Objective:To explore the effective active components of Qi Bi Anshen decoction(QAT)in the treatment of autism spectrum disorder(ASD)and its effects on ASD behaviors and related lipid metabolism abnormalities.Methods:24 adult male Sprague-Dawley rats were randomly divided into 3 groups:Control group,PPA group and PPA+QAT group.The ASD rat model was established by intracerebroventricular injection of propionic acid,and the QAT administration group was given intragastric administration for 7 days.Behavioral tests were conducted to detect the so-cial,repetitive stereotyped and anxiety-like behaviors of rats.UPLC-MS was used to analyze the differential metabolites and enriched pathways of rats.Network pharmacology was used to screen the effective active monomer components of QAT involved in regulating ASD.10 sexually mature C57BL/6J mice were randomly paired in male-female cages.The ASD mouse model was established by a single intraperitoneal injection of sodium valproate to pregnant mice.The preg-nant mice were randomly divided into 3 groups:Control group,VPA group and VPA+QUE group.The administration group was given QUE in the drinking water of pregnant mice until the end of the perinatal period.Behavioral tests were conducted to detect ASD-like behaviors in mice.Reagent kits were used to detect the contents of alkaline phosphatase(AKP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglycerides(TG)and total cholesterol(TC)in the liver and serum of mice.Oil red O staining was used to observe the morphology of liver cells.Results:QAT administration could improve the ASD-like behaviors induced by PPA(P＜0.05).UPLC-MS analysis showed that the differential metabolites of each group of rats were mainly enriched in lipid metabolism pathways.Network pharmacol-ogy screening identified QUE as the effective active monomer component.QUE administration could improve the ASD-like behaviors induced by VPA(P＜0.05).QUE administration could reverse the abnormal changes in AKP,TC and TG in the liver induced by VPA(P＜0.05)and reduce lipid droplet deposition in the liver.Conclusion:The active monomer component QUE in QAT has therapeutic effects on ASD behaviors and related liver lipid metabolism abnormali-ties.

Objective:The minimal ablative margin (MAM) after radiofrequency ablation (RFA) was evaluated based on magnetic resonance imaging (MRI) image registration to analyze its effect on the prognosis of patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 120 patients with HCC undergoing RFA in the General Hospital of Ningxia Medical University from January 2017 to April 2022 were retrospectively analyzed, including 88 males and 32 females, aged (58.4±8.5) years. The enhanced MRI images of patients before and after treatment were imported into a 3D Slicer software to show the ablative margin, and patients were divided into two groups according to whether MAM exceeded the peritumor safety boundary of 5 mm: MAM<5 mm group ( n=75) and MAM≥5 mm group ( n=45). Clinical data were recorded such as gender, age, tumor length and location. Patients were followed up by outpatient review to record whether local tumour progression occurred. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Cox regression analysis was performed to analyze the risk factors of local tumour progression after RFA in patients with HCC. Results:There were significant differen-ces in tumor volume, whether the tumor is located around the vessels, and the mode of RFA guidance between the two groups (all P<0.05). The cumulative local tumour progression-free survival rates at 6, 12 and 24 months after RFA were 100%, 100% and 98% in MAM ≥5 mm group, superior to those in MAM<5 mm group (92%, 84% and 69%, respectively, χ2=47.22, P<0.001). Multivariate Cox regression analysis showed that MAM<5 mm ( OR=9.992, 95% CI: 4.358-22.913), tumor diameter ≥2 cm ( OR=1.758, 95% CI: 1.025-3.015) and perivascular tumor ( OR=2.344, 95% CI: 1.379-3.985) were risk factors for local tumour progression after RFA in patients with HCC (all P<0.05). Conclusion:The MAM evaluated based on MRI image registration is an influential factor on prognosis of patients with HCC. Patients with MAM<5 mm suffer an increased risk of postoperative local tumour progression.

Objective:To explore the effective active components of Qi Bi Anshen decoction(QAT)in the treatment of autism spectrum disorder(ASD)and its effects on ASD behaviors and related lipid metabolism abnormalities.Methods:24 adult male Sprague-Dawley rats were randomly divided into 3 groups:Control group,PPA group and PPA+QAT group.The ASD rat model was established by intracerebroventricular injection of propionic acid,and the QAT administration group was given intragastric administration for 7 days.Behavioral tests were conducted to detect the so-cial,repetitive stereotyped and anxiety-like behaviors of rats.UPLC-MS was used to analyze the differential metabolites and enriched pathways of rats.Network pharmacology was used to screen the effective active monomer components of QAT involved in regulating ASD.10 sexually mature C57BL/6J mice were randomly paired in male-female cages.The ASD mouse model was established by a single intraperitoneal injection of sodium valproate to pregnant mice.The preg-nant mice were randomly divided into 3 groups:Control group,VPA group and VPA+QUE group.The administration group was given QUE in the drinking water of pregnant mice until the end of the perinatal period.Behavioral tests were conducted to detect ASD-like behaviors in mice.Reagent kits were used to detect the contents of alkaline phosphatase(AKP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglycerides(TG)and total cholesterol(TC)in the liver and serum of mice.Oil red O staining was used to observe the morphology of liver cells.Results:QAT administration could improve the ASD-like behaviors induced by PPA(P＜0.05).UPLC-MS analysis showed that the differential metabolites of each group of rats were mainly enriched in lipid metabolism pathways.Network pharmacol-ogy screening identified QUE as the effective active monomer component.QUE administration could improve the ASD-like behaviors induced by VPA(P＜0.05).QUE administration could reverse the abnormal changes in AKP,TC and TG in the liver induced by VPA(P＜0.05)and reduce lipid droplet deposition in the liver.Conclusion:The active monomer component QUE in QAT has therapeutic effects on ASD behaviors and related liver lipid metabolism abnormali-ties.

Objective:The minimal ablative margin (MAM) after radiofrequency ablation (RFA) was evaluated based on magnetic resonance imaging (MRI) image registration to analyze its effect on the prognosis of patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 120 patients with HCC undergoing RFA in the General Hospital of Ningxia Medical University from January 2017 to April 2022 were retrospectively analyzed, including 88 males and 32 females, aged (58.4±8.5) years. The enhanced MRI images of patients before and after treatment were imported into a 3D Slicer software to show the ablative margin, and patients were divided into two groups according to whether MAM exceeded the peritumor safety boundary of 5 mm: MAM<5 mm group ( n=75) and MAM≥5 mm group ( n=45). Clinical data were recorded such as gender, age, tumor length and location. Patients were followed up by outpatient review to record whether local tumour progression occurred. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Cox regression analysis was performed to analyze the risk factors of local tumour progression after RFA in patients with HCC. Results:There were significant differen-ces in tumor volume, whether the tumor is located around the vessels, and the mode of RFA guidance between the two groups (all P<0.05). The cumulative local tumour progression-free survival rates at 6, 12 and 24 months after RFA were 100%, 100% and 98% in MAM ≥5 mm group, superior to those in MAM<5 mm group (92%, 84% and 69%, respectively, χ2=47.22, P<0.001). Multivariate Cox regression analysis showed that MAM<5 mm ( OR=9.992, 95% CI: 4.358-22.913), tumor diameter ≥2 cm ( OR=1.758, 95% CI: 1.025-3.015) and perivascular tumor ( OR=2.344, 95% CI: 1.379-3.985) were risk factors for local tumour progression after RFA in patients with HCC (all P<0.05). Conclusion:The MAM evaluated based on MRI image registration is an influential factor on prognosis of patients with HCC. Patients with MAM<5 mm suffer an increased risk of postoperative local tumour progression.

Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK).Methods:The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results:Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband′s father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions:Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

We reconstructed the erythromycin macrocyclic lactone (6-deoxyerythronolide B, 6dEB) synthesis pathway in Escherichia coli. We first cloned all the genes needed to synthesize the 6dEB into multi-gene co-expressed vectors. Then using the recognition sequences of isoschizomers Xba I/Spe I of vectors, we assembled the related genes into a series multiple-genes recombinant plasmids pBJ144, pBJ130. The recombinant plasmids pBJ144, pBJ130 were cotransformed into BAP1 to get the recombinant BAP1(pBJ144/pBJ130). SDS-PAGE analysis showed that individual genes were expressed correctly. After inducing at low temperature, adding propionate as substrate, we validated the crude product by mass spectrometry and the 6dEB yield was about 10 mg/L. These results indicated that the synthetic pathway of 6dEB was successfully assembled and reconstructed in Escherichia coli, which will greatly facilitate the reconstruction of whole erythromycin synthesis pathway and finally help to establish a stable research platform for developing of new derivatives of erythromycin and combinatorial biosynthesis of polyketide-type antibiotics.
Anti-Bacterial Agents ; biosynthesis ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Erythromycin ; analogs & derivatives ; biosynthesis ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics