The causal relationship between plasma protein-to-protein ratios and type 2 diabetes and its complications: Proteomics mendelian randomization study.

AIM: In recent years, proteomics research has surged, with numerous observational studies identifying associations between plasma proteins and type 2 diabetes. However, research specifically focusing on the ratios of plasma proteins in type 2 diabetes remains relatively scarce. METHODS: This study primarily employed a two-sample, two-step Mendelian randomization (MR) approach, leveraging genetic data from several large, publicly accessible genome-wide association studies, wherein single nucleotide polymorphisms served as proxies for exposures and diseases. Within this framework, we applied two-sample MR to assess the associations between the 2821 plasma protein-to-protein ratios and type 2 diabetes along with its complications and utilized reverse MR to confirm the unidirectionality of these causal relationships. In addition, we employed two-step MR to investigate the potential mediating role of body mass index in these associations. To augment the robustness of our findings, we systematically implemented a series of sensitivity analyses. RESULTS: The results gleaned from the inverse-variance weighted method elucidated that a cumulative sum of 23 protein-to-protein ratios bore a causal nexus with type 2 diabetes across both sample cohorts. With each incremental elevation of 1 standard deviation in the genetically anticipated protein-to-protein ratio, the susceptibility to type 2 diabetes oscillated from 0.93 (95% confidence interval: 0.87, 1.00) for the CNTN3/NCSS1 protein level ratio to 1.13 (1.06, 1.22) for the DBNL/NCK2 protein level ratio. Moreover, a tally of eight protein-to-protein ratios correlated with a minimum of one complication linked to type 2 diabetes. Diverse sensitivity analyses corroborated the robustness of these observations. CONCLUSIONS: The outcomes of our investigation unveiled correlations between 23 plasma protein-to-protein ratios and type 2 diabetes, with eight of these ratios entwined with complications of type 2 diabetes. These discoveries offer novel perspectives on the diagnosis and management of type 2 diabetes and its associated complications.

Association between gut microbiota and adrenal disease: a two-sample Mendelian randomized study.

Background: Some observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear. Methods: This study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran's Q statistic was used to test for heterogeneity of instrumental variables. Results: The IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism. Conclusions: This two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota.

Correlation of renal function indicators and vascular damage in T2DM patients with normal renal function.

Background: This study aimed to assess the correlation between renal function-related indices and vascular damages among patients with type 2 diabetes mellitus (T2DM) and normal renal function. Methods: We screened a cohort of eligible patients with T2DM, ultimately including 826 individuals. Utilizing multifactorial logistic regression, we conducted an in-depth analysis to explore the potential associations between renal function-related indices-specifically BUN, Cr, ALB, ACR, and eGFR-and the incidence of diabetic vascular damage. Additionally, to comprehensively understand the relationships, we employed Spearman correlation analysis to assess the connections between these indicators and the occurrence of vascular damage. Results: In this cross-sectional study of 532 patients with carotid atherosclerosis (CA), the prevalence of CA was positively correlated with Cr (53.1%, 72.3%, 68.0%, P<0.05) and negatively correlated with eGFR (71.6%, 68.5%, 53.1%, P<0.05). the higher the Cr, the higher the predominance ratio of CA (T1: reference; T2:OR. 2.166,95%CI:1.454,3.225; T3:OR:1.677, 95%CI:1.075, 2.616; P<0.05), along with an eGFR of 66.9% and 52.0% in terms of sensitivity and specificity, with a 95% CI of 0.562-0.644. Conclusion: Within our experimental sample, a noteworthy observation emerged: Creatinine (Cr) exhibited a positive correlation with the prevalence of individuals affected by carotid atherosclerosis (CA), underscoring a potential connection between Cr levels and CA incidence. Conversely, the estimated Glomerular Filtration Rate (eGFR) demonstrated a negative correlation with the occurrence of CA, implying that lower eGFR values might be associated with an increased likelihood of CA development.

Correlation study of renal function indices with diabetic peripheral neuropathy and diabetic retinopathy in T2DM patients with normal renal function.

Background: The anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of these complications. This study aims to investigate the association between renal function-related indicators and the occurrence of peripheral neuropathy and retinopathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) who currently have normal renal function. Methods: Patients with T2DM who met the criteria were selected from the MMC database and divided into diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR) groups, with a total of 859 and 487 patients included, respectively. Multivariate logistic regression was used to analyze the relationship between blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), urine albumin(ALB), albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and diabetic peripheral neuropathy and retinopathy. Spearman correlation analysis was used to determine the correlation between these indicators and peripheral neuropathy and retinopathy in diabetes. Results: In a total of 221 patients diagnosed with DPN, we found positive correlation between the prevalence of DPN and eGFR (18.2, 23.3, 35.7%, p < 0.05). Specifically, as BUN (T1: references; T2:OR:0.598, 95%CI: 0.403, 0.886; T3:OR:1.017, 95%CI: 0.702, 1.473; p < 0.05) and eGFR (T1: references; T2:OR:1.294, 95%CI: 0.857, 1.953; T3:OR:2.142, 95%CI: 1.425, 3.222; p < 0.05) increased, the odds ratio of DPN also increased. Conversely, with an increase in Cr(T1: references; T2:OR:0.86, 95%CI: 0.56, 1.33; T3:OR:0.57, 95%CI: 0.36, 0.91; p < 0.05), the odds ratio of DPN decreased. Furthermore, when considering sensitivity and specificity, eGFR exhibited a sensitivity of 65.2% and specificity of 54.4%, with a 95% confidence interval of 0.568-0.656. Conclusion: In this experimental sample, we found a clear positive correlation between eGFR and DPN prevalence.

[Prognostic analysis of 40 cases with rectal gastrointestinal stromal tumor].

OBJECTIVE: To analyze the prognosis of rectal gastrointestinal stromal tumors (GIST). METHODS: Records of 40 patients diagnosed as rectal GIST at the Affiliated Chinese Traditional Medical Hospital of Xinjiang Medical University and the People's Hospital of Tianjin City between June 1979 and June 2010 were reviewed. Clinical features, treatment modalities and outcomes were analyzed. RESULTS: There were 23 males and 17 females with a median age of 54.5 years old (range, 28-81 years old). During the follow-up(median 52.5 months, range 1-300 months), 18 patients developed recurrence including 7 local recurrence, 6 metastasis and 5 local recurrence complicated with metastasis. The overall survival rates at 1, 3 and 5 years were 82.5%, 60.0%, and 42.5% respectively. On univariate analysis, tumor size(P<0.01), Fletcher classification(P<0.01), mitotic index(P<0.01), and post-operative distant metastasis were associated with survival. Multivariate analysis showed that tumor size(P<0.05), mitotic rate (P<0.01), and postoperative distant metastasis(P<0.01) were independent prognostic factors associated with survival. CONCLUSIONS: Surgery is the main treatment for rectal GIST. Tumor size, mitotic rate and metastasis are independent prognostic factors in patients with rectal GIST.

The antinociceptive effect of intrathecal tramadol in rats: the role of alpha 2-adrenoceptors in the spinal cord.

PURPOSES: The alpha 2 (α(2))-adrenoceptor is highly important in the antinociception of tramadol administered systemically and intrathecally. However, it is unclear whether tramadol at the spinal level exerts an antinociceptive effect by directly binding with α(2)-adrenoceptors in the spinal cord. This study was conducted to investigate the relationship between α(2)-adrenoceptors and the antinociception of tramadol at the spinal level. METHODS: The rat formalin test was designed to determine whether the intrathecal α(2)-adrenoceptor antagonist yohimbine could reverse the antinociceptive effect of intrathecal tramadol. The binding affinity of tramadol for α(2)-adrenoceptors in the spinal cord was determined by radioligand binding assay using the labeled α(2)-adrenoceptor antagonist [(3)H]-yohimbine. RESULTS: The nociceptive test showed that intrathecal tramadol induced significant antinociception whereas pretreatment with intrathecal yohimbine partially reversed this antinociception. Scatchard analysis of the binding data showed [(3)H]-yohimbine had high affinity (K(d) = 1.79 nM: ) for the α(2)-adrenoceptor in the rat spinal cord, and that tramadol inhibited specific binding of [(3)H]-yohimbine with the spinal cord membranes with a high affinity constant (K(i) = 34.14 µM: ) and an IC50 of 68.25 µM: , which indicated that tramadol was much less potent than [(3)H]-yohimbine at binding with α(2)-adrenoceptors of the spinal cord. CONCLUSION: The results suggested that, with very weak binding affinity for α(2)-adrenoceptors, the antinociception of intrathecal tramadol is partially related to α(2)-adrenoceptors, and its intrathecal antinociception may mainly involve its indirect activation of α(2)-adrenoceptors in the spinal cord.

[Effect of esmolol on propofol dose requirement for anesthesia in thyroidectomy].

OBJECTIVE: To observe the effect of esmolol application before and during operation on propofol dose required for anesthesia induction and maintenance. METHODS: Forty patients (ASA physical status I or II) undergoing general anesthesia for thyroidectomy were randomized equally into esmolol and control groups. Patients in esmolol group received a loading dose of esmolol at 0.5 mg/kg in 30 ml normal saline over a period of 5 min followed by an intravenous infusion of esmolol at 50 microg.kg(-1).min(-1) until the end of surgery, while patients in the control group were given normal saline in the same manner, in addition to anesthesia with protofol. Perioperative hemodynamic parameters and BIS were measured, and the duration of anesthesia, operation and recovery time from anesthesia were recorded. RESULTS: There were significant differences between the two groups in propofol dose required for anesthesia induction and recovery time from anesthesia, but not in maintenance propofol dose. Patients in esmolol group had significantly lower HR and BIS during tracheal intubation than those in the control group , and no significant differences were found in HR, BP and BIS during operation between the two groups. The hemodynamic parameters during extubation showed less fluctuation in esmolol group. CONCLUSION: Perioperative esmolol administration during anesthesia reduces propofol dose required for anesthesia induction and recovery time from anesthesia, and decreases HR and BIS variation during tracheal intubation and hemodynamic response during extubation without affecting the maintenance propofol dose.

[Effect of ulinastatin on inflammatory responses induced by oesophagectomy].

OBJECTIVE: To examine the effect of ulinastatin (UTI) on the inflammatory responses induced by oesophagectomy. METHODS: Forty patients with esophageal cancer (without serious hypertension, heart disease, or respiratory function impairment, including 34 men and 6 women aged 46 to 70 years) scheduled for oesophagectomy via left thoracotomy were randomly divided into control group (n=20) and UTI group (n=20). Anesthesia induction and perioperative management followed the same protocols in the two groups, and in UTI group, patients received 5000 U/kg UTI while those in the control group were given the same volume of saline. Before operation (T(1)), 10 min after recovery of two-lung ventilation (T(2)), and 24 h (T(3)) and 48 h (T(4)) after operation, the venous blood sample was taken from the internal jugular vein and the plasma was separated and stored at -70 degrees C for later analysis of IL-6 and IL-8 with enzyme-linked immunosorbent assay (ELISA). The bronchoalveoar lavage fluid (BAFL) was also collected at T(1) and T(2) for IL-6 and IL-8 detection. RESULTS: IL-6, IL-8 levels in the plasma and BALF collected at T(2)-T(4) increased significantly as compared with those in samples collected at T(1), and their peak concentration inplasma and BALF samples were similar. IL-6 and IL-8 levels in the UTI group were significantly lower than those in the control group during the time points of T(2)-T(4). CONCLUSION: Inflammatory responses occur during and after oesophagectomy, which can be inhibited with UTI.

Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats.

AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION: High dose Astragalus membranaeus has much better protective effect on hemorrhagic shock-reperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.

[Effects of Astragalus membranaceus injection on nitric oxide and endothelin concentration of intestinal mucosa after hemorrhage shock-reperfusion in rats].

OBJECTIVE: To observe the effects of Stragalus membranaceus injection on nitric oxide and endothelin levels of intestinal mucosa in reperfusion injury after hemorrhage shock. METHOD: 32 SD rats were randomly divided into four groups: normal group, model group, low dosage group, (treated with Astragalus membranaceus 10 g x kg(-1)); high dosage group (treated with Astragalus membranaceus 20 g x kg(-1)). Models of hemorrhagic shock for 60 minutes and reperfusion for 90 minutes were created. The animals were administrated 3 mL therapeutic solution before reperfusion. At the end of study, intestinal pathology was observed, and the concentration of lactic acid (LD), nitric oxide (NO), endothelin (ET) of intestinal mucosa were detected. RESULT: The intestinal pathology showed that intestinal mucosa epithelial cells damage in model group was severe, in low dosage group was medium, in high dosage group was slight, and no obvious damage was found in normal group. The concentration of LD and NO of small intestine mucous membrane in model group and low dosage group were significantly higher than those in high dosage group and normal group (P < 0.05), but there were no significant differences between high dosage group and normal group (P > 0.05). The concentration of ET of small intestine mucous membrane in model group was the highest of the four groups (P < 0.05). The concentration of ET in low dosage group was significantly higher than that in high dosage group and normal group (P < 0.05), but there were no significant differences between high dosage group and normal group (P > 0.05). CONCLUSION: Stragalus membranaceus injection can reduce small intestine mucous damage by protecting endothelium function in injury after hemorrhage shock-reperfusion.