A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis.

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models. Methods: A systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias. Results: This meta-analysis included 24 studies involving 440 animals with methodological quality scores ranging from 4 to 6. The results demonstrated that curcumin treatment significantly improved Aspartate aminotransferase (AST) [standard mean difference (SMD) = -3.90, 95% confidence interval (CI) (-4.96, -2.83), p < 0.01, I2 = 85.9%], Alanine aminotransferase (ALT)[SMD = - 4.40, 95% CI (-5.40, -3.40), p < 0.01, I2 = 81.2%]. Sensitivity analysis of AST and ALT confirmed the stability and reliability of the results obtained. However, the funnel plot exhibited asymmetry. Subgroup analysis based on species and animal models revealed statistically significant differences among subgroups. Furthermore, curcumin therapy improved fibrosis degree, oxidative stress level, inflammation level, and liver synthesis function in animal models of liver fibrosis. Conclusion: Curcumin intervention not only mitigates liver fibrosis but also enhances liver function, while concurrently modulating inflammatory responses and antioxidant capacity in animal models. This result provided a strong basis for further large-scale animal studies as well as clinical trials in humans in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024502671.

Establishment of a mandible defect model in rabbits infected with multiple bacteria and bioinformatics analysis.

Objective: A model of chronic infectious mandibular defect (IMD) caused by mixed infection with Staphylococcus aureus and Pseudomonas aeruginosa was established to explore the occurrence and development of IMD and identify key genes by transcriptome sequencing and bioinformatics analysis. Methods: S. aureus and P. aeruginosa were diluted to 3 × 108 CFU/mL, and 6 × 3 × 3 mm defects lateral to the Mandibular Symphysis were induced in 28 New Zealand rabbits. Sodium Morrhuate (0.5%) and 50 µL bacterial solution were injected in turn. The modeling was completed after the bone wax closed; the effects were evaluated through postoperative observations, imaging and histological analyses. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein‒protein interaction (PPI) network analyses were performed to investigate the function of the differentially expressed genes (DEGs). Results: All rabbits showed characteristics of infection. The bacterial cultures were positive, and polymerase chain reaction (PCR) was used to identify S. aureus and P. aeruginosa. Cone beam CT and histological analyses showed inflammatory cell infiltration, pus formation in the medullary cavity, increased osteoclast activity in the defect area, and blurring at the edge of the bone defect. Bioinformatics analysis showed 1,804 DEGs, 743 were upregulated and 1,061 were downregulated. GO and KEGG analyses showed that the DEGs were enriched in immunity and osteogenesis inhibition, and the core genes identified by the PPI network were enriched in the Hedgehog pathway, which plays a role in inflammation and tissue repair; the MEF2 transcription factor family was predicted by IRegulon. Conclusion: By direct injection of bacterial solution into the rabbit mandible defect area, the rabbit chronic IMD model was successfully established. Based on the bioinformatics analysis, we speculate that the Hedgehog pathway and the MEF2 transcription factor family may be potential intervention targets for repairing IMD.

Changes in serum tumor markers in type 2 diabetes mellitus with microalbuminuria.

Objectives: The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria. Methods: A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis. Results: Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group (P < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724). Conclusion: Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial.

BACKGROUND: Saline nasal irrigation is an effective therapy for relieving common cold symptoms. This study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation (PSNI) on children with mild and asymptomatic infection with Omicron. METHODS: This randomized controlled trial was conducted in Shanghai, China, and 403 children with mild and asymptomatic infection with Omicron were included. These children were allocated into the PSNI group and the control group. The primary outcome was the duration of viral shedding (DVS), and the secondary outcome was the change in clinical symptoms. RESULTS: The median age of all participants was 5.59 (6.26) years old. The DVS was significantly shorter in the PSNI group [2.40 (1.13)] than in the control group [3.09 (2.14)] (P = 0.014). The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group [hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.04-1.55; P = 0.017]. Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI group. The proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group, but there was no evidence showing that PSNI contributes to the benefit compared with the control group. CONCLUSION: PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

Copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of 1,3-enynes and azomethine ylides.

Herein, we report a copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 1,3-enynes, which provides a series of chiral poly-substituted pyrrolidines in high regio-, diastereo-, and enantioselectivities. Both 4-aryl-1,3-enynes and 4-silyl-1,3-enynes serve as suitable dipolarophiles while 4-alkyl-1,3-enynes are inert. Moreover, the method is successfully applied in the construction of both tetrasubstituted stereogenic carbon centers and chiral spiro pyrrolidines. The DFT calculations are also conducted, which imply a concerted mechanism rather than a stepwise mechanism. Finally, various transformations started from the pyrrolidine bearing a triethylsilylethynyl group and centered on the alkyne group are achieved, which compensates for the inertness of 4-alkyl-1,3-enynes in the present reaction.

Concrescence of maxillary second molar and impacted third molar: A case report.

BACKGROUND: Morphological anomalies of teeth, including talon cusp, dens evaginatus, gemination, fusion, concrescence, root dilaceration, and taurodontism, always involve changes in the enamel, cementum and dentin. Diagnosing concrescent teeth through routine clinical examination alone is difficult, and most cases of concrescence are found accidentally during extraction. A definite preoperative diagnosis of concrescence would contribute to a better treatment plan and fewer undesirable complications. CASE SUMMARY: A 47-year-old woman who complained of left maxillary first molar loss for half a year presented to our department seeking treatment by dental implant restoration. Panoramic radiography and cone-beam computed tomography (CBCT) showed an unclear boundary between the distal root of the second molar and the mesial root of the third molar. The teeth were extracted under local anesthesia, and a definite diagnosis of concrescence was made by histopathological examination. CONCLUSION: CBCT is a useful tool for diagnosing and planning the management of tooth concrescence and may be beneficial for reducing unnecessary complications.

Copper(I)-Catalyzed Asymmetric Synthesis of P-Chiral Aminophosphinites.

Herein, a copper(I)-catalyzed reaction of diarylphosphines and O-benzoyl hydroxylamines is developed. In the cases of symmetrical diarylphosphines, a series of aminophosphinites is prepared in high yields. In the cases of unsymmetrical diarylphosphines, an array of P-chiral aminophosphinites is synthesized in high yields with high enantioselectivity by using a copper(I)-(R,RP )-Ph-FOXAP complex as a chiral catalyst. Based on several control experiments and 31 P NMR studies, a two-electron redox mechanism involving the dynamic kinetic asymmetric transformation of unsymmetrical diarylphosphines is proposed for the copper(I)-catalyzed asymmetric reaction. Finally, one representative P-chiral phosphoric amide generated through the oxidation with H2 O2 is transformed to a chiral diarylphosphinate in high yield with retained enantioselectivity, which allows further transformations towards various P-chiral tertiary phosphines.

Nomogram for Early Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using Dynamic Contrast-enhanced and Diffusion-weighted MRI.

RATIONALE AND OBJECTIVES: The study investigated the potential of the combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging in predicting the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) after two cycles of NAC. MATERIALS AND METHODS: Eighty-seven patients with breast cancer who underwent MR examination before and after two cycles of NAC were enrolled. The patients were randomly assigned to a training cohort and a validation cohort (3:1 ratio). MRI parameters including tumor longest diameter, time-signal intensity curve, early enhanced ratio (E90), maximal enhanced ratio and ADC value were measured, and percentage change in MRI parameters were calculated. Univariate analysis and multivariate logistic regression analysis were used to evaluate independent predictors of pCR in the training cohort. The validation cohort was used to test the prediction model, and the nomogram was created based on the prediction model. RESULTS: This study demonstrated that the ADC value after two cycles of NAC (OR = 1.041, 95% CI (1.002, 1.081); p = 0.037), percentage decrease in E90 (OR = 0.927, 95% CI (0.881, 0.977); p =0.004) and percentage decrease in tumor size (OR = 0.948, 95% CI (0.909, 0.988); p = 0.011) were significantly important for independently predicting pCR. The prediction model yielded AUC of 0.939 and 0.944 in the training cohort and the validation cohort, respectively. CONCLUSION: The combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging could accurately predict pCR after two cycles of NAC. The prediction model and the nomogram had strong predictive value to NAC.

Copper(I)-Catalyzed Asymmetric Alkylation of Unsymmetrical Secondary Phosphines.

A copper(I)-catalyzed asymmetric alkylation of HPAr1Ar2 with alkyl halides is uncovered, which provides an array of P-stereogenic phosphines in generally high yield and enantioselectivity. The electrophilic alkyl halides enjoy a broad substrate scope, including allyl bromides, propargyl bromide, benzyl bromides, and alkyl iodides. Moreover, 11 unsymmetrical diarylphosphines (HPAr1Ar2) serve as competent pronucleophiles. The present methodology is also successfully applied to catalytic asymmetric double and triple alkylation, and the corresponding products were obtained in moderate diastereo- and excellent enantioselectivities. Some 31P NMR experiments indicate that bulky HPPhMes exhibits weak competitively coordinating ability to the Cu(I)-bisphosphine complex, and thus the presence of stoichiometric HPAr1Ar2 does not affect the enantioselectivity significantly. Therefore, the high enantioselectivity in this reaction is attributed to the high performance of the unique Cu(I)-(R,RP)-TANIAPHOS complex in asymmetric induction. Finally, one monophosphine and two bisphosphines prepared by the present reaction are employed as efficient chiral ligands to afford three structurally diversified Cu(I) complexes, which demonstrates the synthetic utility of the present methodology.

Liraglutide protects palmitate-induced INS-1 cell injury by enhancing autophagy mediated via FoxO1.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and a progressive loss in mass and function of pancreatic ß-cells. In T2DM, lipotoxicity leads to ß-cells dysfunction and decreases its number. Autophagy serves a crucial role in maintaining the normal islet architecture and the function of ß-cells. Moreover, glucagon-like peptide-1 (GLP-1) and its analogs have beneficial roles in pancreatic ß-cells. However, the protective effects of GLP-1 agents on palmitate (PA)-induced pancreatic ß-cells and their underlying mechanisms are not fully elucidated. Forkhead box O1 (FoxO1) can prevent pancreatic ß-cells from apoptosis. Whether GLP-1 protects against PA-induced ß-cells injury via FoxO1 remains unknown. The present study exposed INS-1 cells to PA to establish a T2DM injury model. Cell viability was evaluated using a Cell Counting Kit-8 assay, and apoptosis was determined via western blotting. Furthermore, autophagy was examined using western blotting, immunofluorescence and transmission electron microscopy. Silencing FoxO1 was used to inhibit the activities of FoxO1. The results suggested that the GLP-1 analog liraglutide enhanced the cell viability, inhibited the protein expression of cleaved caspase-3 and increased the expression levels of microtubule-associated protein 1 light chain3 (LC3) II/I, and FoxO1 in INS-1 cells. The autophagy inhibitor chloroquine inhibited the protective effects of liraglutide on INS-1 cells. Silencing of FoxO1 decreased the expression levels of LC3-II and attenuated the protection of liraglutide on the viability of INS-1 cells. In conclusion, the results indicated that liraglutide ameliorated the PA-induced islet ß-cells injury via the upregulation of autophagy-mediated by FoxO1.

Copper(I)-Catalyzed Asymmetric 1,4-Conjugate Hydrophosphination of α,ß-Unsaturated Amides.

A catalytic asymmetric conjugate hydrophosphination of α,ß-unsaturated amides is accomplished by virtue of the strong nucleophilicity of copper(I)-PPh2 species, which provides an array of chiral phosphines bearing an amide moiety in high to excellent yields with excellent enantioselectivity. Furthermore, the dynamic kinetic resolution of unsymmetrical diarylphosphines (HPAr1Ar2) is successfully carried out through the copper(I)-catalyzed conjugate addition to α,ß-unsaturated amides, which affords P-chiral phosphines with good-to-high diastereoselectivity and high enantioselectivity. 1H NMR studies show that the precoordination of HPPh2 to copper(I)-bisphosphine complex is critical for the efficient deprotonation by Barton's Base. Moreover, the relative stability of the copper(I)-(R,RP)-TANIAPHOS complex in the presence of excessive HPPh2, confirmed by 31P NMR studies, is pivotal for the high asymmetric induction, as the ligand exchange between bisphosphine and HPPh2 would significantly reduce the enantioselectivity. At last, a double catalytic asymmetric conjugate hydrophosphination furnishes the corresponding product in high yield with high diastereoselectivity and excellent enantioselectivity, which is transformed to a chiral pincer palladium complex in moderate yield. This chiral palladium complex is demonstrated as an excellent catalyst in the asymmetric conjugate hydrophosphination of chalcone.

Role of autophagy in LPS­induced inflammation in INS­1 cells.

Inflammation has been implicated in the pathogenesis of type 2 diabetes (T2D), which is a progressive disease characterized by pancreatic ß­cell dysfunction and apoptosis with consequential insufficient insulin secretion. Autophagy is necessary to maintain the structure, mass and function of pancreatic ß­cells. The present study investigated the crosstalk between autophagy and inflammasome activation in T2D. INS­1 cells were stimulated with lipopolysaccharide. Apoptosis and reactive oxygen species (ROS) formation were measured using flow cytometry, and cell proliferation was measured using Cell Counting Kit­8 solution. Autophagy was assayed using western blotting and transmission electron microscopy. The expression levels of interleukin­1ß (IL­1ß) and caspase­1 were detected by western blotting. The results demonstrated that inhibiting autophagy using 3­methyladenine (3­MA) promoted INS­1 cell apoptosis. This response was correlated with an increase in ROS production and the inflammatory response, including IL­1ß maturation and caspase­1 activation. Furthermore, when ROS were inhibited using N­acetyl­L­cysteine, inflammation was decreased. These results demonstrated that inhibition of autophagy enhanced inflammatory injury via the ROS­mediated activation of the Nod­like receptor pyrin domain­containing protein 3 inflammasome. Autophagy may have a protective effect by mitigating inflammation in T2D, which may provide a novel approach for T2D treatment.

Overexpression of transcription factor EB regulates mitochondrial autophagy to protect lipopolysaccharide-induced acute lung injury / 中华医学杂志(英文版)

BACKGROUND@#Acute lung injury (ALI) is characterized by an acute inflammatory process, and oxidative stress in the lung tissue leads to a lack of effective therapeutics. This study aimed to identify whether the overexpression of transcription factor EB (TFEB) regulates mitophagy to protect against lipopolysaccharide (LPS)-induced ALI.@*METHODS@#We detected the expression of inflammatory factors, cytochrome c (Cyt.c) and nicotinamide adenine dinucleotide phosphate (NADPH), and autophagy-related proteins and observed the changes in lung histopathology induced by ALI in rats and the changes in the cell ultrastructure of primary alveolar type II epithelial cells induced by changing the expression of TFEB in the context of ALI.@*RESULTS@#The overexpression of TFEB could reduce the expression of proinflammatory factors, such as IL-1 and IL-6, and increase the expression of anti-inflammatory factors, such as IL-10, both in vitro and in vivo. In addition, the overexpression of TFEB could reduce the Cyt.c and NADPH levels both in vivo and in vitro. The overexpression of TFEB could upregulate the expression of autophagy-related proteins, such as lysosomal-associated membrane protein 1 (LAMP1), microtubule-associated protein light chain 3B (LC3B), and Beclin both in vivo and in vitro, and promote mitochondrial autophagy. The overexpression of TFEB significantly improved the histopathologic changes induced by LPS-induced ALI in rats. However, low TFEB expression produced the opposite results.@*CONCLUSION@#TFEB overexpression can decrease inflammation and mitochondrial damage in the lung tissue and alveolar epithelial cells through regulating mitochondrial autophagy to protect against LPS-induced ALI. Therefore, TFEB is likely a potential therapeutic target in LPS-induced ALI.

Overexpression of transcription factor EB regulates mitochondrial autophagy to protect lipopolysaccharide-induced acute lung injury / 中华医学杂志(英文版)

Background@#Acute lung injury (ALI) is characterized by an acute inflammatory process, and oxidative stress in the lung tissue leads to a lack of effective therapeutics. This study aimed to identify whether the overexpression of transcription factor EB (TFEB) regulates mitophagy to protect against lipopolysaccharide (LPS)-induced ALI.@*Methods@#We detected the expression of inflammatory factors, cytochrome c (Cyt.c) and nicotinamide adenine dinucleotide phosphate (NADPH), and autophagy-related proteins and observed the changes in lung histopathology induced by ALI in rats and the changes in the cell ultrastructure of primary alveolar type II epithelial cells induced by changing the expression of TFEB in the context of ALI.@*Results@#The overexpression of TFEB could reduce the expression of proinflammatory factors, such as IL-1 and IL-6, and increase the expression of anti-inflammatory factors, such as IL-10, both in vitro and in vivo. In addition, the overexpression of TFEB could reduce the Cyt.c and NADPH levels both in vivo and in vitro. The overexpression of TFEB could upregulate the expression of autophagy-related proteins, such as lysosomal-associated membrane protein 1 (LAMP1), microtubule-associated protein light chain 3B (LC3B), and Beclin both in vivo and in vitro, and promote mitochondrial autophagy. The overexpression of TFEB significantly improved the histopathologic changes induced by LPS-induced ALI in rats. However, low TFEB expression produced the opposite results.@*Conclusion@#TFEB overexpression can decrease inflammation and mitochondrial damage in the lung tissue and alveolar epithelial cells through regulating mitochondrial autophagy to protect against LPS-induced ALI. Therefore, TFEB is likely a potential therapeutic target in LPS-induced ALI.

SIRT3 Protects Rotenone-induced Injury in SH-SY5Y Cells by Promoting Autophagy through the LKB1-AMPK-mTOR Pathway.

SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells. Then, a PD cell model was established using rotenone. Our data demonstrate that overexpression of SIRT3 increased the level of the autophagy markers LC3 II and Beclin 1. After addition of the autophagy inhibitor 3-MA, the protective effect of SIRT3 diminished: the cell viability decreased, while the apoptosis rate increased; α-synuclein accumulation enhanced; ROS production increased; antioxidants levels, including SOD and GSH, decreased; and MMP collapsed. These results reveal that SIRT3 has neuroprotective effects on a PD cell model by up-regulating autophagy. Furthermore, SIRT3 overexpression also promoted LKB1 phosphorylation, followed by activation of AMPK and decreased phosphorylation of mTOR. These results suggest that the LKB1-AMPK-mTOR pathway has a role in induction of autophagy. Together, our findings indicate a novel mechanism by which SIRT3 protects a rotenone-induced PD cell model through the regulation of autophagy, which, in part, is mediated by activation of the LKB1-AMPK-mTOR pathway.

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1.

The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health problem and novel therapeutic strategies are required to prevent and treat T2DM. It has been demonstrated that resveratrol (RSV) may prevent T2DM by targeting Sirtuin type 1 (SIRT1), indicating that SIRT1 may be a novel therapeutic target for T2DM prevention. In the present study, a T2DM rat model was established by administering a high fat diet and streptozotocin (STZ) injections. Measurements of blood glucose and insulin confirmed successful establishment of the T2DM model. RSV was used to treat rats with STZ-induced T2DM and the results indicated that RSV reversed the STZ-induced downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, SIRT1 and forkhead box protein O 3a. Furthermore, RSV modulated the activity of superoxide dismutase and malondialdehyde, which are associated with oxidative stress. In vitro, cells from the insulinoma cell line clone 1E were pretreated with palmitic acid (PA) to simulate a high fat environment. The results of reverse transcription-quantitative polymerase chain reaction indicated that PA suppressed the expression of SIRT1 in a dose- and time-dependent manner. Furthermore, PA modulated the expression of mitochondrial biogenesis-associated, lipid metabolism-associated and ß-cell-associated genes, whereas RSV treatment ameliorated the PA-induced changes in the expression of these genes via SIRT1. The results of the present study suggest that RSV participates in the prevention of T2DM by regulating the expression of mitochondrial genes associated with biogenesis, lipid metabolism and ß-cells via SIRT1. The results of the current study provide an insight into the mechanisms by which SIRT1 inhibits T2DM and may be used as a basis for future studies.

Detection of SNPs of T2DM susceptibility genes by a ligase detection reaction-fluorescent nanosphere technique.

OBJECTIVE: To establish a high throughput, low cost, and simple nanotechnology-based method for the detection of single nucleotide polymorphism (SNP) loci in type 2 diabetes mellitus (T2DM). METHODS: Multiplex ligase detection reaction (LDR) amplification was performed using fluorescently labeled magnetic nanosphere-bound upstream LDR probes and downstream probes labeled with a unique fluorescent group for each SNP locus. The amplified LDR products were separated by magnetic nanospheres and then scanned by fluorescence spectroscopy. Four SNP loci associated with T2DM were detected, including the rs13866634 locus in SLC30A8, rs10811661in CDKN2A/2B, rs1111875 in the HHEX gene, and rs7903146 in the TCF7L2 gene. The SNP genotype was also determined by DNA sequencing as a control. RESULTS: The SNP genotypes of the four gene loci determined by the nanosphere-based multiplex LDR method were consistent with the DNA sequencing results. The accuracy rate was 100%. CONCLUSION: A method based on multiplex PCR and LDR was established for simultaneous detection of four SNP loci of T2DM susceptibility genes.

Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS­1 cells.

Type 2 diabetes is a chronic inflammatory disease. Autophagy, the dynamic process of lysosomal degradation of damaged organelles and proteins, may protect ß­cells from destruction by inflammation in type 2 diabetes. The present study investigated the role of autophagy, inflammation and endoplasmic reticulum (ER) stress in type 2 diabetes. INS­1 cells were incubated with lipopolysaccharide. The chemical chaperone 4­phenylbutyric acid was used to inhibit ER stress, and 3­methyadenine (3­MA) was used to inhibit autophagy. Apoptosis was detected by flow cytometry and cell proliferation using Cell Counting kit­8 solution. Light chain­3B, interleukin (IL) 1ß, caspase­1 and C/EBP homologous protein production were assessed by western blotting, and rat activating transcription factor 4 and rat binding immunoglobulin heavy chain protein gene expression were determined by real­time reverse transcription­polymerase chain reaction. The results showed that inhibiting autophagy with 3­MA unexpectedly contributed to cell death in ß­cells. This response was associated with an increase in inflammatory cytokines, including IL1ß and caspase­1. Inhibiting ER stress with 4­phenylbutyric acid led to a decrease in cell apoptosis. These results showed that autophagy may have a protective effect by reducing inflammatory cytokines in ß­cells. In addition, the inositol­requiring enzyme 1 pathway mediated the ER stress associated with autophagy and inflammatory cytokines (IL1ß and caspase­1). Therefore, inflammatory cytokines may be critical signalling nodes, which are associated with ER stress­mediated ß­cell death.

Impact of Different Levels of iPTH on All-Cause Mortality in Dialysis Patients with Secondary Hyperparathyroidism after Parathyroidectomy.

BACKGROUND: Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality. METHODS: An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX. RESULTS: 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21-150 pg/mL; C: 151-600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively. CONCLUSION: The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21-150 pg/mL.