1.Oncolytic influenza virus enhances killing effect of gemcitabine against pancreatic cancer cells
Zihe MENG ; Yongru XU ; Zhaoda DENG ; Yuxin ZHANG ; Penghui YANG ; Ruiping HU
Journal of Army Medical University 2025;47(2):141-150
Objective To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics(RG)technology,in combination with chemotherapy drug,gemcitabine(GEM),against pancreatic cancer cells.Methods The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study.The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay.CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses[multiplicities of infection(MOI):0,0.1,1.0,3.0]on the survival rate of pancreatic cancer cell lines(Panc02,PANC-1,SW1990,BxPC-3)and normal pancreatic ductal epithelial cells(HPDE6-C7)after treatment for 24,48 or 72 h.Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice(6 weeks old)were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group.PBS(100 μL/animal)or OvFlu-GM-CSF virus(1× 107PFU/100 μL)was given to the mice of the corresponding groups through intratumoral injection,while GEM(100 mg/kg)was injected intraperitoneally,once per 3 days,for totally 9 times.Changes in tumor volume and survival rate were monitored.Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues.HE staining was performed to observe the pathological changes in major organs(heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured to evaluate the safety of the recombinant oncolytic virus.Results The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells.At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0(P<0.01).The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time(P<0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells(HPDE6-C7).In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment(P<0.01),and enhanced the infiltration of T cells in the tumor tissues.No obvious pathological changes were observed in the above-mentioned major organs.Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.Conclusion RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host's anti-tumor immune response.
2.Diagnostic value of endoscopic ultrasound-guided tissue acquisition with rapid on-site evaluation performed by endoscopists in immunohistochemistry-required solid pancreatic lesions
Dingkun XIONG ; Yongru LIU ; Yunlu FENG ; Yu ZHAO ; Xi WU ; Tao GUO ; Qingwei JIANG ; Qiang WANG ; Dongsheng WU ; Shengyu ZHANG ; Yingyun YANG ; Aiming YANG
Chinese Journal of Pancreatology 2024;24(1):39-44
Objective:To evaluate the diagnostic value of rapid on-site evaluation (ROSE) performed by endoscopists for solid pancreatic lesions requiring tissue for immunohistochemistry (IHC) staining with different approach of endoscopic ultrasound-guided tissue acquisition (EUS-TA).Methods:After screening 1 573 cases who underwent EUS-TA operation at the Endoscopy Center of Peking Union Medical College Hospital between August 2018 and October 2022, a total of 65 cases of solid pancreatic lesions whose diagnosis rely on IHC staining was collected and summarized with clinical data of each case. Among 65 cases, there were 46 cases of pancreatic neuroendocrine tumors (PNETs), 13 cases of pancreatic solid pseudo-papillary tumors (SPTs), and 6 cases of lymphomas and mesenchymal. Patients were categorized into ROSE group (36 cases) and non-ROSE group (29 cases) according to the presence or absence of endoscopists performed ROSE during EUS-TA operation. They were further divided into subgroups of FNA-ROSE (26 cases), FNB-ROSE (10 cases), FNA-non-ROSE (24 cases) and FNB-non-ROSE (5 cases) according to the type of EUS-TA. Diagnostic accuracy and IHC success rate were compared between different groups and subgroups. Binomial logistic multifactorial regression analysis was used to evaluate the influence of ROSE and EUS-TA type on diagnostic accuracy and IHC success rate.Results:There were no statistically significant differences between ROSE group and non-ROSE group in terms of age, gender, bilirubin level, CA19-9 level, lesion site, lesion size, composition ratio of diagnosis, and surgical rate. The differences in mean size of lesions, needle gauge, location of puncturation, and number of needle pass between subgroups were not statistically significant. The diagnostic accuracy was 88.9% in ROSE group and 79.3% in non-ROSE group, and the difference between the two groups was statistically significant ( P=0.023). The diagnostic accuracy of FNA-ROSE group was higher than that of FNA-non-ROSE group (88.5% vs 75.0%), but the difference was not statistically significant ( P>0.100). The differences in diagnostic accuracy and success rate of IHC between FNB-ROSE group and FNB-non-ROSE group were not statistically significant. Binomial logistic multifactorial regression analysis did not reveal any independent influences on diagnostic accuracy. Conclusions:ROSE performed by endoscopists improved diagnostic accuracy of EUS-TA in solid pancreatic lesions requiring IHC staining, and therefore is potentially valuable for improving the diagnostic efficiency of EUS-TA for such diseases.
3.The role of transoralsonography guiding fine-needle aspiration biopsy in the diagnosis of retropharyngeal or parapharyngeal masses identified on the images of treated patients with malignant carcinoma
Youwang ZHANG ; Yafang HUANG ; Hongmei YING ; Lin KONG ; Yongru WU ; Chengrun DU ; Chaosu HU
Chinese Journal of Radiation Oncology 2015;(4):427-430
Objective To investigate the role of transoralsonography guiding fine?needle aspiration biopsy in the diagnosis of retropharyngeal or parapharyngeal masses identified on the CT, MRI or PET?CT images of treated patients with malignant carcinoma. Methods From 2002 to 2013,this study recruited fifty?five patients with a history of cancer, of which 50 were treated with radiation treatment, including 46 nasopharyngeal carcinoma, 3 esophagus squamous cell carcinoma and1 lung apex carcinoma. There were 4 patients with a history of 1 thyroid papillary carcinoma, 1 buccal mucosa squamous cell carcinoma,1 glottis squamous cell carcinoma and 1 sigmoid colon adenocarcinoma treated with surgery. The rest one patient with nasal olfactory neuroblastoma was treated by postoperative radiation. The enlarged retropharyngeal lymph nodes in 44 cases and parapharyngeal masses in 10 cases were identified on CT or MRI imges. The enlarged retropharyngeal lymph node in the rest case was identified on PET?CT. With transoral ultrasound examination, all lesions were with hypo?intensity echo. Cystic areas were noted on occasion. Biopsy was performed in all cases. Results After cytology examination, carcinoma cells were detected in 37 retropharyngeal lymph nodes, with a detection rate of 82% (37/ 45). In the 10 parapharyngeal masses, carcinoma cells were detected in 3 lesions, with a detection rate of 30%. Conclusions Transor alsonography guiding fine?needle aspiration biopsy can be useful in the cytopathology diagnosis of retropharyngeal or parapharyngeal masses identified on the CT, MRI or PET?CT images of treated patients with malignant carcinoma,which facilitates, early diagnosis and treatment for patients.
4.Nasal endoscope, MRI, and ultrasound-guided fine needle aspiration in the diagnosis of primary head and neck tumor
Youwang ZHANG ; Yafang HUANG ; Yongru WU ; Lin KONG ; Shuang HUANG ; Chaosu HU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2014;49(3):223-226
Objective To investigate the role of muhiple diagnostic methods in the head and neck tumor.Methods One hundred and ninety-six patients without definite pathological diagnosis referred from other hospitals were included in this retrospective study.All patients had a biopsy or fine needle aspiration (FNA) of the suspected region after detailed medical history enquiry,physical examination and imaging examination.Results All patients had ultrasound-guided FNA except 4 patients who had direct FNA.One hundred and seventy-one patients (87.2%) were confirmed to have tumor cells by pathological diagnosis,among them,31 patients by biopsy of primary region alone,106 by FNA,and 34 by both.The positive rate of FNA was 71.4% (140/196) for the whole group,71.1% (123/173),66.7% (10/15) and 87.5% (7/8) for retropharyngeal lymph node subgroup,parapharyngeal space subgroup and oropharynx subgroup.Conclusion The combined use of endoscope,MRI,and ultrasound-guided FNA is useful for the diagnosis of head and neck tumor.
5.The role of Magnetic resonance sialography in evaluating radiation-induced xerostomia for patients with early stage nasopharyngeal carcinoma
Dan OU ; Yunyan ZHANG ; Xiayun HE ; Yajia GU ; Chaosu HU ; Hongmei YING ; Guopei ZHU ; Yongru WU ; Jian MAO ; Xigang SHEN ; Lei YUE
Chinese Journal of Radiation Oncology 2011;20(6):462-466
Objective To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool in evaluating major salivary gland function before and after radiotherapy (RT) for nasopharyngeal carcinoma patients.Methods From August 2009 to June 2010,patients with stage Ⅰ and Ⅱa (AJCC/UICC 2002) nasopharyngeal carcinoma were enrolled.All the patients were treated with intensity modulated radiation therapy alone.MRS with salivary stimulation was performed in patients before and after RT on a 3.0T MR scanner.An MRS categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT.The relationship between MRS score and EORTC Core QOL and EORTC Head and Neck QOL was analyzed.Spearman rank correlation test was performed to analyze the non-stimulated and stimulated MRS findings and the clinical severity of xerostomia.Results All 10 enrolled patients completed planned treatment.The mean dose of the parotid glands and submandibular glands were (37.99 + 3.70) Gy and (55.65 + 2.99) Gy,respectively.Good-quality MRS images were obtained.The visibility scores of both the parotid and submandibular ducts were increased after secretion stimulation.Irradiation decreased the visualization of the salivary ducts and attenuated the response to secretion stimulation.There were specific correlations between post-RT secretion response of the parotid gland and EORTC QLQ scales ( global QOL scale in QLQ-C30 ( rs =0.636,P =0.048 ) and xerostomia scale in QLQ H&N35 ( rs =- 0.694,P =0.026) ).Conclusions MRS can be used as a non-invasive way to evaluated of the functional changes of major salivary glands before and after RT and as a promising approach for investigating radiation-induced xerostomia.
6.Gastrointestinal Endoscope Disinfection Situation:Investigation and Analysis of Health Settings in Xi′an City
Jun LI ; Feng ZHANG ; Jinghong WANG ; Hua LI ; Yongru ZHANG ; Daoqin NIU ; Yingru HOU
Chinese Journal of Nosocomiology 2006;0(02):-
OBJECTIVE To acknowledge the current administrative situation in gastrointestinal endoscopies in Xi′an health settings.METHODS Using standard questionnaire to investigate endoscope disinfection related knowledge of the staff,facilities and layout in endoscopy room,washing and decontamination process and operating records.Samples were collected from gastrointestinal endoscope channels,biopsy forceps,disinfectants and the water in bottles.Then laboratory analysis was employed to check bacteria count,pathogen and efficient components of disinfectants.RESULTS Among 35 hospitals monitored,manual cleaning the endoscope was used by 29 hospitals,from which 75% samples were up to standard of guideline.The qualification rate of using automatic washing devices and acidic electrolytic water to disinfect endoscope was 15% and 78%,respectively.All biopsy forceps were up to standard.78% Efficient components of glutaraldehydes were up to 2%.CONCLUSIONS The rate of using automatic washing devices to clean gastrointestinal endoscopy is still low.It is important to strengthen supervision of hospital gastrointestinal endoscope disinfection to control nosocomial infection.
7.Feasibility of a second course irradiation after ?-knife radiotherapy for nasopharyngeal carcinoma
Chinese Journal of Radiation Oncology 2005;0(06):-
Objective To investigate the feasibility of ?-knife as the only treatment or a second course radiotherapy after ?-knife radiotherapy for nasopharyngeal carcinoma(NPC).Methods From Jan.1998 to Feb.2004,2 recurrent NPC patients and 8 newly diagnosed patients with lesions in nasopharynx and skull base received ?-knife radiotherapy.Among the latter 8 newly untreatment patients,2 had poorly differentiated squamous cell carcinoma in the nasopharynx,while the other 6 patients had been misdiagnosed as nasopharyngeal tumors other than NPC,including 3 clivus chordoma and 2 caverous sinus meningioma diagnosed by MR imaging,and 1 nasopharyneal fibroangioma by direct nasopharyngoscopic examination.After ?-knife radiotherapy,all the 6 non-nasopharyngeal carcinoma patients were pathologically proved to have nasopharyngeal carcinoma.The treatment of this cohort were: 8 untreated patients with ?-knife radiotherapy first as the only treatment,2 recurrent nasopharyngeal carcinoma patients with ?-knife radiotherapy as salvage treatment.Treatment after the initial ?-knife radiotherapy for these patients were: 2 no further treatment,3 with induction chemotherapy followed by conventional radiotherapy,2 with conventional radiotherapy followed by chemotherapy,2 with conventional radiotherapy alone and 1 with chemotherapy alone.The chemotherapy regimen consisted of DDP 30?mg/m~2+5-Fu 500?mg/m~2,d1-3,3 week per cycle,totally 2-3 cycles.The radiotherapy regimen consisted of two opposing faciocervical portals or preauricular plus anterior nasal portals to a total dose of 60-70?Gy within 6-7 weeks for the primary lesion and 5060?Gy for the neck nodes with the residual primary lesion boosted with 500-750 ?cGy. Results No primary lesion of the 8 newly diagnosed patients for whom the ?-knife has been given first as the only treatment was controlled.In the 2 recurrent NPC patients,shrinkage of tumor and relief of symptoms were observed after ?-knife radiotherapy.Among 8 newly diagnosed patients,6 misdiagnosed ones received chemotherapy and radiotherapy before ?-knife radiotheryapy gave survival intervals of 6.0,2.5,2.0 and 1.0 years,while one patient who was refused of radiotherapy died of distant metastasis,and the other patient who received chemotherapy alone died of uncontrolled primary lesion.Conclusions ?-knife radiotherapy alone must not be chosen as the initial only treatment for nasopharyngeal carcinoma.For recurrent NPC,?-knife radiotherapy is indicated,preferably followed by a second course conventional radiotherapy with or without chemotherapy.Giving the green light for the radiation-induced complications of the second course conventional radiotherapy after ?-knife radiotherapy awaits further observation.
8.Advances in the Research and Application of Mammal Defensin
Ying CHEN ; Yiqiang GE ; Wenbin LI ; Liming ZHANG ; Yongru SUN
Progress in Biochemistry and Biophysics 2001;28(1):17-21
Defensin is a kind of antimicrobiol and cytotoxic peptides which have been found in a large range of living organisms. The mammal defensins have the most wide range antimicrobiol spectrum. The distribution, structure, gene expression regulation of mammal defensins in China and abroad were summarized. Its application on medicine and plant resistant gene engineering were prospected.
9.Late side reactions of long-term survivors after radiotherapy for nasopharyngeal carcinoma
Lin KONG ; Youwang ZHANG ; Yongru WU ; Xiaomao GUO
Chinese Journal of Radiation Oncology 1993;0(03):-
15-20 years accounted for 11%,12%,14% and 10% , respectively. 260 patients had grade 3 and 4 other injuries, including 55 skin, 79 muscles/soft tissue, 36 mucosa, 79 xerostomia and 11 trismus. Among 320 patients who suffered from caries of teeth, it involved all teeth in 192 patients. Two patients had mandible necrosis. 225 patients had decline of hearing. Among 672 ears in 336 patients,194 ears had severe deafness. The overall side reaction occurrence rate was 84.5%. Conclusions Different late side reactions do exist in nasopharyngeal carcinoma patients(84.5%) with long-term survival after radiotherapy, and some patients suffer side reactions so serious as to affect their quality of life. Cranial nerve injuries are not rare, and it may occur anytime after radiation, but it dose not stop as the patients survive along.
10.Radiation-induced cranial nerve palsy and its causative factors in nasopharyngeal carcinoma
Lin KONG ; Youwang ZHANG ; Yongru WU ; Xiaomao GUO ; Longgen LI
Chinese Journal of Radiation Oncology 1992;0(01):-
7000?cGy). The cumulative incidence of cranial nerve Ⅸ-Ⅻ palsies increased in patients with advanced N stage. Patients in the first group of treatment field had the highest risk to progress cranial nerve Ⅸ-Ⅻ palsies, followed by the second group, and the third group had the lowest risk. Only 1 in 34 patients with brachytherapy developed cranial nerve palsy. Conclusions Our retrospective data show that the radiation-induced cranial nerve palsy is a common complication in NPC patients after radiotherapy and the incidence seems to increase with the duration of the follow-up. Factors that potentially affect the injury of cranial nerve Ⅰ-Ⅶ and Ⅸ-Ⅻ are different, because of the different anatomy. Controlling the doses to the nasopharyngeal region and using faciocervical fields may help to lower the incidence of cranial nerve palsy.

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