Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Paenibacillus mangrovi sp. nov., a novel endophytic bacterium isolated from bark of Kandelia candel.

A endospore-forming bacterium, designated strain KQZ6P-2T, was isolated from surface-sterilized bark of the mangrove plant Kandelia candel, collected from Maowei Sea Mangrove Nature Reserve in Guangxi Zhuang Autonomous Region, China. Strain KQZ6P-2T was able to grow at NaCl concentrations in the range of 0-3 % (w/v) with optimum growth at 0-1 % (w/v) NaCl. Growth occurred at 20-42 °C (optimal growth at 30-37 °C) and pH 5.5-6.5 (optimal growth at pH 6.5). The 16S rRNA gene sequence similarity between strain KQZ6P-2T and its closest phylogenetic neighbour Paenibacillus chibensis JCM 9905T was 98.2 %. Phylogenetic analyses using 16S rRNA gene sequences showed that strain KQZ6P-2T formed a distinct lineage with Paenibacillus chibensis JCM 9905T. The draft genome of strain KQZ6P-2T was 5 937 633 bp in size and its DNA G+C content was 47.2mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values among strain KQZ6P-2T and its related species were below the cut-off levels of 95, 70 and 95.5%, respec-tively. The cell-wall peptidoglycan of strain KQZ6P-2T contained meso-diaminopimelic acid as the diagnostic diamino acid. Major cellular fatty acids were anteiso-C15:0 and C16:0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified aminophospholipids, four unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. Based on phylogenetic, phenotypic and chemotaxonomic data, strain KQZ6P-2T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus mangrovi sp. nov. is proposed. The type strain is KQZ6P-2T (=MCCC 1K07172T =JCM 34931T).

Prevalence of hyperthyroidism with hypercalcemia in Xindu district and the efficacy of vitamin D3 treatment in these patients: a randomized trial.

BACKGROUND: This trial aimed to analyze the relationship between hyperthyroidism and the morbidity rate of hypercalcemia in the Xindu district, Chengdu, Sichuan province. We observed the level of serum calcium, the bone metabolic and thyroid autoimmune-related antibodies index during vitamin D3 treatment combined with traditional antithyroid drugs (ATD). METHODS: Our research included hyperthyroid patients with a first-time diagnosis of Graves diseases (GD) combined with hypercalcemia on the basis of conventional anti-hyperthyroidism therapy, which were randomized into a vitamin D3 group (vitamin D3, 800-1,200 IU/day) and an ATD group (methimazole, 15-30 mg/day). All hyperthyroidism patients with hypercalcemia were analyzed, and changes in serum calcium (Ca2+), parathyroid hormone (PTH), thyroid function, thyroid autoimmune-related antibodies, and 25-dihydroxyvitamin D (25-OHVit D) levels during treatment of thyrotoxicosis with added vitamin D3 were explored. RESULTS: In total, 184 patients with hyperthyroidism were observed, including 36 (19.57%) patients associated with hypercalcemia, with an age of onset of (56.39±5.80) years old. Twelve (6.52%) of these 36 cases reported digestive symptoms as the first manifestation, and four (2.17%) patients presented with a hypercalcemia crisis as the first manifestation. Serum Ca2+, free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin hormone receptor antibody (TRAb) levels increased in patients with hypercalcemia. Following the addition of vitamin D3 treatment, serum Ca2+, FT3, FT4, and TRAb levels were significantly decreased relative to the ATD group, while the thyroid-stimulating hormone (TSH), PTH, and 25-OHVit D levels were normalized. CONCLUSIONS: Our study highlighted the importance of taking functional digestive disturbance into consideration in hyperthyroidism diagnosis, even in the absence of the typical symptoms. The level of thyroid related antibodies, thyroid function, and bone metabolism in hyperthyroidism patients combined with hypercalcemia could be improved by vitamin D3 adjuvant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100047870.

Abnormalities of the PRMT1-ADMA-DDAH1 metabolism axis and probucol treatment in diabetic patients and diabetic rats.

BACKGROUND: Symmetrical dimethylarginine (ADMA) endogenously inhibits nitric oxide synthase (NOS) and strongly indicates oxidant stress, whose formation primarily derived from type 1 protein arginine N-methyltransferase (PRMT1) and whose metabolism was governed by type 1 dimethylarginine dimethylaminohydrolase (DDAH1). This study aimed to evaluate participation of the PRMT1-ADMA-DDAH1 metabolism axis in the kidneys of type 2 diabetes model rats and human subjects, and the effect of probucol on this axis and renal function. METHODS: A total of 30 rats were randomly assigned to a normal group (NC, n=10), diabetic group (DM, n=10), and a diabetics under probucol treatment group (PM, n=10). Throughout 8 weeks of probucol treatment, plasma NOS, the malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and catalase (CAT) activity were evaluated by chemical colorimetric approach. ADMA concentration was evaluated with an enzyme-linked immunosorbent assay (ELISA) and analysis of expression of PRMT1 and DDAH1 in kidneys with reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blotting were performed. RESULTS: The expression of DDAH1 in the kidney, and the plasma NOS, NO, SOD, and CAT activities in diabetic group were lower, while MDA and the expression of PRMT1 and ADMA were higher in contrast to the control group. In diabetics rats receiving probucol, the expressions of DDAH1 and ADMA were downregulated, whereas that of PRMT1 was upregulated. Probucol inhibited the indexes of oxidative stress and improved the kidney function in both diabetic rats and humans. CONCLUSIONS: We found that the expression of the PRMT1-ADMA-DDAH1 axis was altered in the kidneys of diabetic rats. Moreover, results indicated that probucol therapy regulates expression at both ends of this axis, which may preserve renal function by reducing oxidant stress. Therefore, probucol may partially restore expression of the PRMT1-ADMA-DDAH1 axis in diabetic kidneys, immigrate oxidant stress, and enhance renal function.

Association of menopausal status with COVID-19 outcomes: a propensity score matching analysis.

BACKGROUND: Despite the growing number of studies on the coronavirus disease-19 (COVID-19), little is known about the association of menopausal status with COVID-19 outcomes. MATERIALS AND METHODS: In this retrospective study, we included 336 COVID-19 inpatients between February 15, 2020 and April 30, 2020 at the Taikang Tongji Hospital (Wuhan), China. Electronic medical records including patient demographics, laboratory results, and chest computed tomography (CT) images were reviewed. RESULTS: In total, 300 patients with complete clinical outcomes were included for analysis. The mean age was 65.3 years, and most patients were women (n = 167, 55.7%). Over 50% of patients presented with comorbidities, with hypertension (63.5%) being the most common comorbidity. After propensity score matching, results showed that men had significantly higher odds than premenopausal women for developing severe disease type (23.7% vs. 0%, OR 17.12, 95% CI 1.00-293.60; p = 0.003) and bilateral lung infiltration (86.1% vs. 64.7%, OR 3.39, 95% CI 1.08-10.64; p = 0.04), but not for mortality (2.0% vs. 0%, OR 0.88, 95% CI 0.04-19.12, p = 1.00). However, non-significant difference was observed among men and postmenopausal women in the percentage of severe disease type (32.7% vs. 41.7%, OR 0.68, 95% CI 0.37-1.24, p = 0.21), bilateral lung infiltration (86.1% vs. 91.7%, OR 0.56, 95% CI 0.22-1.47, p = 0.24), and mortality (2.0% vs. 6.0%, OR 0.32, 95% CI 0.06-1.69, p = 0.25). CONCLUSIONS: Men had higher disease severity than premenopausal women, while the differences disappeared between postmenopausal women and men. These findings support aggressive treatment for the poor prognosis of postmenopausal women in clinical practice.

Is jejunostomy output nutrient or waste in short bowel syndrome? Experience from six cases.

BACKGROUND AND OBJECTIVES: Certain patients who undergo proximal jejunum resection are unable to undergo primary anastomosis and require exteriorization of the proximal jejunum. These patients usually have major problems with short bowel due to the high output of the stoma. The output of a proximal jejunostomy contains abundant amounts of enzymes and electrolytes. Therefore, it is a feasible approach to re-infuse jejunostomy output to regain homeostasis. To evaluate the effects of proximal jejunostomy output reinfusion into the distal small bowel for patients with short bowel syndrome, and to determine whether reinfusion could avoid long-term parenteral nutrition (PN). METHODS AND STUDY DESIGN: PN was initiated immediately after surgery. When patients started enteral nutrition, we started the proximal jejunostomy output reinfusion protocol. Proximal jejunostomy output reinfusion was performed by the patients, and continued by them after discharge. When proximal jejunostomy output reinfusion could be performed stably, PN was stopped. RESULTS: The median length of the proximal jejunum was 20 cm and of the distal small bowel was 77.5 cm in patients who could stably receive proximal jejunostomy output reinfusion alone. Three patients did not require home PN; they only required PN during hospitalization. Four patients successfully underwent stoma takedown with intestinal anastomosis after 6-7 months without any nutritional or metabolic complications. CONCLUSION: Short bowel syndrome patients with an adequate length of small bowel and functional colon could avoid long-term PN by receiving reinfusion of proximal jejunostomy output into the distal small bowel.

Influence of preoperative peripheral parenteral nutrition with micronutrients after colorectal cancer patients.

BACKGROUND: The inflammatory reactions are stronger after surgery of malnourished preoperative patients. Many studies have shown vitamin and trace element deficiencies appear to affect the functioning of immune cells. Enteral nutrition is often inadequate for malnourished patients. Therefore, total parenteral nutrition (TPN) is considered an effective method for providing preoperative nutritional support. TPN needs a central vein catheter, and there are more risks associated with TPN. However, peripheral parenteral nutrition (PPN) often does not provide enough energy or nutrients. PURPOSE: This study investigated the inflammatory response and prognosis for patients receiving a modified form of PPN with added fat emulsion infusion, multiple vitamins (MTV), and trace elements (TE) to assess the feasibility of preoperative nutritional support. Methods. A cross-sectional design was used to compare the influence of PPN with or without adding MTV and TE on malnourished abdominal surgery patients. RESULTS: Both preoperative groups received equal calories and protein, but due to the lack of micronutrients, patients in preoperative Group B exhibited higher inflammation, lower serum albumin levels, and higher anastomotic leak rates and also required prolonged hospital stays. CONCLUSION: Malnourished patients who receive micronutrient supplementation preoperatively have lower postoperative inflammatory responses and better prognoses. PPN with added fat emulsion, MTV, and TE provides valid and effective preoperative nutritional support.

A Short Bowel (Small Intestine = 40 cm), No Ileocecal Valve, and Colonic Inertia Patient Works Well with Oral Intake Alone without Parenteral Nutrition.

We present a 50-year-old male who suffered from ischemic bowel disease, having undergone massive resection of small intestine and ileocecal valve. He had to cope with 40 cm proximal jejunum and 70 cm distal colon remaining. In the postoperative period parenteral nutrition (PN) was used immediately for nutrition support and electrolyte imbalance correction. We gave him home PN as regular recommendation for the short bowel status after discharge from hospital. This patient has tolerated regular oral intake 2 months later and did not develop significant short bowel syndrome. There were several episodes of venous access infection which troubled this patient and admitted him for treatment during home PN. Therefore, we changed home PN to cyclic tapering pattern. The patient could maintain his nutrition and hydration with oral intake alone after tapering home PN 15 months later. He has survived more than one year without PN support and still maintained 80% ideal body weight with average albumin of 3.5 ± 0.2 mg/dL. Although patient was hospitalized every two months to supplement nutrients, however, this has greatly improved the quality of life.

[The diagnostic value of serum beta-hydroxybutyrate in diabetic ketosis or diabetic ketoacidosis].

OBJECTIVE: To determine the diagnostic value of serum beta-hydroxybutyrate (betaOHB) in diabetic ketosis or diabetic ketoacidosis. METHODS: We conducted a retrospective review of clinical data, in West China Hospital from May 2011 to May 2013, of 1 209 patients with non-ketosis diabetics (DM group), 262 patients with diabetic ketosis or diabetic ketoacidosis (DK/DKA group), and 480 healthy people undergoing routine medical examinations (normal control group). Logistic regression analyses and ROC curves were performed in determining the diagnostic value of betaOHB for DK/DKA. RESULTS: The level of serum betaOHB was much higher in the DK/DKA patients than that of the participants in the DM group and normal control group (P < 0.01). The serum betaOHB turned negative earlier than urine ketone (P < 0.01) in the DK/DKA patients. The logistic regression analysis indicated that betaOHB was one of the independent risk factors for DK/DKA. The betaOHB had an area under of 0.975 in ROC curve, with 1 mmol/L [sensitivity (Sen.) 85.1%, specificity (Spe.) 95. 3%, positive predictive value (PV+) 80.36%, negative predictive value (PV-) 96.89%] as a diagnostic point for DK/DKA and 0.66 mmol/L (Sen. 95%, Spe. 89.2%, PV+ 66.41%, PV- 99.9%) as a screening point. CONCLUSION: Diabetic patients with a level or higher than 1 mmol/L serum betaOHB can accurately predict DK/DKA. Patients with a level or lower than 0.66 mmol/L serum betaOHB are unlikely to have DK/DKA.

[Study of glycated albumin cut-off point in diabetes mellitus and impaired glucose regulation].

OBJECTIVE: To investigate the cut-off point of glycated albumin (GA) in the detection of diabetes mellitus (DM) and impaired glucose regulation (IGR). METHODS: This study was conducted in 20-84 years-old adults who had risk factors of diabetes but no previously diagnosed diabetes. There were finally 392 individuals included and received the measurement of GA and HbA1c. Receiver operating characteristic curve (ROC) was plotted to determine the performance of GA. RESULTS: (1) Based on the diabetes diagnosis criteria of WHO (1999), the subjects were divided into DM group (n = 131), IGR group (n = 126), and normal glucose tolerance (NGT) group (n = 135). The GA level in the three groups tended to increase (P < 0.05). (2) Spearman correlation analysis demonstrated that GA was positively correlated with glycated haemoglobin A1c (HbA1c) (r = 0.942 1, P < 0.05), fasting plasma glucose (FPG) (r = 0.856 6, P < 0.05) and 2 h post-load plasma glucose (2-hPG) (r = 0.813 7, P < 0.05). (3) The mean levels of serum GA/HbA1c were 2.58 +/- 0.37, 2.44 +/- 0.37 and 2.17 +/- 0.25 for DM, IGR and NGT respectively. (4) The optimal cut-off points for detecting diabetes were 16.6% in GA [area under the carve (AUC) = 0.888], producing the sensitivity of 71.8% and the specificity of 87.4%. CONCLUSION: GA as a single screening test shows adequate to detect newly diagnosed DM, and the optimal GA cut-off point was 16.6% in this study.

Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris.

OBJECTIVES: To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different severity of acne vulgaris and optimize the treatment regimen. METHODS: A self-controlled multicenter clinical trial was carried out in 15 centers throughout China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation. The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120 J/cm(2). Clinical assessment was conducted before and after every treatment up to 8 weeks. RESULTS: The effective rate overall and of grade II, III and IV are 82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises significantly proportionally to the severity of acne (P<0.01). No significant differences are found in the efficacy between patients received 3-session and 4-session PDT treatments (P>0.05). The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment (P<0.01) and during the 8-week follow up (P<0.01 or P<0.05). Maximum efficacy is obtained at 8 weeks after the treatment completion. CONCLUSIONS: A low-dose topical ALA-PDT regimen using 5% ALA, 1h incubation and red light source of 3 treatment sessions is suggested as optimal scheme for the treatment of different severity of acne vulgaris in Chinese patients. Superior efficacy is found in severe cystic acne of grade IV with mild side effects.

[Preparation and application of oligo microarrays for hepatitis virus detection and genotyping].

OBJECTIVE: To prepare oligo microarrays for hepatitis virus detection and genotyping. METHODS: By analyzing the DNA or cDNA of HBV, HDV and 4 different genotypes of HCV with the BLAST program, a group of specific sequences for the candidate probes was specified. Array Designer 3.0 software was applied to analyze the candidates to select probes with high specificity, identical length and similar melting temperature (Tm). Altogether 16, 8 and 68 oligonucleotide probes were designed for diagnosis of HBV, HDV, and genotyping HCV. Following the synthesizing and purification, oligo probes were deposited on oligonucleotide chips as microarrays for hepatitis virus detection and genotyping. The samples were labeled by RD-PCR method. Hybridization results were analyzed to cross out those probes with low specificity and sensitivity, and those with signal to noise ratios (SNR) less than 4.0. RESULTS: Two types of gene chips were successfully developed: microarrays for HBV and HDV simultaneous detection and for HCV genotyping. CONCLUSION: Using oligo probes to construct gene chips for clinical diagnosis of hepatitis virus is a simple and effective method. It may be widely used in detecting hepatitis viruses and their genotyping in clinical settings.

[Construction and expression of HSV-2gD-Hsp70 fusion protein gene].

To construct and express Hsp70-HSV2gD fusion protein. Genes of Hsp70 and HSV-2gD were subcloned into vectors pGEX-4T-1 respectively. After confirmed by DNA sequence analysis, the recombinant plasmids pGEX-4T-HSP-gD was transformed into E. coli DH5alpha and induced to express with IPTG. The expressed protein was characterized by SDS-PAGE and Western blot after purified. BALB/c mice were immunized with fusion proteins respectively via intra-m uscular injection. The proliferation of spleen lymphocytes, the level of y-IFN in culture and anti-HSV-2gD IgG antibody in serum was detected was detected. The expressed protein was analyzed by SDS-PAGE after induced with IPTG, which showed a new band with an apparent molecular mass corresponding to the predicted size (118 kD). Western Blotting analysis demonstrates that the purified Hsp70-HSV2gD fusion protein had specific binding activity. The stimulation indexes of spleen lymphocytes, the level of gamma-IFN in culture and anti-HSV-2gD IgG antibody in serum of GST-Hsp70-gD group was obviously higher than that of other groups (P < 0.05 respectively). The successful expression of the Hsp70-HSV2gD fusion protein, which can induce immune responses, laid a solid foundation for its further research.