1.Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors
Yan CHEN ; Xingguo HOU ; Dapeng LI ; Jin DING ; Jiayue LIU ; Zilei WANG ; Fei TENG ; Hongjun LI ; Fan ZHANG ; Yi GU ; Steven YU ; Xueming QIAN ; Zhi YANG ; Hua ZHU
Journal of Pharmaceutical Analysis 2023;13(4):367-375
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.
2.Association analysis of famine exposure during early life and risk of hypertension in adulthood
Hongjie GUO ; Xiong DING ; Wei JIANG ; Jing JIANG ; Ying WU ; Zhe SHU ; Guiwen LI ; Yuehua HU ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(6):732-736
Objective:To explore the relationship between exposure to famine in early life and the risk of hypertension in adulthood.Methods:The medical data of Yichang Health Management Big Data Center from 2018 to 2019 were analyzed. A retrospective cohort study design was adopted, with hypertension as the study outcome, and different life periods exposed to the Great Famine in China were divided into groups. Multivariate logistic regression model was used to analyze the relationship between famine exposure in early life and hypertension in adulthood. At the same time, the interaction between gender and famine exposure was analyzed.Results:The age of 142 016 subjects was (60. 56±4.43). Among them, men accounted for 46.36% (65 845/142 016) and women accounted for 53.64% (76 171/142 016). There are 42 575(29.98%), 19 644(13.83%), 28 405(20.00%), 28 305(19.93%), 23 087 (19.93%) in non-famine exposure group, fetal famine exposure group, early childhood famine exposure group and late childhood famine exposure group, respectively. The prevalence of hypertension was 17.57% (24 947 cases). Multivariate logistic regression model analysis showed that after adjusting for related confounding factors, compared with non-famine exposure group, the risk of hypertension in fetal, early childhood, middle childhood and late childhood famine exposure group was higher and the OR (95% CI) values were 1.16 (1.11-1.22), 1.27 (1.21-1.33), 1.54 (1.47-1.60) and 1.84 (1.76-1.92), respectively. There was an interaction between sex and famine exposure group ( P<0.001). The above association is stronger among women than among men. Conclusion:Famine exposure in early life may increase the risk of hypertension in adulthood, and the risk of women is greater than that of men.
3.Study on the incidence of adult herpes zoster in Yichang city and its association with early-life famine exposure
Xiong DING ; Wei JIANG ; Yuehua HU ; Jing JIANG ; Ying WU ; Chengzhong XU ; Zhouzhi WU ; Yunfang YU ; Xiaojun LIU ; Guiwen LI ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(11):1328-1331
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ ( OR=1.21; 95% CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females ( OR=1.28, 95% CI:1.02-1.61, P=0.034).
4.Study on the incidence of adult herpes zoster in Yichang city and its association with early-life famine exposure
Xiong DING ; Wei JIANG ; Yuehua HU ; Jing JIANG ; Ying WU ; Chengzhong XU ; Zhouzhi WU ; Yunfang YU ; Xiaojun LIU ; Guiwen LI ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(11):1328-1331
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ ( OR=1.21; 95% CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females ( OR=1.28, 95% CI:1.02-1.61, P=0.034).
5.Association analysis of famine exposure during early life and risk of hypertension in adulthood
Hongjie GUO ; Xiong DING ; Wei JIANG ; Jing JIANG ; Ying WU ; Zhe SHU ; Guiwen LI ; Yuehua HU ; Dapeng YIN
Chinese Journal of Preventive Medicine 2021;55(6):732-736
Objective:To explore the relationship between exposure to famine in early life and the risk of hypertension in adulthood.Methods:The medical data of Yichang Health Management Big Data Center from 2018 to 2019 were analyzed. A retrospective cohort study design was adopted, with hypertension as the study outcome, and different life periods exposed to the Great Famine in China were divided into groups. Multivariate logistic regression model was used to analyze the relationship between famine exposure in early life and hypertension in adulthood. At the same time, the interaction between gender and famine exposure was analyzed.Results:The age of 142 016 subjects was (60. 56±4.43). Among them, men accounted for 46.36% (65 845/142 016) and women accounted for 53.64% (76 171/142 016). There are 42 575(29.98%), 19 644(13.83%), 28 405(20.00%), 28 305(19.93%), 23 087 (19.93%) in non-famine exposure group, fetal famine exposure group, early childhood famine exposure group and late childhood famine exposure group, respectively. The prevalence of hypertension was 17.57% (24 947 cases). Multivariate logistic regression model analysis showed that after adjusting for related confounding factors, compared with non-famine exposure group, the risk of hypertension in fetal, early childhood, middle childhood and late childhood famine exposure group was higher and the OR (95% CI) values were 1.16 (1.11-1.22), 1.27 (1.21-1.33), 1.54 (1.47-1.60) and 1.84 (1.76-1.92), respectively. There was an interaction between sex and famine exposure group ( P<0.001). The above association is stronger among women than among men. Conclusion:Famine exposure in early life may increase the risk of hypertension in adulthood, and the risk of women is greater than that of men.
6.Curative effect of micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis
Zhixing NIE ; Chenxin GAO ; Dapeng HAN ; Sheng DING ; Lingchun WANG ; Jianpo ZHANG ; Guilin OUYANG
Clinical Medicine of China 2019;35(1):49-53
Objective To study the short-term and medium-term effects of mini- strip anchor and capsulotomy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis (RA). Methods From January 2015 to December 2016,fifty-eight RA patients with first metacarpophalangeal joint dislocation were randomly divided into study group (20 cases),joint replacement group (19 cases) and non-operation group (19 cases). Postoperative evaluation indexes: the wound healing was observed in accordance with "trial standard of functional evaluation of upper limbs of Chinese Medical Association Hand Surgery Society". The surgical outcomes of the three groups were compared. The hand function and quality of life were assessed by Michiga Hand Outcomes Questionnaire ( MHQ ) and arthritis impact measurement scale 2 (AIMS2) before treatment, 6 months after treatment and 12 months after treatment. Results All the patients in the study group and the joint replacement group healed by first intention without any early complications. According to the criteria of upper extremity functional evaluation of Chinese Medical Association,the curative effect of the operation was evaluated. In the study group,15 cases were excellent,3 cases were good,2 cases were poor,the excellent and good rate was 90. 0%. In the joint replacement group, 15 cases were excellent,3 cases were good,1 case was poor,and the excellent and good rate was 94. 7%. After treatment for 6months, the MHQ scores were improved significantly in the three groups (( 48. 36 ±8. 24) vs. (73. 06±10. 55); (47. 56±7. 75) vs. (81. 42±8. 54); (48. 75±8. 85) vs. (65. 91±8. 26)) (F=33. 19,35. 12,28. 42, P<0. 05). The MHQ scores of study group ( (73. 06±10. 55)points) and joint replacement group ( ( 81. 42 ± 8. 54) points) were significantly higher than those of non-operation group ((65. 91± 8. 26) points) ( P<0. 05), and the MHQ scores of joint replacement group were significantly higher than those of study group (P<0. 05). At 12 months after treatment,there was no significant difference in MHQ score between the study group ((82. 45±7. 18)points) and the arthroplasty group ((84. 36±6. 33) points) (P>0. 05) . At 6 and 12 months after treatment, AIMS2 scores of each group were significantly improved,but AIMS2 scores of study group (( 216. 51 ± 35. 28) points, ( 230. 28 ± 23. 51) points) and arthroplasty group ((221. 45±31. 63) points,(234. 15±21. 42) points) were significantly higher than those of non-operation group ((192.69±41.31) points,(200.43 ±28.42) points) (P<0.05).At 6 and 12 months after treatment,there was no significant difference in AIMS2 scores between the study group and the arthroplasty group ( P > 0. 05 ) . Conclusion Micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis can achieve good stability of articular reduction,significantly improve the joint function and quality of life and have ideal short-term and mid-term effect.
7.Ultrasound-guided intraabdominal aortic balloon control technique for reducing intraoperative hemorrhage of high-risk placenta previa
Junle LIU ; Yanggang HU ; Heyi DING ; Jinhui DING ; Dapeng FU
Chinese Journal of General Surgery 2018;33(9):776-779
Objective To explore the value of ultrasound-guided balloon control technique in abdominal aorta for reducing intraoperative hemorrhage in high-risk placenta previa undergoing cesarean section.Methods From Aug 2013 to Oct 2017,40 cases were admitted,among them,16 cases were treated with ultrasound-guided towed balloon prophylactic control technique of abdominal aorta (the study group) before cesarean,and 24 cases did not receive balloon occlusion (the control group) during the cesarean.Clinical data were compared between the two groups.Results The time used for uterine suture (t =10.34,P =0.01),the amount of intraoperative blood loss (t =9.51,P =0.01) and blood transfusion (t =3.41,P=0.005)in the two groups were all statistically different.While the differences in PT (t =1.02,P =0.32),ALT (t =0.54,P =0.59),AST(t =0.91,P =0.37),creatinine(t =0.75,P =0.46) were not statistically significant between the two groups.Conclusion Ultrasound-guided abdominal aortic balloon control technique can reduce the blood loss significantly in cesarean section with high-risk placenta previa.
8.Masquelet technique combined with antibiotic coated intramedullary nail fixation for the treatment of lower limb infected bone defects
Guocheng DING ; Xinwei LIU ; Bing LIU ; Dapeng ZHOU ; Liangbi XIANG ; Tianyu HAN ; Jing TIAN ; Bing XIE
Chinese Journal of Orthopaedics 2018;38(9):530-535
Objective To explore the clinical effect of Masquelet membrane induction technique combined with antibiotic coated intramedullary nail fixation in the treatment of lower limb large segment infected bone defects.Methods From June 2009 to August 2015,53 patients who have lower limb large segment infected bone defects were analyzed retrospectively,including 40 males and 13 females,aged from 23 to 61 years,with an average age of 36.2±8.4 years.37 cases were secondary to infection after fracture surgery,and 16 cases were caused by open fractures.There were 17 cases of femoral shaft defects and 36 cases of tibia diaphysis defects.All 53 cases were treated with Masquelet technique.The first stage was infection debridement,then bone defect was filled by bone cement mixed with sensitive or broad-spectrum antibiotics,and then temporary fixation was given.When the infection was controlled,debridement was given again and sensitive antibiotic bone cement was replaced to induce membrane,and antibiotic coated intramedullary nail was used for internal fixation.In the second stage,after intramedullary nailing internal fixation for 4-6 weeks,the bone cement occupying device was taken out and the autologous cancellous bone was planted in the induced membrane.Then the membrane was covered and sutured.The cure rate of infection,the time of bone healing and the related complications were observed.Results 53 patients were followed up for 24 to 63 months (with an average of 39±4.7 months).The length of tibia bone defect after debridement was 6-15 cm (average 8.7±4.9 cm).49 patients' infection were cured in 12 months after operation,and the bone defects were healed,with healing time of 5.3-9.7 months (mean 7.4±3.2 months).No refracture occurred.The healing time of tibia was 7.8±2.1 months,while the healing time of the femur was 7.2±3.9 months.1 case of femoral shaft defect had recurrence of infection 4 months after membrane induced bone grafting,and the first stage treatment was restarted which were debridement and implantation of sensitive antibiotic bone cement occupying device.After 6 weeks,the infection was controlled and the second stages continued.3 cases' s (2 cases of femoral shaft,1 case of tibial shaft) autologous cancellous bone were absorbed 3 to 6 months after operation,and no bone density increased in the bone defect area.The autologous cancellous bone was reimplanted and the bone defect was cured in 8 months.Conclusion Masquelet technology combined with antibiotic coated intramedullary nailing can effectively control infection and create a good biological and mechanical environment for bone defect repair.It has good clinical efficacy.
9. Comparison and evaluation of laboratory test techniques for severe fever with thrombocytopenia syndrome
Xiaolin JIANG ; Xiaomei ZHANG ; Bo PANG ; Dapeng SUN ; Xianjun WANG ; Shujun DING
Chinese Journal of Experimental and Clinical Virology 2018;32(1):38-42
Objective:
Compare the detection result of blood samples of severe fever with thrombocytopenia syndrome (SFTS) patients using different detection techniques, and observe the dynamic characteristics of the virus specific RNA, IgM antibody and IgG antibody, to provide theoretical basis for selection of diagnostic methods of disease.
Methods:
Acute phase serum of suspected SFTS cases and convalescent serum samples of lab-confirmed cases were collected. Real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the virus specific RNA, IgM antibody and IgG antibody. The detection results of different methods, the relationship between positive results and the acquisition time, and the dynamic characteristics of viral nucleic acid and antibodies were analyzed.
Results:
A total of 87 serum samples of the suspected SFTS patients were collected, the positive rate of virus specific RNA, IgM antibody and IgG antibody were 53.41%, 31.03% and 3.41%, respectively. Among 55 confirmed cases of SFTS, the consistent rate of virus specific RNA and IgM antibody detection methods was 36.36%, and the difference between the two methods was significant (χ2=6.82,
10.Comparative study on bone destruction of maxillary sinus malignant tumor with CT scan and histopathologic examination
Qingjun JI ; Wei DING ; Wei CHAI ; Hui HUANG ; Dapeng LI ; Tao GUO ; Jingwu SUN ; Yongxiang WEI
Chinese Archives of Otolaryngology-Head and Neck Surgery 2017;24(2):90-94
OBJECTIVE To explore and evaluate the value of CT in diagnosis of malignant tumor of maxillary sinus and the accuracy of the involved bone wall by comparing the preoperative CT imaging with the pathologic examination.METHODS 11 patients without maxillary sinus squamous cell carcinoma and lymph node metastasis received pathological examination and enhanced CT scan before operation,partial or total maxillary resection were implemented according to the CT features and scope.The position and azimuth of the cut bone tissue samples were marked.The specimens were routinely fixed,decalcified,embedded,sliced and HE stained to observe the bone tissue pathological changes on the bone wall under light microscope.RESULTS Nasal sinus enhancement CT scan showed that the medial wall of maxillary sinus were all resorped and invaded(4 cases lack inner wall).Anterior wall was invaded in 6 cases,superior wall in 7 cases and bottom wall in 3 cases,posterior and exterior wall in 9 cases;After ruling out the cases without internal wall of maxillary sinus,the inner wall of the maxillary sinus was invaded by cancer cells,so was the front wall and the bottom wall.Those showed bone wall erosion on preoperative CT with continuous change but without interruption and accompanied by bone wall thickening and hardening were found without tumor invasion by postoperative pathological verification.CONCLUSION Bone wall damage on preoperative CT does not mean tumor invasion,and the probability of each maxillary sinus wall invasion is different;the comprehensive analysis found that for wormhole like change of bone wallon preoperative CT with continuous bone wall thickening and hardening of the 'reconstruction of bone destruction',there was no tumor invasion by postoperative pathological validation;Routine selection analysis of bone tissue pathology can supplement the extent diagnosis of malignant tumor of maxillary sinus on preoperative CT scan,so it can accurately estimate the T staging of tumor.It may provide a more effective basis for selection of minimally invasive surgery,postoperative evaluation of surgical effect and formulating more comprehensive treatment protocol.

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