Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

Objective:To carry out the policy diffusion analysis of centralized and volume-based drug procurement in China in recent years,and to provide reference for the formulation of centralized and volume-based drug procurement policy.Methods:Through the official websites of the central and provincial governments,the official websites of the Health Commission and the official websites of the Medical Security Bureau,the policy documents related to centralized and volume-based drug procurement from January 1,2009 to December 31,2023 were searched.Based on the policy diffusion theory,the reference network analysis method is used to analyze the intensity,breadth and speed of policy diffusion,and the sequential analysis method of policy keywords is used to analyze the direction of policy diffusion.Results:In the two stages of the development of centralized and volume-based drug procurement policy,the number of policies issued in the medical insurance management stage reached the peak;The top ten policies with the highest diffusion intensity and breadth are all central policies,and most of them are notices and opinions.In addition,the newly promulgated policies have a faster diffusion speed.In the direction of diffusion,top-down and parallel diffusion trends are obvious.Conclusion:The diffusion of centralized and volume-based drug procurement policy in China focuses on the central policy,and the diffusion speed is increasing year by year.It is suggested to strengthen the policy coordination between the central and local governments,establish a unified national information platform for centralized drug procurement,optimize the learning and competition mechanism between governments at all levels,and give play to the advantages of"policy experiment".

Humans ; Enhanced Recovery After Surgery ; Stomach Neoplasms/surgery* ; Length of Stay ; Laparoscopy ; Postoperative Complications ; Gastrectomy

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.
RNA, Circular/metabolism* ; Multiomics ; Poaceae/metabolism* ; Seedlings/genetics* ; Hormones/metabolism* ; MicroRNAs/metabolism* ; Gene Expression Regulation, Plant

Arabidopsis thaliana is an important and long-established model species for plant molec-ular biology,genetics,epigenetics,and genomics.However,the latest version of reference genome still contains a significant number of missing segments.Here,we reported a high-quality and almost complete Col-0 genome assembly with two gaps(named Col-XJTU)by combining the Oxford Nanopore Technologies ultra-long reads,Pacific Biosciences high-fidelity long reads,and Hi-C data.The total genome assembly size is 133,725,193 bp,introducing 14.6 Mb of novel sequences compared to the TAIR1 0.1 reference genome.All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality(QV)scores＞60(ranging from 62 to 68),which are higher than those of the TAIR10.1 reference(ranging from 45 to 52).We completely resolved chro-mosome(Chr)3 and Chr5 in a telomere-to-telomere manner.Chr4 was completely resolved except the nucleolar organizing regions,which comprise long repetitive DNA fragments.The Chr1 cen-tromere(CEN1),reportedly around 9 Mb in length,is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats.Using the cutting-edge sequencing data and novel computational approaches,we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2.We also investigated the structure and epigenetics of centromeres.Four clusters of CEN180 monomers were detected,and the centromere-specific histone H3-like protein(CENH3)exhibited a strong preference for CEN 180 Cluster 3.Moreover,we observed hypomethylation patterns in CENH3-enriched regions.We believe that this high-quality genome assembly,Col-XJTU,would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms,as well as the genetic and epigenetic features in plants.

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.
Carcinoma, Adenoid Cystic/pathology* ; Humans ; Paranasal Sinus Neoplasms/therapy* ; Prognosis ; Proportional Hazards Models ; Retrospective Studies

As cataract surgery has entered the era of minimally invasive and accurate refractive surgery, higher requirements for perioperative infection control are needed. In recent years, “dropless cataract surgery” has been proposed and is gradually applied in clinical practice. It is based on the combination of different local injection forms in cataract surgery, in which antibiotics and steroids are applied to the operative eye through immediate or sustained release, so that patients do not need to use eye drops throughout the perioperative period.It can not only achieve the purpose of anti-inflammation and anti-infection after surgery, but also reduce the burden of patients, patients' family members and doctors.This article reviews the concept of “dropless cataract surgery”, the combined treatment methods, including combined anterior chamber antibiotic injection, triamcinolone acetonide and moxifloxacin hydrochloride(TriMoxi)and triamcinolone -moxifloxacin and vancomycin(TriMoxiVanc)intravitreal injection, combined dexamethasone lacrimal puncture implantation, continuous or sustained release drug delivery mechanism, as well as its efficacy and safety, with a view to provide a new idea and direction for the prevention of postoperative cataract infection.

This study selected three typical Chinese herbs with cold property(Rhei Radix et Rhizoma, Scutellariae Radix, and Coptidis Rhizoma) and another three with heat property(Cinnamomi Cortex, Zingiberris Rhizoma, and Aconiti Lateralis Radix Praeparata) to observe their regulatory effects on metabolism in animal organism, especially on lipid and energy metabolism in mice after a short-(7 d) and long-term(35 d) intervention. The mRNA expression levels of lipid metabolism genes in epididymal adipose tissue and liver were determined by real-time PCR. The oxygen consumption, carbon dioxide production, and energy consumption were detected by metabolic system. After the short-term intervention, the Chinese herbs with heat property significantly reduced epididymal adipose tissue index and elevated the expression levels of acetyl-CoA carboxylase(ACC), lipoprotein lipase(LPL), and carnitine-palmityl transferase 1(CPT-1) in liver and epididymal adipose tissues. However, those with cold property promoted the expression of above-mentioned genes in epididymal adipose tissue. After the long-term intervention, cold and heat Chinese herbs had no significant effect on epididymal adipose tissue index of animals, while cold Chinese herbs could increase carbon dioxide production and energy consumption and reduce activity. These findings demonstrated that the short-term intervention effects of cold and heat Chinese herbs on animal metabolism were significantly stronger than the long-term intervention effects. Specifically, the short-term intervention with cold Chinese herbs enhanced the lipid metabolism in epididymal adipose tissue, while the heat Chinese herbs promoted lipid metabolism in epididymal adipose tissue and liver. The long-term intervention with cold and heat Chinese herbs resulted in no obvious change in lipid level, but long-term intervention with cold Chinese herbs accelerated energy consumption of the body. This study preliminarily observed the effects of cold and heat Chinese herbs on normal animal physiology from lipid and energy metabolism, which would provide reference for explaining the biological basis of Chinese herbs with cold or heat property based on biological response.
Aconitum ; Animals ; Carbon Dioxide ; China ; Drugs, Chinese Herbal/pharmacology* ; Energy Metabolism ; Hot Temperature ; Lipids ; Mice

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ² test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.
Adolescent ; Adult ; Bilirubin ; Child ; End Stage Liver Disease/surgery* ; Fatty Liver/surgery* ; Female ; Graft Survival ; Humans ; Infant ; Infant, Newborn ; Liver ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Tissue Donors ; Young Adult

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome