POEMS Syndrome with Peripheral Edema and Ascites as the Main Manifestations:Report of One Case / 中国医学科学院学报

POEMS syndrome is a rare disease caused by monoclonal plasma cell proliferative disorder.The typical signs include peripheral neuropathy,organ enlargement,endocrine disease,M proteinemia,and skin changes.In clinical practice,the atypical,complex,and changeable clinical manifestations of this syndrome can easily lead to misdiagnosis and missed diagnosis.A case of POEMS syndrome with peripheral edema and ascites as the main manifestations is reported in this paper.

A comparative study of the effects of different treatment strategies on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer / 中华胃肠外科杂志

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.

Phylogenetic analysis of Echinococcus granulosus genotypes based on the GenBank database / 中国血吸虫病防治杂志

Objective To analyze the sequences of the cytochrome C oxidase subunit I (Cox1) gene of various Echinococcus granulosus genotypes that are currently recorded in the GenBank database, so as to investigate the genetic variation and differentiation of the E. granulosus genotypes across the world. Methods The sequences of the Cox1 gene of various E. granulosus genotypes that are currently recorded in the GenBank database were collected, and the same sequences of the Cox1 gene identified from a region were excluded. The mutation sites among the Cox1 gene sequences were identified and a phylogenetic tree was created based on the Cox1 gene. Results Transversion mutation was the predominant type of mutation in the Cox1 gene of E. granulosus. The same Cox1 gene sequence was found in E. granulosus G1, G6 and G7 genotypes isolated from various geographical locations across the world, with the corresponding GenBank accession numbers of KY766891, MH300971 and MH301007, respectively. Phylogenetic analysis revealed that E. granulosus G10 genotype had a remarkable geographical aggregation. Conclusions E. granulosus G1, G6 and G7 genotypes have primitive Cox1 gene sequences. There is a geographical aggregation of the E. granulosus G10 genotype in the phylogenetic tree, which has a tendency towards reproductive isolation.

Analysis of related factors for hepatic alveolar echinococcosis and gallbladder complications of children in Qinghai Province / 中国血吸虫病防治杂志

Objective To investigate the distribution characteristics of gallbladder diseases in children with hepatic alveolar echinococcosis, and to analyze the related factors for hepatic alveolar echinococcosis and gallbladder diseases. Methods The clinical data of hepatic alveolar echinococcosis patients under 18 years were collected in Qinghai Provincial People’s Hospital-from January 2012 to December 2017, and the gallbladder-related complications in the surgically treated patients with hepatic al-veolar echinococcosis were analyzed. Results The clinical data of 51 child patients with hepatic alveolar echinococcosis were collected and analyzed. According to the PNM classification criteria of WHO, P1, P2 and P3 in the 51 patients accounted for 37.25% (19/51), 41.18% (21/51) and 19.60% (10/51), respectively. According to the diagnostic criteria (WS 257–2006) of China for echinococcosis, the patients of infiltration type, calcification type and liquefaction cavitary type accounted for 66.67% (34/51), 21.57% (11/51) and 11.76% (6/51), respectively. Among the 51 patients, 78.43% (40/51) of the patients had clinical symptoms of biliary tract disease, and 58.82% (30/51) had gallbladder-related complications. The operations were performed on 40 patients, and 77.50% (31/40) of them had the postoperative complications. The results of binary multivariate logistic regression analysis showed that the clinical image classification, the liver segment distribution, size, location and number of lesions of hepatic alveolar echinococcosis were important correlative factors for the occurrence of gallbladder complications in hepatic alveolar echinococcosispatients. Conclusions The incidence of complications related to gallbladder diseases is higher in the children with hepatic alveolar echinococcosis in Qinghai Province, and it has great influence on the operation mode and the occurrence and prognosis of postoperative complications. The early diagnosis and treatment of alveolar echinococcosis in children is particularly important.

Thy-1 promotes EMTprocess of livercancercells by regulating Notch1 pathway / 中国肿瘤生物治疗杂志

@# Objective: To explore the role of Thy-1 cell surface antigen（Thy-1）in promoting epithelial-mesenchymal transition (EMT) in liver cancer HepG2 and MHCC-97 cells by regulating Notch1 pathway. Methods: MHCC-97 cells with high metastatic characteristics and HepG2 cells with low metastatic characteristics were selected as subjects. WB was used to detect the expression levels of Thy-1 and Notch1 in cells. MHCC-97 and HepG2 cells were transfected with lentivirus to construct cells with high and low expression of Thy-1 protein. Cells were treated with Notch1 agonist rhNF-κB (1 gsu/ml) and Notch1 inhibitor MW167 (100 μmol/L) for 24 h respectively. Transwell assay was used to detect the effect of Thy-1 expression on cell invasion; qPCR was used to detect the effect on Notch1 mRNA expression; WB was used to detect the effect on intracellular EMT-related protein expression. Results: The expression levels of Thy-1 and Notch1 in MHCC-97 cells were higher than those in HepG2 cells (P<0.05). Thy-1 overexpressing HepG2 cells and Thy-1 low expressing MHCC-97 cells were successfully constructed. Compared with HepG2 cells, the invasion ability of Thy-1 overexpressing HepG2 cells was significantly enhanced (183.23±55.34 vs 475.78±80.37, P<0.05), vimentin expression was significantly increased (P<0.05), epithelial cadherin protein expression was significantly decreased (P<0.05), and the expression level of Notch1 mRNAwas significantly increased (P<0.05). Compared with MHCC-97 cells, the invasion ability of Thy-1 silenced MHCC97 cells was significantly decreased (543.56±77.94 vs 237.44±62.18, P<0.05), the expression of vimentin was significantly decreased (P<0.05), epithelial cadherin protein expression was significantly increased (P<0.05), and Notch1 mRNA expression level was significantly decreased (P<0.05). Treatment of liver cancer cells with Notch1 activators or inhibitors can reverse the changes caused by Thy-1 silencing or overexpression. Conclusion: Thy-1 can affect the EMT process of HepG2 and MHCC-97 cells by regulating the expression of Notch1.

Analysis of related factors for hepatic alveolar echinococcosis and gallbladder complications of children in Qinghai Province / 中国血吸虫病防治杂志

Objective To investigate the distribution characteristics of gallbladder diseases in children with hepatic alveolar echinococcosis, and to analyze the related factors for hepatic alveolar echinococcosis and gallbladder diseases. Methods The clinical data of hepatic alveolar echinococcosis patients under 18 years were collected in Qinghai Provincial People’s Hospital-from January 2012 to December 2017, and the gallbladder-related complications in the surgically treated patients with hepatic al-veolar echinococcosis were analyzed. Results The clinical data of 51 child patients with hepatic alveolar echinococcosis were collected and analyzed. According to the PNM classification criteria of WHO, P1, P2 and P3 in the 51 patients accounted for 37.25% (19/51), 41.18% (21/51) and 19.60% (10/51), respectively. According to the diagnostic criteria (WS 257–2006) of China for echinococcosis, the patients of infiltration type, calcification type and liquefaction cavitary type accounted for 66.67% (34/51), 21.57% (11/51) and 11.76% (6/51), respectively. Among the 51 patients, 78.43% (40/51) of the patients had clinical symptoms of biliary tract disease, and 58.82% (30/51) had gallbladder-related complications. The operations were performed on 40 patients, and 77.50% (31/40) of them had the postoperative complications. The results of binary multivariate logistic regression analysis showed that the clinical image classification, the liver segment distribution, size, location and number of lesions of hepatic alveolar echinococcosis were important correlative factors for the occurrence of gallbladder complications in hepatic alveolar echinococcosispatients. Conclusions The incidence of complications related to gallbladder diseases is higher in the children with hepatic alveolar echinococcosis in Qinghai Province, and it has great influence on the operation mode and the occurrence and prognosis of postoperative complications. The early diagnosis and treatment of alveolar echinococcosis in children is particularly important.

Different subtypes of estrogen receptor α and related signal molecules in the hippocampus are associated with spatial cognitive impairment of diabetic mice / 生理学报

To study the correlation between the spatial cognitive impairment and different subtypes of estrogen receptor α (ERα) of hippocampus in diabetic mice, we used alloxan (intraperitoneal injection) to induce type 1 diabetes in male Kunming mice and compared the spatial cognitive ability of the model mice with that of control mice through Morris water maze test. Meanwhile, using Western blot, we detected the protein expressions of ER-α36, ER-α66, caveolin-1, PKCα, cAMP-response element binding protein 2 (CREB2), and synaptophysin (Syn) in the hippocampus of the mice. The results showed that on the 3rd and 5th days of training, the ability of spatial learning and memory in the diabetic mice was significantly inferior to that of the control mice (P < 0.05). In the diabetic mice, the protein expressions of caveolin-1 and PKCα were decreased (P < 0.05), but ER-α66 expression was unaffected, while ER-α36 and CREB2 expressions were significantly increased (P < 0.05) compared with those of the control mice. The results suggest that abnormal expression of ER-α36 and related signal molecules may be important factors for diabetes-induced spatial cognitive impairment.

Potassium channels and autophagy / 生理学报

Potassium channels have multitudinous subtypes, which are widely distributed on cell membranes. They affect various cellular physiological functions through participating in processes such as resting potential formation, substance transportation, enzyme activity and cellular communication. Autophagy is a significant mechanism to maintain intracellular metabolic homeostasis. The abnormity of autophagy may lead to the occurrence and development of multiple diseases. Recently, it has been reported that Kchannels and cell autophagy are closely related. Here, we reviewed the recent research progresses on regulation of autophagy signaling, autophagy flux or autophagolysosome formation by Kchannel, and discussed the physiological significance of autophagy regulation by Kchannel.

Body Position Adjustment May Facilitate Capsule Endoscopic Real-Time Examination in Patients with a Large Amount of Food Retention in the Stomach

A patient with acute obscure gastrointestinal bleeding was found to have a large amount of food retention in the stomach after fasting for >12 hours. We tried to adjust the patient's body position to facilitate capsule endoscopic examination. The patient laid on the bed on his right side, which is the position required for a normal procedure, and then his hip was raised while his upper body was lowered gradually until the pylorus appeared at the center of the screen of the real-time monitor. It took 15 minutes of body position adjustment to make the pylorus appear at the center of the monitor and another 5 minutes for the capsule endoscope to enter the duodenum. The lesion was ultimately found at the terminal small intestine.

Surgical management of postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study surgical treatment of postoperative stricture of anastomosis for lower rectal cancer.</p><p><b>METHODS</b>The data of 9 cases who were diagnosed as postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer during January 2008 to June 2011 were analyzed retrospectively. Transanal excision of stricture were used in 3 cases diagnosed as membranous stricture. Transanal radial incision of stricture were used in 5 cases diagnosed as tubulous stricture. Biologic patch was used to repair the defect of the posterior wall of rectum after excision of severe stricture in 1 case.</p><p><b>RESULTS</b>All 9 cases of postoperative stricture of anastomosis were cured by surgery. Anal dilation were performed every day by patients themselves after discharge. Digital examination showed that 1 to 2 fingers could pass through the anastomosis after operation. The patient whose rectal defect was repaired by biological patch underwent colonoscopy examination two weeks after operation. Colonoscopy showed that the biological patch had been filled with granulation and integrated into the surrounding intestinal tissue. All patients defecated without difficulty and the anal function of all patients was good after restoration of intestinal continuity.</p><p><b>CONCLUSION</b>Aggressive surgery, combining with the use of biological patch if necessary is an effective therapy of postoperative stricture of anastomosis for lower rectal cancer.</p>

Technical improvements and results of individual cylindrical abdominoperineal resection for locally advanced low rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of individual cylindrical abdominoperineal resection (CAPR) for locally advanced low rectal cancer.</p><p><b>METHODS</b>From June 2011 to February 2012, 11 patients with locally advanced low rectal cancer underwent individual CAPR. There were 7 male and 4 female patients, aged from 32 to 74 years with a median of 64 years. Forty-seven patients underwent classic CAPR from January 2008 to February 2012. Preoperative and postoperative parameters such as clinical information of patients, tissue morphometry and complications were compared.</p><p><b>RESULTS</b>In the individual surgical group, 6 patients were treated with one side levator ani muscle totally or partially reserved, 3 patients with sacrococcyx reserved, and 2 patients with dissection close to the anterior rectal wall. Compared with classical surgery, the individual surgical specimens of horizontal section area ((2197 ± 501) mm(2)) and intrinsic muscle layer outer area ((1722 ± 414) mm(2)) were small, but the difference was not statistically significant (P = 0.150 and 0.167). The operative time, intraoperative blood loss, circumferential resection margin, total cross sectional tissue area, cross sectional tissue area outside the muscularis propria and bowel perforation rate between the two groups were not significantly different. Individual CAPR showed less incidence of chronic perineal pain (2/11, χ(2) = 6.116, P = 0.013) and sexual dysfunction (2/9, χ(2) = 4.412, P = 0.036) compared with classic CAPR.</p><p><b>CONCLUSIONS</b>Individual CAPR has the potential to reduce the risk of chronic perineal pain and sexual dysfunction without influencing the radical effect when compare with classic CAPR for the treatment of low rectal cancer.</p>

Analysis of PTPN11 mutation in children leukemia and its clinical significance / 中国实验血液学杂志

This study was aimed to explore the frequency of PTPN11 mutation in children with leukemia and its clinical significance. Genomic DNAs were extracted from peripheral leukocytes of 131 patients with leukemia, including 101 cases of ALL, 26 cases of AML, 3 cases of CML and 1 case of juvenil myelomonocytic leukemia (JMML). The sequences of PTPN11 exons 3, 8, 13 were amplified by polymerase chain reaction (PCR), and the clinical characteristics of positive patients were analyzed. The results indicated that the PTPN11 mutation was found in 10 cases (9.9%) from newly diagnosed 101 cases of ALL. Grouping the newly diagnosed ALL children by various clinical features, it was found that the PTPN11 mutation did not show associations with sex, age, white blood cell (WBC) count, prednisone test sensitivity, clinical risk and disease recurrences at the first visit (P > 0.05). PTPN11 mutations were found in 2 cases out of 26 AML patients, including one AML-M(2) and one AML-M(4). No PTPN11 mutation in 3 CML patients was found. Exon 13 mutation of PTPN11 gene was found in 1 case of JMML. It is concluded that the E76 of exon 3 is the hot spot of PTPN11 mutation in children leukemia. The novel G503E (1508G > A) mutation is detected in one JMML patient. The PTPN11 mutation does not associate with the sex, age, WBC count, prednisone sensitive test and early recurrence.

Efficacy evaluation of anal intersphincteric resection with direct coloanal anastomosis for T1-2 ultra-low rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the oncological and functional outcomes of intersphincteric resection (ISR) in T(1-2) ultra-low rectal cancer.</p><p><b>METHODS</b>From March 2000 to March 2007, ISR with total mesorectal excision (TME) was performed in 40 patients with very low rectal cancer,among whom total ISR in 5 patients, partial ISR in 23 patients, and partial ISR with partial dentate line preservation (modified partial ISR) in 12 patients. The preoperative tumor staging was T(1-2)N(0-1)M(0).</p><p><b>RESULTS</b>Morbidity was identified in 3 patients including anastomotic leakage in 1 patient and wound infection in 2 patients, and there was no postoperative mortality. The 5-year overall survival rate was 97%, and 5-year disease-free survival rate was 86%. Both patients with modified partial ISR (P=0.004) and patients with partial ISR (P=0.008) had significantly better continence than those with total ISR, and patients with a diverting stoma had significantly better continence (P=0.043) than those without a stoma at 12 months after surgery.</p><p><b>CONCLUSIONS</b>ISR is a safe procedure for sphincter-saving rectal surgery in selected patients with very low rectal tumors. A temporary diverting stoma may be beneficial to the improvement of anal function. Modified partial ISR under the precondition of radical resection shows better anal function and lower rate of incontinence.</p>

Application of pelvic floor dynamic MRI combining defecography with homemade high conformable sacculus in the management of obstructed defecation syndrome / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity and feasibility of pelvic floor dynamic MRI combining defecography with homemade high conformable sacculus in the management of obstructed defecation syndrome.</p><p><b>METHODS</b>One hundred and nine female with pelvic floor disorders, such as difficult defecation, fecal incontinence or urinary incontinence, pelvic pain, were treated from July 2007 to March 2009. Pelvic floor dynamic MRI and defecography with homemade high conformable sacculus was performed in the patients to evaluate pelvic floor anatomy.</p><p><b>RESULTS</b>Fifty-four cases (49.6%) of cystocele and 11 cases (10.1%) of rectouterine pouch hernia, 29 cases (26.6%) of perineum prolapse and 71 cases (65.2%) of rectocele were found by dynamic MRI. The dynamic MRI also revealed 19 cases (18.2%) of external sphincter trophy and 32 cases (29.4%) of spastic pelvic floor syndrome. Compared with defecography, dynamic MRI was more positive in diagnosing enterocele. Defecography Of the patients, sacrum-rectal separate was found in 33 cases (30.3%) and rectal mucosal prolapse or internal rectal intussusceptions in 41 cases (37.7%) by defecography, while dynamic MRI found none.</p><p><b>CONCLUSIONS</b>As a new noninvasive imaging technique to evaluate the pelvic floor function, dynamic MRI is more sensitive, especially for patients with complicated multi-organs prolapse, and its deficiency could be remedied by defecography.</p>

Expression of hRad21 and clinicopathological analysis in gastrointestinal malignant tumors maintained their telomeres by a mechanism of alternative lengthening of telomeres / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the proportion between tumors which maintain their telomeres by a mechanism of alternative lengthening of telomeres(ALT) and telomerase-dependent tumors in gastrointestinal malignant tumors, the expression difference of hRad21 between the two groups and the clinicopathological characteristics of ALT tumors were also explored.</p><p><b>METHODS</b>One hundred and four cases of gastrointestinal malignant tumors were divided into 2 groups: ALT group and telomerase group by detecting telomerase activity using TRAP method. Expression difference of hRad21 was investigated between the two groups. All the patients were followed up and clinicopathological data of these patients were analyzed.</p><p><b>RESULTS</b>Of 104 cases, there were 12 cases in ALT group and 94 cases in telomerase group. Expression of hRad21 in ALT group was higher than that in telomerase group. Tumors in ALT group had a thinner invasion depth (lower T stage) as compared to telomerase group (P=0.021). Other indexes, such as age, gender, tumor size, tumor grade, location of tumor, CEA and CA199, were not significantly different between the two groups. Results of follow-up showed that the survival rate of ALT group was 100% while that of telomerase group was 56% at 30 months postoperatively.</p><p><b>CONCLUSIONS</b>There are tumors which maintain their telomeres by ALT in gastrointestinal malignant tumors, accounting for 10%-12% of the total tumors. As compared to telomerase group, ALT group presents higher expression of hRad21, thinner tumor invasion depth, and higher survival rate.</p>

Influence of Wnt-1 recombinant adenovirus on differentiation of human epidermal stem cells / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the influence of Wnt-1 recombinant adenovirus on differentiation tendency of human epidermal stem cells.</p><p><b>METHODS</b>Wnt-1 recombinant adenovirus was transduced into hESCs (E group), while normal hESCs were used as control (C) group. The diameter, proliferation,and labeling molecular expression of hESC were determined. The content of MMP-2 and MMP-7 in supernate were also assayed.</p><p><b>RESULTS</b>There was no obvious difference in diameter of hESC between two groups. The density of hESC in E group was (1.45 +/- 0.09) x 10(5)/mL, which was obviously higher than that in C group [(1.18 +/- 0.10) x 10(5)/mL, P < 0.05]. There were no obvious differences in expression of markers between two groups,including keratin 5 (KS), K6, K7, KS, K14, CD44, carcinoembryonic-like antigen (CEAA), ER, PR (P > 0.05) ,while the expression of K 10 was different among groups [(60 +/- 3)% in E group, 0 in C group], also K18 [(34.3 +/- 2.1)% in E group vs. (13.8 +/- 1.7)% in C group, P < 0.05], and K19 [(17.1 +/- 1.8)% in E group vs. (24.4 +/- 1.5)% in C group, P < 0.05].The contents of MMP-2 and MMP-7 in E group were higher than those in C group (P < 0.01).</p><p><b>CONCLUSION</b>Wnt-1 recombinant adenovirus can induce the differentiation of hESCs to glandular epithelium-like cells.</p>

Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma.</p><p><b>METHODS</b>Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy.</p><p><b>RESULTS</b>Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group.</p><p><b>CONCLUSION</b>This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.</p>

Inhibition of HBV replication and antigen expression by RNA interference against different targets / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To observe the inhibition of HBV replication and antigen expression by RNA interference aimed at different parts of the HBV genome.</p><p><b>METHODS</b>Following the rules of shRNA expression vector design and construction, we constructed seven kinds of sequence specific vectors and two kinds of mutant shRNA expression ones. We then cotransfected those shRNA and HBV expression vectors into HepG2 cells using lipofectamine2000. The level of HBV replication was investigated using Southern blot and the antigen expression using ELISA.</p><p><b>RESULTS</b>The replication of HBV DNA was inhibited by many shRNAs, especially the ones against P1, S2, C2, S1 and X. The inhibition rate against P1 was as high as 95%. Results obtained with ELISA showed that the shRNAs targeting C2, C1 and S2 had high rates of inhibition to HBsAg.</p><p><b>CONCLUSION</b>The replication and antigen expression of HBV could be inhibited by shRNAs aimed at four different open read frames, and higher inhibition rates of HBV replication and surface antigen expression could be obtained by P1 and C2, respectively.</p>

Inhibition of HCV IRES controlled reporter gene expression by RNA interference / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To develop a RNAi approach that specifically targets the HCV IRES sequence by vector-expressed short hairpin RNA (shRNA) in vitro, and to assess the inhibitory effect of the shRNA on reporter gene expression.</p><p><b>METHODS</b>Eukaryotic expressing plasmids, pIRES-GFP and p5' UTR-Luc containing GFP or luciferase gene controlled by HCV IRES were cotransfected into HepG2 cells with either a RNAi plasmid pshRNA-HCV or a control plasmid pTZU6+1. At 24, 48, 72 hours post transfection, the fluorescence in the transfected cells was studied using fluorescence microscopy. The levels of GFP RNA were determined using RT-PCR and those of protein were determined using Western blot. The activities of luciferase were assayed using a dual luciferase assay system.</p><p><b>RESULTS</b>The introduction of RNAi plasmid efficiently and specifically down-regulated the expression of the reporter gene. RT-PCR showed that the RNAs of GFP gene were distinctly reduced (about 60%) when the pIRES-GFP was cotransfected with pshRNA-HCV, whereas the control vector did not exhibit inhibitory effect on the mRNA level, according to Western blot assay. The luciferase activity also decreased by 60%-70% in comparison to the control plasmid.</p><p><b>CONCLUSION</b>Our results demonstrate that the shRNA targeting HCV IRES shows a strong inhibitive effect on the expression of the reporter gene controlled by this sequence, suggesting that RNAi-based anti-HCV strategy may represent a potential approach in the therapy of HCV infection.</p>

Phage Display Technology and Its Applications for Tumor Research / 中国生物工程杂志

Phage display technology has been developed as a powerful tool for selecting polypeptides or proteins with desired biological and physicochemical properties from huge random peptide libraries.Fragments of foreign peptides or proteins that are expressed as fused proteins displayed on the phage surface can keep their relatively independent spatial structure and biological activity,so that they can interact with their ligands to mimic selection of specific molecular epitopes,thus providing an efficient high-throughput screening system.Phage display has been used to allow rapid identification of peptide ligands for a variety of target molecules by an in vitro selection process called "panning".Phage display techniques can be widely exploited to construct tumor-associated antibody libraries,select polypeptides tumor-associated antigen,investigate antigen epitope and design vaccines and medicine,and are used especially as a tool for the diagnosis and treatment of tumor,gene therapy and tumor cell signal transduction research.Recent applications and advanced developments of phage display in cancer research are discussed in this article for the further reference to investigators.