GLP-1RAs inhibit the activation of the NLRP3 inflammasome signaling pathway to regulate mouse renal podocyte pyroptosis.

OBJECTIVE: Podocytes are closely related to renal function as an important part of the glomerulus. The reduction and damage of podocytes lead to further decline of renal function and aggravate the progression of DKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAS) have recently attracted great attention in improving podocyte dysfunction, but the specific mechanism remains uncertain. METHODS: We used mouse kidney podocyte MPC5 to construct a high-glucose injury model. Cell viability was detected by the MTT method; RT-qPCR and western blotting were used to detect the expressions of NF-κB p65, NLRP3, GSDMD, N-GSDMD, caspase-1 and cleaved-caspase-1, and we used ELISA to detect the expressions of inflammatory factors IL-1ß and IL-18. RESULTS: Our results showed that high glucose decreased podocyte survival, while liraglutide and semaglutide increased podocyte survival under high glucose. Liraglutide and semaglutide can inhibit the expression of pyroptosis-related genes and proteins and also inhibit the expression of inflammatory factors IL-1ß, IL-18 increase. CONCLUSION: The protective effect of liraglutide and semaglutide on podocytes may be achieved by regulating the NLRP3 inflammasome pathway and inhibiting pyroptosis, and there were no significant differences between the two GLP-1RAs (liraglutide and semaglutide) in inhibiting podocyte pyroptosis.

Potential therapeutic role of pyroptosis mediated by the NLRP3 inflammasome in type 2 diabetes and its complications.

As a new way of programmed cell death, pyroptosis plays a vital role in many diseases. In recent years, the relationship between pyroptosis and type 2 diabetes (T2D) has received increasing attention. Although the current treatment options for T2D are abundant, the occurrence and development of T2D appear to continue, and the poor prognosis and high mortality of patients with T2D remain a considerable burden in the global health system. Numerous studies have shown that pyroptosis mediated by the NLRP3 inflammasome can affect the progression of T2D and its complications; targeting the NLRP3 inflammasome has potential therapeutic effects. In this review, we described the molecular mechanism of pyroptosis more comprehensively, discussed the most updated progress of pyroptosis mediated by NLRP3 inflammasome in T2D and its complications, and listed some drugs and agents with potential anti-pyroptosis effects. Based on the available evidence, exploring more mechanisms of the NLRP3 inflammasome pathway may bring more options and benefits for preventing and treating T2D and drug development.

How to Approach Submucosal Lesions in the Gastrointestinal Tract: Different Ideas between China and USA.

Between 2019 and 2020, the author Gao pursued advanced endoscopic training at the University of Mississippi Medical Center in the USA. She experienced certain different ideas between the East (China) and the West (USA) in terms of endoscopic approach to the submucosal tumors (SMTs) or lesions in the gastrointestinal (GI) tract. In the West (USA), when SMTs are found on gastroscopy, the main goal of endoscopists is to obtain a tissue diagnosis through endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA or FNB) or single incision needle-knife biopsy (SINK); if immunohistochemical tests confirmed the GISTs, the first-line treatment is local surgery, that is, diagnosis before treatment, whereas in China, SMTs will be completely resected with endoscopic technology for those with no lymph node metastasis or extremely low risk of lymph node metastasis. There may not be pathological tissue at first, that is, treatment before diagnosis.

Trifocal diffractive intraocular lens implantation in patients after previous corneal refractive laser surgery for myopia.

BACKGROUND: With the difficulties in IOL power calculation and the potential side effects occurring postoperatively, multifocal IOL implantation after previous corneal refractive surgery are rarely reported especially for the trifocal IOL. Herein we report the clinical observation of trifocal IOL implantation in patients with previous myopia excimer laser correction. In this study, a multi-formula average method was performed for the IOLs power calculation to improve the accuracy. Visual and refractive outcomes were analyzed, and the subjective quality of patients' life was evaluated by questionnaires survey. METHODS: This retrospective case series included patients with previous myopia excimer laser correction who underwent femtosecond laser assisted phacoemulsification and trifocal IOL (AT LISA tri 839 MP) implantation. Follow-up was done at 1-day, 1-month and 3-month to assess the visual outcomes. Outcome measures were uncorrected distance, intermediate and near visual acuity (UDVA, UIVA, UNVA), manifest refraction, defocus curve, and subjective quality of vision. RESULTS: Twenty-one Eyes from sixteen patients (14 eyes with previous laser in situ keratomileusis and 7 eyes with previous photorefractive keratectomy) were included. Mean postoperative spherical equivalent (SE) at 3-month was - 0.56 D ± 0.49 SD, wherein, 10 eyes (47.6%) were within ±0.50 D of the desired emmetropia and 19 eyes (90.5%) were within ±1.0 D. Mean monocular UDVA, UIVA and UNVA (logMAR) at last visit were 0.02 ± 0.07, 0.10 ± 0.10, and 0.15 ± 0.11 respectively. Three patients (19%) reported halos and glare in postoperative 3 months, two of them needed to use spectacles to improve the intermediate visual acuity. Fifteen patients (94%) reported a satisfaction score of ≥3.5 out of 4.0, without any difficulty in daily activity. Thirteen patients (81%) did not need spectacles at all distances, while the other 3 patients (19%) used spectacles for near-distance related visual activity. Mean composite score of the VF-14 questionnaire was 95.00 ± 7.29 out of 100. CONCLUSIONS: Trifocal IOL implantation after myopia excimer laser correction could restore good distance, intermediate visual acuity and acceptable near visual acuity, and provide accurate refractive outcomes as well as high spectacles independence rate.

Effect of high-quality nursing intervention on anxiety and depression in patients with chronic heart failure companied malnutrition: A protocol for systematic review and meta-analysis.

BACKGROUND: This study will assess the effect of high-quality nursing intervention (HQNI) on anxiety and depression in patients with chronic heart failure companied malnutrition (CHFM). METHODS: We will retrieve electronic databases from the respective dates to February 29, 2020 without language and publication status restrictions: Cochrane Library, Web of Science, MEDLINE, EMBASE, Scopus, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All potential randomized controlled trials (RCTs), which examined the effect of HQNI on anxiety and depression in patients with CHFM will be included. Two team members will separately perform article retrieval, duplicates excluding, scanning, data collection, and study quality assessment. In addition, this study will carry out data analysis by RevMan 5.3 software. RESULTS: This study will provide high-quality synthesis and/or descriptive analysis of the latest evidence to assess the effect of HQNI on anxiety and depression in patients with CHFM. CONCLUSION: The findings of this study will exert evidence to judge whether or not HQNI is effective on anxiety and depression in patients with CHFM. REGISTRATION NUMBER: INPLASY202040069.

Effect of tunneled and nontunneled peripherally inserted central catheter placement: A randomized controlled trial.

PURPOSE: To compare the effect of tunneled and nontunneled peripherally inserted central catheter placement under B-mode ultrasound. METHODS: A single center, randomized, controlled, nonblinded, prospective trial was conducted in Guangzhou, China, between July 2018 and May 2019. A total of 174 participants were randomized to the experimental group (tunneled peripherally inserted central catheter) or the control group (nontunneled peripherally inserted central catheter) and were followed until extubation. Basic characteristics, peripherally inserted central catheter characteristics, the incidence of complications, and the costs of peripherally inserted central catheter placement and maintenance were collected. Data were analyzed by intention-to-treat. RESULTS: A total of 168 of the participants had successful peripherally inserted central catheter placements (85/87, 97.7% in the experimental group and 83/87, 95.4% in the control group, P = 0.682). Compared to the control group, the experimental group had a lower incidence of complications during the placement (18.4% vs 32.2%, P = 0.036), a lower incidence of wound oozing (27.6% vs 57.5%, P < 0.001), a lower incidence of medical adhesive-related skin injury (9.2% vs 25.3%, P = 0.005), a lower incidence of venous thrombosis (1.1% vs 9.2%, P = 0.034), a lower incidence of catheter dislodgement (1.1% vs 9.2%, P = 0.034), and lower costs of peripherally inserted central catheter maintenance at 1, 2, and 3 months (P < 0.05). CONCLUSION: Tunneled peripherally inserted central catheter may be recommended for good effectiveness.

[Adsorption of Cu on Core-shell Structured Magnetic Particles: Relationship Between Adsorption Performance and Surface Properties].

In order to reveal the relationship between the adsorption performance of adsorbents and their compositions, structure, and surface properties, the core-shell structured Fe3O4/MnO2 and Fe-Mn/Mn22 magnetic particles were systematically characterized using multiple techniques and their Cu adsorption behaviors as well as mechanism were also investigated in details. It was found that both Fe3O4 and Fe-Mn had spinel structure and no obvious crystalline phase change was observed after coating with MnO2. The introduction of Mn might improve the affinity between the core and the shell, and therefore enhanced the amount and distribution uniformity of the MnO2 coated. Consequently, Fe-Mn/MnO2 exhibited a higher BET specific surface area and a lower isoelectric point. The results of sorption experiments showed that Fe-Mn had a higher maximal Cu adsorption capacity of 33.7 mg · g⁻¹ at pH 5.5, compared with 17.5 mg · g⁻¹ of Fe3O4. After coating, the maximal adsorption capacity of Fe-Mn/MnO2 was increased to 58.2 mg · g⁻¹, which was 2.6 times as high as that of Fe3O4/MnO2 and outperformed the majority of magnetic adsorbents reported in literature. In addition, a specific adsorption of Cu occurred at the surface of Fe3O4/MnO2 or Fe-Mn/MnO2 through the formation of inner-sphere complexes. In conclusion, the adsorption performance of the magnetic particles was positively related to their compositions, structure, and surface properties.

[Expression of Pax3 and Cx43 in NTD embryos induced by hyperglycemia].

OBJECTIVE: To find out the molecular mechanisms of togenesis, especially neural tube defects (NTDs) caused by hyperglycemia and thiadiazole. METHODS: Mice were raised with a ratio of 2:1 between females and males. Forty-five pregnant female mice were randomly divided into 5 groups: blank control group (without any treatment), high-glucose group (treated with subcutaneous injection of 25% glucose), glucose-control group (n = 12, treated with subcutaneous injection of 5% glucose), thiadiazole group (treated with gastric perfusion of thiadiazole), and thiadiazole-control group (n = 11, treated with the solvent of thiadiazole). The blood sugar was examined among the mice of the first three groups on the 8th gestational day. All of the mice were killed on the 15th gestational day and the embryos were taken. The existence of teras was observed. RT-PCR was used to detect the expression of Pax3 and of Cx43 genes and immunohistochemistry was used to examine the Pax3 and Cx43 proteins in the embryos. RESULTS: The blood sugar of the pregnant mice in the high-glucose group was 13.4 mmol/L +/- 0.8 mmol/L, significantly higher than those in the 2 control groups (4.9 mmol/L +/- 0.4 mmol/L and 4.8 mmol/L +/- 0.4 mmol/L respectively, both P < 0.01). The teras rate, absorbed embryo rate and still embryo rate in high-glucose group were significantly higher than those in the 2 control groups (all P < 0.01). The embryo weight of the high-glucose group was significantly lower. The expression of Pax3 in the hyperglycemia group was significantly lower than those in the 2 control groups (both P < 0.01), while the expression of Cx43 in high-glucose group was significantly higher than those in the 2 control groups (both P < 0.01). In the thiadiazole group, the expression of Pax3 was not significantly different from, and the expression of Cx43 was significantly higher than those in the 2 control groups. CONCLUSION: Hyperglycemia is induced in nondiabetic pregnant mice by subcutaneous glucose injection, and elevated glucose appears to be critical in the diabetic embryopathy. Hyperglycemic episodes disturb the essential embryonic control genes: decrease the expression of Pax3 gene and increase the expression of Cx43 gene, thus causing congenital defects. Thiadiazole induces NTDs by increasing the expression of Cx43.