Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective:To explore the construction of abdominal aortocaval fistula (ACF) model in adenine-induced renal failure rats, and to provide a suitable animal model for subsequent mechanism and intervention researches.Methods:Adult female Sprague-Dawley rats (250-300 g) were fed with 0.75% adenine diet (renal failure group, n=60) and the same diet without adenine (control group, n=10) for 4 weeks, and the rats were randomly grouped by block randomization method with a ratio of 6∶1. Thirty rats in the renal failure group were randomly selected by block randomization method at a ratio of 1∶1 to undergo laparotomies to establish ACF models (renal failure+ACF group). The serum creatinine, blood urea nitrogen detection and Masson staining were used to evaluate the establishment of renal failure model. Small animal ultrasound imaging system was applied to verify the successful construction of the ACF model. After 6 weeks of ACF observation, blood samples were collected from the heart of rats, and ACF-vascular tissues were collected for pathological study (HE staining). Results:At 4 weeks of feeding, compared with the control group, serum creatinine [(63.8±23.5) μmol/L vs. (33.0±3.8) μmol/L, Z=3.651, P<0.001] and blood urea nitrogen [(13.1±6.9) mmol/L vs. (5.3±0.6) mmol/L, Z=3.254, P=0.001] in the renal failure group were both higher. Masson staining showed renal tubulointerstitial inflammatory cell infiltration, renal tubular epithelial cell atrophy, interstitial fibrosis and vascular injury. Five rats sacrificed after ACF surgeries, and the survival rate was 83.3%. Doppler ultrasound showed turbulent blood flow of arterial to venous shunt at the anastomosis of open ACF (23/25) in the renal failure+ACF group. HE staining showed typical eccentric neointimal hyperplasia in the outflow tract of ACF vein in the renal failure+ACF group. Conclusions:The adenine-induced ACF rat model is successfully constructed, and ACF shows typical eccentric neointimal hyperplasia. The ACF construction would provide a reliable animal model to study the mechanism and intervention of neointimal hyperplasia for autologous arteriovenous fistula.

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Autism spectrum disorder(ASD)is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic structure.Current preclinical trials,however,mainly rely on rodent models to test the effects of non-pharmacological and pharmacological interventions on the core and related symptoms of ASD.This paper considers the brain regions that affect social interaction behaviors from the perspective of cognitive neural mechanisms,and reviews behavioral testing experiments,such as the three-chamber social interaction test,visible burrow system,and eco-HAB system.We also summarize effective non-pharmacological and pharmacological interventions,such as baclofen,oxytocin,and metformin,in the core and related symptom areas of ASD.This review aims to provide reference directions to promote the development of preclinical trials using rodent models.

Objective:To explore the association between thyroid function and chronic kidney disease (CKD) in adults.Methods:A cross-sectional study was conducted in adults who received health checkup in the First Affiliated Hospital of Shandong First Medical University from January to December in 2021. Clinical data were collected, including age, gender, height, weight, blood pressure, etc. And blood glucose, blood lipid, blood creatinine, blood uric acid, routine urine function, thyroid function (free triiodine, free thyroxine, thyroid stimulating hormone) were measured. Multivariate logistic regression model was used to investigate the correlation between thyroid function indicators and the onset of CKD; and receiver operator characteristic (ROC) curve was used to explore the ability of thyroid function indicators in evaluating CKD.Results:In the study, 46 342 adults with an average age of (47.6±14.3) years were enrolled, of which 56.2% were males. The prevalence of DeGFR (eGFR<60 ml·min -1·(1.73 m 2) -1), proteinuria and CKD was 1.15%, 0.53% and 1.58%, respectively. The TSH subgroup analysis showed that the prevalence of DeGFR, albuminuria and CKD in the hypothyroidism group was significantly increased to 1.07%, 2.36% and 3.20%, respectively (all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis showed that FT3 was negatively associated with CKD ( OR=0.63, 95% CI: 0.54-0.74), however FT4 ( OR=1.05, 95% CI: 1.03-1.07) and TSH ( OR=1.03, 95% CI: 1.01-1.04) were positively correlated with CKD. Similar results were obtained in the subgroup without hypertension and diabetes ( P<0.05). The ROC analysis indicated that FT3 had a better capability for evaluating CKD than FT4 and TSH, with an area under the curve of 0.63, a cut-off value of 4.18 pmol/L, and a sensitivity and specificity of 57.5% and 62.6%, respectively. Conclusions:Thyroid function status is closely associated with the onset of CKD in the adult population receiving health check-up. FT3 is a risk factor for the onset of CKD.

Lymphocytic choriomeningitis virus/physiology* ; Allosteric Regulation ; Nucleotidyltransferases

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal

【Objective】 To continuously improve the management of blood donors and ensure blood safety in the Yangtze River Delta(Zhejiang province, Jiangsu province, Anhui province and Shanghai city). 【Methods】 The information sharing system for donation interval query in the Yangtze River Delta was established in July 2020 to provide data and technical support to block blood donors who should not redonate due to insufficient intervals. 【Results】 Blood stations in the Yangtze River Delta unified the information sharing standard, developed the query service and realized the information sharing of donation interval query. 【Conclusion】 The establishment of this system could reduce the risk of blood donation from eligible donos with insufficient donation interval, and further improve the management of blood donors and blood safety in the Yangtze River Delta.

【Objective】 To introduce the construction of the electronic blood-donation certificate information system(EBDCIS) in Zhejiang province, including the construction foundation, system design, system function and preliminary development achieved. 【Methods】 A provincially unified EBDCIS, based on Internet and cloud computing technology relying on the Zhejiang blood cloud platform with Alipay and WeChat applet as service carriers, was developed in 2019, which was oriented towards " the Internet Plus blood donation service" . 【Results】 In addition to the realization of electronic blood-donation certificate, the system mainly improved the online service, including 6 categories as blood donation information query, blood donation navigation, facial recognition, satisfaction evaluation, blood use exemption and blood knowledge area, covering 21 functions. 【Conclusion】 The application of EBDCIS in Zhejiang province has provided better care and service for blood donors, and is conductive to establish one-stop blood donation service platform.