1.Mechanism of Gexia zhuyu decoction in the intervention of metabolic-related fatty liver disease by inhibiting ferroptosis
Yuqiang ZHAO ; Ziyou WANG ; Anqi LI ; Peiran ZHAO ; Rui WANG ; Jing YANG
China Pharmacy 2024;35(24):2977-2983
OBJECTIVE To explore the potential mechanism of action of Gexia zhuyu decoction in the intervention of metabolic-associated fatty liver disease (MAFLD) based on ferroptosis. METHODS With the help of network pharmacology, the central targets of Gexia zhuyu decoction intervening in ferroptosis of MAFLD were screened, then gene ontology, Kyoto Encyclopedia Gene and Genomes enrichment analysis and molecular docking were performed. Juvenile zebrafish with normal development at 3 d post-fertilization were randomly divided into control group, model group (5 mmol/L thioacetamide), magnesium isoglycyrrhizinate group (positive control, 5 mg/mL), and Gexia zhuyu decoction low- , medium- and high- concentration groups (20, 40, 80 μg/mL, calculated by crude drugs). After cultured for 72 h, the contents of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS) and Fe2+ were determined; the cellular structure of the liver tissues and hepatic steatosis were observed; the protein expression of silence information regulator 1 (SIRT1), nuclear factor- erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) were detected. RESULTS The central targets of potential active ingredients of Gexia zhuyu decoction that act on ferroptosis in MAFLD included tumor proteins p53, SIRT1, Nrf2, etc., which were enriched in biological processes such as positive/negative regulation of RNA polymerase Ⅱ promoter transcription, cellular components such as nucleus and cytoplasm, molecular functions such as protein binding, as well as signaling pathways such as ferroptosis and the cancer pathway, and they might be tightly linked to the main active ingredients. Compared with model group, the contents of ALT, AST, TC, TG, MDA, ROS and Fe2+ were all decreased significantly in each administration group, while the contents of SOD and GSH were increased significantly (P<0.05); the pathological damage of liver tissue cells had improved, and the accumulation of liver lipids had decreased. The protein expressions of SIRT1, Nrf2 and GPX4 had been significantly upregulated (P<0.05). CONCLUSIONS Gexia zhuyu decoction can regulate lipid metabolism, improve the level of oxidative stress, maintain Fe2+ homeostasis, and inhibit the process of ferroptosis in juvenile zebrafish with MAFLD, and the above effects may be related to the activation of the SIRT1/Nrf2/GPX4 axis.
2.Mechanism of action of sterol regulatory element-binding proteins in nonalcoholic fatty liver disease and related therapeutic targets
Anqi LI ; Peiran ZHAO ; Yuqiang ZHAO ; Rui WANG ; Jing YANG
Journal of Clinical Hepatology 2024;40(7):1459-1465
Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.
3.Treatment strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for gastric cancer with peritoneal metastasis: a systematic review
Chenghao JI ; Linpo ZHOU ; Yebin YANG ; Junqiang HU ; Haoran WEI ; Fanhe DONG ; Yuqiang SHAN ; Wencheng KONG
Chinese Journal of Gastrointestinal Surgery 2024;27(7):740-748
Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m 2 of Cisplatin and 30-40 mg/m 2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.
4.Clinical and genetic analysis of a child with Canavan disease due to compound heterozygous variants of ASPA gene
Shasha NIU ; Yanyan MA ; Yuqiang LYU ; Hongmei XIN ; Dong WANG ; Yanxin WANG ; Ya′nan YANG ; Zilong LI ; Yi LIU ; Zhongtao GAI
Chinese Journal of Medical Genetics 2024;41(2):225-229
Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.
5.Evaluation value of serum troponin Ⅰ combined with soluble CD163 in disease condition and prognosis of patients with acute cholecystitis
Pengfei LI ; Zhongjie YANG ; Chunyan XIE ; Yuqiang YANG
Chongqing Medicine 2024;53(21):3284-3288,3294
Objective To analyze the evaluation value of serum troponin Ⅰ(TnⅠ)combined with soluble CD163(sCD163)in the disease condition and prognosis of the patients with acute cholecystitis.Methods The clinical data of 125 patients with acute cholecystitis admitted and treated in the hospital from October 2022 to October 2023 were retrospectively collected.The patients were divided into the mild group(n=33),moderate group(n=51)and severe group(n=41)according to the severity of disease condition.The levels of serum TnⅠ,sCD163,interleukin(IL)-6,C reactive protein(CRP),total bilirubin(TBIL)and alanine aminotrans-ferase(ALT)were detected.The patients were divided into the good prognosis group(n=95)and poor prog-nosis group(n=30)according the occurrence of complications such as abdominal pain,dyspepsia and cholan-gitis within postoperative 3 months.The preoperative indicators were compared between the two groups.The influencing factors of prognosis in the patients were evaluated by the logistic regress analysis.The receiver op-erating characteristic(ROC)curve was used to analyze the diagnostic efficiency of TnⅠ and sCD163 in evalua-ting the disease condition and prognosis of the patients.Results The levels of TnⅠ,sCD163,IL-6,CRP,TBIL and ALT in the mild group were(0.78±0.23)μg/L,(25.01±3.15)mg/L,(62.52±7.61)pg/mL,(32.47±4.11)mg/L,(35.65±4.61)μmol/L and(79.75±7.23)U/L respectively,which were lower than those in the moderate group and severe group(P<0.05).The TnⅠ level in the good prognosis group was(0.99±0.37)μg/L,which was lower than(1.82±0.51)μg/L in the poor prognosis group(P<0.05);the sCD163 level in the good prognosis group was(27.46±3.50)mg/L,which was lower than[(33.12±4.13)mg/L]in the poor prognosis group(P<0.05).The logistic analysis showed that TnⅠ,SCD163,IL-6,CRP,TBIL and ALT all were the important factors affecting the prognosis in the patients;the ROC curve showed the area under the curve(AUC)of TnⅠ combined with SCD163 for evaluating the disease condition was 0.966(95%CI:0.937-0.995),which for evaluating the prognosis was 0.948(95%CI:0.903-0.993).Conclusion Serum TnⅠ com-bined with sCD163 has a high application value in the assessment of the disease condition and prognosis in the patients with acute cholecystitis.
6.Treatment strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for gastric cancer with peritoneal metastasis: a systematic review
Chenghao JI ; Linpo ZHOU ; Yebin YANG ; Junqiang HU ; Haoran WEI ; Fanhe DONG ; Yuqiang SHAN ; Wencheng KONG
Chinese Journal of Gastrointestinal Surgery 2024;27(7):740-748
Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m 2 of Cisplatin and 30-40 mg/m 2 of Mitomycin C in 3-4 L saline solution at 42-43℃. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.
7.Application and prospect of artificial intelligence in metabolic associated fatty liver disease based on bibliometrics
Anqi LI ; Peiran ZHAO ; Yuqiang ZHAO ; Rui WANG ; Jing YANG
Journal of Clinical Medicine in Practice 2024;28(5):1-9
Objective To explore the application and prospects of artificial intelligence (AI) in metabolic associated fatty liver disease (MAFLD) based on bibliometrics. Methods Relevant literature on the application of AI technology in MAFLD was retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using CiteSpace, VOSviewer, R package "bibliometrix", and online bibliometric analysis was platformed to identify hotspots and trends in this field. Results A total of 303 eligible articles were obtained. Since 2017, the number of papers in this field had experienced explosive growth. The United States was leading the research on the application of AI in MAFLD and was the most frequent participant in international cooperation. San Diego of University of California was the institution with the highest number of publications. Rohit Loomba was the author with the highest number of publications, having published 14 articles. The co-cited keyword clustering labels revealed 10 major clusters: digital image analysis, machine learning, computer-aided diagnosis, fibrosis stage, automated quantitative analysis, metaproteomics, non-invasive diagnosis, ultrasonography, electronic health records, and knowledge representation. Current research on the application of AI in MAFLD mainly focused on the diagnosis, differential diagnosis, and staging of MAFLD. Image recognition and analysis, intelligent assisted diagnosis, AI algorithms, and monitoring disease progression will be important research directions for AI in MAFLD. Conclusion Research on the application of AI in MAFLD is experiencing exponential growth. Given enormous potential and clinical application prospects of this field, the application of AI in MAFLD-related areas will remain a research hotspot in the future.
8.Clinical efficacy of neoadjuvant chemotherapy combined with radical surgery for elderly patients with locally advanced gastric cancer
Qi JIANG ; Yuqiang DU ; Chenggang ZHANG ; Ming YANG ; Jun FAN ; Jianbo LYU ; Gan MAO ; Qian SHEN ; Xiangyu ZENG ; Weizhen LIU ; Yuping YIN ; Kaixiong TAO ; Peng ZHANG
Chinese Journal of General Surgery 2023;38(4):263-268
Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.
9.Analysis of clinical features and ATRX gene variants in a Chinese pedigree affected with X-linked alpha thalassemia mental retardation (ATR-X) syndrome.
Rui DONG ; Yali YANG ; Hui GUO ; Min GAO ; Yuqiang LYU ; Yue LI ; Xiaomeng YANG ; Yi LIU
Chinese Journal of Medical Genetics 2023;40(12):1508-1511
OBJECTIVE:
To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome.
METHODS:
An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS).
RESULTS:
The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother.
CONCLUSION
The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans
;
Infant
;
Male
;
alpha-Thalassemia/diagnosis*
;
Ataxia Telangiectasia Mutated Proteins/genetics*
;
East Asian People
;
Intellectual Disability/genetics*
;
Mental Retardation, X-Linked/diagnosis*
;
Pedigree
;
X-linked Nuclear Protein/genetics*
10.Analysis of the clinical effect of single J tube of bilateral ureter through the bladder stoma to treat vesicovaginal fistula after radiotherapy of cervical cancer
Yuqiang SHI ; Shenghan WANG ; Zhentao LEI ; Lin YANG ; Qiang GAO ; Kaishuang WANG ; Bao ZHANG
Chinese Journal of Urology 2023;44(1):58-59
This article retrospectively analyzed the clinical data of 8 patients with vesicovaginal fistula after radiotherapy for cervical cancer admitted in our hospital from January 2015 to October 2021. All of them underwent cystostomy under local anesthesia. A single J tube of bilateral ureters was retained under cystoscope, and the single J tube was introduced into the fistula bag through the cystostomy opening. All patients wore diapers for a long time before operation, and used urine pads 0-2 pieces/day after operation. QOL score was 5.3±0.5 points before operation, and 2.5±0.5 points after operation. The patient's body odor basically disappeared. The vesicovaginal fistula can be repaired by surgery, but for patients who cannot be operated or failed repeatedly due to various reasons, a single J tube of bilateral ureters can be drawn out through the cystostomy opening, which can improve the quality of life of patients through minor trauma.


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