ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

68Ga-DOTATATE/18F-FDG two-day low-dose total-body PET/CT imaging is increasingly employed to facilitate the diagnosis,prognosis,and heterogeneity assessment of neuroendocrine neoplasms.We present a consensus on operational guideline for a two-day combined imaging from experts in low-dose/ultra-low-dose total-body PET/CT from several domestic medical institutions.

Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.

OBJECTIVE To evaluate the short-term efficacy of single-session microwave ablation for benign thyroid nodule.METHODS Patients with benign thyroid nodules treated by microwave ablation between June 2019 and December 2022 at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,were included for analysis.Thyroid function was tested 1 month after treatment,and ultrasound and thyroid function were performed 3 months,6 months and 1 year after treatment.Volume reduction rates(VRR)of nodules were calculated.Data of the last follow-up within 1 year were included for analysis.Variables including gender,age,whether Hashimoto's thyroiditis was present,longitudinal diameter of nodules,solid volume of nodules were included for univariate and multivariate analysis.RESULTS A total of 151 patients with 163 nodules were included.The perioperative complication rate was 1.99%(3/151).The VRR at half year after treatment was(79.58±17.70)%,and the success rate at half year after treatment was 93.43%(128/137).The VRR of at 1year after treatment was(81.24±24.29)%.The 1-year treatment success rate was 92.77%(77/83).Univariate and multivariate analysis showed that nodular solid volume and age were independent factors affecting VRR after ablation.Regression coefficient of age and solid volume was 0.34(P<0.05)and-0.47(P<0.05),respectively.For every 1 cm3 increase in solid volume,1-year VRR(%)decreased by 0.47.Regression equation:1-year VRR=68.92+0.34×age-0.47×solid volume.Serum FT4 gradually decreased and the thyroid stimulating hormone(TSH)gradually increased within 6 months after ablation,and the differences were statistically significant(P<0.05).After 6 months,serum FT4 gradually recovered to the normal level and TSH gradually recovered.However,TSH still did not reach the preoperative level one year after ablation.FT3 decreased gradually after treatment,but there was no significant difference between the values at each time point(P=0.40).After the ablation of thyroid nodule,the mean value of thyroid function index fluctuated,but all of them were within the normal reference range.CONCLUSION Microwave ablation is a safe and effective treatment method for benign thyroid nodules,with an overall success rate of over 90%.Solid nodule volume and age are independent factors affecting the microwave ablation effect of benign thyroid nodules.

ObjectiveTo assess the quality of randomized controlled trials （RCTs） of compound traditional Chinese medicine （TCM） prescriptions in the treatment of nonalcoholic steatohepatitis （NASH）， and to provide recommendations for standardizing the design and reporting of RCTs in this field. MethodsDatabases such as PubMed， Web of Science， Embase， the Cochrane Library， CNKI， VIP， and Wanfang Data were searched for RCTs of compound TCM prescriptions in the treatment of NASH published from January 1， 2018 to December 31， 2023， and the articles were screened and assessed based on the Cochrane risk-of-bias assessment tool （RoB 2）， the unified standard for clinical trial reporting （CONSORT 2010）， and CONSORT-CHM Formulas 2017 for compound TCM prescriptions. ResultsA total of 45 articles were finally included， and most of these studies were rated as high-risk bias by RoB 2.0. The analysis based on the CONSORT control checklist showed a relatively low reporting rate for most of the key items regarding the quality of RCT studies. ConclusionA relatively large risk of bias is observed in the clinical studies on compound TCM prescriptions in the treatment of NASH published in the past six years， which may lead to the poor quality of reporting and evidence. It is suggested that the top-level design of clinical studies should be taken seriously in addition to investigating the advantages of TCM， so as to improve the quality of clinical studies.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

ObjectiveTo observe the clinical efficacy of Danzhi Jiangtang capsules with the functions of replenishing Qi， nourishing Yin， and dredging collaterals on patients with type 2 diabetes mellitus （T2DM） combined with lower-extremity macroangiopathy and serum levels of homocysteine （Hcy） and cystatin C （Cys C）. MethodA total of 80 eligible patients who were treated in the department of endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2017 to December 2019 were randomized into the treatment group （40 cases） and control group （40 cases）. Both groups received the basic therapies for diabetes and Danzhi Jiangtang capsules （oral） was added to the treatment group. The levels of glycosylated hemoglobin A1c （HbA1c）， fasting plasma glucose （FPG）， 2-hour postprandial glucose （2 hPG）， fasting C-peptide （C-P）， and 2-hour postprandial C-peptide （2 hC-P）， triglycerides （TG）， total cholesterol （TC）， high density lipoprotein cholesterol （HDL-C）， and low density lipoprotein cholesterol （LDL-C） and serum levels of Hcy and Cys C were measured and the traditional Chinese medicine（TCM） syndrome scores were calculated before and after treatment in the two groups. ResultAfter 12 weeks of treatment， levels of HbA1c， FPG， and 2 hPG were lower than those before treatment in the two groups （P<0.05）. Levels of C-P （P<0.05） and 2 hC-P were higher than those before treatment in the two groups. After treatment， levels of HbA1c， FPG， and 2 hPG in the treatment group were lower than those in the control group （P<0.05）， while levels of C-P and 2 hC-P showed no significant difference between two groups. After treatment， the levels of TG， TC， and LDL-C were lower than those before treatment （P<0.05） and HDL-C level was higher than that before treatment （P<0.05） in both groups. After treatment， levels of TG and LDL-C in the treatment group were lower than those in the control group （P<0.05）， and levels of TC and HDL-C demonstrated no significant difference between two groups. After the treatment， the TCM syndrome score was lower than that before the treatment in both groups （P<0.05） and lower in the treatment group than in the control group （P<0.05）. The overall effective rate of the treatment group was higher than that of the control group （χ^２=7.585， P<0.05）. The levels of Cys C and Hcy were lower than those before treatment in the two groups （P<0.05） and lower in the treatment group than in the control group （P<0.05）. Doppler echocardiography of the lower limbs showed no obvious improvement in the control group after treatment. However， for the treatment group， slight decrease in intima-media thickness of the lower limb arteries and a slight reduction in the plaque area were observed， but the difference was not statistically significant. ConclusionDanzhi Jiangtang capsules has definite therapeutic effect on T2DM combined with lower-extremity macroangiopathy， which can improve glucolipid metabolism and reduce serum levels of Hcy and Cys C. This study can serve a reference for the prevention and treatment of T2DM combined with macroangiopathy.