1.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
2.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.
3.Application of"rotation-correction loop technique"in the retrieval of complex inferior vena cava filters
Jie HU ; Maolin QIAO ; Qinqin TIAN ; Heng WANG ; Sheng YAN ; Wenbo ZHAO ; Yongbin SHI ; Peilu SHI ; Miao XING ; Haifeng LI ; Haijiang JIN ; Ping WANG ; Wenkai CHANG ; Yuwen WANG ; Honglin DONG
Journal of Interventional Radiology 2024;33(3):289-294
Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P<0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)
4.Research progress on superficial modification of artificial ligaments to promote tendon bone healing
Zhengrong ZHAO ; Peng ZHOU ; Dongzi TIAN ; Maolin CAI ; Dengke LIU ; Taotao LIU ; Qiuming GAO
The Journal of Practical Medicine 2024;40(17):2508-2512
Anterior cruciate ligament(ACL)injury is caused by strong violence,which can destabilize the knee joint,cause joint cartilage degeneration,meniscus injury,and in severe cases,develop osteoarthropathy.The gold standard for the treatment of ACLR injuries at this stage is arthroscopic anterior cruciate ligament recon-struction(ACLR).In clinical practice,the LARS(Ligament advanced reinforcement system)artificial ligament made of polyethylene terephthalate(PET)as the material has a good effect in the short and medium term,but the long-term biological healing between the graft and the host bone is poor,and the real"ligamentization"requirement of the postoperative graft cannot be met.Coating-modified modification of artificial ligaments can improve their hydrophilicity and biocompatibility,which in turn can promote the healing of graft-bone tunnels.Tendon bone healing is a bone-derived progressive process from indirect insertion to direct insertion,which takes a relatively long time and is closely related to the prognosis and early rehabilitation effect of patients.This article reviews the progress of superficial modification of artificial ligaments to promote ACLR tendon bone healing.
5.Death and life expectancy of residents in coal-burning-borne arsenic poisoning area of Yuzhang Town, Xingren City, Guizhou Province after comprehensive prevention and control of the disease
Xuan RUAN ; Maolin YAO ; Yu TIAN ; Jingyuan YANG ; Aihua ZHANG
Chinese Journal of Endemiology 2020;39(9):663-668
Objective:To understand the overall health status of residents in coal-burning-borne arsenic poisoning areas in Yuzhang Town, Xingren City, Guizhou Province after the implementation of comprehensive prevention and control measures, and to provide references for formulating endemic arsenic poisoning prevention strategies in the new era.Methods:Yuzhang Town, Xingren City of Qianxinan Autonomous Prefecture, Guizhou Province was selected as the survey site. According to the "Standards for Determination and Classification of Endemic Arsenic Poisoning Areas"(WS 277-2007), eleven administrative villages in Yuzhang Town were divided into 5 arsenic-exposed villages and 6 non-arsenic-exposed villages. The basic population data of each administrative village were collected, and the changes of mortality rate, standardized mortality rate, average age of death and life expectancy of residents in the whole town, arsenic-exposed villages and non-arsenic-exposed villages from 2006 to 2018 were calculated and analyzed.Results:From 2006 to 2018, the average annual mortality in arsenic-exposed villages was 597.28/100 000 (756.62/100 000 for males and 432.91/100 000 for females), which was higher than that in non-arsenic-exposed villages (503.79/100 000, 600.82/100 000 for males and 405.02/100 000 for females). Using the overall gender composition of the town as criterion, the standardized mortality rate for arsenic-exposed villages and non-arsenic-exposed villages were 598.79/100 000 and 503.04/100 000, respectively. The population mortality rate in the town showed a downward trend from 2006 to 2018, and the mortality rate of residents in arsenic-exposed villages was higher than that of non-arsenic-exposed villages. The annual mortality rate of males was higher than that of females. From 2006 to 2018, the average age of death in the town increased year by year, from 53.93 years old in 2006 to 67.11 years old in 2018. Among them, the age of death of arsenic-exposed villages was increased from 55.22 years old to 65.17 years old, and non-arsenic-exposed villages increased from 52.64 years old to 68.93 years old. The life expectancy of males, females and total in arsenic-exposed villages (66.29, 75.65, 70.33 years in 2006 and 79.38, 86.39, 83.01 years in 2018) were lower than those in non-arsenic-exposed villages (69.86, 80.77, 74.50 years in 2006 and 83.25, 91.85, 87.25 years in 2018).Conclusion:After the comprehensive prevention and control measures are fully covered in the coal-burning-borne arsenic poisoning area, the health level of the residents in the town is significantly improved, but the long-term health effect, disease distribution, disease burden and other issues of the residents in the arsenic poisoning area are still need to be paid attention to.
6.Efficacy of laparoscopic surgery on the treatment of Dong Type C adult biliary dilatation
Songqiang ZHOU ; Yannan BAI ; Yifeng TIAN ; Zhide LAI ; Funan QIU ; Maolin YAN ; Yaodong WANG
International Journal of Surgery 2019;46(6):382-385
Objective To investigate the technical and therapeutic effects of laparoscopic surgery for adult patients with Dong Type C bile duct dilatation.Methods A retrospective cohort study approach was used.The clinical data of 47 patients with Dong Type C adult biliary dilatation who underwent surgery in Fujian Provincial Hospital from January 2014 to December 2017 were collected.There were 12 males and 35 females.The age ranged from 16 to 68 years,with a median age of 30 years.According to different surgical methods,the patients were divided into the laparoscopic group (treated with laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy,n =21) and the open group (treated with traditional open operation,n =26).The intraoperative blood loss,complication rate,operation time,postoperative intestinal function recovery time and postoperative hospital stay were observed.Measurement data with normal distribution were expressed as mean ± standard deviation (Mean ±SD) and analyzed by t test.Comparison of count data was done by the chi-square test.Results There was no perioperative deaths in either group.There was no significant difference in intraoperative blood loss and complication rate between the two groups (P > 0.05).The operation time of the laparoscopic group was significantly longer than that of the open group[(333.7 ±61.1) min vs (235.9 ±64.3) min],with statistically significant difference between graps (P =0.000).The recovery time for the intestinal function of the laparoscopic group was significantly shorter than that of the open group [(2.2 ± 0.5) d vs (2.9 ± 0.6) d],with statistically significant difference between groups (P =0.000).The postoperative hospital stay in the laparoscopic group was significantly shorter than the open group [(7.1 ± 1.8) d vs (12.0 ± 5.9) d],with statistically significant difference between groups (P =0.001).Conclusion For adult biliary dilatation patiens with Dong Type C,laparoscopic surgery is safe and feasible with the advantages of mini-invasive and quick recovery.
7.Superior mesenteric artery boundary characteristics predicts postoperative survival status in pancreatic head ductal adenocarcinoma
Meng LU ; Dianrong XIU ; Lingfu ZHANG ; Ying PENG ; Lianyuan TAO ; Chunhui YUAN ; Maolin TIAN
Chinese Journal of General Surgery 2017;32(9):728-732
Objective To examine whether the boundary patterns of the superior mesenteric artery (SMA) in the preoperative contrasted enhanced computer tomography (CE-CT) could predict poor postoperative prognosis.Methods From January 2010 to December 2015,104 patients of pancreatic head ductal adenocarcinoma received radical pancreaticoduodenectomy by a single group of surgeons.All patients underwent CE-CT before operation.The clinicopathological characteristics and the prognosis were comparatively analyzed among the patients with different SMA boundary patterns.Results The patients with obscure SMA boundary in CE-CT had a lower overall survival rate (P =0.012) and a higher liver metastasis rate (P < 0.01) compared to the patients with clear SMA boundary.38.2% of patients with obscure SMA boundary died within 6 months,69.1% of them died within 12 months while the mortality rate was 6% within 6 months and 29.2% within 12 months in patients with clear SMA boundary.Only 2.2% of patients with clear SMA boundary presented liver metastasis within 6 months,but that was 53% in patients with obscure SMA boundary.18.4% of patients developed liver metastasis within 12 months in patients with clear SMA boundary,whereas the rate was 82% in patients with obscure SMA boundary.Furthermore,the tissues around the SMA presented a higher CT value in any phase in patients with obscure SMA boundary than in patients with clear SMA boundary (P < 0.01).Conclusions The patterns of the SMA boundary in CE-CT is a potential prognostic factor in pancreatic head ductal adenocarcinoma after radical operation,and the obscure SMA boundary may be associated with early liver metastasis and high mortality.
8.A vitro experiment study of role of TLR4/NF-κB signal pathway in pathogenesis of brain injury during deep hypothermia circulatory arrest
Zhixian TANG ; Zongren ZHONG ; Ziyou LIU ; Dan GUO ; Liang XIONG ; Zhiming DU ; Chengnan TIAN ; Zhenghong LAI ; Chunfa XIE ; Maolin ZHONG
The Journal of Practical Medicine 2017;33(20):3344-3347
Objective To investigate the role of TLR4/NF-κB signal pathway in pathogenesis of brain inju-ry during deep hypothermia circulatory arrest(DHCA). Methods BV2 microglia cells were subjected to oxygen-glucose deprivation/reoxygenation(OGD/R),in vitro model for DHCA. The BV2 were randomly divided into the control group(C group)and the experimental group(O group). BV2 viability was determined by CCK-8 assay. TLR4 and its downstream signaling molecules ,MyD88 and phosphorylated NF-κB (p-p65) expressions were detected by Western blotting. TLR4 mRNA expression in BV2 microglial cells were determined by RT-PCR. Level of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in culture medium was detected by ELASA. Results Compared with the group C,BV2 microglia cell viability in experiment group was obviously weaker(P<0.05). Expressions of TLR4,MyD88 and phosphorylated NF-κB(p-p65)from the experiment group increased remarkedly than those from the group C (P < 0.05). TLR4 mRNA level was higher significantly in the group O than in the group C (P < 0.01). Production of IL-6 and TNF-α in the group O were up-regulated apparently compared to the group C(P<0.01). Conclusion TLR4/NF-κB signaling pathway contributed to activation of BV2 microglia cells treated by OGD/Reoxygenation ,which was probably the exactly way that involved in pathogenesis of brain injury during deep hypothermia circulatory arrest.
9.Clinical efficacy of the laparoscope-assisted transanal total mesorectal excision for middle-low rectal cancer
Zhipeng ZHANG ; Hongwei YAO ; Ning CHEN ; Yang BAI ; Maolin TIAN ; Dechen WANG ; Jiong YUAN ; Dianrong XIU
Chinese Journal of Digestive Surgery 2017;16(7):695-700
Objective To explore the clinical efficacy of laparoscope-assisted transanal total mesorectal excision (La-TaTME) for middle-low rectal cancer.Methods The retrospective cross-sectional study was conducted.The clinical data of 16 patients with middle-low rectal cancer who underwent La-TaTME in the Peking University Third Hospital from August 2015 to August 2016 were collected.Sequential surgery of La-TaTME was applied to patients in the same team,with laparoscopic surgery first and then transanal surgery.Observation indicators:(1) operation and postoperative recovery situations:conversion to open surgery,anastomosis method,operation time,volume of intraoperative blood loss,intraoperative complications,time for out-of-bed activity,time for liquid diet intake,postoperative complications and duration of postoperative hospital stay.(2) postoperative pathological situations:length of surgical specimen,tumor diameter,distance from tumor to resected distant intestinal canal,complete degree of mesorectum,circumferential resection margin,pathological T stage,pathological N stage,number of lymph node detected and tumor cell differentiation.(3) follow-up.Patients in stage Ⅲ-ⅣV of TNM stage of RC underwent postoperative adjuvant chemotherapy.Follow-up using outpatient examination was performed once every 3 months postoperatively to detect the patients' survival and tumor recurrence up to December 2016.Measurement data were represented as M (range).Results (1) Operation and postoperative recovery situations:all the 16 patients underwent successful La-TaTME without conversion to open surgery,including 10 with colorectal anastomosis,3 with colon-canalis analis anastomosis and 3 with permanent colostomy.Operation time and volume of intraoperative blood loss were 290 minutes (range,215-420 minutes) and 50 mL (range,30-100 mL),respectively.One patient had intraoperative complication,showing broken ends ischemia of sigmoid colon after dragging out resected rectum from the anus,following free splenic flexure of colon,about 5 cm ischemic sigmoid colon were resected,and descending colon-rectum anastomosis was performed.Time for out-of-bed activity and time for liquid diet intake were 1 days (range,1-3 days) and 2 days (range,1-9 days),respectively.Among 3 patients with postoperative complications (Ⅱ stage of ClavienDindo),2 with incomplete intestinal obstruction were improved by gastrointestinal decompression and total parenteral nutrition,and 1 with presacral infection was improved by drainage and antibiotic therapy.Duration of postoperative hospital stay was 7 days (range,5-21 days).(2) Postoperative pathological situations:length of surgecal specimen,tumor diameter and distance from tumor to resected distant intestinal canal were respectively 18.0 cm (range,12.0-24.0 cm),3.5 cm (range,0.5-6.8 cm) and 2.5 cm (range,1.0-5.0 cm).Evaluation of mesorectum of surgical specimen:14 patients had complete mesorectum of surgical specimen and 2 had nearly complete mesorectum.There was no residual tumor at circumferential resection margin,proximal and distal ends.Pathological T stage of 16 patients:T0 (pathological complete response after neoadjuvant therapy),T1,T2 and T3 stages were found in 1,1,4 and 10 patients,respectively.Pathological N stage:12,2 and 2 patients were detected in N0,N1 and N2 stages,respectively.Number of lymph node detected was 16 (range,6-32).Tumor cell differentiation:no tumor cell (pathological complete response after neoadjuvant therapy),high-,moderateand low-differentiated tumors were respectively detected in 1,2,7 and 6 patients.(3) Follow-up.All the patients were followed up for 12 months (range,4-16 months).There were no local tumor recurrence or distant metastasis and death.Conclusion La-TaTME may be a new,safe and effective resection for middle-low rectal cancer.
10.Transabdominal-transanal total mesorectal excision combined with liver metastasis resection for synchronous low rectal liver metastasis
Zhipeng ZHANG ; Maolin TIAN ; Chunhui YUAN ; Yimu JIA ; Hongwei YAO ; Dianrong XIU
Chinese Journal of Digestive Surgery 2016;15(2):123-127
Objective To investigate the application value of transabdominal-tansanal total mesorectal excision combined with liver metastasis resection for synchronous low rectal liver metastasis.Methods The retrospective descriptive study was adopted.The clinical data of a male patient with synchronous low rectal liver metastasis who was admitted to the Peking University Third Hospital in November 2015 was collected.Transabdominal-transanal total mesorectal excision combined with liver metastasis resection was performed after multidisciplinary team conference.The liver metastasis resection,vascular disconnection,lymph node dissection and upper and middle mesorectal disconnection were done by transabdominal approach.Then complete mesorectal excision and specimen removal of rectum and liver were done by transanal approach.The intraoperative status (operation method,operation time,volume of intraoperative blood loss,blood transfusion),occurrence of postoperative complications,results of pathological examination and follow-up were observed.The patient was followed up by outpatient examination till January 2016.Results The operation was performed successfully without severe perioperative complications.The operation time and volume of intraoperative blood loss were 360 minutes and 170 mL,respectively.The patient did not receive intraoperative blood transfusion,without urinary retention and presacral abscesses.The patient was discharged at postoperative day 9.The postoperative pathological results showed high-differentiated rectal protruded adenoma and high-middle differentiated adenocarcinoma metastasis in the liver tissue with the negative resection margins.The tumor sizes of rectum and liver metastasis were 5.0 cm × 5.0 cm× 1.5 cm and 1.5 cm × 1.0 cm × 1.5 cm,respectively.The tumor node metastasis (TNM) stage was stage Ⅳ (pT3N0M1).The patient had a good life quality during the follow-up of 1 month.Conclusion Transabdominal-transanal approach might provide an alternative operative approach and resection method for synchronous low rectal liver metastasis,with a good short-term outcome.

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