1.Mechanism of Action of Chinese Medicinal Herbs in the Treatment of Primary Myelofibrosis based on Bioinformatics and Molecular Dynamics
Jiayuan GUO ; Jile XIN ; Man ZHANG ; Mingxin LIU ; Jingwen LIU ; Yajing SU ; Huihui SHI ; Jue GUO ; Wenqing LIU ; Kailu WEI ; Yalin SONG ; Qiuling MA
Journal of Traditional Chinese Medicine 2024;65(21):2250-2258
		                        		
		                        			
		                        			ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis (PMF) using Chinese medicinal herbs (CMH) by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI, Chinese Science and Technology Journal Database (CCD), and China Academic Journal Database (CSPD). TCMSP, SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database, and R software was used for data normalization and differentially expressed genes (DEGs) screening. Key module hub genes were obtained by weighted gene co-expression network analysis (WGCNA) analysis. The common intersection genes of active ingredient targets, DEGs and key module hub genes of CMH were selected, and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis, while key pathways were selected by GO and KEGG pathway enrichment analysis, and protein interaction relationships were obtained from the String database, so as to construct drug-ingredient-target network and protein interaction network (PPI) relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking, and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times, which were Danshen (Radix et Rhizoma Salviae Miltiorrhizae), Huangqi (Radix Astragali), Baizhu (Rhizoma Atractylodis Macrocephalae), Danggui (Radix Angelicae Sinensis), Dangshen (Radix Codonopsis), Gancao (Radix et Rhizoma Glycyrrhizae), Baishao (Radix Paeoniae Alba), Fuling (Poria) and Shudihuang (Radix Rehmanniae Praeparata) from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples, including 14 of the healthy control group and 10 of the PMF group, and identified 319 DEGs between the two groups, including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink, MEdarkred, MEblack, MEgrey, and MEturquoise, involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF, which included six hub protein targets: HSP90AA1, HSP90AB1, SRC, MAPK1, IL1B and IL10. From the drug-ingredient-target network, seven active ingredients of CMH targeting at these six hub targets were found, including verbascoside, verbascos isoflavone, kaempferol, luteolin, naringenin, quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang, Huangqi, Baishao, Danshen, Gancao and Fuling, and among the seven active ingredients, calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang, Huangqi, Baishao, Danshen, Gancao and Fuling, and the active ingredients include verbascoside, verbascos isoflavones, kaempferol, luteolin, naringenin, quercetin and pachymic acid. The relevant targets are HSP90AA1, HSP90AB1, SRC, MAPK1, IL-10, and IL-1β, and the most critical pathways are lipid and atherosclerosis pathways. 
		                        		
		                        		
		                        		
		                        	
2.2022 Multiple-country Monkeypox Outbreak and Its Importation Risk into China: An Assessment Based on the Risk Matrix Method.
Min DU ; Shi Mo ZHANG ; Wei Jing SHANG ; Wen Xin YAN ; Qiao LIU ; Chen Yuan QIN ; Min LIU ; Jue LIU
Biomedical and Environmental Sciences 2022;35(10):878-887
		                        		
		                        			OBJECTIVE:
		                        			To analyze the 2022 multiple-country monkeypox outbreak and assess its importation risk into China.
		                        		
		                        			METHODS:
		                        			Data was from United States Centers for Disease Control and Prevention. We described the global epidemic and calculated concentration index to measure economic-related inequality. Importation risk into China was evaluated and ranked by using risk matrix method and Borda count method, respectively.
		                        		
		                        			RESULTS:
		                        			As of July 29, 2022, of 79 countries or territories, 39 (49.37%, 39/79), 17 (21.52%, 17/79), 6 (7.59%, 6/79), 12 (15.19%, 12/79), and 5 (6.33%, 5/79) country or territories identified cases < 10, 10-, 51-, 101-, and > 1,000. There were economic-related health disparities exist in the distribution of cases (the concentration index = 0.42, P = 0.027), and the inequality disadvantageous to the rich (pro-poor). There were 12 (15.38%, 12/78), 15 (19.23%, 15/78), 6 (7.69%, 6/78), and 45 (57.69%, 45/78) countries or territories with extremely high, high, moderate, and low importation risk. United States and France ranked first with the highest Borda points of 156, and counts of zero.
		                        		
		                        			CONCLUSION
		                        			Of 78 countries or territories, the key attention need be paid to the United States and France, relatively. As the epidemic progresses, preparing prevention and control measures to further reduce importation risk was crucial.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			China/epidemiology*
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		                        			Disease Outbreaks/prevention & control*
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		                        			France
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		                        			Monkeypox/prevention & control*
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		                        			Risk Assessment
		                        			
		                        		
		                        	
3.Application of optical trocar insertion in laparoscopic surgery after previous abdominal surgery
Xiang'an WU ; Yue SHI ; Xueshuai WAN ; Jue WANG ; Yuke ZHANG ; Bao JIN ; Xiao LIU ; Haifeng XU ; Yongchang ZHENG ; Xin LU ; Yilei MAO ; Xinting SANG ; Shunda DU
Journal of Clinical Hepatology 2021;37(10):2380-2383
		                        		
		                        			
		                        			 Objective To investigate the value of optical trocar insertion technique in establishing pneumoperitoneum in patients undergoing laparoscopic surgery after previous abdominal surgery. Methods A total of 29 patients, with a history of abdominal surgery, who planned to undergo laparoscopic liver surgery were enrolled and randomly divided into optical trocar insertion group and open approach group. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U  test was used for comparison of non-normally distributed continuous data between groups; the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U  test was used for comparison of ranked data between groups. Results There were no procedure-related complications in either group. Compared with the open approach group, the optical trocar insertion group had a significantly shorter time required to establish pneumoperitoneum [35.00 (21.00-46.00) seconds vs 180.00 (152.50-252.50) seconds, U =0, P  < 0.001] and a significantly smaller incision length [1.10(1.00-1.20) cm vs 2.80(2.45-3.00) cm, U =0, P  < 0.001]. Conclusion Both optical trocar insertion and open approach for establishing pneumoperitoneum is relatively safe in patients undergoing laparoscopic liver surgery after previous abdominal surgery, while optical trocar insertion has the advantages of high efficiency and minimal invasiveness in establishing pneumoperitoneum. 
		                        		
		                        		
		                        		
		                        	
4.Early and intermediate outcomes of second-grade false-lumen endovascular occlusive repair for aortic dissection
Min ZHOU ; Zhenyu SHI ; Lixin WANG ; Daqiao GUO ; Xin XU ; Bin CHEN ; Junhao JIANG ; Jue YANG ; Weiguo FU
Chinese Journal of General Surgery 2021;36(1):5-9
		                        		
		                        			
		                        			Objective:To summarize the early and intermediate outcomes of second-grade false-lumen endovascular occlusive repair (FLEVOR) for aortic dissection.Methods:The clinical data of 12 patients undergoing second-grade FLEVOR after proximal repair of aortic dissection at our center from Aug 2016 to Aug 2019 was retrospectively analyzed.Results:The mean age was (51.3±14.9) years old. Four patients received open repair due to Stanford type A aortic dissection previously, the other 8 patients underwent thoracic endovascular aortic repair for Stanford type B aortic dissection. The time to the proximal repair varied from 3 months to 16 years. The technical success rate was 100%. Visceral ischemia, early spinal cord ischemia and in-hospital death did not occur perioperatively. The mean follow-up time was 16.7 months. Persistent false lumen perfusion was found in 3 patients, complete thrombosis of false lumen was achieved in the other 8 patients. The maximum diameter of abdominal aorta decreased in 8 (72.7%) patients.Conclusions:FLEVOR could block the blood flow from the false lumen and induce the thrombosis of false lumen, which promotes the aortic remodeling. Meanwhile, FLEVOR could protect the blood supply of spinal cord and viscera, and reduce the risk of type Ⅱ endoleaks.
		                        		
		                        		
		                        		
		                        	
5.Short term result of COOK-ZFEN custom-made endovascular stent graft system for the treatment of short-neck abdominal aortic aneurysm
Yulong HUANG ; Yue LIN ; Kai HOU ; Daqiao GUO ; Xin XU ; Bin CHEN ; Junhao JIANG ; Jue YANG ; Zhenyu SHI ; Zhihui DONG ; Xiao TANG ; Yi SI ; Lixin WANG ; Weiguo FU ; Yuqi WANG
Chinese Journal of General Surgery 2021;36(6):457-460
		                        		
		                        			
		                        			Objective:To evaluate the safety and efficacy of a Zenith fenestrated aortic stent-graft (ZFEN) system in the treatment of short-necked aneurysms.Methods:The clinical data of 5 patients receiving F-EVAR in Zhongshan Hospital, Fudan University from Mar 2018 to Sep 2019 according to the standards of short-necked abdominal aortic aneurysm and COOK ZFEN custom stent were retrospectively analyzed.Results:Patients' average age was (69±11) years old. The time of stent customization was 4-6 weeks. The average maximum diameter of AAA was (60.8±14.0) mm. The average proximal neck diameter was (26.0±2.6) mm and the average length anchoring zone was (6.4±2.2) mm. The rate of technical success was 100%. There was no intraoperative loss of visceral vessels and stent displacement. The meane follow-up time was 6.8 months. The perioperative mortality was 0, and there were no other major complications. There were 3 patients with simple type Ⅱ endoleak and 1 patient with type Ⅲ endoleak. The endoleaks disappeared in 4 patients during follow-up of 3-12 months. 1 patient suffered with type Ⅱ and type Ⅲ endoleak, and the visceral vessels and branching stents were patent in all patients.Conclusion:The short term result of COOK ZFEN stent-graft system was safe and feasible for the treatment of short-necked AAA.
		                        		
		                        		
		                        		
		                        	
6.Long-term follow up outcomes of surgical resection of Shamblin Ⅱ/Ⅲ carotid body tumor: a single center analysis
Wei ZHANG ; Fei LIU ; Lixin WANG ; Daqiao GUO ; Xin XU ; Bin CHEN ; Junhao JIANG ; Jue YANG ; Zhenyu SHI ; Weiguo FU
Chinese Journal of General Surgery 2020;35(3):195-198
		                        		
		                        			
		                        			Objective:To evaluate the correlation between tumor size and surgical outcomes of Shamblin Ⅱ/Ⅲ carotid body tumor (CBT) and the prognosis.Methods:From Apr 2011 to Dec 2017, 88 patients with Shamblin Ⅱ and Ⅲ CBTs undergoing tumor resection were retrospectively analyzed. The long-term prognosis of surgical resection was also evaluated.Results:One patient died of multi-organ failure postoperatively, two patients abandoned surgery. The perioperative mortality was 1%. 85 patients having 87 lesions successfully resected were analyzed. There were 13 Shamblin Ⅱ and 74 Shamblin Ⅲ CBTs resection. Two patients had bilateral CBTs resection. The median of tumor size, procedural blood loss, procedural time, and length of hospital stay was 3.0 (1.2-5.5) cm, 200 (0-2 500) ml, 162 (85-430) min, and 10 (6-28) d, respectively. Seventy-two patients had carotid vascular intervention during the procedure, and thirty-three patients had neurological complications after the procedure. Correlation analysis showed that the tumor size had positive relationship with blood loss (Spearman R=0.35, P<0.01) and procedural time (Spearman R= 0.54, P<0.01). Tumor size was positively associated with the risk of cranial neurological complication ( OR=1.72, 95% CI 1.08-2.73, P=0.02) and carotid vascular intervention ( OR=2.69, 95% CI 1.27-5.69, P=0.01). There were four patients who were diagnosed with malignant CBT due to the metastasis. Three suffered CBT recurrence after 1, 5, and 7 years during the follow up. Conclusions:Shamblin Ⅱ or Ⅲ CBTs should be intervened as early as possible to facilitate the surgical resection, as well as to reduce the risk of carotid vascular and neurological complications.
		                        		
		                        		
		                        		
		                        	
7.Treatment for arteriosclerosis obliterans complicated with acute thrombosis of lower extremity
Hao LIU ; Bin CHEN ; Junhao JIANG ; Yun SHI ; Tao MA ; Daqiao GUO ; Xin XU ; Jue YANG ; Zhenyu SHI ; Ting ZHU ; Gang FANG ; Chao FANG ; Xiaolang JIANG ; Zhihui DONG ; Weiguo FU
Chinese Journal of General Surgery 2020;35(7):540-544
		                        		
		                        			
		                        			Objective:To discuss the clinical treatment for arteriosclerosis obliterans combined with acute thrombosis (ASOCAT) of lower extremities.Methods:The treatment methods and results of 30 patients with ASOCAT admitted to our center from Jan 2009 to May 2019 were retrospectively analyzed.Results:The course of acute thrombosis in 30 patients was (9.5±5.2) days, and the average course of ASO was (2.1±1.4) years. Among 30 patients, 13 patients had aortoiliac occlusion (type Ⅰ), and 17 patients had femoropopliteal lesion (type Ⅱ). Twenty-eight patients underwent endovascular treatment, 1 had hybrid operation, and 1 was given aorto-bilateral femoral bypass. One patient died perioperatively. 24 patients were followed up for (16.3±16.1) months. One died during follow-up.Two patients underwent above-knee amputation within 6 months. Two patients had distal superficial femoral artery reocclusion within 12 months. The restenosis/reocclusion rates within 12 months of type Ⅰ and Ⅱ patients were 12.5% and 21.4%, respectively. The 6/12-month amputation-free survival rates for type Ⅰ and type Ⅱ were 87.5%/87.5% and 92.8%/85.7%, respectively.Conclusion:Reasonable and active use of open surgery, endovascular treatment or hybrid operation could achieve acceptable outcomes in patients with ASOCAT.
		                        		
		                        		
		                        		
		                        	
8.Proliferation of MicroRNA-365 and E74-like Factor 4 in Cervical Cancer Cells and Its Clinical Significance.
Ying GUO ; Dong MA ; Shi Feng JIA ; Jia LIU ; Shao Bei FAN ; Meng ZHANG ; Lin Ran SHI ; Li Li JIANG ; Jue Xin SHI ; Hai Qiu WANG ; Huan Yu ZHENG ; Ou LI
Acta Academiae Medicinae Sinicae 2019;41(2):220-227
		                        		
		                        			
		                        			Objective To investigate the expressions,roles,and clinical significance of microRNA-365(miR-365)and E74-like factor 4(ELF4)in cervical cancer. Methods The expressions of miR-365 in normal cervical tissues(n=34),cervical intraepithelial neoplasia 1(CIN 1)(n=31),cervical intraepithelial neoplasia2-3(CIN 2-3)(n=37),squamous cell carcinoma of the cervix(SCC)(n=33),and three cervical cancer cell lines(C33A cells,Hela cells,and SiHa cells)were detected by real-time quantitative polymerase chain reaction(qPCR).Bioinformatic prediction and luciferase reporter gene assay were performed to verify whether ELF4 was a direct target of miR-365.Western blot and immunohistochemistry were used to detect ELF4 expression in cervical cancer cells and in different pathological cervix tissues.CCK8 assay was used to detect the effect of overexpression or inhibition of miR-365 on the proliferation of cervical cancer cells at different time points.The relationships among the miR-365 expression,ELF4 expression,and clinicopathological parameters of cervical cancer were analyzed by correlation analysis. Results qPCR results showed that compared with the normal cervical cell HcerEpic,the expressions of miR-365 in CIN1,CIN2-3,and cervical cancer tissues gradually decreased with the increased pathologic grade,and its expressions also decreased in different cervical cancer cell lines.The luciferase reporter gene assay confirmed that ELF4 was the direct target of miR-365.Western blot showed that the expression of ELF4 increased in all three cervical cancer cell lines compared with normal cervical epidermal cell(P=0.013,P=0.002,P=0.004).Immunohistochemistry showed that ELF4 expression was up-regulated in CIN and cervical cancer tissues.CCK8 assay showed that overexpression of miR-365 inhibited cell proliferation,while inhibition of miR-365 promoted the proliferation of three cervical cancer cells(P<0.05).Further analysis confirmed that there was a negative correlation between the expression levels of miR-365 and ELF4 in CIN2-3 and SCC(r=-0.351,P=0.045;r=-0.349,P=0.035).Clinical analysis showed that the expressions of both miR-365 and ELF4 were correlated with tumor size,pathological grade,and clinical stage in SCC(all P < 0.05).Conclusion The decreased expression of miR-365 in human cervical cancer cells relieves its inhibitory effect on ELF4,which promotes the proliferation of cervical cancer cells and the formation of tumor.
		                        		
		                        		
		                        		
		                        			Cell Proliferation
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		                        			DNA-Binding Proteins
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		                        			genetics
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		                        			Female
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		                        			HeLa Cells
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		                        			Humans
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		                        			MicroRNAs
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		                        			genetics
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		                        			Transcription Factors
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		                        			genetics
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		                        			Uterine Cervical Neoplasms
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		                        			genetics
		                        			
		                        		
		                        	
9.Transplantation of peripheral purified CD34+ cells in treatment of thromboangiitis obliterans
Zhihui DONG ; Zheng WEI ; Weiguo FU ; Yuan FANG ; Tianyue PAN ; Bin CHEN ; Daqiao GUO ; Xin XU ; Peng LIU ; Junhao JIANG ; Jue YANG ; Zhenyu SHI ; Ting ZHU ; Yun SHI
Chinese Journal of General Surgery 2017;32(4):323-327
		                        		
		                        			
		                        			Objective To evaluate the safety and efficacy of transplantation of purified CD34 + cells (PCCs) in treatment of critical limb ischemia (CLI) caused by thromboangiitis obliterans (TAO).Methods From May 2009 to June 2015,34 TAO-induced-CLI cases underwent PCCs transplantation.None of these patients were eligible for surgical or endovascular revascularization.G-CSF was subcutaneously injected for 5 days before peripheral CD34 + cells were isolated,purified and intramuscularly injected in the limbs.Patients were regularly follow-up.Results Technical success was achieved in all cases.The mean number of transplanted cells was (7.5 ± 2.4) × 105/kg.The follow-up was accomplished in 32 cases,ranging from 6 to 79 months (mean 45 ±24 months),and two patients were lost.Wong-Baker FACES pain rating scale score significantly decreased from 8.0 ±2.0(4-10)to 2.2 ±3.1 (P <0.05) at 1 month.The Peak pain-free walking time improved from (4.0 ± 2.0) min to (13.5 ± 5.3) min (P < 0.05) at 3 months and (19.0 ± 3.1) min (P < 0.05) at 6 months.The ankle-brachial index increased from 0.42 ± 0.20 to 0.50 ± 0.10 (P < 0.05) at 3 months and 0.52 ± 0.11 (P < 0.05) at 6 months,respectively.Transcutaneous partial oxygen pressure rose from (25 ± 11) mmHg to (48 ± 11) mmHg(P < 0.05) at 3 months and (58 ± 10) mmHg (P < 0.001) at 6 months,respectively.Ulcers healed in 21 out of 22 patients at (5 ± 4) months.The overall amputation-free survival rate was 94.1% at 6 months and 91.2% at 48 months.No major adverse events were observed perioperatively or postoperatively.Conclusions Transplantation of PCCs could yield safe,satisfactory and durable treatment outcomes in patients with TAO-induced-CLI.
		                        		
		                        		
		                        		
		                        	
10. Endovascular aortic repair of abdominal aortic aneurysm of short neck with Endurant stent graft
Yonggang WANG ; Zhenyu SHI ; Weiguo FU ; Daqiao GUO ; Xin XU ; Bin CHEN ; Junhao JIANG ; Jue YANG ; Ting ZHU ; Zhihui DONG ; Yun SHI ; Lixin WANG ; Xiao TANG ; Jianing YUE
Chinese Journal of Surgery 2017;55(6):451-454
		                        		
		                        			 Objective:
		                        			To evaluate the safety and effectiveness of the Endurant stent graft for abdominal aortic aneurysm cases with proximal neck length <10 mm.
		                        		
		                        			Methods:
		                        			This study was a retrospective analysis. From January 2010 to May 2015, 22 consecutive abdominal aortic aneurysm patients with proximal neck length <10 mm were treated with endovascular aortic repair by Endurant stent graft in Department of Vascular Surgery, Zhongshan Hospital, Fudan University. There were 19 (86.3%) male cases, aging from 57 to 84 years. All patients underwent preoperative CT angiography and the anatomic parameters of abdominal aortic aneurysm were measured. All patients performed standard endovascular aortic repair first and if there was obvious proximal typeⅠ endoleak, the CUFF or the chimney technology were applied to observed the perioperative technical and the clinical success rate. During follow-up, the incidence of adverse events and the reintervention rate were observed.
		                        		
		                        			Results:
		                        			These 22 cases had proximal neck length 5 to 9 mm with the average of (7.2±1.4) mm. Immediate endoleak occurred in 5 patients with 4 cases of proximal typeⅠ endoleak, 3 cases were implanted proximal CUFF, 1 case implanted CUFF and left renal artery chimney. One case died perioperatively, the clinical success rate was 95.4%, the technical success rate was 77.3%. During the follow-up of 6 to 54 months, there was 1 case with delayed proximal type-1 endoleak, during operation the patient had no endoleak, but disappeared 6 months later without further intervention. So the incidence of adverse event was 4.5% and reintervention rate was 0.
		                        		
		                        			Conclusion
		                        			The Endurant stent graft for abdominal aortic aneurysm cases with proximal neck length < 10 mm is safe and effective. 
		                        		
		                        		
		                        		
		                        	
            
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