Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Non-alcoholic fatty liver disease(NAFLD)is a series of diseases characterized by hepatic steatosis and is also a metabolism-associated disease and an important factor for liver fibrosis,liver cirrhosis,and hepatocellular carcinoma.Endoplasmic reticulum is a core organelle for the regulation of lipid metabolism,and unfolded protein response is an important process of endoplasmic reticulum stress(ERS).Based on the important stress role of endoplasmic reticulum in metabolism-associated diseases,this article explores the influencing mechanism between ERS and NAFLD and reviews the research advances in lipid metabolism,inflammatory response,hepatocyte death,fibrosis,and ERS-targeted therapies in the pathological development of NAFLD.

AIM: To avoid the problem of retinal dissection in guinea pig large eyeball tissue sections, different methods were used to optimize the fixation effect of the posterior pole of the eyeball.METHODS: A total of 75 normal guinea pigs(2 weeks old)were randomly divided into 5 large groups. Group A(1-3 small groups), the entire eyeball was fixed with FAS, Davidson fixative 1(D1), and Davidson fixative 2(D2)for 24 h; group B(4-6 small groups), the entire eyeball was fixed with FAS, D1, and D2 for 1 h, then cut the cornea and fix it in their respective fixatives for 2 h; group C(7-9 small groups), the eyeball was fixed in FAS, D1, and D2 for 1 h, divided into left and right halves along the direction of the optic nerve, and then placed them in their respective fixation solutions for 2 h; group D(10-12 small groups), after fixation for 3 h in FAS, D1, and D2, the eyeball was divided into left and right halves along the optic nerve direction; group E(13-15 small groups), the cornea was cut after fixation for 3 h in FAS, D1, and D2. Hematoxylin-eosin(HE)staining was used to compare the fixation effect on posterior eyeball in each group.RESULTS: After fixation, the surface of the eyeballs in groups, 1-6 and 11-15 was smooth and round, with a transparent and bright color. In groups 7-10, the eyeballs were sunken, wrinkled, and deformed. The HE staining showed that the eyeball morphology of groups 1, 5, 6, 14, and 15 was significantly better than the other groups, with a regular internal tissue structure. The eyeballs of the other groups were sunken and wrinkled, and the internal tissue was curled and tangled, with severe retinal detachment. In groups 1, 5, 6, 14, and 15, the retina, choroid, and sclera tissues of group 14 were closely connected, without obvious retinal detachment, rupture, or curling. The tissue structure was clear and visible, and the cells were arranged neatly.CONCLUSION: The fixation effect of cutting the cornea after fixing guinea pig eyeball with D1 fixative for 3 h is the most ideal, and this operation method is simple and suitable for studying the related structures of the posterior pole of the eye.

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To search and summarize the relevant evidences for perioperative hydration in prevention of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary intervention, and to provide evidence-based basis for clinical nursing staff to develop personalized perioperative hydration plan and prevent CIAKI.Methods:Evidence-based nursing was used to search evidences for perioperative hydration in prevention of CIAKI in patients undergoing coronary intervention in UpToDate, National Guideline Clearing-house (NGC) , European Society of Cardiology (ESC) , JBI Evidence Summary Database, Cochrane Database, PubMed, Wanfang Database, China National Knowledge Infrastructure (CNKI) and China Biomedical Literature Database (CBM) , including evidence summary, guidelines, expert consensus and systematic reviews. The search time was from the establishment of the database to February 2019. Two researchers evaluated the quality of included literatures and extracted evidence from literatures that met the quality standards.Results:A total of 9 articles of evidence were included, including 1 evidence summary, 3 guidelines, 3 expert consensus and 2 systematic evaluations. Finally, a total of 10 pieces of evidence from 5 aspects, including CIAKI risk assessment, hydration fluid type, hydration path and timing, hydration rate and urine volume monitoring, were summarized.Conclusions:This study summarizes the best evidence for perioperative hydration in prevention of CIAKI in patients undergoing coronary intervention and provides an evidence-based basis for clinical medical staff.

Objective:To investigate the induction of tanshinoneⅡA (TanⅡA) on the differentiation of human placenta-derived mesenchymal stem cells (hPDMSCs) into cardiomyocytes, and to provide an experimental basis for TanⅡA as a cardiomyocyte differentiation inducer.Methods:The hPDMSCs were treated with different concentrations of TanⅡA (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0mg·L-1) , and the nontoxic dose of TanⅡA (0.1mg·L-1) was screened by MTT assay for experiment.The hPDMSCs were divided into control group, 5-aza induction (10μmol·L-1) group, and TanⅡA induction (0.1mg·L-1) group.After culture for 20d, the expressions ofα-sarcomeric actin (α-SCA) in the cells in various groups were detected with immunohistochemistry;the positive expression rates of cardiac troponin I (cTnI) in the cells in various groups were detected with immunofluorescence, and the differentation rates of cardiomyocytes were calculated.The expression levels of GATA-binding protein 4 (GATA4) , atrial natriuretic factor (ANF) , cTnI, glycogen synthase kinase-3β (GSK-3β) andβ-catenin in the cells were detected with Western blotting method.Results:The biological characteristics of hPDMSCs accorded with the mesenchymal stem cells.The MTT results showed that when the concentration of TanⅡA was more than 0.1mg·L-1, the cell survival rates were decreased with the increase of concentration;the cells in control group showed a rapid growth trend before 12d, and the proliferation activities of the cells began to decrease on the 12th day.Compared with control group, the cell activities in 5-aza induction group and TanⅡA induction group were significantly decreased (P＜0.05) .The immunohistochemistry staining results showed that the cells in control group didn't expressα-SCA, and the cells in 5-aza induction group and TanⅡA induction group expressedα-SCA, especially in TanⅡA induction group.Compared with control group, the expression levels of GATA4 (t5-aza=2.937, P5-aza＜0.05;tTanⅡA=4.769, PTanⅡA＜0.05) , ANF (t5-aza=3.728, P5-aza＜0.05;tTanⅡA=5.912, PTanⅡA＜0.05) , cTnI (t5-aza=3.623, P5-aza＜0.05;tTanⅡA=7.153, PTanⅡA＜0.05) and GSK-3β (t5-aza=2.995, P5-aza＜0.05;tTanⅡA=5.420, PTanⅡA＜0.05) proteins in the cells in 5-aza induction group and TanⅡA induction group were significantly increased, and the expression levels ofβ-catenin (t5-aza=2.985, P5-aza＜0.05;tTanⅡA=6.951, PTanⅡA＜0.05) protein were significantly decreased;compared with 5-aza induction group, the expression levels of GATA4, ANF, and GSK-3βproteins in TanⅡA induction group were increased (P＜0.05) .Conclusion:TanⅡA can induce the differentiation of hPDMSCs into cardiomyocytes, which has better effect than 5-aza, and its mechanism may be related to inhibiting the Wnt/β-catenin signaling pathway.

Objective To evaluate the feasibility and efficacy of the ultrasonic technology,digital subtraction angiography(DSA) combined guide line of liver abscess drainage tube.Methods 70 patients with liver abscess received ultrasonic technology,DSA joint drainage tube after treatment.Using ultrasound technology and DSA of complementary advantages,enhancement in the operation was good,especially the liver abscess of abdominal pneumatosis was more and more room,enhancement effect was better than that of pure guided by ultrasound.Results 70 patients were all successful puncture and catheter,development was good,all 70 cases cured,without any serious complication.Conclusion Ultrasound technology,DSA joint guided puncture catheter drainage is a safe,minimally invasive treatment,has significant efficacy and important clinical value.