ObjectiveTo summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma (PDAC), and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC. MethodRelevant literatures on cholesterol metabolism in the occurrence, development, and diagnosis and treatment of PDAC in recent years were searched and reviewed. ResultsMetabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes. Signaling regulation within tumor cells affects cholesterol metabolism, characterized by increased de novo cholesterol synthesis and esterification, and reduced efflux. Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism. Inhibiting cholesterol metabolism could suppress the proliferation, invasion and migration of PDAC tumor cells, and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect. ConclusionsRemodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment, and is closely related to the occurrence, development, invasion, metastasis, and treatment response of PDAC. Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects. However, more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.
Objectives To investigate the correlation between blood total cholesterol (TC) and prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and to provide references for clinical treatment and prognosis assessment. Methods We included 232 ISSNHL patients with total deafness in Wenzhou Central Hospital from June 2015 to March 2017 using a prospective cohort design. Recording information including age, gender, hypertension, diabetes mellitus, vertigo, level of blood total cholesterol (TC), level of triglyceride (TG), level of low-density lipoprotein (LDL-C) and LDL/HDL ratio (LDL-C/HDL-C) were collected. Correlation between the prognosis of ISSNHL and blood total cholesterol were analyzed by univariable and multivariable logistic regression analysis. Results The clinical effective rate of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L was higher than that of patients with TC lower than 5.2 mmol/L (univariable: RR=6.49, 95%CI 3.16 to 13.30, P<0.001; multivariable-adjusted covariates: RR=6.15, 95%CI 2.66 to 14.3,P<0.001) with significant difference. No significant difference was found between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (univariable: RR=1.02, 95%CI 0.52 to 2.00,P=0.960; multivariable-adjusted covariates: RR=1.61, 95%CI 0.55 to 4.73, P=0.386). Gender-specific analysis showed for both male and female groups, the effective rates of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L were significantly higher than those of patients with TC lower than 5.2 mmol/L. There was no significant difference between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (P>0.05) in either male group or female group. Conclusion The current study suggests that patients with levels of TC ranging from 5.2 mmol/L to 6.2 mmol/L predicts the best prognosis.
ObjectiveTo conduct a systematical evaluation and meta-analysis of the relation between serum total cholesterol (TC) level and the risk of gastric cancer. MethodsThe PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to March 5, 2023. Two independent reviewers performed the literature search, identification, and screening, as well as performed the quality assessment and data extraction. ResultsA total of 12 studies with 5 143 671 participants and 40 551 patients with gastric cancer were included in the meta-analysis. The results of meta analysis showed that 9 studies reported that the elevated serum TC level decreased the risk of gastric cancer [OR (95%CI) was 0.91 (0.85, 0.98)], and 5 studies reported that the decreased serum TC level increased the risk of gastric cancer [OR (95%CI) was 1.93 (1.17, 3.18)]. Also the results of the subgroup analyses showed that the decreased serum TC level increased the risk of gastric cancer in the studies with cohort study, larger overall sample sizes and gastric cancer sample sizes, with longer duration of follow-up, and in those with habits of alcohol and smoking [0.89 (0.87, 0.92), 0.90 (0.87, 0.94), 0.90 (0.87, 0.93), 0.86 (0.82, 0.90), 0.90 (0.87, 0.93), and 0.90 (0.87, 0.93), respectively] , which was consistent with the overall results. In contrast, there was no statistical difference in the relation between the elevated serum TC level decreased the risk of gastric cancer between male and female patients in the gender subgroup. ConclusionsThe results of this systematical evaluation and meta-analysis suggest that serum TC level [135–294 mg/dL (3.49–7.62 mmol/L)] may be a protective factor for gastric carcinogenesis. The risk of gastric carcinogenesis may be increased when serum TC level decreases, and this change is a long-term and insidious process.
目的:对无明显心血管病(CVD)临床症状者的高甘油三酯(TG)≥1.60 mmol/L低高密度脂蛋白胆固醇(HDL-C)≤1.18 mmol/L伴有活动平板运动试验(TET)心电图(ECG)阳性和TET ECG阴性的缺血性心脏病(IHD)的危险因素进行了对比观察。〖HTH〗方法:〖HT5”SS〗对无明显CVD临床症状的2900例受试者检测TG/HDL-C、其中伴有TET ECG阳性(缺血型ST-T改变)者500例和TET ECG阴性(不伴有缺血型ST-T改变)者2500例进行了5年对比观察, 预测其预后。〖HTH〗结果〖HTSS〗:在 5年随访的观察中高TG(≥1.60 mmol/L)/低HDL-C(≤1.18 mmmol/L)伴有TET ECG阳性者500例的IHD的发生(30例)率为6.00%;IHD死亡(14例)率为2.80%。而高TG/低HDL-C TET ECG 阴性者2500例的IHD发生(25例)率为2.80%, 死亡(8例)率为0.32%, Plt;0.001。表明高TG/低HDL-C伴有TET ECG阳性者是IHD的较大危险因素。结论:高TG/低H DL-C, 伴有TET ECG阳性对IHD者的死亡率的预测有重要意义, 提示二者指标共同作用对IHD者极为不利。
Objective To review the mechanisms of cholesterol gallstones caused by female hormone so as to explore new treatments to prevent gallstones associated with estrogen and progesterone. Methods The literatures on gallstones related with female hormone were reviewed and the mechanisms of cholesterol gallstones were summarized. Results The cholesterol gallstones mechanisms was affected by estrogen through genomic effects，and the nucleation of cholesterol was promoted by estrogen through nongenomic，which resulted in the formation of cholesterol gallstones. And the bile empty dysfunction associated with estrogen through nongenomic effects was also the reason of cholesterol gallstone formation. The G proteins α subunit responsible for the motility of gallbladder were disrupted by progesterone through genomic effects，and the ionic channels and signal transduction were also interfered through nongenomic pathway，which impaired the contraction of gallbladder. However，the nongenomic effects might not play an important role in the gallstones formation caused by progesterone. Conclusions The mechanisms of cholesterol gallstones formation associated with female hormone are complicated，the understanding of chelesterol gallstones formation mechanisms might be helpful to prevent gallstones associated with estrogen and progesterone.
ObjectiveTo summarize progress of 25-hydroxycholesterol (25-OHC), 27-hydroxycholesterol(27-OHC), and 7α,25-hydroxycholesterol (7α,25-OHC) three oxidized cholesterols in inflammation and immunology and to provide evidence for related basic researches and diseases treatments.MethodThe relevant literatures about these three important oxidized cholesterols in the inflammation and immunology in recent years were reviewed.ResultsThe 25-OHC and 27-OHC could exert the antiviral effects by interfering with various viruses invading the host via various mechanisms. Moreover, the 25-OHC and 27-OHC also played the important regulatory roles in a variety of inflammatory processes and inflammatory diseases. The 7α,25-OHC played the important role in a variety of inflammatory processes by acting on the inflammatory and immune cell membrane receptor G-protein coupled receptor 183 (also known as Epstein-Barr virus-inducible receptor 2).Conclusion25-OHC, 27-OHC and 7α,25-OHC play an important roles in occurrence and development of various inflammatory and immune responses and diseases of inflammatory and immune by acting on a variety of nuclear receptors and membrane receptors.
ObjectivesTo systematically review the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on hypercholesteremia.MethodsDatabases including The Cochrane Library, PubMed, EMbase, CNKI, WanFang Data and CBM were searched electronically for randomized controlled trials (RCTs) of PCSK9 inhibitor on the treatment of hypercholesteremia from inception to June 2019. Two reviewers independently screened literatures, extracted data, and assessed risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.ResultsA total of 42 RCTs involving 90 058 patients were included. Alirocumab, evolocumab, bococizumab and LY3015014 were retrieved. Placebo, statin or ezetimibe were used to treat the patient in the control group. The efficacy results showed that there were significant differences between alirocumab combined statin and placebo combined statin (MD=−49.89, 95%CI −56.34 to −43.44, P<0.00001) or evolocumab combined statin and placebo combined statin (MD=−56.54, 95%CI −61.09 to −52.00, P<0.00001) in reducing LDL-C levels. There was significant difference between alirocumab combined statin and ezetimibe combined statin (MD=−29.41, 95%CI −36.08 to −22.75, P<0.00001) in reducing LDL-C levels. The results of Safety showed that there were no significant differences between alirocumab and placebo (RR=0.99, 95%CI 0.97 to 1.01, P=0.37) or evolocumab and placebo (RR=1.05, 95%CI 1.00 to 1.10, P=0.07) in the incidence of adverse events (AEs). There was significant difference between bococizumab and placebo (RR=1.09, 95%CI 1.01 to 1.18, P=0.03) in the incidence of AEs. There was significant difference between evolocumab and ezetimibe (RR=0.89, 95%CI 0.80 to 0.99, P=0.04) in the incidence of AEs. There was no significant difference between alirocumab and statin (RR=0.93, 95%CI 0.84 to 1.03, P=0.90) in the incidence of AEs.ConclusionsPCSK9 inhibitor can reduce LDL-C levels in patients with hypercholesterolemia and has good safety. Due to the limitation of the quantity and quality of the included studies, the above conclusions are needed to be verified by more high quality studies.
Objective To investigate the effect of monocyte count to high density lipoprotein ratio (MHR) on early complications after off-pump coronary artery bypass grafting and to explore the predictive factors for early complications in patients after off-pump coronary artery bypass grafting. Methods The clinical data of patients who underwent simple off-pump coronary artery bypass grafting from October 2021 to September 2023 in our hospital were retrospectively analyzed. The patients were divided into a low value group and a high value group according to the median MHR value. The clinical data of the two groups were compared, and binary logistic regression analysis was used to explore the and predictors of atrial fibrillation (AF) and acute kidney injury (AKI) after coronary artery bypass grafting. Results A total of 220 patients were included, with a median MHR of 0.48. There were 108 patients in the low value group (MHR<0.48), including 71 males and 37 females, with an average age of 65.28±7.85 years. There were 112 patients in the high-value group (MHR≥0.48), including 84 males and 28 females, with an average age of 64.57±8.75 years. There was no statistical difference between the two groups in terms of general basic data such as gender or age (P>0.05). The incidence of postoperative AF and AKI in the high-value group was significantly higher than that in the low-value group (P<0.05), and no statistical difference in terms of other postoperative complications was observed. Binary logistic regression analysis showed that MHR was a risk factor for postoperative AKI and postoperative AF (P<0.05). Conclusion The study shows that MHR is a risk factor for new-onset AF and AKI after coronary artery bypass grafting.
ObjectiveTo observe the effects of oral Xiaoyan Lidan tablets(XYLDT) on the bile composition(total bile acids, cholesterol, phospholipids) in patients with intrahepatic duct stones after common bile duct exploration(CBDE) with T tube drainage, to explore its possible preventive effects on stone recurrence. MethodsForty consecutive patients with intrahepatic bile duct stones who underwent CBDE with T tube drainage were randomly divided into experi mental group and control group. XYLDT were administrated at day 4 after surgery in experimental group(n=20), while none of medication were given in control group(n=20). 2 mL of bile was collected through T tube in both groups at day 1, 2, 3, 7, 14, and 21 postoperatively. Total bile acids(TBA), cholesterol(CHO), and phospholipids(PLIP) in bile were measured, and TBA/CHO ratio and PLIP/CHO ratio were calculated respectively. The results were statistical analyzed. ResultsThe demographic data in both groups including age, gender, height, weight, preoperative concomitant diseases, operative time, postoperative complications, hospital stays, serum total bilirubin, direct bilirubin, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and amylase were not significantly different(P > 0.05). The measurements of TBA, CHO, PLIP, and the ratio of TBA/CHO and PLIP/CHO in bile were not significant on day 1, 2, and 3 after surgery in both groups(P > 0.05). In experimental group, the TBA, CHO, and PLIP on day 7, 14, and 21 after surgery were significantly increased compared with the control group(P < 0.05). The ratio of TBA/CHO on day 7, 14, and 21 was 2.17±0.29, 2.29±0.44, and 2.59±0.58, the ratio of PLIP/CHO was 2.03±0.68, 2.84±0.64, and 2.86±0.77, respectively, which were also significantly increased compared with the control group(P < 0.05). ConclusionsOral XYLDT can increase the secretion of TBA, CHO, and PLIP, elevate the TBA/CHO and PLIP/CHO ratio, and change the bile composition which may increase the dissolution of cholesterol in the bile. Presumably, oral XYLDT may have preventive effects in the recurrence of intrahepatic bile duct stones.