Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic ß-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic ß-cells and subsequent insulin secretion in T2DM.

Case report: A case study of neoadjuvant immunochemotherapy for locally advanced esophageal squamous carcinoma.

In locally advanced esophageal cancer, the controversy over the two traditional treatment modalities, neoadjuvant radiotherapy and neoadjuvant chemotherapy, has been unending and also challenged by the addition of neoadjuvant immunotherapy. Neoadjuvant immunotherapy has led to an increasing diversity of neoadjuvant combination treatment modalities, among which neoadjuvant immunochemotherapy has emerged, with current clinical studies initially demonstrating its efficacy and safety. We report a case of a patient with locally advanced esophageal cancer who underwent two cycles of neoadjuvant immunochemotherapy and successful surgery and achieved a pathological complete response (pCR). A 73-year-old elderly female patient presented with progressive dysphagia for more than 1 month with an Eastern Cooperative Oncology Group (ECOG) score of 1. After completing gastroscopy + pathological biopsy, chest enhanced CT, barium esophageal meal, PET-CT, and other related examinations, the clinical diagnosis was thoracic segmental esophageal poorly differentiated squamous carcinoma cT2N2M0 stage III. After a multidisciplinary discussion of the comprehensive treatment plan, two cycles of neoadjuvant therapy were given on February 16, 2023, and March 9, 2023, and the treatment plan was as follows: cisplatin 30 mg d1-3 + albumin paclitaxel 200 mg d1 and 100 mg d8 + sintilimab 200 mg d4, q3w. After the neoadjuvant therapy, the patient underwent an imaging examination. The chest enhanced CT suggested that the lesion range was significantly reduced compared with the previous scan, and mediastinal lymph nodes were partially reduced. Then, thoracoscopic radical esophageal cancer surgery was performed on April 23, 2023. pCR was achieved by pathological evaluation, and the postoperative diagnosis was thoracic segmental esophageal hypofractionated squamous carcinoma ypT0N0M0. Two cycles of adjuvant immunochemotherapy were performed after surgery on May 30, 2023, and June 21, 2023, and the regimen was as follows: cisplatin 30 mg d1-3 + albumin paclitaxel 200 mg d1 and 100 mg d8 + sindilizumab 200 mg d4, q3w. As of the latest review on March 20, 2024, the patient was not seen to have any significant postoperative complications and remains in a state of complete response (CR). Neoadjuvant immunochemotherapy has positive significance for the treatment of patients with locally advanced esophageal cancer. Whether neoadjuvant immunochemotherapy can replace neoadjuvant synchronous radiotherapy is a future direction of research, which needs to be further verified by more reliable clinical trials.

Evaluation safety and efficacy of immune checkpoint blockers (ICB) and radiotherapy combination versus ICB in non-small cell lung cancer patients with recurrence or metastasis: A systematic review and meta-analysis.

BACKGROUND: Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non-small cell lung cancer (NSCLC) patients. However, meta-analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta-analysis of previous clinical data will be presented in this article. METHODS: A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single-arm studies were analyzed using Stata 14.0. RESULTS: 10 comparative studies and 15 arms of combination therapy were included for this meta-analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression-free survival (PFS) of ICB (I-square value (I2 ) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09-1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00-1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72-0.92, I2 = 34.5%, OR 0.80, and 95% CI 0.71-0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr-AEs (I2 = 0.00%, OR 1.05, 95% CI 0.91-1.22, I2 = 0.00%, OR 1.46, 95% CI 0.90-2.37, respectively). Subgroup analyses based on single-arm studies showed that applications of SRS/SBRT, PD-1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p < 0.05). CONCLUSION: RT can significantly improve ORR, DCR, OS, and PFS of ICB in patients with recurrent or metastatic NSCLC without increasing toxicity. PD-1 inhibitor following SRS/SBRT could be the best option to maximally benefit the patients.

Perfusion preparation of the rat bladder decellularized scaffold.

Introduction: Bladder reconstruction is a huge challenge in the field of urology. In recent years, perfusion methods have brought promising results in the field of tissue engineering. We prepared bladder decellularized scaffolds by improved perfusion, which may be suitable for bladder reconstruction. Methods: We prepared decellularized scaffolds of rat bladder by perfusion of SDS (0.5% sodium dodecyl sulfate), SDS-SDC (0.5% sodium dodecyl sulfate +0.5% sodium deoxycholate). Histological characteristics of bladder decellularized scaffolds were assessed by Hematoxylin and eosin, Masson, and DAPI staining. Moreover, we also prepared a murine bladder transplantation model to evaluate the regenerative potential of scaffolds. Results: Hematoxylin and eosin, Masson, and DAPI staining indicated almost no cellular component residues in the SDS-SDC group. Histological analysis (hematoxylin and eosin staining, Masson staining), CD31 and F4/80 staining analysis, one month after implantation, revealed that the decellularized scaffolds had regenerative characteristics, and the SDS-SDC scaffold had better regenerative properties than the SDS scaffold. Conclusions: We successfully prepared the decellularized scaffold for the rat bladder by perfusion. Our results showed that the SDS-SDC scaffold had better decellularization efficiency and reconstruction ability than the SDS scaffold, which provides a new perspective on bladder reconstruction materials.

Early Changes of Serum Interleukin 14α Levels Predicts the Response to Anti-PD-1 Therapy in Cancer.

Background: Programmed cell death-1 (PD-1) blockade has been shown to confer clinical benefit in cancer patients. Here, we assessed the level of serum interleukin 14α (IL14α) in patients receiving anti-PD-1 treatment. Methods: This prospective study recruited 30 patients with advanced solid cancer who received pembrolizumab treatment in Northern Jiangsu People's Hospital between April 2016 and June 2018. The western blot analysis was used to assess the expression level of serum IL14α in patients at baseline and after 2 cycles of treatment. Interleukin 14α was performed using the unpaired 2-tailed Student test. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and compared by the log-rank test. Results: The early change of IL14α after 2 cycles of anti-PD-1 therapy was calculated as delta IL14α % change = (IL14α level after 2 cycles - IL14α level before treatment)/IL14α level before treatment × 100%. Receiver operating characteristic (ROC) was analyzed to get a cutoff point of delta IL14α % change as 2.46% (sensitivity = 85.71%, specificity = 62.5%; area under the ROC curve [AUC] = 0.7277, P = .034). Using this cutoff to subgroup the patients, an improved objective response rate was observed in patients with a delta IL14α change higher than 2.46% (P = .0072). A delta IL14α change over 2.46% was associated with a superior PFS (P = .0039). Conclusions: Early changes of serum IL14α levels may be a promising biomarker to predict outcomes in patients with solid cancer following anti-PD-1 treatment.

[Foodborne diseases occurred in 2003--report of the National Foodborne Diseases Surveillance System, China].

OBJECTIVE: To study the foodborne disease outbreaks in the areas covered by National Foodborne Disease Surveillance System. METHODS: Total 13 provinces were included in the surveillance system, and the foodborne disease data in 2003 was collected. RESULTS: A total of 802 outbreaks of foodborne disease were reported. These outbreaks caused a reported 17462 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (46.4%) and the largest percentage of cases (60.4%). Vibrio parahaemolyticus (40.1%) accounted for the largest number of outbreaks and cases. Chemical agents caused 24.1% of outbreaks and 13.9% of cases. CONCLUSION: More work needs to be done to improve the foodborne disease surveillance system.

[Study on national active monitoring for food borne pathogens and antimicrobial resistance in China 2001].

OBJECTIVE: To survey food borne pathogens and antimicrobial resistance in China. METHODS: A total of 4034 samples of foods (raw meats, raw milk, cooked meats, ice cream, yoghurt, aquatic product and vegetable) were examined for the presence of Escherichia coli O157:H7 Salmonella spp and Listeria monocytogens by national active foodborne pathogens surveillance system. The samples were obtained from 11 provinces in 2001. RESULTS: Approximate 5.50% of the all samples yielded 3 pathogenes, whereas Escherichia coli O157:H7 (0.82%), Salmonella servoars (3.32%) and Listeria monocytogens (1.29%). The most heavy contamination by three food borne pathogens are in raw meat (12.96%). Top seven serotype of the 137 Salmonella isolates are S. derby, S. agona, S. enteritidis, S. reading, S. anatum. S. muenster, S. typhimurium. CONCLUSION: Serotypes and antibiotic resistance patterns of Salmonella isolates are different in 11 provinces. E. coli O157:H7 strains that are isolated from raw meat and cooked meat have VT2, eae, Hly genes. Salmonella and E. coli strains of multidrug resistance were isolated and identified.

[Survey on the cadmium levels in fish, crustaceans and bivalve mollusks in China of 2002].

A survey on the cadmium content of fresh water, marine fish bivalve mollusks and crustaceans in China was carried out by the National Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention in 2002. The fish from fresh water (n = 193), marine (n = 367), crustaceans (n = 318) and bivalve mollusks (n = 512) were collected from 14 provinces and cities and analyzed by AAS. It was found that the samples with mean concentration between 0.06-0.53 mg/kg. However, some of samples were up to 8 mg/kg, indicating that the cadmium content of some fishes exceeded the maximum level of national standards.

[Study on food contaminants monitoring in China during 2000-2001].

The contamination levels of 10 main kinds of foodstuffs in 11 provinces and cities were monitored by the national food contamination monitoring system from 2000-2001. About 45 thousand data were obtained in strict quality control. The data indicated that the contamination level of lead was increased in 10 years in meat, eggs, milk-based products especially in preserved eggs, but the contamination levels of arsenic, cadmium and hydrargyrum were not serious by adopting the national standards. Organochlorine pesticides residues (666, DDT) maintained downtrend and organophosphorus pesticides residues met the national associated criteria except methyl parathion in cereals.

[Study on the safe edible of puffer fish resources].

In order to utilize the puffer fish resources furthest and to develop traditional diet culture, a project on the safe eating of puffer fish resources was conducted. The results showed that the distributing of teterodotoxin(TTX) in puffer body was not in uniformity. Owing that the content of TTX changes in different seasons and bodies, different methods were selected to crank out the delicious globefish food. The number of globefish food consumer has reached the amount to 121239 person-time since 1998. The technological process on teterodotoxin was proved reliable by mice bioassay and feeding trial in human.

[Study on the toxicological effect of chloropropanols on rats].

Toxicological effect of 3-chloro-1,2-propanediol on rats were studied to provide scientific basis for assessing the effect of Chloropropanols on human health. 170 SD rats were divided randomly into 8 groups and the dose of 0, 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0 mg/kg 3-chloro-1,2-propanediol were given to rats for 90 days by gavages per day, respectively. The weight and food efficiency, hematology and clinical chemistry, NAG, GGT and total protein in urine, sperm number, sperm survive rate and sperm aberration rate, the LDH and LDH-X activity in testis, rate of organ/weight and histopathological analysis were measured. The results showed that different dose of 3-chloro-1,2-propanediol did not has adverse effect on body weight, food efficiency, Hb, red cell, white cell, serum AST, ALT, creatine, ALP, LDH, total protein and albumin, urine GGT and total protein, LDH activity in testis. At the dose of 4.0, 8.0 and 16.0 mg/kg group, the activity of NAG in urine and the rate of kidney/weight was significantly increased compared with negative control groups; the pathological changes in kidney were observed in the same groups, and the sperm number was also significantly decreased. At the dose of 8.0 and 16.0 mg/kg group, sperm survive rate and the X-LDH activity were significantly decreased and pathological changes were also observed in testis and caudal epididymis. It was concluded that the activity of NAG in urine and sperm number is the sensitive biological effective marker. Because urine is a kind of convenient available biological material, NAG activity in urine is a good biological effective marker for assessing effect of Chloropropanols on health. If the NAG activity can be used as sensitive marker for assessment on human health need to be tested further in human study.