1.A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy.
Xiaozhi XI ; Yanqing WANG ; Guiqi AN ; Shitao FENG ; Qiumei ZHU ; Zhongqiu WU ; Jin CHEN ; Zhicheng ZUO ; Qiang WANG ; Ming-Wei WANG ; Yuchao GU
Acta Pharmaceutica Sinica B 2024;14(11):4806-4818
TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.
2.Status and thinking of clinical development of enhanced recovery after surgery nursing in Anhui Province
Xiaofei QIAO ; Lingchen ZHANG ; Xiaoyu ZHU ; Yaqin JIANG ; Guiqi SONG ; Jiangying HAN ; Jing LU ; Hong ZHOU ; Weidong JIA
Chinese Journal of Practical Nursing 2024;40(36):2820-2826
Objective:To understand the current status of core measures of enhanced recovery after surgery (ERAS) nursing in Anhui Province and analyze its promotion strategies, so we can provide reference for further implementation and promotion of clinical practice guidelines of ERAS.Methods:Design a Development Questionnaire of Enhanced Recovery After Surgery in Anhui Province based on the Clinical Practice Guidelines for Enhanced Recovery After Surgery in China (2021 edition) (I) and, a cross-sectional survey was conducted on surgical nurses in 132 secondary and above hospitals in Anhui Province from July to September 2023 by the convenience sampling method.Results:A total of 1 375 nurses from 13 cities in Anhui province participated in the survey. The nurses′ awareness rate of ERAS concept was 100.00%, but only 52.51% (722/1 375) of the nurses had received standardized ERAS training, and only 26.11% (359/1 375) of the nurses indicated that they had a multidisciplinary team such as medical care, anesthesia and nutrition were involved in the implementation of the ERAS. Nearly 38.33% (527/1 375) of the nurses said that the department lacked the relevant nursing quality control system, and the overall implementation rate of quality control training, development, feedback and monitoring was not high. Only 55.71% (766/1 375) of nurses reported that a quality control team has been established within their department, and only 40.44% (556/1 375) of departments conduct monthly checks on the implementation and progress of ERAS. In terms of the implementation of core measures, preoperative thromboprevention therapy, intraoperative temperature monitoring and management, postoperative multimodal analgesia were better; however, the implementation of preoperative fasting time ≤ 6 h, water ban time≤ 2 h, oral carbohydrate drinks or clean streaming drinks, oral intake of enteral nutritional supplementation when less than 60% of the normal amount was poor.Conclusions:There are still many deficiencies in the overall development of ERAS nursing in Anhui Province, and the implementation level of core measures also needs to be improved. It is necessary to combine the concept of precision nursing, strengthen the whole process management and quality control, so as to promote the clinical practice and promotion of ERAS.
3.Status and thinking of clinical development of enhanced recovery after surgery nursing in Anhui Province
Xiaofei QIAO ; Lingchen ZHANG ; Xiaoyu ZHU ; Yaqin JIANG ; Guiqi SONG ; Jiangying HAN ; Jing LU ; Hong ZHOU ; Weidong JIA
Chinese Journal of Practical Nursing 2024;40(36):2820-2826
Objective:To understand the current status of core measures of enhanced recovery after surgery (ERAS) nursing in Anhui Province and analyze its promotion strategies, so we can provide reference for further implementation and promotion of clinical practice guidelines of ERAS.Methods:Design a Development Questionnaire of Enhanced Recovery After Surgery in Anhui Province based on the Clinical Practice Guidelines for Enhanced Recovery After Surgery in China (2021 edition) (I) and, a cross-sectional survey was conducted on surgical nurses in 132 secondary and above hospitals in Anhui Province from July to September 2023 by the convenience sampling method.Results:A total of 1 375 nurses from 13 cities in Anhui province participated in the survey. The nurses′ awareness rate of ERAS concept was 100.00%, but only 52.51% (722/1 375) of the nurses had received standardized ERAS training, and only 26.11% (359/1 375) of the nurses indicated that they had a multidisciplinary team such as medical care, anesthesia and nutrition were involved in the implementation of the ERAS. Nearly 38.33% (527/1 375) of the nurses said that the department lacked the relevant nursing quality control system, and the overall implementation rate of quality control training, development, feedback and monitoring was not high. Only 55.71% (766/1 375) of nurses reported that a quality control team has been established within their department, and only 40.44% (556/1 375) of departments conduct monthly checks on the implementation and progress of ERAS. In terms of the implementation of core measures, preoperative thromboprevention therapy, intraoperative temperature monitoring and management, postoperative multimodal analgesia were better; however, the implementation of preoperative fasting time ≤ 6 h, water ban time≤ 2 h, oral carbohydrate drinks or clean streaming drinks, oral intake of enteral nutritional supplementation when less than 60% of the normal amount was poor.Conclusions:There are still many deficiencies in the overall development of ERAS nursing in Anhui Province, and the implementation level of core measures also needs to be improved. It is necessary to combine the concept of precision nursing, strengthen the whole process management and quality control, so as to promote the clinical practice and promotion of ERAS.
4. Effects of scacia honey on serum uric acid level and renal injury in rats
Xiuhe XU ; Xiaoli HE ; Jiashun ZHOU ; Lizhu PAN ; Zhuojun ZHOU ; Jiayue LI ; Guiqi ZHU ; Caixia WANG ; Wei YUAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(7):743-750
AIM: To observe the effect ofacacia honey (AH) on serum uric acid level and renal function in potassium oxonate modelrats after drinking AH aqueous solution. METHODS: Sixty male SD rats were selected and randomly divided into control group (CON group), potassium oxonate model group (OA model group), 10% fructose group (10% F group) and different concentration honey groups (25%, 12.5% and 6.25% AH groups). All rats were fed with normal diet.The rats in CON group were subcutaneously injected with 5% sodium carboxymethyl cellulose (CMC-Na) solution and drunk sterile water every day, while rats in other groups were injected with 100 mg / kg OA solution suspended with 5% CMC-Na subcutaneouslyand drunksterile water orfructose solution or AH solution of different concentrations every day. Before and during the 4-week test, rats were weighed and blood was taken once a week. At the end of test, urine and feces specimens or kidney tissues were collected and blood was taken from the abdominal aorta. The uric acid content in blood, urine, and feces and the levels of serum creatinine (Cre) and blood urea nitrogen (BUN) or inflammatory factors in kidney tissues were measured. Renal function and histology were evaluated. RESULTS: Compared with CON group, AH could significantly reduce the body weight of rats (P<0.05), increase the kidney organ coefficient, the levels of serum uric acid, and uric acid in urine or feces, and reduce the level of fecal uric acid (FUA) in rats. AH can down regulate the level of tumor necrosis factor alpha (TNF-a) (P< 0.05) and up regulate the expression of monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor β - 1 (TGF - β1) in rats kidneys; AH can cause slight to mild dilatation of renal tubules and mild to moderate basophilic lesions of renal rubules in rat kidney in a dose dependent manner. CONCLUSION: In the doses rang of present study, AH can cause hyperuricemia, renal tubular dilatation and basophilic lesions, and lead to renal function damage in rats.
5.Endoscopic submucosal dissection for early hypopharyngeal carcinoma and precancerous lesions
Yu GONG ; Yueming ZHANG ; Jiqing ZHU ; Shun HE ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Ying LYU ; Guiqi WANG
Chinese Journal of Digestive Endoscopy 2022;39(9):691-694
Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Clinical data of 41 patients who received ESD for early hypopharyngeal carcinoma and precancerous lesions from August 2013 to August 2019 in the Department of Endoscopy of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively analyzed. Main outcome measurements included operation completion rate, operation time, en bloc resection rate, R0 resection rate, complication rate and recurrence.Results:ESD was successfully completed in all 41 cases, with a success rate of 100.0% and a mean time of 49.1 min (ranged 10-110 min). Fifty-four lesions underwent en bloc resection, with an en bloc resection rate of 98.2% (54/55), of which 41 had negative horizontal and vertical margins, and the R0 resection rate was 74.5% (41/55). During the operation of 55 lesions, there was a small amount of blood oozing on the wound surface, and electrocoagulation with thermal biopsy forceps could successfully stop the bleeding. No perforation occurred, and 2 cases (4.3%) had delayed bleeding after ESD, and hemostasis was successful under emergency endoscopy. Postoperative endoscopy showed that 1 case (2.2%) had esophageal entrance stenosis, and the obstruction was relieved after repeated water balloon dilatation. The follow-up period ranged from 3 to 72 months, and the median time was 18 months. One case was found to have mucosal lesions in the same part of the hypopharynx and received ESD treatment again. Follow-up to October 2020, no residual lesions and recurrence were found.Conclusion:ESD is a safe and effective option for the treatment of early hypopharyngeal carcinoma and precancerous lesions, which is worthy of clinical application.
6.A content analysis of the provincial laws and regulations for voluntary blood donation
Huiying HU ; Li CHEN ; Zijia ZHANG ; Ying CHANG ; Guiqi ZHAO ; Lifen LU ; Yan ZHANG ; Qingming WANG ; Yingjia JIANG ; Hai QI ; Ming ZHU
Chinese Journal of Blood Transfusion 2022;35(8):873-877
【Objective】 To perform quantitative analysis on the sample provincial laws and regulations for voluntary blood donation, and provide reference for further revision of laws and regulations. 【Methods】 31 study samples were current provincial laws and regulations for voluntary blood donation that can be collected from open sources. The issue date and the revision date of each sample were recorded. With "The Blood Donation Law of the People’s Republic of China" as reference, 5 categories were formed and additional clauses in samples were coded and rated following content analysis procedures. Sample provinces were divided into two groups based on donation rate and their differences in evaluation scores of categories were examined using rank sum test. 【Results】 Until December, 2021, 31 sample provinces had issued and implemented provincial laws and regulation for voluntary blood donation, and 14 of which had been revised. Many detailed clauses (total score 9.32±3.09) were added in sample provincial laws and regulations, more clauses were added in the categories of 'related government agencies and their responsibilities’, 'management of clinical blood use’ and 'rewards and punishment’. Sample provinces were divided into two groups according to the donation rate per 1 000 people recommended by World Health Organization(10‰). Compared to lower donation rate group, the total score and sub score in the categories of 'basic principles’, 'management of blood collection and supply’ were significantly higher in higher donation rate group. 【Conclusion】 In revision and improvement of provincial laws and regulations, 'basic principles’ and 'management of blood collection and supply’ could be considered. This assay mainly tries to provide a new research perspective and perform quantitative analysis on content of sample provincial laws and regulation for voluntary blood donation, the actual effect of the results in this study need longer time to be examined, and we will keep following its new advances.
7.Efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms
Jian WANG ; Shun HE ; Jiqing ZHU ; Liyan XUE ; Lan AN ; Yueming ZHANG ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Pingping LIU ; Huaying XUN ; Xue ZHANG ; Xinzhang JIA ; Guiqi WANG
Chinese Journal of Oncology 2021;43(3):329-334
Objective:To discuss the efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms.Methods:The clinical-pathological data of 21 patients who were admitted to the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences and underwent endoscopic papillectomy of major duodenal papilla neoplasms from January 2014 to January 2020 were retrospectively studied, their postoperative outcomes and complication were also analyzed.Results:Tweenty-one patients were successfully performed endoscopic papillectomy of major duodenal papilla neoplasms. The resected lesions varied between 0.5-2.8 cm. Completed lesion was resected in 19 cases and lesion blocks in 2 cases. The incidence of postoperative complication was 52.4% (11/21), including 8 cases of postoperative bleeding (38.1%). Five patients stopped bleeding after endoscopic hemostasis and 3 patients stopped after interventional embolization. Two patients experienced perforation (9.5%) and recovered after conservative treatment including anti-inflammatory treatment and abdominal drainage. Five patients had pancreatitis (23.8%) and recovered after treatment with pre-somatostatin and anti-inflammatory rectal suppository. Preoperative pathological results of 21 patients suggested that 11 were high-grade intraepithelial neoplasia and 8 were low-grade intraepithelial neoplasia, and 2 were chronic inflammation. Postoperative pathological results suggested that 4 were adenocarcinoma, and the rest 17 were adenoma. The coincidence rate of preoperative biopsy results and postoperative pathology was 38.1%(8/21), and underestimate of the pathological stage occurred in 11 patients (52.4%) during the preoperative biopsy, overestimate occurred in two patients (9.5%). Four cases had a positive incisal margin. All patients had good prognoses and no death event occurred during the follow-up period.Conclusions:Early-stage major duodenal papilla neoplasms should be treated with aggressive resection. Endoscopic papillectomy of duodenal papilla neoplasms is safe, effective, and can be recommended as the preferred procedure for major duodenal papilla neoplasms.
8.Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm
Yu GONG ; Yueming ZHANG ; Jiqing ZHU ; Shun HE ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Ying LYU ; Guiqi WANG
Chinese Journal of Oncology 2021;43(8):861-865
Objective:To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions.Methods:The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding.Results:A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group ( P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm ( OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion ( OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions:The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.
9.Efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms
Jian WANG ; Shun HE ; Jiqing ZHU ; Liyan XUE ; Lan AN ; Yueming ZHANG ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Pingping LIU ; Huaying XUN ; Xue ZHANG ; Xinzhang JIA ; Guiqi WANG
Chinese Journal of Oncology 2021;43(3):329-334
Objective:To discuss the efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms.Methods:The clinical-pathological data of 21 patients who were admitted to the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences and underwent endoscopic papillectomy of major duodenal papilla neoplasms from January 2014 to January 2020 were retrospectively studied, their postoperative outcomes and complication were also analyzed.Results:Tweenty-one patients were successfully performed endoscopic papillectomy of major duodenal papilla neoplasms. The resected lesions varied between 0.5-2.8 cm. Completed lesion was resected in 19 cases and lesion blocks in 2 cases. The incidence of postoperative complication was 52.4% (11/21), including 8 cases of postoperative bleeding (38.1%). Five patients stopped bleeding after endoscopic hemostasis and 3 patients stopped after interventional embolization. Two patients experienced perforation (9.5%) and recovered after conservative treatment including anti-inflammatory treatment and abdominal drainage. Five patients had pancreatitis (23.8%) and recovered after treatment with pre-somatostatin and anti-inflammatory rectal suppository. Preoperative pathological results of 21 patients suggested that 11 were high-grade intraepithelial neoplasia and 8 were low-grade intraepithelial neoplasia, and 2 were chronic inflammation. Postoperative pathological results suggested that 4 were adenocarcinoma, and the rest 17 were adenoma. The coincidence rate of preoperative biopsy results and postoperative pathology was 38.1%(8/21), and underestimate of the pathological stage occurred in 11 patients (52.4%) during the preoperative biopsy, overestimate occurred in two patients (9.5%). Four cases had a positive incisal margin. All patients had good prognoses and no death event occurred during the follow-up period.Conclusions:Early-stage major duodenal papilla neoplasms should be treated with aggressive resection. Endoscopic papillectomy of duodenal papilla neoplasms is safe, effective, and can be recommended as the preferred procedure for major duodenal papilla neoplasms.
10.Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm
Yu GONG ; Yueming ZHANG ; Jiqing ZHU ; Shun HE ; Lizhou DOU ; Yong LIU ; Yan KE ; Xudong LIU ; Yumeng LIU ; Hairui WU ; Ying LYU ; Guiqi WANG
Chinese Journal of Oncology 2021;43(8):861-865
Objective:To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions.Methods:The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding.Results:A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group ( P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm ( OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion ( OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions:The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

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