1.Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment.
Hao CAI ; Yufan XIANG ; Yujun ZENG ; Zhiqian LI ; Xiuli ZHENG ; Qiang LUO ; Hongyan ZHU ; Qiyong GONG ; Zhongwei GU ; Yanhui LIU ; Hu ZHANG ; Kui LUO
Acta Pharmaceutica Sinica B 2021;11(2):544-559
Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd
2.Progression of pathogenesis, diagnosis and treatment of diversion colitis
Qiang SUN ; Yu HUANG ; Zhiqian HU
Chinese Journal of Gastrointestinal Surgery 2020;23(11):1117-1122
Diversion colitis (DC) is a common non-specific inflammation of the malfunctioning bowel segment after diversion of feces. Although most patients develop DC during stoma, there are no obvious clinical symptoms, and a small number of patients show abdominal pain, mucus discharge and hematochezia. The erythema, diffuse particles and vascular texture blur are the most prominent endoscopic manifestations, and the lymphatic follicular hyperplasia is the most prominent pathological manifestations.Reconstruction of intestinal continuity is the best way to cure recanted colitis. In this review, we summarize and review the mechanism of occurrence, clinical features, diagnosis and treatment of DC, which will be helpful for the effective control and prevention of DC.
3.Progression of pathogenesis, diagnosis and treatment of diversion colitis
Qiang SUN ; Yu HUANG ; Zhiqian HU
Chinese Journal of Gastrointestinal Surgery 2020;23(11):1117-1122
Diversion colitis (DC) is a common non-specific inflammation of the malfunctioning bowel segment after diversion of feces. Although most patients develop DC during stoma, there are no obvious clinical symptoms, and a small number of patients show abdominal pain, mucus discharge and hematochezia. The erythema, diffuse particles and vascular texture blur are the most prominent endoscopic manifestations, and the lymphatic follicular hyperplasia is the most prominent pathological manifestations.Reconstruction of intestinal continuity is the best way to cure recanted colitis. In this review, we summarize and review the mechanism of occurrence, clinical features, diagnosis and treatment of DC, which will be helpful for the effective control and prevention of DC.
4.Research progression of endoscopic anastomosis technique and digestive tract reconstruction after totally laparoscopic gastrectomy for gastric cancer.
Qiang SUN ; Haiyang ZHOU ; Zhiqian HU
Chinese Journal of Gastrointestinal Surgery 2019;22(2):191-195
With the development of laparoscopic skills and instruments,totally laparoscopic gastrectomy for gastric cancer has become widely used in the clinic,mainly including totally laparoscopic proximal gastric reconstruction,distal gastrectomy for gastric cancer and total gastrectomy. Digestive tract reconstruction is the key procedure of totally laparoscopic gastrectomy for gastric cancer. Totally laparoscopic surgery has less trauma and better visualization than reconstruction in a small incision. At present,feasibility and safety of totally laparoscopic gastrectomy for gastric cancer have been preliminarily confirmed. However,higher level of evidence is needed for the evaluation of long-term oncologic efficacy. In the future,it is possible for patients to best benefit from totally laparoscopic surgery with minimal trauma,safe anastomosis under the principle of radical resection of gastric cancer. The digestive tract reconstruction includes Delta anastomosis (Billroth I),Billroth II anastomosis,and gastrojejunal Roux-en-Y anastomosis in totally laparoscopic distal gastrectomy (TLDG). Billroth I with delta anastomosis has strict indications in TLDG. Gastrojejunal Roux-en-Y anastomosis is now more popular. Billroth II with Braun anastomosis and uncut Roux-en-Y anastomosis is technically easier to carry out in TLDG than Roux-en-Y. Totally laparoscopic proximal gastric reconstruction includes esophagogastric stump anastomosis,esophagogastric tubular anastomosis and interposition jejunostomy. The digestive tract reconstruction includes anastomosis using linear stapler and circular stapler in totally laparoscopic total gastrectomy (TLTG). In order to better serve the clinic,we review the progress of different endoscopic anastomotic techniques and digestive tract reconstruction.
Anastomosis, Surgical
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methods
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Gastrectomy
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methods
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Humans
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Laparoscopy
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Stomach Neoplasms
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surgery
5.Diagnostic value of endoscopic ultrasonography in staging of rectal cancer
Jue WEI ; Jie SHEN ; Zhiqian HU ; Canping RUAN ; Xin ZENG ; Weifen XIE
Chinese Journal of Digestion 2018;38(3):177-181
Objective To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in staging of rectal cancer (RC).Methods From January 2015 to January 2017,the clinical data of 204 patients with RC and received EUS and surgery were retrospectively analyzed.Patients were divided into surgery alone group (155 cases) and preoperative neoadjuvant chemoradiation therapy (CRT) plus surgery group (49 cases).The preoperative staging by EUS and postoperative pathological staging of two groups were compared.Kappa test was performed for statistical analysis.Results Compared with postoperative pathologic diagnosis,the accuracy rate of EUS in the evaluation of invasion depth of RC in surgery alone group was 81.9% (127/155),and the accuracy rates in the diagnosis of Tis,T1,T2,T3 and T4 were 3/4,11/13,82.1%(32/39),91.1%(41/45) and 74.1%(40/54),respectively,with a good consistency (kappa=0.751,P<0.01).However,the accuracy rate of EUS in the invasion depth of RC in CRT plus surgery group was 34.7% (17/49),and the accuracy rates in the diagnosis of T2,T3 and T4 were 1/13,2/7 and 14/16,respectively,with a poor consistency (kappa =0.107,P=0.850).Compared with postoperative pathologic diagnosis,the diagnostic accuracy rate of EUS in evaluating regional lymph node metastasis in surgery alone group was 70.3% (109/155),and the accuracies in the diagnosis of cases with or without regional lymph node metastasis were 40.7% (24/59) and 88.5% (85/96),respectively,with a poor consistency (kappa=0.317,P<0.01).The diagnostic accuracy rate of EUS in evaluating regional lymph node metastasis of preoperative CRT plus surgery group was 51.0% (25/49),and the accuracies in the diagnosis of cases with or without regional lymph node metastasis were 5/11 and 52.6% (20/38),respectively,with a poor consistency (kappa =0.014,P =0.911).Conclusions EUS can accurately evaluate the depth of tumor invasion and lymph node metastasis in preoperative staging of RC,which may be helpful for determining clinical treatment strategy.However,for patients received CRT treatment,EUS has a limited value in diagnosing and staging the tumor.
6.Induced membrane technique combined with antibiotic calcium sulfate pellets in treating infected bone defect in lower extremity
Yi ZHANG ; Xiaobin TIAN ; Rongfeng SHE ; Yuanzheng WANG ; Ruyin HU ; Li SUN ; Bo LI ; Zhiqian WANG ; Jianyang LI
Chinese Journal of Orthopaedics 2017;37(9):513-519
Objective To evaluate the clinical effects of the Masquelet technique combined with antibiotic calcium sulfate pellets in treating infected bone defects.Methods From February 2014 to February 2016,9 patients with infected bone defects were treated in our department,including 7 males and 2 females,with an average age of 37.0 years (range,24-56 years).6 cases were infected because of open fractures,3 infected after internal fixation operation.All defects were located in the lower limb diaphysis and metaphysis (3 cases in femur,6 cases in tibia).The length of the bone defects were 4-12 cm after debridement,all defects filled with PMMA loaded with Vancomycin,and fixed with exterual fixators.After 6-10 weeks,the bone cement spacers were taken out and the antibiotic calcium sulfate pellets were implanted into the membrane.A certain amount of autogenous cancellous bone granules would be mixed into the calcium sulfate pellets if the defect was larger than 6-8 cm.5 cases remained fixed with external fixators,3 cases replaced for plates,1 case replaced for plaster external fixator.Regular X-ray follow-ups were taken and complications recorded as well.Evaluate the healing of bone defect and functional recovery of adjacent joints by Samantha X score system,visual analogue scale (VAS) and Paley method,respectively.Results The 9 cases were followed up for a mean duration of 9.3 months (range,6-15 months).All bone defects healed after a mean time of 14 weeks (range,10-24 weeks).The wound poor healing occurred in only 1 case in the first stage of surgery,and cured by dressing changes.No complications of the recurrence of infection and implant failure.At the last follow-up,the average Samantha X score was 4.9,the VAS score was 0 to 3 (average 1.5) for patients standing on crutches and all the bone defect healing graded excellent evaluated by Paley method,the functional recovery of the adjacent joints graded:excellent in 6 cases,good in 2 cases,and fair in 1 case (the excellent and good rate was 89%).Conclusion Masquelet technique combined with antibiotic calcium sulfate particles is effective in the treatment of infected bone defects.
7.Biomechanical properties of PDO-SIS patch and its effect on repairing the abdominal wall defect of rats
Yayun XIE ; Jun WANG ; Wenyue CHENG ; Weidong WU ; Jian ZHANG ; Haiyang ZHOU ; Zhiqian HU
Medical Journal of Chinese People's Liberation Army 2017;42(5):366-371
Objective To explore the mechanical properties of the hybrid patch made of porcine acellular small intestinal submucosa (P-SIS) and polydioxanone (PDO) and its effect on repairing the abdominal wall defects of rats.Methods The PDOSIS patch and 8SIS patch were constructed by weaving and vacuum lamination and the mechanical properties were measured.In the both sides of abdomen of 36 healthy female SD rats,a partially defect (lcm × lcm) was created by surgery and repaired with a same area of PDO-SIS patch or 8SIS patch,each 12 rats were randomly sacrificed at 2,4 and 8 weeks after surgery,respectively,and tissue regeneration was evaluated.Results The bending length and tensile strength of the PDO-SIS patch were stronger than the 8SIS patch (P<0.05) with the increase of diameter.No acute inflammation occurred at the repaired sites of the two groups,but a moderate chronic inflammation was observed 2 weeks after surgery,and the inflammatory response reduced gradually over time,no obvious chronic inflammation was found in the 8th week after surgery,with no statistical differences between the two groups (P>0.05).Two patch materials were degraded gradually in the repaired area,and the regenerated collagen tissues were deposited continuously,but no significant differences existed between the two groups in the collagen content and collagen arrangement (P>0.05).Conclusion The PDO-SIS patch has better mechanical properties than the 8SIS patch,and does not cause strong immune rejection when used to repair abdominal partially defect of SD rats.
8.Research on Promotion of Wound Healing by Amputated lumbricus Extract
Wenqi WANG ; Haicong HU ; Zhiqian ZHANG ; Huaqi TANG ; Shuofeng ZHANG ; Yikun SUN
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1449-1453
On the basis of pre-experiment research and the hypothesis of“amputated lumbricus”, this research was aimed to explore mechanism of active components of the amputated lumbricus to promote wound healing. Skin excision was used to establish the mice model. The amputated lumbricus extract was prepared. HE staining and immunohistochemistry techniques were used in the determination of the wound healing rate and changes of VEGF, bFGF, TGF-β1 expression during wound healing period. The results showed that compared with the blank control group, the healing rate of the amputated lumbricus extract group was better. And the HE staining showed better improvement of traumatic tissues. There was no statistic differences on the expression of VEGF and TGF-β1 between the amputated lumbricus extract group and the normal saline group (P> 0.05). The expression of bFGF in amputated lumbricus extract group reached peak earlier than the control group and also lasted a longer time. The amputated lumbricus extract group reached peak on the first day, which had a significant difference (P < 0.05) compared with the control group at the same timepoint. It was concluded that the external application of amputated lumbricus extract had wound healing effect on traumatic skin of mice. Its mechanism may be irrelevant to the expression of VEGF and TGF-β1. However, it may be related to the increasing of bFGF expression in the injured regions during the inflammation stage and proliferation stage.
9.Research progress of immunohistochemical markers related with pancreatic cancer prognosis
Peng ZHU ; Huiying LIU ; Zhiqian HU ; Weijun WANG
Journal of International Oncology 2014;41(10):767-770
Pancreatic cancer is a malignant with very poor prognosis.Although methods and technologies of diagnosis and treatment in connection with pancreatic cancer have made great progresses,the prognoses of patients with pancreatic cancer still have not a significant upgrade,which are closely related with the degree of malignancy of pancreatic cancer cells.Earlier studies have shown that normal pancreatic cells need to have a total of six capabilities,which are intimate connection with the degree of malignancy of pancreatic cancer cells,during the process of deterioration.A variety of immunohistochemical markers that correlate with prognosis of pancreatic cancer involve in the process of pancreatic cells obtaining these six capabilities.
10.Clinical significance of hepatocyte nuclear factor 4αin rectal cancer and its relationship with prognosis
Juan WANG ; Weiping JI ; Houshan YAO ; Liangzhe WANG ; Zhiqian HU
Journal of International Oncology 2014;(9):704-708
Objective To investigate the clinical significance of hepatocyte nuclear factor 4α(HNF4α)in rectal cancer and its relationship with prognosis.Methods Real-time PCR was designed to detect the expression of HNF4αon mRNA level and the immunohistochemistry was used to determine the expression of HNF4αon protein level in rectal cancer tissue.The relationship between HNF4αexpression and clinical characteristics was also analysed.The Kaplan-Meier method was used for univariate analysis and a Cox proportional hazards regression model was performed for multivariate analysis.Results HNF4αwas low expressed both on mRNA (t=6.092,P<0.001)and protein level (χ2 =15.230,P<0.001)in rectal cancer tissue.HNF4αexpression on protein level was related with the clinical stage (χ2 =48.311,P<0.001),depth of invasion (χ2 =23.911,P<0.001),histological differentiation (χ2 =20.787,P<0.001),lymph node metastasis (χ2 =39.064,P<0.001)and distant metastasis (χ2 =5.146,P=0.04),while age and gender were not relevant.The cumulative 3-year overall survival of patients with low HNF4αexpression (43.8%)was much worse than the patients with high HNF4αexpression (95 .5%),and the difference was statistically sig-nificant (P<0.001).Univariate analysis revealed that HNF4αexpression (χ2 =28.778,P<0.001),differ-entiation (χ2 =26.680,P<0.001 ),clinical stage (χ2 =32.702,P<0.001 ),depth of invasion (χ2 =6.226,P=0.013),lymph node invasion (χ2 =15.270,P<0.001)and distant metastasis (χ2 =21.817, P<0.001)were statistically significant worse predictors for rectal cancer,whereas age and gender were not rel-evant.The multivariate Cox proportional hazard analysis revealed that HNF4αlow expression (RR=6.084, P=0.028)was independent prognostic markers for 3-year overall survival in the patients with rectal cancer. Conclusion HNF4αwas closely related to the tumorigenesis and progression of rectal cancer,which is an independent prognostic marker for rectal cancer,and which may be an effective target for the therapy of rectal cancer.

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