Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

Objective To analyze the application characteristics,trends,and special advantages of anti-infection research using the Bayesian method,and to provide methodological reference for the development of anti-infection research.Methods PubMed,CNKI and WanFang Data were electronically searched for the studies on anti-infection using Bayesian method published from January 1,2015 to November 21,2023.The relevant information of publication time,anti-infection type,sample size,Bayesian characteristics and Bayesian application pattern were analyzed descriptively and reviewed.Results A total of 86 studies were included,of which 41.9％were observational studies,only 7.0％were enterprise-initiated studies,and 48.8％were mentioning prior information studies.There was no domestic intervention study.The application characteristics and advantages of Bayesian method in intervention study,observational study and pharmacokinetic study are different.In intervention researches and observational researches,the application of Bayesian design decision and the application of Bayesian analysis and estimation accounts for 69.2％and 52.8％at most,respectively.Conclusions The Bayesian method is flexible,can be used for small sample sizes and complex model research,and can deal with uncertainty.In intervention studies in the field of anti-infection in China,the Bayesian method has not been applied widely.Only a handful of studies applying Bayesian method have been initiated by companies.In the future,it is still necessary to promote the advantages and application scenarios of Bayesian methods in the field of anti-infection research and strengthen the standardization of the application of Bayesian method.

Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.

Objective To analyze the application characteristics,trends,and special advantages of anti-infection research using the Bayesian method,and to provide methodological reference for the development of anti-infection research.Methods PubMed,CNKI and WanFang Data were electronically searched for the studies on anti-infection using Bayesian method published from January 1,2015 to November 21,2023.The relevant information of publication time,anti-infection type,sample size,Bayesian characteristics and Bayesian application pattern were analyzed descriptively and reviewed.Results A total of 86 studies were included,of which 41.9％were observational studies,only 7.0％were enterprise-initiated studies,and 48.8％were mentioning prior information studies.There was no domestic intervention study.The application characteristics and advantages of Bayesian method in intervention study,observational study and pharmacokinetic study are different.In intervention researches and observational researches,the application of Bayesian design decision and the application of Bayesian analysis and estimation accounts for 69.2％and 52.8％at most,respectively.Conclusions The Bayesian method is flexible,can be used for small sample sizes and complex model research,and can deal with uncertainty.In intervention studies in the field of anti-infection in China,the Bayesian method has not been applied widely.Only a handful of studies applying Bayesian method have been initiated by companies.In the future,it is still necessary to promote the advantages and application scenarios of Bayesian methods in the field of anti-infection research and strengthen the standardization of the application of Bayesian method.

Objective: To investigate the prevalence and influencing factors of caries among Tibetan primary school students in Maqu County, Gansu Province, so as to provide insights into caries control among children living in ethnic minority areas. Methods: Tibetan primary school students at grades three to six were sampled from two primary schools in Maqu County using a multi-stage cluster sampling method. Primary school students' demographics, dietary habits and oral health habits were collected using questionnaire surveys, and the caries was tested. Factors affecting the development of caries were identified using a multivariable Poisson regression model. Results: A total of 378 Tibetan primary school students were tested, and there were 334 students with caries, with a caries prevalence rate of 86.30%, and a mean caries number of (4.72±2.69) teeth. Multivariable Poisson regression analysis showed that grade (grade 5, IRR=0.791, 95%CI: 0.706-0.886; grade 6, IRR=0.698, 95%CI: 0.593-0.822), frequency of vegetable intake (less than once daily, IRR=0.872, 95%CI: 0.778-0.978; once daily, IRR=0.769, 95%CI: 0.677-0.873; twice and more daily, IRR=0.571, 95%CI: 0.469-0.696), frequency of tooth brushing (once daily, IRR=0.814, 95%CI: 0.734-0.904; twice and more daily, IRR=0.606, 95%CI: 0.521-0.703) and frequency of oral examinations (IRR=0.736, 95%CI: 0.594-0.911) were influencing factors of caries. Conclusion The prevalence of caries is 86.30% among Tibetan primary school students at grades 3 to 6 in Maqu County, and age, dietary habit and oral health habit are factors affecting the development of caries.

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

In this study,a functionalized covalent-organic framework(COF)was first synthesized using porphyrin as the fabrication unit and showed an edge-curled,petal-like and well-ordered structure.The synthesized COF was then introduced to prepare porous organic polymer monolithic materials(POPMs).Two com-posite POPM/COF monolithic materials with rod shapes,referred to as sorbent A and sorbent B,were prepared in stainless steel tubes using different monomers.Sorbents A and B exhibited relatively uniform porous structures and enhanced specific surface areas of 153.14 m2/g and 80.01 m2/g,respectively.The prepared composite monoliths were used as in-tube solid-phase extraction(SPE)sorbents combined with HPLC for the on-line extraction and quantitative analytical systems.Indole alkaloids(from Catharanthus roseus G.Don and Uncaria rhynchophylla(Miq.)Miq.Ex Havil.)contained in mouse plasma were extracted and quantitatively analyzed using the online system.The two composite multifunctional monoliths showed excellent clean-up ability for complex biological matrices,as well as superior selec-tivity for target indole alkaloids.Method validation showed that the RSD values of the repeatability(n=6)were≤3.46％,and the accuracy expressed by the spiked recoveries was in the ranges of 99.38％-100.91％and 96.39％-103.50％for vinca alkaloids and Uncaria alkaloids,respectively.Furthermore,sorbents A and B exhibited strong reusability,with RSD values≤5.32％,which were based on the peak area of the corresponding alkaloids with more than 100 injections.These results indicate that the composite POPM/COF rod-shaped monoliths are promising media as SPE sorbents for extracting trace compounds in complex biological samples.

Objective:The aim of the study is to investigate correlation between HVPG and other clinical parameters and risk factors of clinically significant portal hypertension (CSPH) in patients with compensated cirrhosis based on hepatic vein pressure gradient (HVPG).Methods:82 patients with compensated cirrhosis were prospectively recruited in the Department of Infectious Diseases of Shulan Hospital from April 2021 to August 2021. Collected the basic data of each patients, laboratory examination results, liver stiffness, gastroscopy, and HVPG. Pearson correlation analysis, univariate logistic regression analysis and multivariate regression analysis are used to find the risk factors of patients with CSPH.Results:The median HVPG of 82 patients were 9.0(8.3)mmHg. There are 31 cases (27.8%) have developed CSPH, and the correlation analysis shown that CSPH was positively correlated with total bilirubin, INR and liver stiffness, but negatively correlated with albumin, hemoglobin and platelet count. According to univariate logistic regression analysis, the factors which can affecting CSPH include male, diabetes, esophageal gastric varices, albumin, hemoglobin, INR, blood sodium, white blood cells, platelet count, liver stiffness and CTP, FIB-4, ALBI, etc. After adjusted by multivariate analysis, only platelet counts, liver stiffness, esophageal gastric varices were independent risk factors for CSPH in patients with compensated cirrhosis.Conclusion:HVPG is the gold criteria for assessment of portal hypertension. The platelet count, liver stiffness, esophageal gastric varices are independently associated with the development of CSPH in patients with compensated cirrhosis, which can help assess PH and give early diagnosis and treatment to improve their prognosis.

Objective:To investigate the prevalence and severity of anemia and its effect on one-year survival in HBV related decompensated cirrhosis patients (HBV-DC).Methods:647 consecutive HBV-DC patients were prospectively enrolled from January 2016 to December 2018 in Hwamei Hospital, University of Chinese Academy of Sciences. Anemia and the baseline characterics of patients were evaluated. Cox regression analysis was used to evaluate the impact on one-year survival.Results:Of 647 HBV-DC patients, 406 were complicated with anemia, accounting for 62.8% of the total population, including 254 patients with mild anemia (39.3%), 122 with moderate anemia (18.9%), and 30 with severe anemia (4.6%). 133 died in 1 year, with a mortality rate of 20.6%. On cox regression analysis, age ( HR, 1.033; 95% CI, 1.017-1.049), hemoglobin ( HR, 0.992; 95% CI, 0.985-0.999), WBC ( HR, 1.069; CI, 1.028-1.111), MELD score ( HR, 1.095; 95% CI, 1.070-1.120) were independent associated with 1-year mortality. The 1-year survival KM curve of anemia and its severity was significantly different ( P<0.001). Conclusions:The incidence of anemia in HBV-DC patients is as high as 62.8%. Anemia and its severity are important factors affecting the one-year prognosis of HBV-DC patients, which provide new ideas for clinical evaluation and prognosis assessment.

Literature about functional dyspepsia treated with acupuncture in recent 5 years is retrieved in China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed. The research achievements are arranged and summed up to explore the mechanism of acupuncture for functional dyspepsia. It is found that acupuncture can regulate the secretion of braingut petide, and cause the coordination response of limbic system-brain. Also, it adjusts serum molecule metabolin and the gene expression of the transduction pathway of adjustment signal for rats. It is believed that functional dyspepsia treated with acupuncture is through multiple ways, and adjusting the function of braingut axis is one of the important mechanisms.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Dyspepsia ; genetics ; metabolism ; therapy ; Humans ; Rats ; Signal Transduction