Roux-en-Y Gastric Bypass Surgery for the Prevention of Long-term Renal Function Damage in Type 2 Diabetes: A Clinical Study.

Objective: Type 2 diabetes mellitus (T2DM) is strongly associated with obesity, a significant risk factor for the occurrence and progression of chronic kidney disease. In recent years, weight loss surgery has become an important treatment option for diabetes. This study examined whether Roux-en-Y gastric bypass surgery, a new metabolic bariatric surgery approach, can effectively reduce the risk of long-term renal impairment in individuals with type 2 diabetes. Methods: In a cohort study, 60 individuals suffering from both obesity and type 2 diabetes were stratified and randomly divided into 2 groups based on gender and weight. The control group (30 cases) received internal medicine treatment; the observation group (30 cases) received Roux-en-Y gastric bypass surgery. The study compared the changes in glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI before and at 6, 12, and 18 months after treatment. Kidney function-related indicators such as urinary protein excretion, microalbuminuria, and creatinine clearance were also compared. Results: There were no significant differences in the above indicators between the 2 groups before treatment (P > .05). After 6, 12, and 18 months of treatment, the levels of glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI were significantly decreased compared to before treatment (P < .05). Urinary protein excretion and microalbuminuria decreased, while creatinine clearance increased after 6, 12, and 18 months of surgery (P < .05). The differences in indicators between the 2 groups at each point after surgery were statistically significant (P < .05). Conclusion: Roux-en-Y gastric bypass surgery was more effective than medical treatment in treating type 2 diabetes and mitigating long-term kidney function damage. These findings confirm the clinical utility of Roux-en-Y gastric bypass surgery in these conditions, indicating its potential for generalization and reference.

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

MiR-499a-5p promotes 5-FU resistance and the cell proliferation and migration through activating PI3K/Akt signaling by targeting PTEN in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) can be considered a representative cancer type of the human body. As demonstrated by some studies, microRNA (miR)-499 is dysregulated in various cancer types including PC, for which chemotherapy involving 5-fluorouracil (5-FU) has long been considered the first-line therapy. However, there are complex and comprehensive mechanisms related to 5-FU, which have not been fully elucidated. This study thus aimed to examine the molecular mechanisms of 5-FU resistance through miR-499a-5p in PC. METHODS: The expression of miR-499a-5p in PC was measured using quantitative polymerase chain reaction (PCR). MiR-499a-5p was examined in-vivo for its effects on the malignant phenotypes of PC cells. RESULTS: The results of the present study demonstrated miR-499a-5p to be upregulated in PC and 5-FU resistant PC tissues. According to in vitro assays in PC cells (PANC1/FR), miR-499a-5p was found to affect adenosine triphosphate (ATP) binding cassette subfamily B member 1 (P-gp), ATP binding cassette subfamily C member 1 (MRP1), and ATP binding cassette subfamily G member 2 (BCRP), thereby facilitating 5-FU resistance in PC cells. Functions assays indicated that suppressed miR-499a-5p expression inhibited the proliferation and migration of cells but facilitated apoptosis in the PC cell line; by contrast, miR-499a-5p overexpression triggered the inverse phenotypic changes of cells. Concerning the mechanisms involved, miR-499a-5p increased PI3K/Akt signaling by targeting phosphatase and tensin homolog (PTEN). CONCLUSIONS: Taken together, these findings demonstrate that miR-499a-5p can be potentially applied to PC therapy.

[LONG-TERM EFFECTS ON LOWER LIMB FUNCTION AFTER S1 NERVE ROOT TRANSECTION AS DYNAMIC SOURCE].

OBJECTIVE: To evaluate the long-term effects on the lower limb function after S nerve root transection as dynamic source. METHODS: Between January 2007 and December 2011, 47 patients with atonic bladder dysfunction underwent S1 nerve root transposition to reconstrut the bladder function. There were 43 males and 4 females, with an average age of 40.7 years (range, 22-66 years). The locations were L1 in 33 cases, L2 in 5 cases, L3 in 2 cases, T12, L, in 3 cases, L1, L2 in 1 case, L1, L3in 1 case, L1, L4 in 1 case, and L2, L3 in 1 case. The anastomosis of the S2 or S3 nerve root to S1 nerve root was performed from 4 to 24 months (mean, 8 months) after spinal cord injury. The strength of ande plantar flexion was grade 4 in 5 cases and grade 5 in 42 cases before operation. RESULTS: The strength of ande plantar flexion had no obvious decrease (grade 4 or 5) in 31 cases, reduced 0.5 grade in 16 cases at 2 days after operation. All the patients were followed up 3-8 years (mean, 5.1 years). At 2 weeks after operation, the nerve electrophysiological examination showed neurogenic damage at operated side in most patients, including reduced amplitude tibial nerve in 19 cases, for common peroneal nerve in 13 cases, and for tibial nerve and common peroneal nerve in 9 cases. Except the velocity of common peroneal nerve (t = -1.881, P = 0.093), the other electric physiological indexes showed significant differences between at pre- and post-operation (P < 0.05). The muscle strength basically recovered to preoperative level (grade 4 or 5) during follow-up, and there was no impairment of lower limb function. CONCLUSION: S1 transection has no significant effects on lower limb function, so S1 nerve can be used as dynamic nerve for nerve function reconstruction.

[Experimental study on long-term prevention effect of chitosan electrospun membrane on cerebrospinal fluid leakage].

OBJECTIVE: To study the long-term prevention effect of self-developed chitosan electrospun membrane on cerebrospinal fluid leakage. METHODS: Twenty-five healthy adult New Zealand rabbits were selected to prepare the bilateral dural defect (0.8 cem x 0.8 cm in size) via midline incision of head. Defect of the right was repaired with chitosan electrospun membrane as the experimental group; defect of the left was not repaired as the control group. At 2-16 weeks after operation, one rabbit was sacrificed for the general observation of inflammatory response surrounding bone window and absorption of chitosan electrospun membrane; at 3 and 6 weeks after operation, 5 rabbits were sacrificed for sampling to observe histological change and collagen expression by_HE and Masson staining, and to measure the expressions of epidermal growth factor receptor (EGFR) and basic fibroblast growth factor (bFGF) by immunohistochemical staining. RESULTS: No inflammatory reaction of swelling, exudation, and sppuration appeared in the skin and subcutaneous tissue after operation in 2 groups. There was no adhesion around the chitosan electrospun membrane, and new fiber membrane formed under the chitosan electrospun membrane in the experimental group; no cerebrospinal fluid leakage happened; the chitosan electrospun membrane was gradually degraded with time, and was completely absorbed at 16 weeks. There was uneven scar around the dural detect in control group. Histological observation showed less inflammatory cell infiltration in the experimental group, showing significant difference in the number of inflammatory cells compared with control group at 3, 6 weeks (P < 0.05); capillary, granulation tissue and collagen fiber massively proliferated; collagen fiber arranged in line, and there was a clear borderline between chitosan electrospurn membrane and adjacent collagen fiber. The immunohistochemical staining showed that there were high expressions of bFGF and EGFR in the experimental group, and low expressions of bFGF and EGFR in the control group. CONCLUSION: Chitosan electrospun membrane for dural defect of rabbit can effectively reconstruct the dura, and it has exact long-term prevention effect on cerebrospinal fluid leakage.