Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.

Objective To investigate the current status of frailty in patients on maintenance hemodialysis(MHD),and explore the correlation of frailty with anxiety and depression.Methods General information,clinical data and blood biochemical data of 101 cases who underwent MHD in Department of Nephrology,Shunde Hospital Affiliated to Jinan University from January 2023 to January 2024 were collected.FRAIL scale was applied to evaluate the frailty of the patients,and they were accordingly classified into frailty group and non-frailty group(including pre-frail and non-frail participants).Anxiety and depression were evaluated by GAD-7 and PHQ-9 scale.Univariate analysis and logistic regression were used to explore the association of frailty with anxiety,depression and other possible influencing factors.Results Among the 101 cases,29 cases(28.71%)were includedin frailty group and 72 cases(71.29%)in non-frailty group.There were 42 patients with depression(41.58%)and 25 with anxiety(24.75%).In the frailty group,the prevalence of depression was 65.52%and that of anxiety 55.17%.There were significant differences in age,grip strength,exercise,stroke and coronary heart disease,anxiety and depression,ferritin and CRP between the two groups(P＜0.01).Multivariate regression analysis showed that depression,anxi-ety,no exercise,stroke and high ferritin concentration were independent risk factors for frailty in MHD patients(P＜0.05).Conclusion In patients on MHD,frailty is closely associated with depression,anxiety,and lack of exercise,and stroke as well as high ferritin concentration are independent risk factors for frailty.

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.
Adult ; Humans ; Cohort Studies ; Zinc ; Diet ; Hypertension/epidemiology* ; Eating ; China/epidemiology*

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Objective:To investigate the potential guiding role of fractional flow reserve(FFR) in surgical revascularization by comparing the relationship between coronary fractional flow reserve(FFR) and blood flow pattern status of bypass graft.Methods:A total of 86 patients with coronary artery disease between March 2016 to October 2019 were included in the study, with 59 males and 27 females; the age ranged from 42 to 77 years old, with an average of(58±12) years old. According to the measured FFR value of the left anterior descending artery, they were divided into severe ischemic group(FFR<0.75), boundary group(0.75≤FFR<0.80) and mild ischemic group(FFR≥0.80). Transit time flow meter(TTFM) was used to evaluate the blood flow status of the bridge vessel from the left internal thoracic artery to the left anterior descending coronary artery.Results:Mean graft flow(MGF) was measured at(21.24±5.71)ml/min, (18.25±7.72)ml/min, (16.47±7.83)ml/min in severe ischemic group, boundary group and mild ischemic group. The results of mean pulsatility index(PI) was 2.58±0.96, 3.14±1.19 and 3.53±1.34, the ratio of diastolic flow during the entire graft flow was 0.63±0.10, 0.55±0.11 and 0.53±0.11, patients appeared systolic reverse flow was 2 cases(3.6%), 3 cases(18.8%) and 3 cases (20.0%), respectively. There were statistically significant differences in MGF( P=0.027)、PI( P=0.007)、the ratio of DF( P=0.001) and the quantity of patients appeared systolic reverse flow( P=0.027) between the three groups. Conclusion:Due to increasing severity of coronary artery stenosis, MGF and the ratio of diastolic flow increased, and there appears to be an decreased PI and quantity of patients appeared systolic reverse flow. The chance of bypass graft occlusion may increase for the near and middle term in mild to moderate functional coronary artery stenosis(FFR≥0.75). For patients with severe functional coronary artery stenosis(FFR<0.75), it can obtain satisfactory flow parameters and ideal clinical outcomes.

Objective:To assess the effects of heart valve replacement under extracorporeal circulation(ECC)on left ventricular function and regulatory T cells in elderly patients with rheumatic heart disease(RHD).Methods:113 elderly patients with rheumatic heart disease receiving ECC heart valve replacement at our hospital from September 2018 to September 2020 were selected retrospectively as subjects.Another 113 healthy people from the same period were selected as the control group.Patients in the observation group received ECC heart valve replacement.Left heart function and regulatory T cells were compared between the two groups.Results:Before surgery, the left atrial transverse diameter(LA)of RHD patients was significantly increased compared with the control group[(56.2±9.3)mm vs.(29.4±3.5)mm, t=28.670, P<0.001], and the left ventricular end diastolic diameter(LVDD)[(32.4±7.7)mm vs.(38.4±8.5)mm, t=5.561, P<0.001], left ventricular ejection fraction(LVEF)[(58.4±11.5)% vs.(65.6±10.5)%, t=4.915, P<0.001]and cardiac output(CO)[(3.7±2.6)L/min vs.(4.7±1.6)L/min, t=3.482, P<0.001]were significantly decreased compared with the control group.There were no significant changes in left heart function parameter values 10 min and 1 day after surgery(all P>0.05).One month after surgery, the inner diameter of pulmonary artery(PA)[(25.2±3.8)mm vs.(31.2±5.6)mm, t=9.659, P<0.001]and LA[(46.2±7.8)mm vs.(56.2±9.3)mm, t=8.758, P<0.001]were decreased compared with those before surgery, while changes in right ventricular end diastolic inner diameter(RVDD)and left ventricular end diastolic inner diameter(LVDD)were not significant, and there were no significant differences in LVEF, CO and LVFS(all P>0.05).The proportion of CD25 + CD4 + T cells in lymphocytes and the proportion of CD4 + CD25 + Foxp3 + Treg cells in CD4 + T cells in RHD patients before surgery were significantly lower than those in the control group( P<0.01).The proportions decreased 10 min and 1 day after surgery, but increased 3 days after surgery and returned to preoperative levels 7 days after surgery, but were still significantly lower than those in the control group( P<0.05). Conclusions:After ECC heart valve replacement in elderly RHD patients, the left atrium will shrink for a short time and tricuspid regurgitation can recover, with reduced damage of cellular immune function, but its contractile function remains unchanged.

Objective:Based on the occupational cohort of Beijing Medical Examination Center, to explored the relevant factors of nonalcoholic fatty liver disease (NAFLD), and to provide scientific basis for screening and early diagnosis of NAFLD in high-risk population.Methods:Based on the cohort of occupational population who underwent physical examination in Beijing physical examination center from January to December 2009, the physical examination indexes were collected, and a retrospective survival cohort with a follow-up period of 3 years was established.According to the idea of nested case-control study, each case was randomly matched with the same gender, age and physical examination time in the same month by using the method of random sampling without putting back.Conditional logistic regression model was established by using the matched data.The diagnostic value of related indicators for NAFLD was analyzed by receiver operating characteristic curve (ROC).Results:A total of 1 194 subjects were included, including 684 males (57.3%, 684/1 194) and 510 females (42.7%, 510/1 194). The age was (50.8±11.6) years.The age ranged from 24.0 to 88.0 years.There were 597 patients with NAFLD, including 342 males and 255 females.Logistic regression analysis showed that body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid and urea nitrogen were statistically significant in male model (all P<0.05). Body mass index( OR=1.242, 95% CI 1.143-1.349, P<0.001), hemoglobin( OR=1.034, 95% CI 1.015-1.053, P<0.001), platelet( OR=1.005, 95% CI 1.002-1.009, P=0.005), uric acid( OR=1.004, 95% CI 1.001-1.006, P=0.004), high density lipoprotein cholesterol( OR=0.377, 95% CI 0.184-0.775, P=0.008) and urea nitrogen( OR=0.807, 95% CI 0.693-0.938, P=0.005) were protective factors for NAFLD in male patients..Body mass index( OR=1.552, 95% CI 1.366-1.762, P<0.001), triglyceride ( OR=2.606, 95% CI 1.616-4.204, P<0.001), blood glucose( OR=2.199, 95% CI 1.332-3.631, P=0.002), uric acid( OR=1.005, 95% CI 1.001-1.010, P=0.024) in female model were statistically significant ( P<0.05), and were risk factors for NAFLD in female patients. Conclusion:The incidence rate of NAFLD was different among different gender and age, body mass index, high density lipoprotein cholesterol, hemoglobin, platelet count, uric acid, urea nitrogen, triglyceride and blood glucose were closely related to the incidence of NAFLD.

Objective:To analyze the effect of home quarantine on blood glucose and lipids in healthy adults during the COVID-19 epidemic times.Method:From April 7, 2020 to May 1, 2020, 512 adults wereexamined in Beijing physical examination center, of which 87 adults aged olderthan 18, received community closed management or home quarantine from January 23, 2020 to March 30, 2020, and theadultshad physical examination in Beijing physical examination center in the same month of 2018 and 2019 were selected as controls. The change trend of blood glucose and blood lipid acrossthe three years was analyzed by one-way repeated measurement of variance, and the difference of blood lipid and blood glucose between two years of physical examination was further analyzed by Bonferroni method. Datawereanalyzed by gender.Result:Among the 87 subjects, 36 (41.4%) were male and 51(58.6%) were female. The average age was (46.3±13.2) years and ranged from 24 to 74. The difference of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting blood glucose (FBG) among 2018, 2019 and 2020 was statistically significant (all P<0.05), while differences in LDL-C, TC and FBG were statistically significant for males (all P<0.05) and HDL-C, LDL-C, TC and FBG were statistically significant for females (all P<0.05). HDL-C in 2018and 2020were significantly lower than that in 2019 [(1.27±0.29), (1.30±0.31) vs. (1.36±0.34) mmol/L], LDL-C in 2020was significantly higher than that in 2018and 2019 [(3.11±0.88) vs. (2.81±0.77), (2.84±0.71) mmol/L], TG in 2020 was significantly higher than that in 2019[(1.54±1.17) vs. (1.32±0.80) mmol/L], TC in 2019and 2020were significantly higher than that in 2018 [(4.88±0.94), (5.10±0.99) vs. (4.63±0.90) mmol/L], and the FBG in 2019and 2020were significantly lower than that in 2018 [(5.34±1.17), (5.44±1.58) vs. (5.84±1.70) mmol/L] (all P<0.05). The comparative analysis of men and women showed that the means of LDL-C, TG, TC and FBG of men were higher than those of women while the mean of HDL-C was lower than that of women in each year; compared with 2019, the increase of LDL-C and TC of men was obvious while the decrease of HDL-C of women was obvious (all P<0.05) in 2020. Conclusion:During the epidemic period of COVID-19, the home quarantine has adverse effects on blood glucose and lipid.