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Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

The quantitative measurement of finger-joint range of motion plays an important role in assessing the level of hand disability and intervening in the treatment of patients. An industrial monocular-vision-based knuckle-joint-activity-measurement system is proposed with short measurement time and the simultaneous measurement of multiple joints. In terms of hardware, the system can adjust the light-irradiation angle and the light-irradiation intensity of the marker by actively adjusting the height of the light source to enhance the difference between the marker and the background and reduce the difficulty of segmenting the target marker and the background. In terms of algorithms, a combination of multiple-vision algorithms is used to compare the image-threshold segmentation and Hough outer- and inner linear detection as the knuckle-activity-range detection method of the system. To verify the accuracy of the visual-detection method, nine healthy volunteers were recruited for experimental validation, and the experimental results showed that the average angular deviation in the flexion/extension of the knuckle was 0.43° at the minimum and 0.59° at the maximum, and the average angular deviation in the adduction/abduction of the knuckle was 0.30° at the minimum and 0.81° at the maximum, which were all less than 1°. In the multi-angle velocimetry experiment, the time taken by the system was much less than that taken by the conventional method.

Objective This study aimed to investigate the effects of catecholamine administration on ICU patients with acute gastrointestinal injury undergoing invasive mechanical ventilation (IMV). Results During the study period, 425 patients with a median age of 60 years (interquartile range, 48–70), including 290 males (68%), received IMV during their ICU stay. AGI occurred in 287 patients, with an incidence rate of 67.5%. The most common symptom of AGI was gastric retention (50.52%). Multivariate regression analysis results showed the following as risk factors for AGI: the administration of catecholamine drugs (OR: 2.881, 95% CI 1.525 to 5.441, P  = 0.001), Acute Physiology and Chronic Health Evaluation II score (OR: 1.119, 95% CI 1.055 to 1.186, P  < 0.001), Nutritional Risk Screening 2002 score (OR: 1.416, 95% CI 1.154 to 1.737, P  = 0.001), duration of IMV (OR: 1.142, 95% CI 1.108 to 1.207, P  < 0.001), and primary disease involving the respiratory system (OR: 2.097, 95% CI 1.179 to 3.731, P  = 0.012).

To evaluate the diagnostic performance of ultrasound-derived fat fraction (UDFF) and clinical prediction models in assessing hepatic steatosis grades in MASLD patients, with liver biopsy as reference standard.A total of 85 obese patients who were found to have fatty liver by B-mode ultrasound and underwent UDFF measurement, with liver biopsy available, were enrolled. The diagnostic performance of UDFF, clinical prediction models including fatty liver index (FLI), hepatic steatosis index (HSI), ZheJiang University index (ZJU index) and lipid accumulation product (LAP) for hepatic steatosis was assessed. The areas under receiver operating characteristics curves (AUROCs) were utilized to determine the diagnostic efficacy. DeLong test was used to compare the diagnostic performance of different noninvasive methods for hepatic steatosis. The UDFF values of S1, S2 and S3 groups were 17.53 ± 7.49%, 25.00 ± 5.41% and 27.58 ± 6.55%, respectively (P < 0.001). UDFF values were significantly positively correlated with histologic steatosis grades (r = 0.531, P < 0.001). In the ≥ S2 group, the AUROC of UDFF was higher than that of FLI and LAP (P < 0.05), but not significantly different from that of HSI and ZJU index (P > 0.05). In the ≥ S3 group, the AUROC of UDFF was higher than that of FLI, ZJU index and LAP (P < 0.05), but not significantly different from that of HSI (P > 0.05). The UDFF proves effective in assessing hepatic steatosis in patients with MASLD, and its diagnostic efficacy exceeded that of FLI and LAP, but there was no significant difference with HSI, ZJU index in the ≥ S2 group, and with HSI in the ≥ S3 group.

Background: In recent years, laparoscopic sleeve gastrectomy (LSG) has become the main surgical procedure for weight loss, and most clinical studies have focused on the postoperative complications and treatment of metabolic syndrome after LSG. However, it is not clear whether there is a difference in the postoperative weight loss effect between patients with central and noncentral obesity after LSG. Purpose: To investigate the effect of LSG on weight loss in patients with central obesity and relationship between preoperative waist–hip ratio and weight loss effect. Methods: We conducted a retrospective study comprising 360 patients who underwent LSG at the Qianfoshan Hospital, Jinan, Shandong Province, China, between 2019 and 2024. Based on the preoperative waist‐to‐hip ratio (WHR), the participants were divided into central and noncentral obesity groups, and various quantitative and preoperative biochemical indices were measured. Most patients were followed up for at least 6 months. Results: There were significant differences in weight loss outcomes between women in the central and noncentral obesity groups in the first and third months after surgery; however, no significant differences were observed in the sixth and twelfth months. No significant differences were observed in weight loss outcomes between men in the central and noncentral obesity groups. There were significant differences in the development of central obesity between the two sexes and between those with and without type 2 diabetes. There were significant differences in body mass index (BMI) and white blood cell counts between women in the central and noncentral obesity groups, with patients with central obesity having higher BMI values and white blood cell counts before surgery. There were significant differences in the platelet count (PLT), gamma‐glutamyl transferase (GGT), glycosylated hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) levels between men in the central and noncentral obesity groups, with patients with central obesity having lower PLT, higher GGT, HbA1c, and FPG levels. There was a significant correlation between WHR and early weight loss outcomes after surgery.

BackgroundBariatric surgeries have been shown to be effective in reversing damaged pulmonary function in individuals suffering from obesity and type 2 diabetes mellitus, whereas its underlying mechanisms remain largely unknown.MethodsSleeve gastrectomy (SG) was performed on obese and diabetic Wistar rats, and their pulmonary function and lung tissues were compared to sham-operated (SH) obese and diabetic rats, and age-matched healthy controls (C) to explore the improvements in microstructures and expression of surfactant protein (SP)-A and -C at postoperative 4th, 8th, and 12th week.ResultApart from the profound metabolic changes and improvement in pulmonary function, lung volume was restored along with an improved diffusion capacity noted by thinned capillary basement membrane and decreased harmonic mean length of diffusion barrier in SG rats. The digital slices of light microscope showed the general changes brought on by the SG, including normalized basic structures, ameliorated inflammatory status, as well as reduced lipid deposition, where the hydroxyproline (HYP), triglyceride (TG) assays, and electron microscope further suggested that the improvement in alveolar structures lies in reduced collagen fibers, lipids and septal tissues, increased capillary blood, and normalized alveolar type 2 (AT2) cells. Besides, disrupted SP-A and SP-C expression were also normalized after SG.ConclusionThe improvement of lung function after SG is related to the ameliorated alveolar structures, and surface protein expression induced by weight loss and improved glucose metabolism.

PurposeOxidative stress and inflammation are important pathogenic mediators in diabetes-related organ damage. Accumulating evidence suggests that immunodeficiency in diabetes is associated with diabetes-induced spleen damage. Sleeve gastrectomy (SG) has been proved to improve diabetes and its multiple associated complications. However, the ameliorative role of SG against spleen damage in diabetes has not been investigated.Materials and MethodsAnimal model of diabetic obese rats induced by high-fat diet (HFD) combined with streptozotocin (STZ) was treated with sham operation, caloric restriction, and SG. Metabolic parameters were measured, and the morphological and histopathological changes, status of oxidative stress, and levels of inflammatory factors were evaluated.ResultsSG reduced body weight and improved glucose tolerance and insulin sensitivity in diabetic obese rats. SG significantly reversed splenic atrophy and alleviated abnormalities of white and red pulp. Additionally, SG also reversed the increased splenocyte apoptosis (P < 0.001). Meanwhile, indicators of oxidative stress including reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and protein carbonylation were reduced, and the activity and expression of antioxidant enzymes including SOD and CAT were improved after SG. The mRNA expression of inflammatory factors in SG groups such as TNF-α (P < 0.001), IL-6 (P < 0.001), MCP-1 (P < 0.01), and ICAM-1 (P < 0.001) was also significantly reduced.ConclusionSG ameliorates diabetes-related splenic injury by restoring the balance between oxidative stress process and antioxidant defense systems as well as reducing inflammation in the spleen. These findings indicate that SG is an appropriate therapeutic strategy for diabetes-related spleen damage.

PurposeDiabetic nephropathy (DN) is the leading cause of end-stage renal disease, and sleeve gastrectomy (SG) is considered to be an effective strategy to improve pre-existing DN. However, the mechanism remains unknown.Materials and MethodsAnimal model of DN was induced by high-fat diet (HFD) and streptozotocin (STZ). SG or sham surgery was performed and rats were sacrificed at 4, 8, and 12 weeks after surgery. The basic parameters (blood glucose, body weight, kidney weight), indicators of renal function including serum creatinine (Scr), blood urea nitrogen (BUN), urine microalbumin, urine creatinine (Ucr), microalbumin creatinine ratio (UACR), ultrastructural changes of glomerulus, and the expression of nephrin gene and protein in glomerular podocytes were compared among groups.ResultsBlood glucose and body weight of SG rats were significantly lower than those of the sham-operated rats, and renal function of SG groups were also significantly improved within the postoperative period of 12 weeks. The results of periodic acid-Schiff staining (PAS) and transmission electron microscopy (TEM) showed that glomerular hypertrophy and accumulation of extracellular matrix proteins were significantly alleviated after SG, and the thickness of basement membrane and the fusion or effacement of foot processes were also significantly improved. The mRNA and protein expression of nephrin in SG groups was significantly higher than that in the sham group.ConclusionThese results suggest that SG attenuates DN by upregulating the expression of nephrin and improving the ultrastructure of glomerular filtration membrane. This study indicates that SG can be used as an available therapeutic intervention for DN.

The impact of metabolic dysfunction-associated steatohepatitis (MASH) on post-operative weight loss outcomes remains unclear. This study aims to investigate the effects of preoperative concomitant MASH on weight loss outcomes and metabolic improvements following laparoscopic sleeve gastrectomy (LSG). A retrospective analysis was performed on the clinical data of 226 patients with obesity who underwent LSG and concurrent intraoperative liver biopsy. Univariate analysis, multivariate analysis, and general linear models were employed to evaluate differences in the dynamic trajectories of post-operative weight loss between the groups. Additionally, Kaplan-Meier survival analysis was utilized to compare the time required to achieve successful weight loss outcomes. Preoperative body mass index (BMI) and the presence of MASH were independent negative predictors of percentage excess weight loss (%EWL) and percentage total weight loss (%TWL) ( < 0.01). The post-operative %EWL difference between the two groups reached up to 28.9%. Compared with non-MASH patients, patients with preoperative MASH had a significantly lower cumulative incidence of achieving 80% EWL within 1 year post-operatively (χ = 35.17, < 0.05, HR = 2.058). Preoperative MASH is significantly associated with lower post-operative weight loss. Compared to non-MASH patients, patients with MASH experienced a delay in achieving satisfactory weight loss outcomes within the first year after surgery, and this was significantly associated with a lower post-operative %EWL.

Pharmacological treatment and mechanisms of bariatric surgery for diabetic comorbidities. Continuously rising trends in diabetes render this disease spectrum an epidemic proportion worldwide. As the disease progresses, the pathological effects of diabetes may impair the normal function of several vital organs, eventually leading to increase the risk of other diabetic comorbidities with advanced fibrosis such as non-alcoholic fatty liver disease, diabetic cardiomyopathy, and diabetic kidney disease. Currently, lifestyle changes and drug therapies of hypoglycemic and lipid-lowering are effective in improving multi-organ function, but therapeutic efficacy is difficult to maintain due to poor compliance and drug reactions. Bariatric surgery, including sleeve gastrectomy and Roux-en-Y gastric bypass surgery, has shown better results in terms of prognosis for diabetes through long-term follow-up. Moreover, bariatric surgery has significant long-term benefits on the function of the heart, liver, kidneys, and other organs through mechanisms associated with reversal of tissue fibrosis. The aim of this review is to describe the impact of type 2 diabetes mellitus on hepatic, cardiac and renal fibrosis and to summarize the potential mechanisms by which bariatric surgery improves multiple organ function, particularly reversal of fibrosis.