer cells by downregulating lysine specific demethylase 1. On the basis of our data, it can be concluded that USP28 may be a novel therapeutic target for gastric cancer.

Involvement of MrgprC in Electroacupuncture Analgesia for Attenuating CFA-Induced Thermal Hyperalgesia by Suppressing the TRPV1 Pathway.

Mas-related G-protein-coupled receptor C (MrgprC) plays an important role in modulating chronic inflammatory pain. Electroacupuncture (EA) has a satisfactory analgesic effect on chronic pain. This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain. Chronic inflammatory pain was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the left hind paw. EA (2/100 Hz) stimulation was administered. MrgprC siRNAs were intrathecally administered to inhibit MrgprC expression, and bovine adrenal medulla 8-22 (BAM8-22) was used to activate MrgprC. The mechanical allodynia was decreased by EA significantly since day 3. The piled analgesic effect of EA was partially blocked by 6 intrathecal administrations of MrgprC siRNA. Both EA and BAM8-22 could downregulate the expression of TRPV1 and PKC in both the DRG and the SCDH. Both EA and BAM8-22 could also decrease the TRPV1 translocation and p-TRPV1 level in both the DRG and the SCDH. The effects of EA on PKCε, TRPV1 translocation, and p-TRPV1 in both the DRG and the SCDH were reversed by MrgprC siRNA. The results indicated that MrgprC played crucial roles in chronic pain modulation and was involved in EA analgesia partially through the regulation of TRPV1 function at the DRG and SCDH levels.

[Analgesic Effect and Mechanism of Electroacupuncture on Rats with Chronic Inflammatory Pain].

OBJECTIVE: To observe analgesic effect of electroacupuncture ( EA) on rats with chronic inflammatory pain and its regulatory mechanism on ispilateral dorsal root ganglion (DRG) and spinal dorsal horn (SDH) Mas-related G protein-coupled C receptor (MrgprC). METHODS: Totally 40 healthy male SD rats were divided into 4 groups according to random number table, i.e., the normal (N) group, the model (M) group, the acupuncture (Acu) group, the EA group, 10 rats in each group. The model of chronic inflammatory pain was established by subcutaneous injecting 0. 1 mL complete Freund's adjuvant (CFA) into right hind paw. Paw withdrawal thresholds (PWTs) were measured before modeling, at day 1, 3, 5, 7, and after CFA injection, respectively. Expression levels of MrgprC in ispilateral DRG and SDH were detected by Western blot. The content of bovine adrenal medulla 22 (BAM22) in SDH was detected by immunohistochemical assay. RESULTS: Compared with N group at each time point, PWTs significantly decreased in M group (P <0. 01). Compared with M group, PWTs significantly increased at day 5 of EA and after EA in EA group (P < 0.05, P < 0.01). Compared with Acu group at each time point, post-EA PWTs significantly increased in the EA group (P < 0.05). Compared with N group, expression of MrgprC in ispilateral DRG and ratio of BAM22 positive cells in ispilateral SDH increased in M group (P < 0.01). Compared with M group, expression of MrgprC in ispilateral DRG and ratio of BAM22 positive cells in ispilateral SDH increased in the EA group (P < 0.05). CONCLUSION: EA had favorable analgesic effect on chronic inflammatory pain induced by CFA, and its mechanism might be possibly associated with up-regulating MrgprC expression in ispilateral DRG and BAM22 content in ispilateral SDH.

Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin.

Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through αB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.

[The clinical application of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy].

OBJECTIVE: To evaluate the effect of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy. METHODS: From October 2002 to October 2012, 52 patients with rectal cancer received neoadjuvant radiotherapy and developed presacral venous plexus hemorrhage during rectectomy, included 36 male and 26 female cases. Their age were 36-65 years. The hemostasis time and blood loss were analyzed. RESULTS: All 52 patients achieved R0 resection. Of which 13 patients achieved suture hemostasis within 15 minutes, whereas 22 patients unsuccessfully treated within 15 minutes received compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx. The median blood loss was (196 ± 44)ml and hospitalization time was (15.2 ± 1.7)days in this group. Additionally, 7 patients achieved suture hemostasis within 20 minutes except 4 patients who received compression hemostasis, with a median blood loss of (1016 ± 86)ml and hospitalization time of (21.7 ± 6.3)days. Other 6 patients achieved suture hemostasis within 30 minutes except 3 patients who received compression hemostasis, with a median blood loss of (2508 ± 73)ml and the hospitalization time was (28.8 ± 3.3)days. There was statistically significant difference of bleeding (F = 4289.562) and hospitalization time (F = 50.121) in 3 groups of patients (P = 0.000). CONCLUSIONS: Once intraoperative presacral venous plexus hemorrhage can't be stopped timely, compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx is an effective alternative for the patients with rectal cancer who received neoadjuvant radiotherapy.