Aberrant expression of LGALS3BP drives an unfavorable prognosis and more aggressive in HCC via regulating PI3K/AKT signaling.

Lectin galactoside-binding soluble 3-binding protein (LGALS3BP) is associated with cancer metastasis and is a promising prognostic marker in neoplasms. In hepatocellular carcinoma (HCC), the prognostic impact and pro-metastatic function of LGALS3BP remain unclear. This study evaluated the endogenous LGALS3BP expression in HCC tissue and its association with prognosis. LGALS3BP protein levels were significantly elevated in clinical HCC tissues and cell lines. Increased LGALS3BP expression was closely associated with disease progression in HCC patients, and they also exhibited an unfavorable prognosis. Furthermore, the knockdown of LGALS3BP inhibited the growth, migration, and invasion of HCC cells in vitro. In mice xenografts, silencing LGALS3BP significantly inhibited tumor cell growth in vivo. Mechanically, upon LGALS3BP depletion, the tumor-suppressive function was dependent on inactivating Phosphatidylinositol 3-kinase (PI3K)/V-akt murine thymoma viral oncogene homolog (AKT) signaling pathway. Collectively, these findings suggest that LGALS3BP employs a pro-tumorigenic function in HCC and may be a promising HCC prognostic marker.

Metabolic dysfunction-associated fatty liver disease is associated with the presence of coronary atherosclerotic plaques and plaque burden.

OBJECTIVE: Atherosclerosis is closely related to cardiovascular disease risk. The present study aims to evaluate the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and the presence of coronary atherosclerotic plaques and plaques burden, as detected by computed tomography angiography (CTA), and further test the screening value of MAFLD on the presence of coronary atherosclerotic plaques and plaques burden. METHODS: We used data from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study, a community-based cohort. Hepatic steatosis was assessed using the fatty liver index. Coronary atherosclerotic plaques and burden were detected by CTA. The association of MAFLD with the presence of coronary atherosclerotic plaques and burden was assessed by binary and ordinal logistic regression models, respectively. RESULTS: Among the 3029 participants (mean age 61.2 ± 6.7 years), 47.9% (1452) presented with MAFLD. MAFLD was associated with an increased odds of the presence of coronary atherosclerotic plaques (OR, 1.27; 95% CI: 1.03-1.56), segment involvement score [cOR (common odds ratio), 1.25; 95% CI, 1.03-1.51], and segment stenosis score (cOR, 1.29; 95% CI, 1.06-1.57). Participants with severe fibrosis or diagnosed as DM-MAFLD subtypes had with higher odds for the presence of coronary atherosclerotic plaques and plaques burden. In addition, MAFLD demonstrated a higher sensitivity for detecting the presence of coronary atherosclerotic plaques and plaque burden (54%-64%) than conventional CVD risk factors (such as diabetes, obesity, and dyslipidemia). CONCLUSION: MAFLD is associated with higher odds of having coronary atherosclerotic plaques and plaque burden. Moreover, MAFLD may offer better screening potential for coronary atherosclerosis than established CVD risk factors.

Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes.

BACKGROUND/OBJECTIVES: Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in "adiponectin paradox", we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation. METHODS: This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α. RESULTS: This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036-0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03-0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5-49.2, P = 0.02). CONCLUSIONS: In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.

CCR9+CD4+ T cells are associated with disease activity in patients with rheumatoid arthritis.

An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated CD4+ T cell levels and to explore the factors influencing disease activity in RA. Fifty-five RA patients, including 28 with active RA (ARA), 27 with inactive RA, and 22 healthy controls, were recruited for this study. The proportion of CCR9+CD4+ T cells and the expression of chemokine receptor 9 (CCR9) on CD4+ T cells were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to evaluate interleukin (IL)-17A and IL-6 levels, respectively. The proportion of CCR9+CD4+ T cells and the expression of CCR9 on CD4+ T cells increased significantly in peripheral blood (PB) and synovial fluid (SF) in ARA compared to those in inactive RA. Furthermore, SF contained more CCR9+CD4+ T cells, IL-6, and IL-17A than PB in RA patients. Moreover, CD4+ T cells in the PB of patients with RA, especially ARA, expressed more CCR9 and secreted more IL-6 and IL-17A after activation. Here, we also demonstrated that both the percentage of CCR9+ cells in CD4+ T cells and the expression of CCR9 on circulating CD4+ T cells were positively correlated with erythrocyte sedimentation rate, hypersensitive C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. CCR9+CD4+ T cells are elevated in PB and SF, and are associated with disease activity in patients with RA.

Diabetic kidney disease screening status and related factors: a cross-sectional study of patients with type 2 diabetes in six provinces in China.

OBJECTIVE: To understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices. METHODS: From December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services. RESULTS: 89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients. CONCLUSION: The results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.

Modulation of cecal microbiota and fecal metabolism in mice by walnut protein.

Walnut meal is a by-product of walnut oil pressing, in which the protein content is more than 40%, which is an excellent food raw material, but at present, it is basically used as animal feed or discarded, which results in a great waste of resources, and its modulating effect on the intestinal microbiota is not clear. In this study, we used supercritically extracted walnut meal as a raw material, prepared walnut meal isolate protein (WP) by alkaline extraction and acid precipitation, and systematically analyzed its structure by Fourier infrared spectroscopy (FTIR), Raman spectroscopy (Raman), and scanning electron microscopy (SEM); meanwhile, we explored the effects of WP on the cecal bacterial flora and fecal metabolites of mice by microbiological and metabolomic techniques. The results showed that the protein content of WP prepared using alkaline extraction and acid precipitation was as high as 83.7%, in which arginine and glutamic acid were abundant, and it has the potential to be used as a raw material for weight-loss meal replacement food; FTIR and Raman analyses showed that the absorption peaks of WP's characteristic functional groups were obvious, and that the content of the α-helix and ß-fold in the secondary structure was greater than 30%, which indicated that it was structurally stable; differential scanning calorimetry (DSC) and SEM analyses showed that WP is a typical spherical particle, its denaturation temperature is 73.6 °C, and it has good thermal stability. Supplementation of WP significantly altered the composition of the intestinal flora in mice, with an increase in beneficial bacteria and a decrease in harmful bacteria; the strongest modulation of the intestinal flora was achieved by altering the composition of the intestinal flora and by increasing the number of Akkermansia (p < 0.01), which consequently affects the function of the microbiota. Based on LC-MS metabolomic results, we identified a total of 87 WP-regulated metabolites, mainly enriched in the bile secretion pathway, which had the highest relevance, followed by benzoxazine biosynthesis. In summary, walnut protein is an important plant protein and has a positive impact on intestinal health, which may provide new ideas for the development of functional foods.

Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.

Analysis of 10 cases of monkeypox in Changning District， Shanghai / 上海预防医学

ObjectiveTo analyze the clinical and epidemiological characteristics of confirmed cases of human monkeypox infection in Changning District， Shanghai， and to explore their clinical and epidemiological characteristics. MethodsClinical data from 10 reported cases of monkeypox in individuals residing in Changning District or identified by local medical institutions between July 20 and September 30， 2023， were collected. Epidemiological case investigations were conducted， and throat swabs， anal swabs， and rash swabs were collected by the treating medical institutions. Real-time fluorescence quantitative PCR was used for monkeypox virus nucleic acid testing， and descriptive epidemiological analysis was applied to analyze the epidemiological characteristics of the cases. ResultsAll 10 confirmed cases of human monkeypox infection were all young males with an average age of 35.4 years， all of whom belonged to the men who have sex with men （MSM） population， with no occupational clustering. The primary clinical symptoms included fever， rash， enlarged inguinal lymph nodes， and muscle soreness. Nine cases presented with a rash， and seven cases experienced fever symptoms. Among the 10 cases， one experienced fever， rash， enlarged lymph nodes， and muscle soreness； two had fever， rash， and enlarged lymph nodes； two had fever， rash， and systemic soreness； two had only a rash； one had fever or rash； and one was asymptomatic. Among the nine cases with a rash， the rash was mainly localized to the genital or anal area， with fewer cases presenting rashes on the limbs or trunk simultaneously. All cases reported a history of non-exclusive MSM behavior within 21 days before the onset of the disease. The interval between the last suspected high-risk exposure and the onset of symptoms was 4 to 10 days， with an average interval of 6.9 days. The time from the onset of fever to the appearance of a rash was 0 to 5 days， with an average of 1.87 days. ConclusionThe main clinical manifestations of human infection with monkeypox are fever， rash， and enlarged inguinal lymph nodes. The MSM population is a high-risk group for monkeypox infection， and its source of infection may be associated with MSM exposure. Early-stage symptoms are mild， leading to potential underdiagnosis. Additionally， patients may conceal information during the investigation process， which increases the difficulty of epidemic prevention and control.

Association of metabolic dysfunction-associated fatty liver disease with systemic atherosclerosis: a community-based cross-sectional study.

BACKGROUND: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). METHODS: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. RESULTS: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85-2.48) and stenosis (cOR, 1.47, 95% CI 1.26-1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24-1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14-2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). CONCLUSIONS: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis.

Apolipoprotein Particle and Cardiovascular Risk Prediction (from a Prospective Cohort Study).

The present study aimed to examine the association between discordant apolipoprotein B (Apo B) with low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) and cardiovascular disease (CVD) risk in the Chinese population and to determine whether adding information on Apo B to LDL-C and HDL-C improves CVD risk prediction. This study collected data from the China Health and Nutrition Survey from 2009 to 2015. Discordant Apo B with LDL-C and non-HDL-C were defined based on residual differences and medians. Logistic regression was used to examine the association between discordant Apo B with LDL-C or non-HDL-C and CVD risk. Areas under the receiver operating characteristic curve and categorical net reclassification improvement were utilized to assess the incremental predictive value of Apo B levels for CVD risk. A total of 7,117 participants were included, the mean age was 50.8 ± 14.3 years, 53.6% were female. During the 6-year follow-up, 207 CVD cases were identified. Participants with discordant high Apo B relative to LDL-C or non-HDL-C were at higher risk of CVD than those with the concordant group (odds ratio 1.38, 95% confidence interval 1.01 to 1.87; odds ratio 1.40, 95% confidence interval 1.01 to 1.94, respectively). However, Apo B had no significant contribution to the predictive value of the China atherosclerotic CVD (ASCVD) risk score (areas under the receiver operating characteristic curve 0.788 for China ASCVD score alone vs 0.790 for China ASCVD score plus Apo B). In conclusion, Apo B has the strongest association with CVD risk in healthy Chinese participants than LDL-C and non-HDL-C. However, it has minimal value in CVD risk assessment and discrimination.

Fuzheng Huayu preparation (/) combined with tenofovir disoproxil fumarate on hepatitis B: a systematic review and Meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of Fuzheng Huayu preparation (/, FZHY) plus tenofovir disoproxil fumarate (TDF) on hepatitis B. METHODS: Numerous databases - PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database, WanFang Database, China Science and Technology Journal Database, and China Biological Medicine Database - were searched to identify the randomized controlled trials published from the inception of the database to November 2021. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. RevMan 5.4 software was used for Meta-analysis. RESULTS: Eight studies involving 990 patients met the inclusion criteria in the current Meta-analysis. Levels of alanine transaminase, aspartate aminotransferase, total bilirubin, hyaluronic acid, type III procollagen, laminin, and type IV collagen after combination therapy were significantly lower than those after TDF therapy alone. However, albumin levels did not differ significantly between the two regimens. Subgroup analysis based on disease progression suggested that the combination therapy improved albumin levels in patients with chronic hepatitis B but not in patients with hepatitis B-related cirrhosis. Moreover, subgroup analysis based on treatment duration suggested that the albumin levels were increased and the type III procollagen levels were decreased with the > 24-week combination therapy but not with the ≤ 24-week combination therapy. CONCLUSIONS: A combination regimen of TDF and FZHY is more effective in treating hepatitis B than TDF alone. The combination therapy can effectively alleviate hepatic fibrosis and improve liver function. However, more standardized, high-quality studies with larger sample sizes are warranted to validate the study results.

Association between residual islet beta-cell function and achieving the target of time in range in inpatients with type 2 diabetes undergoing antidiabetic treatment: An observation study.

AIM: To assess whether the beta-cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. MATERIALS AND METHODS: This cross-sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta-cell function was assessed by the insulin secretion-sensitivity index-2 (ISSI2). RESULTS: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19-8.06) and TAR (OR = 3.40, 95% CI: 1.35-8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90-9.36, P = .07; TAR, OR = 3.14, 95% CI: 1.01-9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91-8.81, P = .07; TAR, OR = 3.24, 95% CI: 1.08-9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66-0.80) and 0.71 (95% CI: 0.63-0.79), respectively. CONCLUSIONS: Beta-cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta-cell function on glycaemic control.

Post-Load Insulin Secretion Patterns are Associated with Glycemic Status and Diabetic Complications in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: To examine whether the different patterns of post-load insulin secretion can identify the heterogeneity of type 2 diabetes mellitus (T2DM). METHODS: Six hundred twenty-five inpatients with T2DM at Jining No. 1 People's Hospital were recruited from January 2019 to October 2021. The 140 g steamed bread meal test (SBMT) was conducted on patients with T2DM, and glucose, insulin, and C-peptide levels were recorded at 0, 60, 120, and 180 min. To avoid the effect of exogenous insulin, patients were categorized into three different classes by latent class trajectory analysis based on the post-load secretion patterns of C-peptide. The difference in short- and long-term glycemic status and prevalence of complications distributed among the three classes were compared by multiple linear regression and multiple logistic regression, respectively. RESULTS: There were significant differences in long-term glycemic status (e. g., HbA1c) and short-term glycemic status (e. g., mean blood glucose, time in range) among the three classes. The difference in short-term glycemic status was similar in terms of the whole day, daytime, and nighttime. The prevalence of severe diabetic retinopathy and atherosclerosis showed a decreasing trend among the three classes. CONCLUSIONS: The post-load insulin secretion patterns could well identify the heterogeneity of patients with T2DM in short- and long-term glycemic status and prevalence of complications, providing recommendations for the timely adjustment in treatment regimes of patients with T2DM and promotion of personalized treatment.

Co-expression of soluble guanylyl cyclase subunits and PDE5A shRNA to elevate cellular cGMP level: A potential gene therapy for myocardial cell death.

BACKGROUND: Genetic manipulation on the NO-sGC-cGMP pathway has been rarely achieved, partially due to complexity of the soluble guanylyl cyclase (sGC) enzyme. OBJECTIVE: We aim to develop gene therapy directly targeting the pathway to circumvent cytotoxicity and tolerance after prolonged use of NO-donors and the insufficiency of PDE inhibitors. METHODS: In this study, we constructed lentivirus vectors expressing GUCY1A3 and GUCY1B3 genes, which encoded the α1 and ß1 subunits of soluble guanylyl cyclase (sGC), respectively, to enhance cGMP synthesis. We also constructed lentiviral vector harboring PDE5A shRNA to alleviate phosphodiesterase activity and cGMP degradation. RESULTS: Transductions of human HEK293 cells with the constructs were successful, as indicated by the fluorescent signal and altered gene expression produced by each vector. Overexpression of GUCY1A3 and GUCY1B3 resulted in increased sGC enzyme activity and elevated cGMP level in the cells. Expression of PDE5A shRNA resulted in decreased PDE5A expression and elevated cGMP level. Co-transduction of the three lentiviral vectors resulted in a more significant elevation of cGMP in HEK293 cells without obvious cytotoxicity. CONCLUSION: To the best of our knowledge, this is the first study to show that co-expression of exogenous subunits of the soluble guanylyl cyclase could form functional enzyme and increase cellular cGMP level in mammalian cells. Simultaneous expression of PDE5A shRNA could alleviate feedback up-regulation on PDE5A caused by cGMP elevation. Further studies are required to evaluate the effects of these constructs in vivo.

Progress in research of risk prediction model for chronic kidney disease / 中华流行病学杂志

Chronic kidney disease (CKD) is an important global public health problem that greatly threatens population health. Application of risk prediction model is a crucial way for the primary prevention of CKD, which can stratify the risk for developing CKD and identify high-risk individuals for more intensive interventions. By now, more than twenty risk prediction models for CKD have been developed worldwide. There are also four domestic risk prediction models developed for Chinese population. However, none of these models have been recommended in clinical guidelines yet. The existing risk prediction models have some limitations in terms of outcome definition, predictors, strategies for handling missing data, and model derivation. In the future, the applications of emerging biomarkers and polygenic risk scores as well as advances in machine learning methods will provide more possibilities for the further improvement of the model.

Development of parenting behavior scale for caregivers of children aged 2 to 6 years and analysis for its reliability and validity / 中华预防医学杂志

To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.

Two new phenylpropanoids from wine-processed Corni Fructus / 中国中药杂志

Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-β-glucopyranoside(3),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-β-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) μmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 μmol·L~(-1) was 96.09%±1.77%.

Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway / 中国中药杂志

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

A new norsesquiterpenoid from Arctium lappa leaves / 中国中药杂志

Chemical constituents were isolated and purified from ethyl acetate fraction of Arctium lappa leaves by silica gel, ODS, MCI, and Sephadex LH-20 column chromatography. Their structures were identified with multiple spectroscopical methods including NMR, MS, IR, UV, and X-ray diffraction combined with literature data. Twenty compounds(1-20) were identified and their structures were determined as arctanol(1), citroside A(2), melitensin 15-O-β-D-glucoside(3), 11β,13-dihydroonopordopicrin(4), 11β,13-dihydrosalonitenolide(5), 8α-hydroxy-β-eudesmol(6), syringin(7), dihydrosyringin(8), 3,4,3',4'-tetrahydroxy-δ-truxinate(9),(+)-pinoresinol(10), phillygenin(11), syringaresinol(12), kaeperferol(13), quercetin(14), luteolin(15), hyperin(16), 4,5-O-dicaffeoylquinic acid(17), 1H-indole-3-carboxaldehyde(18), benzyl-β-D-glucopyranoside(19), and N-(2'-phenylethyl) isobutyramide(20). Among them, compound 1 is a new norsesquiterpenoid, and compounds 2-5, 7-8, and 18-20 are isolated from this plant for the first time.

Effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor level and morning stiffness time in patients with refractory rheumatoid arthritis / 中国医师杂志

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.