1.PDGFC secreted by CAFs promotes resistance of breast cancer cells to doxorubicin by PI3K-mTOR signalling pathway
Hao DONG ; Xue-Jie WANG ; Wan-Li DUAN ; Zhi-Mei SHENG ; Li-Hong SHI ; Bao-Gang ZHANG
Chinese Pharmacological Bulletin 2024;40(5):833-839
Aim To explore whether platelet-derived growth factor C(PDGFC)derived from cancer-associat-ed fibroblasts(CAFs)can promote resistance of breast cancer cells to doxorubicin(DOX)and the underlying mechanisms.Methods CAFs and normal fibroblasts(NFs)were extracted from freshly resected breast cancer tissue and adjacent normal breast tissue respec-tively.Conditioned medium(CM)from CAFs and NFs was collected and co-cultured with breast cancer cells.Cell proliferation and toxicity were assessed using a Cell Counting Kit-8(CCK-8).The expression of PDG-FC in CAFs,NFs and corresponding CM was detected by Western blot and ELISA respectively.The influence of CAFs-CM on intracellular doxorubicin content in breast cancer cells was observed by fluorescence mi-croscopy.The impact of CAFs-CM on apoptosis-related proteins BAX and BCL2 was predicted and valifated u-sing the Starbase database and Western blot.The changes in ROS levels,mitochondrial membrane po-tential,and mitochondrial membrane proteins TOM20 and COX Ⅳ in breast cancer cells were measured using DCFH-DA fluorescence staining,JC-1 assay,and Western blot.Results CAFs-CM decreased the intra-cellular doxorubicin content and inhibited the sensitivi-ty of breast cancer cells to doxorubicin.Additionally,the expression of apoptosis protein BAX decreased while the anti-apoptotic protein BCL2 increased in breast cancer cells cultured with CAFs-CM.Further-more,CAFs-CM led to decreased ROS levels and in-creased mitochondrial membrane potential in breast cancer cells accompanied with elevated expression of mitochondrial membrane proteins TOM20 and COX Ⅳ.Further study found that PDGEF was highly expressed in CAFs and CAFs-CM,recombinant human PDGFC produced resistance of breast cancer cells to DOX simi-lar to CAFs-CM,and the specific inhibitors of PDGFRα significantly inhibited CAFs-CM.Further mechanistic studies revealed that PDGFC in CAFs-CM induced chemoresistance by activating PI3K-mTOR signaling pathway.Conclusion PDGFC secreted by CAFs promotes doxorubicin resistance in breast cancer cells through PI3K-mTOR signaling pathway,which provides a new perspective for the development of anti-cancer drugs targeting CAFs.
2.Clinical study on the treatment of postoperative recurrence of lumbar disc herniation with intervertebral fusion
Lian-Sheng ZHENG ; Xue-Min LI ; Yu-Long LI
China Journal of Orthopaedics and Traumatology 2024;37(3):235-241
Objective To explore clinical effect of different intervertebral fusion devices(cage)in treating postoperative recurrent lumbar disc herniation(LDH).Methods One hundred and forty-two LDH patients with recurrence after simple in-tervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed.All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage.There were 51 patients in a single anatom-ical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of(53.74±5.68)years old;body mass index(BMI)ranged from 18.62 to 28.13 kg·m-2 with an average of(22.08±2.15)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of(2.7±0.8)years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted.There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of(54.52±6.02)years old;BMI ranged from 18.25 to 28.44 kg· m-2 with an average of(21.74±1.83)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.7±0.9)years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were im-planted.There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of(54.49±6.45)years old;BMI ranged from 18.85 to 28.20 kg·m-2with an average of(21.63±1.59)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.6±1.0)years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted.Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared.The height of intervertebral space before and after operation,curvature of lordosis and the postoperative interverte-bral fusion were compared.Visual analogue scale(VAS)and Oswestry disability index(ODI)were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively.Results All patients among 3 groups were followed up at least 6 months,and no cases were fell out.There were no significant difference in operation time,in-traoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups(P>0.05).At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were[(11.08±1.78)mm,(10.95±1.62)mm],curvature of lordosis were[(12.05±1.86)°,(11.63±1.57)°],which were higher than those in a sin-gle dissection group(10.14±1.54)mm,(10.92±1.45)°,and the difference were statistically significant(P<0.05).The inter-body fusion rate between two-anatomical and a banana group(95.65%,95.56%)were higher than that in a single anatomical group(78.43%)at 6 months after operation(P<0.05).VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation(P<0.05).There was no significant difference in complications among 3 groups(P>0.05).Conclusion The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis cur-vature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.
3.Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring frac-tures
Xue-Lin WANG ; Zheng-Jie WU ; Yan-Hui ZENG ; Can-Hui LI ; Jian-Sheng ZHOU ; Shi HONG
China Journal of Orthopaedics and Traumatology 2024;37(6):605-608
Objective To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture.Methods The clinical data of 24 patients with posterior pelvic ring frac-ture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed,including 10 males and 14 females;aged from 21 to 73 years old with an average of(49.29±14.48)years old;according to Tile pelvic fractures,13 patients were type B and 11 were type C.The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results.At the final follow-up,fracture healing was evaluated according to Matta score,and functional recovery was evaluated by Majeed score.Results All patients were followed up for 3 to 13 months with an aver-age of(6.00±3.28)months.Totally 36 sacroiliac penetrating screws,18 S1 penetrating screws,18 S2 penetrating screws were inserted,a total of 29 were excellent and 7 good according to Gras standard.Screw adjustment times was 0.00(0.00,0.75)times.At the final follow-up,Matta score was excellent in 18 patients,5 good and 1 moderate,and the maximum displacement distance was 2.55(0.00,5.65)mm.Majeed score was 84.37±8.38,15 patients were excellent,7 good and 2 moderate.Con-clusion Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures,and promote postoperative functional recovery of patients.
4.Epidemic characteristics and food traceability of listeriosis in China,and the United States,and implications for China
Zhi-Fang ZHANG ; Xue-Jie LIU ; Sheng-Gen WU ; Qu-Wen LI ; Wei-Wei CHEN ; Yan-Qin DENG
Chinese Journal of Zoonoses 2024;40(7):636-643
This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4%(191/1 037),20.5%(185/902),and 22.4%(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8%to 89.6%.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.
5.Clinical Features and Prognosis of Acute T-cell Lymphoblastic Leukemia in Children——Multi-Center Data Analysis in Fujian
Chun-Ping WU ; Yong-Zhi ZHENG ; Jian LI ; Hong WEN ; Kai-Zhi WENG ; Shu-Quan ZHUANG ; Xing-Guo WU ; Xue-Ling HUA ; Hao ZHENG ; Zai-Sheng CHEN ; Shao-Hua LE
Journal of Experimental Hematology 2024;32(1):6-13
Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1%during induction therapy,and MRD ≥ 0.01%at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P<0.05).The expected 10-year EFS and OS of T-ALL were 59.7%and 66.0%,respectively,which were significantly lower than those of B-ALL(P<0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8%vs 34.6%,P=0.042),but higher EFS and OS(73.9%vs 57.2%,PEFS=0.090;86.5%vs 62.3%,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.
6.A quantitative research on China's basic medical insurance policy text for Traditional Chinese Medicine from the perspective of policy instrument
Sheng-Hui SHI ; Mao YOU ; Rui-Feng LI ; Xue-Qing TIAN ; Ping REN ; Lan-Tao WU ; Qiu-Ying ZHENG
Chinese Journal of Health Policy 2024;17(4):16-22
Objective:To summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.
7.Identification of genes related to prognosis of retroperi-toneal liposarcoma based on transcriptome sequencing
Chang-Chun YE ; Miao-Miao CHI ; Yan-Sheng HU ; Ge LI ; Xue-Jun SUN ; Qi SUN
Chinese Journal of Current Advances in General Surgery 2024;27(4):292-297
Objective:To analyze and compare the differences of expression profiles between RPL and normal adipose tissue by transcriptome sequencing(RNA-Seq),then identify the key genes related to prognosis and explore their potential mechanisms.Methods:Tumor tissues and normal adipose tissues of patients with RPL were collected for RNA-Seq,and then the differentially ex-pressed genes were analyzed by GO and KEGG enrichment analysis.Based on TCGA,the high-risk genes related to prognosis were screened and verified by Kaplan-Meier curve and receiver operat-ing characteristic(ROC)curve.Results:Compared with normal adipose tissue,279 differentially expressed genes were simultaneously up-regulated in RPL tissues,which were mainly enriched in immune response and PPAR signaling pathway.Combined with TCGA,7 stable prognostic high risk genes were identified and the overall survival rate of the high risk group was significantly lower than that of the low risk group(P<0.05).Conclusion:KCNQ5,RBPJ and some other genes may be re-lated to the poor prognosis of RPL patients.The analysis of the mechanism of these genes in RPL is expected to provide new evidence for the formulation of diagnosis and treatment strategies for RPL patients.
8.Effect and mechanism of CP-31398 on proliferation and metastasis of gallbladder carcinoma cells
Xue-Di SUN ; Sheng-Qin CAO ; Chong-Yang LI ; Jing-Hua LIU ; Qiang HE
Chinese Journal of Current Advances in General Surgery 2024;27(5):364-368
Objective:To investigate the effects of CP-31398 on proliferation and metastasis of gallbladder carcinoma cell lines expressing mutant P53GBC-SD and wild-type p53NOZ.Meth-ods:The effects of CP-31398 on the proliferation of wild-type and mutant p53 gallbladder carci-noma cells were detected by CCK8 cell proliferation assay and clonal formation assay.The effect of CP-31398 on cell cycle and apoptosis of gallbladder carcinoma was detected by flow cytometry.The effects of CP-31398 on the migration and invasion of gallbladder carcinoma cells were detected by scratch,cytoskeleton and Transwell assay.The effect of CP-31398 on the expression of p53 protein was detected by Western blot and the related mechanism was discussed.Results:In mutant P53GBC-SD cells,the proliferation of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treatment group was slower than that in control group(P<0.01).The cycle experiment showed that compared with the control group,the proportion of cells in S phase in-creased in CP-31398 treatment group,and the proportion of cells in G0 and G1 phase decreased,so the cells were blocked in S phase(P<0.001).Apoptosis experiment showed that the apoptosis rate of control group was lower than CP-31398 treatment group(P<0.05).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 pro-tein in CP-31398 treatment group was increased(P<0.05).In wild-type p53NOZ cells,the prolifera-tion of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treat-ment group was slower than that in control group.The number of cell clones in the control group was higher than that in the CP-31398 treatment group(P<0.001).The cycle test showed that the propor-tion of cells in G2 and M phases increased significantly,while the proportion of cells in G0 and G1 phases decreased,and the cells were blocked in G2 and M phases(P<0.001).Apoptosis experiment showed that the apoptosis rate of control group was(14.04±3.08)%,and that of CP-31398 treat-ment group was(34.55±3.30)%(P<0.01).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 protein in CP-31398 treatment group was increased(P<0.01).Conclusion:CP-31398 can effectively inhibit the prolif-eration and metastasis of gallbladder cancer cells,and is independent of p53 mutation,and CP-31398 has a good effect on NOZ gallbladder cancer cell lines expressing wild-type p53,which can be used as a new drug treatment for gallbladder cancer.
9.Awareness Investigation and Strategy Analysis on Pharmaceutical Services and Fees in Hospitals in Guizhou Province
Dongmei LI ; Qian YANG ; Shuimei SUN ; Ling HE ; Dirong WU ; Mingji LIU ; Pingping CHEN ; Libin WANG ; Zhongyuan WANG ; Hong ZHANG ; Zhu ZHU ; Xue BAI ; Changcheng SHENG ; Jiaxing ZHANG ; Lei LU ; Xue WANG ; Qi CHEN
Herald of Medicine 2024;43(9):1410-1415
Objective To investigate the current status and awareness of pharmaceutical services in hospitals in Guizhou province and to provide a reference for exploring and carrying out pharmaceutical service fees.Methods The questionnaire was designed by the"wjx.cn"website.Three kinds of questionnaires were designed for pharmacists,doctors,nurses,and patients as the research objects,with corresponding differences in some questions,and promoted on WeChat,Dingxiangyuan,and other network platforms.Results A total of 655 questionnaires were collected,and 639 valid questionnaires were recovered,with an effective recovery rate of 97.56%.324 pharmacists(50.70%),82 doctors and nurses(12.83%),233 patients(36.46%)were surveyed.The average approval score of these three groups of respondents on pharmaceutical service fees was 4.67,4.23,and 4.22,respectively(full score:5).Conclusions Overall,pharmacists'professional services have received support from medical staff and patients.However,patients'pharmaceutical service projects currently focus on dispensing services.The recognition of pharmacists'work and the public's awareness of pharmaceutical services can be improved by enhancing the professional ability of pharmacists,strengthening publicity and guidance,and exploring"Internet+pharmaceutical services",etc.,to promote the sustainable development of pharmaceutical services.
10.Application of high-throughput drug sensitivity testing in children with relapsed and refractory acute leukemia
Wen-Jing QI ; Xue-Ju XU ; Bai LI ; Tao WANG ; Guang-Yao SHENG ; Ping ZHU ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2024;26(10):1093-1100
Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

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