1.Using Pre-Clinical Studies to Explore the Potential Clinical Uses of Exosomes Secreted from Induced Pluripotent Stem CellDerived Mesenchymal Stem cells
Andrew Kailin ZHOU ; Eric JOU ; Victor LU ; James ZHANG ; Shirom CHABRA ; Joshua ABISHEK ; Ethan WONG ; Xianwei ZENG ; Baoqiang GUO
Tissue Engineering and Regenerative Medicine 2023;20(6):793-809
Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.
2.Clinical characteristics and prognosis of duodenal neuroendocrine neoplasms
Xinyu ZENG ; Chengguo LI ; Jianbo LYU ; Gan MAO ; Liwu ZENG ; Yuqiang DU ; Zhenyu LIN ; Peng ZHANG ; Rong LIN ; Kailin CAI ; Kaixiong TAO
Chinese Journal of General Surgery 2023;38(6):418-422
Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.
3.Characteristics and clinical significance of nailfold capillaroscopy in patients with systemic lupus erythematosus
Danmin WANG ; Zhaopeng CHEN ; Zhiduo HOU ; Hongjin LIANG ; Kailin ZENG ; Fengcai SHEN ; Ling LIN
Chinese Journal of Rheumatology 2020;24(9):580-585
Objective:To summarize the characteristics of nailfold capillaroscopy (NC) in patients with systemic lupus erythematosus (SLE) and explore its clinical significance.Methods:NC examination was performed in 162 SLE patients. The clinical data of SLE patients was collected. Tianniu NC scoring standard was used. The t test was applied to analyze the measurement data, the χ2 test was applied to analyze the counting data. the Pearson or Spearman test was used to evaluate the correlative factors of NC in patients with SLE. Results:NC abnormalities were seen in 87.7%(142/162) of SLE patients, and the incidence of mild, moderate and severe abnormalities was 29.0%(47 cases), 45.1%(73 cases) and 13.6%(22 cases) respectively. The most common NC abnormal manifestation in SLE patients was decreased blood flow velocity (86.4%). In patients with moderate to severe NC abnormalities, the proportions of patients with Raynaud's phenomenon (37.9% vs 23.9%, χ2=2.955, P=0.043) and interstitial lung disease (8.0% vs 0, χ2=5.213, P=0.023), and the level of D-Dimer [(1 992±2 279) μg/L vs (1 248±1 721) μg/L, t=-1.624, P=0.013] were significantly higher than those in the groups with normal/mild NC abnormalities. Correlation analysis demonstrated that Raynaud's phenomena, interstitial lung disease, pulmonary hypertension and D-Dimer were positively correlated with the NC abnormality. Conclusion:NC abnormalities are common in SLE patients. Decreased blood flow velocity is the most frequent manifestation. SLE patients with moderate to severe NC abnormalities should be actively screened for pulmonary hypertension and interstitial lung disease.
4. Early postoperative complications and risk factors in laparoscopic D2 radical gastrectomy for gastric cancer
Ming CAI ; Xiangyu ZENG ; Zhen XIONG ; Jinbo GAO ; Xiaoming SHUAI ; Kailin CAI ; Jiliang WANG ; Zheng WANG ; Peng ZHANG ; Xinghua LIU ; Jie BAI ; Ji CHENG ; Guobin WANG ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(8):742-747
Objective:
To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors.
Methods:
A case-control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non-complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with
5.Parvovirus B19 infection in patients after renal transplantation :a report of 22 cases
Xiaowei ZHANG ; Lei ZHANG ; Wenyu ZHAO ; Mingxing SUI ; Kailin LIN ; Zhe LIU ; Li ZENG
Chinese Journal of Organ Transplantation 2019;40(6):323-327
Objective To summarize the pathogenic characteristics and treatments of parvovirus B19 infection in patients after renal transplantation .Methods Twenty-two cases of parvovirus B19 infection after renal transplantation were diagnosed by quantitative polymerase chain reaction (qPCR) from March 2016 to January 2019 .And the pathogenic characteristics and treatments of parvovirus B19 infection after renal transplantation were analyzed .Results The overall incidence rate of parvovirus B19 after renal transplantation was 2 .97% .The median diagnostic time was 39 (15~572) days .Administration of intravenous immunoglobulin (IVIG) ,conversion of immunosuppressants and other comprehensive regimens were adopted .Except for 1 patient dying from cardiovascular accident at 4 days post-diagnosis , the remainders were cured . The accumulative dosage of IVIG was (7 .7 ± 3 .8) g/kg in 5 patients with delayed conversion and un-conversion of immunosuppressants ,and (2 .7 ± 1 .9) g/kg in 16 patients with early conversion of immunosuppressants .During a follow-up period of (13 .0 ± 9 .1) months ,the level of hemoglobin remained stable .Conclusions Parvovirus B19 infection after renal is predominant immediately after transplantation .And the dosage of IVIG may be lowered by an early conversion of immunosuppressants after a definite diagnosis .
6.Early postoperative complications and risk factors in laparoscopic D2 radical gastrectomy for gastric cancer
Ming CAI ; Xiangyu ZENG ; Zhen XIONG ; Jinbo GAO ; Xiaoming SHUAI ; Kailin CAI ; Jiliang WANG ; Zheng WANG ; Peng ZHANG ; Xinghua LIU ; Jie BAI ; Ji CHENG ; Guobin WANG ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(8):742-747
Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.
7.Early postoperative complications and risk factors in laparoscopic D2 radical gastrectomy for gastric cancer
Ming CAI ; Xiangyu ZENG ; Zhen XIONG ; Jinbo GAO ; Xiaoming SHUAI ; Kailin CAI ; Jiliang WANG ; Zheng WANG ; Peng ZHANG ; Xinghua LIU ; Jie BAI ; Ji CHENG ; Guobin WANG ; Kaixiong TAO
Chinese Journal of Gastrointestinal Surgery 2019;22(8):742-747
Objective To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors. Methods A case?control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non?complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications. Results Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non?surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6 ± 12.6) days vs. (14.2 ± 6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960?8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862?29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357?21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214?12.658, P<0.001) were the independent risk factors of postoperative complications. Conclusions Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.
8.Clinical efficacy and safety analysis of domestic imatinib for treatment of gastrointestinal stromal tumor
Peng ZHANG ; Wenze WAN ; Ruizhi ZHANG ; Xiangyu ZENG ; Zhen XIONG ; Ming CAI ; Xiaoming SHUAI ; Kailin CAI ; Jinbo GAO ; Guobin WANG ; Kaixiong TAO
Cancer Research and Clinic 2018;30(10):660-664
Objective To investigate the clinical efficacy and safety of domestic imatinib in the treatment of gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of GIST patients who received domestic imatinib treatment from January 2014 to December 2017 in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were analyzed retrospectively. The treatment efficacy and adverse reactions were analyzed. Results A total of 35 patients included 20 males and 15 females with a median age of 53 years old (28-79 years old). Among all the patients, 25 with primary GIST underwent complete resection, in which 20 cases were classified as high risk and 5 as moderate risk according to the risk stratification. Of the remaining 10 recurrent/metastatic or unresectable GIST patients, 6 cases had metastasis in liver, 2 cases had metastasis in peritoneum, 1 case had extensive abdominal and pelvic metastasis, and the other 1 case was initially unresectable. The follow-up data of all the 35 patients were available, with a median follow-up time of 25 months (4-49 months). Twenty-five primary patients with complete resection received adjuvant therapy with a median time of 14 months (4-44 months). The median time of follow-up was 25 months (4-49 months), and none of the primary patients was detected with recurrence or metastasis of GIST. Meanwhile, of the 10 patients with recurrent/metastatic or unresectableGIST, the median time of medicine-taking was 24 months (3-49 months). Seven of 10 patients received imatinib monotherapy, including 5 cases of partial remission and 2 cases of stable disease. The other 3 patients with localized progression received complete resection along with imatinib therapy. All the 10 patients achieved durable clinical benefit. Twenty-seven patients (77.1%) experienced adverse events, and only 1 case (2.9 %) had grade 3 adverse events. Conclusion Domestic imatinib is effective and safe for patients who received adjuvant therapy after complete resection of primary GIST as well as those with recurrent/metastatic or unresectable GIST, but it remains to be further confirmed by large samples of prospective studies.
9.A Network Pharmacology Approach to Explore the Molecular Mechanism of Taoren-Honghua Pair on Syndrome of Blood Stasis
Kailin YANG ; Liuting ZENG ; Anqi GE ; Jinwen GE ; Zhiyong LONG ; Tingting BAO ; Yan JIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(12):2208-2216
Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis
10. Effects of allogeneic hematopoietic stem cell transplantation in combination with infusion of endothelial progenitor cells on bone marrow inflammatory injury
Wen LI ; Mingfeng LI ; Pingping ZHAO ; Jianlin QIAO ; Kailin XU ; Lingyu ZENG
Chinese Journal of Hematology 2017;38(4):318-324
Objective:
To explore effects of allogeneic hematopoietic stem cell transplantation (HSCT) in combination with infusion of endothelial progenitor cells (EPC) on bone marrow inflammatory injury.
Methods:
6-8 weeks BALB/c (H-2Kd) mice after lethal dose of irradiation (TBI) were subjected to allogeneic bone marrow transplantation (BMT group) or co-transplantation of EPC (EPC group) . Samples of bone marrow cells of mice in each group on days 7,14,21,28 after transplantation were obtained to detect EPC cultural and cell chimeric rates by flow cytometer. Mice were sacrificed on days 7, 14, 21 and 28 post HSCT to analyze bone marrow pathology by H&E staining, the infiltration of macrophages and neutrophils by Western blot, validation expression levels of inflammatory complexes nlrp1、nlrp6 and its downstream molecules casepase-1 by Q-PCR and Western blot.
Results:
Cell chimeric rate on day 7 after transplantation in EPC group[ (91.65±2.77) %] was significantly higher than in BMT group[ (83.69±1.26) %]. Alleviated osteomyelitis injury and inflammatory cell infiltration in EPC group were observed when compared with BMT mice. Also significant reductions of the levels of nlrp1、nlrp6、casepase-1 transcription complexes in EPC mice were noted when compared with BMT ones.
Conclusion
Co-transplantation of HSC and EPC could alleviate inflammatory cell infiltration and activation of the complex to promote the repair of bone marrow.

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