1.Therapeutic effect of anti-PD-L1&CXCR4 bispecific nanobody combined with gemcitabine in synergy with PBMC on pancreatic cancer treatment
Hai HU ; Shu-yi XU ; Yue-jiang ZHENG ; Jian-wei ZHU ; Ming-yuan WU
Acta Pharmaceutica Sinica 2025;60(2):388-396
Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8+ to CD4+ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8+ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).
2.Expert consensus on integrated diagnosis and treatment techniques for oropharyngeal squamous cell carcinoma
Wei SHANG ; Haoyue XU ; Zongxuan HE ; Xiaoying LI ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Yan SUN ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Jie ZHANG ; Jichen LI ; Yue HE ; Chunjie LI ; Jianhua WEI ; Lizheng QIN ; Yaowu YANG ; Qing XI ; Wei WU ; Kai YANG ; Bing HAN ; Lingxue BU ; Shuangyi WANG ; Kai SONG ; Jiaqi ZHU ; Hongyu HAN ; Yu KONG ; Jieying LI ; Man HU ; Mingjin XU ; Moyi SUN
Journal of Practical Stomatology 2025;41(6):725-736
In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.
3.Antiviral mechanism of Euphorbia helioscopia diterpenoids against Zika virus in vitro
Pan-pan PANG ; Xiong QIU ; Ying-jie JIANG ; Xin-yue LIU ; Wei-zhe MA ; Jian-qiu-rong YIN ; Wei-lie XIAO ; Chang-bo ZHENG
Chinese Pharmacological Bulletin 2025;41(8):1436-1444
Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.
4.Comparison of magnetic resonance images of the temporomandibular joint using different coils
Xiaojie ZHANG ; Tingting WU ; Ye ZHANG ; Ruiqiang GUO ; Zhi YIN ; Yue ZHAO ; Jian WANG ; Tingjun LI ; Hongmei LIU ; Xicheng GUO ; Xinhua ZHANG ; Wei HOU ; Tingting LIU ; Xuefang MA ; Xinhua LIU
Chinese Journal of Stomatology 2025;60(7):713-722
Objective:To explore and compare the clinical application value of 8-channel head phased-array coil, an 8-channel temporomandibular joint (TMJ)-specific surface coil, and a single-channel surface coil in TMJ MRI examinations.Methods:A total of 600 temporomandibular disorders (TMD) patients (1 200 joints) who underwent TMJ MRI examination in the First People′s Hospital of Jinzhong from June 2020 to January 2025 were retrospectively screened. Based on inclusion/exclusion criteria, 120 TMD patients (240 joints) with closed-mouth oblique sagittal proton density weighted imaging (OSag PDWI), coronal T2 fat-suppression weighted imaging (OCor fs T2WI) and open-mouth oblique sagittal proton density weighted imaging (OSag PDWI) were included. Patients were divided into groups A, B, and C, with 40 cases in each group. Group A (31female, 9male, median age 24 years old), underwent 8-channel head phased-array coil imaging. Group B (29 female, 11male, median age 23.5 years old) underwent TMJ imaging with an 8-channel surface coil. Group C (29 female, 11male, median age 22.5 years old) underwent single-channel surface coil imaging. There were no significant differences in age, gender, type or disease types among groups ( P>0.05). Six healthy volunteers without TMD (4 female, 2 male, range 19 to 45 years old) underwent imaging with all three coils as self-control. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image quality were compared for five regions of interest (ROI) in both patients and volunteers. Results:Under the same sequence and the same parameters, SNR and CNR in group B were higher than those in group A, and SNR and CNR in group C were also higher than those in group A, the differences were statistically significant ( P<0.05). However, there were significant differences in SNR and CNR between group B and group C in the closed and open positions of ROI1, the open positions of ROI3 and the open positions of ROI5 ( P<0.05), and there were no significant differences in other positions ( P>0.05). Group B had the best image quality, followed by group C and group A had the worst image quality. There were significant differences in the visualization of OSag PDWI in the closed mouth position, OCor T2WI in the coronal position, and OSag PDWI in the open mouth position, such as condyle, anterior attachment, joint disc, double lamina area, joint cavity and lateral pterygoid muscle ( P<0.05). There were significant differences between group B and group C in showing the joint cavity in the closed mouth position and showing the structure of the bilaminar area in the open mouth position ( P<0.05). There was no significant difference in other regions of interest ( P>0.05). The subjective scores of condyle, anterior attachment, articular disc, bilaminar area, articular cavity, lateral pterygos muscle and other structures were medium to high in group A, high in group B, and high or high in group C by two radiologists independently. In the five rois, the 8-channel TMJ surface coil showed more details, especially in the articular disc, condyle and lateral pterygoid muscle regions, and had more advantages in both volunteers and patients. Conclusions:The 8-channel TMJ-specific surface coil provides significantly clearer visualization of critical anatomical details within the ROIs, demonstrating the highest clinical application value and is recommended as the preferred choice.
5.Epidemiological distribution characteristics and transmission patterns of Campylobacter in a Shandong broiler slaughterhouse
Shuai MIAO ; Xiu-mei HUANG ; Lin WANG ; Jun-hui LIU ; Jian-mei ZHAO ; Yu-bin GAO ; Shi-ping SONG ; Si-yu ZHANG ; Na LIU ; Ge ZHAO ; Xi-yue ZHANG ; Jun-wei WANG ; Juan WANG ; Zhi-na QU
Chinese Journal of Zoonoses 2025;41(6):583-591
This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.
6.Antiviral mechanism of Euphorbia helioscopia diterpenoids against Zika virus in vitro
Pan-pan PANG ; Xiong QIU ; Ying-jie JIANG ; Xin-yue LIU ; Wei-zhe MA ; Jian-qiu-rong YIN ; Wei-lie XIAO ; Chang-bo ZHENG
Chinese Pharmacological Bulletin 2025;41(8):1436-1444
Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.
7.Expert consensus on holistic integrative management of oral squamous cell carcinoma
Moyi SUN ; Zongxuan HE ; Haoyue XU ; Xiaoying LI ; Jie ZHANG ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Shizhu BAI ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Jian MENG ; Zhijun SUN ; Jichen LI ; Yue HE ; Chunjie LI ; Lizheng QIN ; Kai YANG ; Qing XI ; Lin KONG ; Bing HAN ; Lingxue BU ; Yuanyong FENG ; Kai SONG ; Hongyu HAN ; Jieying LI ; Qianwei NI ; Yun LI ; Juan CHAI ; Xiaochen YANG ; Man HU ; Mingjin XU ; Wei SHANG
Journal of Practical Stomatology 2025;41(4):437-449
Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80%of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.
8.Epidemiological distribution characteristics and transmission patterns of Campylobacter in a Shandong broiler slaughterhouse
Shuai MIAO ; Xiu-mei HUANG ; Lin WANG ; Jun-hui LIU ; Jian-mei ZHAO ; Yu-bin GAO ; Shi-ping SONG ; Si-yu ZHANG ; Na LIU ; Ge ZHAO ; Xi-yue ZHANG ; Jun-wei WANG ; Juan WANG ; Zhi-na QU
Chinese Journal of Zoonoses 2025;41(6):583-591
This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.
9.Expert consensus on the assessment and rehabilitation management of speech disorders following oral and maxillofacial tumor surgery
Xiaoying LI ; Moyi SUN ; Wei GUO ; Zhangui TANG ; Longjiang LI ; Guoxin REN ; Zhijun SUN ; Wei SHANG ; Jie ZHANG ; Jian MENG ; Jichen LI ; Kai YANG ; Yue HE ; Chunjie LI ; Lizheng QIN ; Bo LI ; Wei WU ; Qinlong LI-ANG ; Qianwei NI ; Jianhu LI ; Xiangming YANG ; Xiaoyan ZHOU ; Fan YANG ; Jiacun LI ; Tao GAO
Journal of Practical Stomatology 2025;41(1):5-15
The advancement of surgical techniques enables effective treatment for many patients with oral and maxillofacial tumors.How-ever,post-surgery problems such as chewing,swallowing and speech difficulty may arise due to the defects in speech organs and inade-quate compensatory function of tissue flap repair.Speech disorders,in particular,isolate patients by making it difficult for them to com-municate with others,not only impact their quality of life but also potentially lead to psychological problems and social interaction disor-ders.Although the decline in life quality and other related issues caused by speech dysfunction due to surgery and radiotherapy or chemo-therapy have been widely recognized,there is currently no standardized and universally applicable assessment method and standardized re-habilitation treatment management guideline or consensus for speech disorders following oral and maxillofacial tumor surgery at home and abroad.Based on previous clinical practice,combined with the characteristics of speech disorders in patients after oral and maxillofacial tumor surgery,the clinical experience of the experts in maxillofacial tumor surgery and rehabilitation and the relevant domestic and foreign literature,relevant experts organized discussions and modifications,reach a consensus on core content such as the assessment of speech disorders and the implementation plan for early rehabilitation treatment management,providing a reference for clinical practice,in order to improve patients'speech-related life quality and enhance the assessment and rehabilitation treatment techniques for speech disorders after oral and maxillofacial tumor surgery.
10.Effect and mechanism of LINC00839 on the malignant biological behavior of endometrial cancer cells
Yuan-yuan SHI ; Fen TIAN ; Wei-yue ZHOU ; Mei-yan LI ; Jian-cai MA ; Ju-rong WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(1):21-27
Objective To investigate the effect of LINC00839 on the malignant biological behavior of endometrial cancer cells by regulating the miR-625-5p/cytoplasmic polyadenylation element binding protein 4 (CPEB4) axis. Methods The cancer tissues and adjacent tissues of 46 patients with endometrial cancer were obtained,endometrial cancer cells of HEC-1B,Ishikawa and RL95-2 and human endometrial epithelial cells (HEEC) were cultured in vitro,and the expression levels of LINC00839,miR-625-5p and CPEB4 in tissues and cells were detected. HEC-1B cells were divided into the HEC-1B group (conventional culture),sh-Ctrl group (transfected with sh-Ctrl),sh-LINC00839 group (transfected with shRNA-LINC00839),anti-miR-625-5p group (transfected with shRNA-LINC00839 and miR-625-5p inhibitor),and anti-NC group (transfected with shRNA-LINC00839 and inhibitor-NC). The proliferation,apoptosis,migration and invasion abilities of HEC-1B cells in each group were compared,and the expressions of CPEB4 and epithelial-mesenchymal transition (EMT) related proteins were determined. The targeting relationships between LINC00839 and miR-625-5p,and miR-625-5p and CPEB4 were analyzed. Results The mRNA expression of LINC00839 and CPEB4,as well as the positive expression rate of CPEB4 protein in endometrial cancer tissues were higher than those in adjacent tissues,and the expression of miR-625-5p was lower than that in adjacent tissues (P<0.05). Compared with HEEC cells,the expression of LINC00839 and the mRNA and protein expression of CPEB4 in Ishikawa,RL95-2 and HEC-1B cells increased (P<0.05),and the expression of miR-625-5p decreased (P<0.05). Compared with the sh-LINC00839 group and anti-NC group,the protein expression of N-cadherin,Vimentin,and CPEB4,24-hour absorbance,and migration and invasion cell numbers of HEC-1B cells in the HEC-1B group,sh-Ctrl group and anti-miR-625-5p group increased (P<0.05),while the expression of E-cadherin protein and cell apoptosis rate decreased (P<0.05). There were binding sites between LINC00839 and miR-625-5p,miR-625-5p and CPEB4,with targeting regulatory relationships. Conclusion LINC00839 is related to the malignant biological behavior of endometrial cancer cells,interference with LINC00839 expression can inhibit the proliferation,invasion and migration,and promote apoptosis of HEC-1B cells,and its mechanism may be achieved by regulating the miR-625-5p/CPEB4 axis.

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