[Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus].

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) µg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) µg/ml] and complication group 2 [30.42 (12.53, 47.26) µg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

Strengthening exercise and motor control among football players with ankle sprain: A scoping review.

INTRODUCTION: The ankles and feet of footballers are the most commonly affected areas by acute and chronic injuries, especially sprains. The durability of changes in motor control for the sprained injury strongly suggests that central motor commands have been reorganized and restructured involving the sensorimotor system. Indirectly, providing strength training improves muscular strength and benefits cardiometabolic health, coordination, sensorimotor, and motor performance. Thus, this study aimed to identify the effects of strengthening exercises on motor control among footballers with sprained ankles. MATERIALS AND METHODS: This scoping review selected studies published from January 2002 to November 2022. The articles were searched through PubMed Central, BMJ Journal, Science Direct, and Scopus using "motor control", "ankle sprain" and "strengthening exercise" as the keywords. After finding the articles, the information extracted included author, year of publication, country, objective, type of study, and motor control analysis summary. The literature search strategy used Preferred Reporting Items for Systematic Review and a meta-analysis (PRISMA) where studies that are related to strengthening exercise and motor control were selected. RESULTS: From the initial search, 50 articles were found. After processing, only ten articles were further reviewed. The findings demonstrated strengthening exercises provide changes in neurophysiological parameters with motor performance, improved motor control, strength, balance, pain, and functional movement in footballers with sprained ankles. CONCLUSION: This review suggests the application of strengthening exercise interventions not only improves motor control, but strength, balance, pain, and functional performance among footballers with sprained ankles.

Nurse-led renal cell carcinoma clinic: a single center review.

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

The primary prevention of pancreatic fistula using a vascularised rectus abdominis muscle flap - A porcine model.

Background: A pancreatic fistula is one of the most devastating complications following a Whipple's procedure. Fistula rates remain high despite various modifications to surgical techniques. We propose the use of a vascularised muscle flap in the primary prevention of pancreatic fistulas. Method: A distal pancreatectomy was performed on 5 pigs in our porcine model. A pancreaticojejunal (PJ) anastomotic leak was simulated. The pigs were divided into treatment (4 pigs) and control groups (1 pig). A left pedicled rectus abdominis flap was wrapped around the PJ anastomosis for the treatment group and omitted for the control group. Serum and drain amylase levels were recorded. The PJ-rectus abdominis flap complex was evaluated histologically. Results: There was no biochemical evidence of anastomotic leak in the treatment group. The drain-serum amylase ratio was less than 1.5 in the treatment group (p=0.006). Microscopically, the muscle adjacent to the anastomotic leak showed mild necrotic changes with an affected muscle depth of less than 10%. Conclusion: The vascularised rectus abdominis muscle is a durable flap to withstand proteolytic pancreatic enzymes. It is able to provide a water-tight seal around the PJ anastomosis and mitigate intraperitoneal haemorrhage and infection caused by erosion from the pancreatic fistula.

Variation in mortality following hip fracture across the Asia Pacific region: Systematic review and proportional meta-analysis.

OBJECTIVE: To determine country/region-specific mortality (in-hospital, 30-day and 1-year) following hip fracture across the Asia Pacific region. METHODS: Five databases MEDLINE, PUBMED, EMBASE, Web of Science and the Cochrane Library were searched to identify studies that reported mortality following hospitalisation for low-trauma hip fracture in adults aged ≥50 years with data from 2010 to 30 September 2021. There were no restrictions on study design or language. Pooled mortality estimates for countries/regions with ≥2 studies were calculated using random-effects models. RESULTS: In total 244 studies were included in the meta-analysis. 123 studies (1,382,810 patients, 13 countries/regions) reported in-hospital mortality which ranged from 1.4 % in Japan [95 %CI 1.2-1.7], Singapore [95 %CI 1.0-1.6], China [95 %CI 0.8-2.3] and Hong Kong SAR [95 %CI 0.8-2.6] to 5.5 % [95 %CI 4.1-7.2] in New Zealand. 92 studies (628,450 patients, 13 countries/regions) reported 30-day mortality which ranged from 1.2 % in Japan [95 %CI 0.9-1.5] and Thailand [95 %CI 0.7-2.0] to 7.4 % [95 %CI 7.0-7.8] in Australia. 142 studies (1,139,752 patients, 14 countries/regions) reported 1-year mortality which ranged from 10.8 % [95 %CI 9.6-12.1] in Singapore to 23.3 % [95 %CI 22.3-24.5] in Australia and 23.8 % in New Zealand. CONCLUSION: There is substantial variation in mortality across the Asia Pacific region. Short-term mortality rates in Asian countries, notably Japan and Singapore, are up to four-fold lower than for Australia and New Zealand. This difference, although less marked, is sustained at 1-year with a two-fold lower mortality rate in Asia. This meta-analysis is the first to delineate these differences, further studies are required to understand the reasons for this variation.

C-terminally phosphorylated p27 activates self-renewal driver genes to program cancer stem cell expansion, mammary hyperplasia and cancer.

In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.

Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma.

BACKGROUND: The major histocompatibility complex type II is downregulated in glioblastoma (GB) due to the silencing of the major transcriptional regulator class II transactivator (CIITA). We investigated the pro-immunogenic potential of CIITA overexpression in mouse and human GB. METHODS: The intracerebral growth of wildtype GL261-WT cells was assessed following contralateral injection of GL261-CIITA cells or flank injections with GL261-WT or GL261-CIITA cells. Splenocytes obtained from mice implanted intracerebrally with GL261-WT, GL261-CIITA cells or phosphate buffered saline (PBS) were transferred to other mice and subsequently implanted intracerebrally with GL261-WT. Human GB cells and (syngeneic) GB-infiltrating immune cells were isolated from surgical samples and co-cultured with GB cells expressing CIITA or not, followed by RT-qPCR assessment of the expression of key immune regulators. RESULTS: Intracerebral vaccination of GL261-CIITA significantly reduced the subsequent growth of GL261-WT cells implanted contralaterally. Vaccination with GL261-WT or -CIITA subcutaneously, however, equivalently retarded the intracerebral growth of GL261 cells. Adoptive cell transfer experiments showed a similar antitumor potential of lymphocytes harvested from mice implanted intracerebrally with GL261-WT or -CIITA. Human GB-infiltrating myeloid cells and lymphocytes were not activated when cultured with CIITA-expressing GB cells. Tumor-infiltrating NK cells remained mostly inactivated when in co-culture with GB cells, regardless of CIITA. CONCLUSION: these results question the therapeutic potential of CIITA-mediated immunotherapy in glioblastoma.