1.Research progress of phosphatidylinositol 3-kinase inhibitors in relapsed refractory peripheral T-cell lymphoma
Zhijuan PAN ; Yiqun ZHANG ; Zhiping GUO
Clinical Medicine of China 2024;40(6):422-426
Peripheral T-cell lymphoma (PTCL) is a relatively common subtype of non-Hodgkin lymphomain in China. PTCL is clinically highly aggressive, and it progresses rapidly. The current treatment methods are ineffective and the overall prognosis is poor, especially in patients with relapsed and/or refractory. In recent years, the treatment of phosphatidylinositol 3-kinase (PI3K) inhibitors has developed rapidly, which can effectively improve the prognosis of patients with relapsed and/or refractory PTCL. This article reviews the therapeutic mechanism, effectiveness and safety of PI3K inhibitors in the treatment of relapsed and/or refractory PTCL.
2.Models based on contrast enhanced CT radiomics and imaging genomics for predicting prognosis of ovarian serous cystadenocarcinoma
Diliang HE ; Jianxin ZHAO ; Nini PAN ; Liuyan SHI ; Lianqiu XIONG ; Lili MA ; Zhiping ZHAO ; Lianping ZHAO ; Gang HUANG
Chinese Journal of Medical Imaging Technology 2024;40(5):745-751
Objective To explore the value of model established with radiomics features based on contrast enhanced arterial phase CT and model with radiogenomics for predicting prognosis of ovarian serous cystadenocarcinoma(OSC).Methods Enhanced arterial phase CT images of 110 OSC patients were retrospectively collected from 2 centers and The Cancer Imaging Archive(TCIA)database.The radiomics features were extracted,among those related to prognosis were selected to establish a radiomics Cox regression model.Genes data of 399 OSC patients were obtained from The Cancer Genome Atlas(TCGA)database,and genes related to the radiomics features included in the above radiomics model were identified with high Pearson correlation coefficient,and then enrichment gene analyses were performed.For 57 OSC cases with complete enhanced CT and gene data,the hub genes which had the highest connectivity with radiomics prognosis predicting model were detected using Cox regression and protein-protein interaction(PPI).Furthermore,a radiogenomics prognosis predicting model was established with the hub genes.The efficiencies of these 2 models for predicting prognosis of OSC patients were analyzed.Results Finally,the radiomics model included 5 OSC prognosis-related radiomics features,with C-index of 0.782 and 0.735 in corresponding training and test set,respectively.Meanwhile,the radiogenomics model included 30 prognostic hub genes,with C-index of 0.673 and 0.659 in corresponding training and test set,respectively.The survival rates of patients with better predicted prognosis according to radiomics model and radiogenomics model were both higher compared with the others(both P<0.05).Totally 1 135 mRNA genes were found being associated with radiomics model,including biological behaviors such as cell adhesion,and signaling pathways such as PI3K-Akt,extracellular matrix receptor interaction pathway and type 1 diabetes pathway.Conclusion The radiomics model was effective for predicting prognosis of OSC patients.Analysis of mRNA bioinformatics in OSC patients might provide biological interpretations for the radiomics model.
3.Improvement effects of tilianin on atherosclerosis model mice and its mechanism study
Wenjiang CAO ; Pan XIN ; Yunli ZHAO ; Yong YUAN ; Xinhong GUO ; Xiaoli MA ; Chuansheng HUANG ; Zhiping WEN ; Xinchun WANG
China Pharmacy 2022;33(1):19-25
OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis (AS)model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE-/- mice were randomly divided into model group ,tilianin low-dose ,medium-dose and high-dose groups [ 2.1,3.5,7.0 mg/(kg·d)] and simvastatin group [positive control drug ,3.5 mg/(kg·d)],with 8 mice in each group. Normal group was given normal diet ,and other groups were given high-lipid diet to induce AS model. At the same time ,normal group and model group were given normal saline intragastrically , administration groups were given relevant drug intragastrically ,once a day ,for 12 consecutive weeks. The levels of TC ,TG, LDL-C,HDL-C,Ox-LDL,IL-1β,IL-6,MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1,VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2,MMP-9,TGF-β1,Smad2 and Smad 3 as well as protein expressions of TGF-β1,Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ,the plasma levels of TC ,TG,LDL-C,Ox-LDL,IL-1β, IL-6,MCP-1 and TNF-α in model group were increased significantly(P<0.01),while HDL-C level was significantly reduced (P<0.01). Lipid plaques were formed in the aorta ,and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2,MMP-9,TGF-β1,Smad2 and Smad 3 as well as positive rate of ICAM- 1,VCAM-1,PCNA and protein expression TGF-β1,Smad2/3,and p-Smad 2/3 in the aorta were significantly increased (P<0.01). Compared with model group , most of above indexes of medication groups were improved significantly (P<0.05 or P<0.01). CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ,reduce , inflammation and regulate lipid metabolism to inhibit the No.81960766) formation of AS.
4.Splenic vascular flow control in the use of laparoscopic spleen-preserving distal pancreatectomy (Kimura)
Xu SUN ; Guoliang CAO ; Zhiping PAN ; Mingjie ZHANG ; Feng CEN ; Wenbin YUAN ; Zhenhua SHEN ; Shusen ZHENG ; Qiang YAN
Chinese Journal of General Surgery 2022;37(10):755-760
Objective:To investigate the techniques used in blood flow control of Kimura laparoscopic spleen-preserving pancreatectomy (LSPDP).Methods:Forty·five patients with benign or low-grade malignant pancreatic diseases undergoing LSPDP at Huzhou Central Hospital from May 2014 to Oct 2021 were analyzed retrospectively. Patients were divided into splenic vascular flow control group ( n=22) and routine management group ( n=23). Results:There was no significant difference in gender, age, BMI, accompanying symptoms, hypertension, diabetes, lesion size and pathological diagnosis between the two groups (all P>0.05). A higher overall spleen preservation rate (90.9% vs. 52.2%, χ2=8.213, P=0.004), lower incidence of morbidity with Clavien grade ≥ Ⅱ (22.7% vs. 73.9%, χ2=9.911, P=0.002) and shorter postoperative hospital stay [(9.6±4.5) d vs. (14.3±6.6) d, t=2.447, P=0.008] were achieved in the vascular flow control group compared with those in the routine group. Conclusion:Splenic vascular flow control techniques improve the success rate of spleen preservation in laparoscopic distal pancreatectomy, reduce the postoperative complications and shorten the postoperative hospital stay.
5.Prognostic factors of salvage radiotherapy after radical prostatectomy
Yang LIU ; Feng WEN ; Yali SHEN ; Qiwen PAN ; Jinxia HE ; Lixin MAI ; Hao ZENG ; Jianming GAO ; Xiang LI ; Zhiping LI ; Yonghong LI ; Xin WANG ; Liru HE ; Qiang WEI ; Fangjian ZHOU
Chinese Journal of Urology 2021;42(9):650-655
Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.
6. Post-marketing observation on safety of inactivated enterovirus A71 vaccine (human diploid cell)
Lingzhi SHEN ; Jian FU ; Xuejiao PAN ; Hui LIANG ; Shuyun XIE ; Zhiping CHEN
Chinese Journal of Preventive Medicine 2019;53(3):258-261
Objective:
To evaluate the post-marketing safety of inactivated Enterovirus type 71 (EV-A71) vaccine (human diploid cell) .
Methods:
A total of 20 191 healthy children aged 6 to 59 months were invited to receive 2 doses of EV-A71 vaccine in Zhejiang Province from September 2016 to December 2017. Child caregivers were followed up on the 4th or 5th day after each EV-A71 vaccination, and the incidence of local, systemic, and other adverse events within 3 days after vaccination was recorded to assess vaccine safety. Describe the differences in adverse events among children with different characteristics.
Results:
A total of 32 230 doses were observed in this study, of which 20 191 and 12 039 were vaccinated for the first and the second dose, respectively; and the incidence of adverse events within 3 days was 2.045% (413 doses) and 1.611% (194 doses), respectively. After the first and the second dose, the number of systemic adverse events was the highest, 371 and 175 cases, respectively, with an incidence of 1.837% and 1.454%, respectively; the number of local adverse events was the lowest, 14 and 2 doses, respectively, with an incidence of 0.069% and 0.017%. Local adverse events occurred after vaccination were generally mild, and only 2 patients had level of 3; among the systemic adverse events, 39 patients had a fever level of 3 or higher, accounting for 8.2% of the total fever. Most of the symptoms in the local adverse events did not require treatment, only 3 cases of vaccination site rash and 2 cases of pruritus were self-purchased drugs or outpatient treatment; except for 5 cases of fever, the other symptoms were not hospitalized in the case of systemic adverse events.
Conclusion
The incidence of adverse events within 3 days after vaccination with EV-A71 vaccine was low in children, mainly systemic adverse events, and the prognosis was good.
7. Post-marketing safety analysis of inactivated enterovirus A71 vaccines
Yan LUO ; Jian FU ; Xuejiao PAN ; Lingzhi SHEN ; Zhenzhen LIANG ; Yingping CHEN ; Xiaosong HU ; Huakun LYU ; Zhiping CHEN
Chinese Journal of Preventive Medicine 2019;53(3):262-266
Objectives:
To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community.
Methods:
We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher′s exact test were used to compare the difference of AEs incidence in various characteristics among two groups.
Results:
A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively.
Conclusion
Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.
8. Current status of treatment for osteosarcoma of head and neck
Zhiping LIU ; Daxin ZHANG ; Jie PAN ; Yisi ZHANG
Chinese Journal of Radiation Oncology 2019;28(10):780-783
Head and neck osteosarcoma is a rare tumor. Its clinical features and recurrence pattern are different from those of osteosarcoma in other parts. Osteosarcoma of the head and neck occurs late with a high local recurrence rate and a low distant metastasis rate. Local recurrence is the main cause of death. Surgery is the main treatment. Postoperative radiotherapy is recommended for patients with positive surgical margin, proximal incisional margin and uncertain surgical margin. The role of chemotherapy remains controversial. Effective molecular targeted therapeutics need to be further explored for recurrent, metastatic and unresectable osteosarcoma, .
9.Effect of polylactic-co-glycolic acid/graphene oxide nanofibers combined with brain derived neurotrophic factor on spinal cord injury repair
Su PAN ; Zhiping QI ; Shuang ZHENG ; Yue MA ; Chuan FU ; Weijian KONG ; Shuangqi YU ; Xiaoyu YANG ; Zhuo ZHANG
Chinese Journal of Trauma 2019;35(7):597-604
Objective To investigate the effect of polylactic-co-glycolic acid (PLGA)/graphene oxide (GO) nanofibers combined with brain derived neurotrophic factor (BDNF) on neural stem cells (NSCs) proliferation and differentiation as well as on the spinal cord injury repair.Methods PLGA/GO nanofibers were manufactured and absorbed with BDNF,and the microstructure of PLGA/GO nanofibers was observed by scanning electron microscope.The loading efficiency and release curve of BDNF on PLGA/GO nanofibers were measured by ELISA.NSCs were implanted on the surface of PLGA/GO and PLGA/GO/BDNF nanofibers.The absorbance values of each group were measured by MTT method,and the expression of Tuj-1 was observed by immunofluorescence and PCR.A total of 30 female SD rats were divided into control group (n =10),PLGA/GO group (n =10) and PLGA/GO/BDNF group (n =10) according to random number table.T9 spinal cord tissue was cut by Venus scissors to establish spinal cord hemisection injury model of rats.PLGA/GO and PLGA/GO/BDNF nanofibers were implanted onto the surface of injury site.BBB score was used to assess the motion functional recovery of the rats at 1,7,14 and 28 days after operation.Immunofluorescence staining of neuron specific nucleoprotein (NeuN)and glial fibrillary acidic protein (GFAP) were performed to observe the expressions of neurons and astrocytes at the injured site respectively one month after injury.Results The PLGA/GO nanofibers showed an irregular smooth fiber-like structure,and the average fiber diameter was (987.5 ± 176.3)nm.NSCs could differentiate into neurons on the nanofibers.The result of ELISA showed loading rate of BDNF on PLGA/GO nanofibers was about 47.5%.The release curve showed that BDNF was first released about 30% on the first day and then about 60% on the 21st day.The results of MTT and PCR showed that optical density value and Tuj-1 gene expression in the PLGA/GO/BDNF group were significantly higher than those in the PLGA/GO group (P < 0.05).The animal experiment results showed that the BBB score of PLGA/GO/BDNF group was (15.3 ±0.7) points at 28 days after injury,which was significantly higher than that of the injury control group [(11.8 ± 0.8) points] and that of PLGA/GO group [(12.7 ±0.8) points] (P < 0.05).Immunofluorescence results showed that the expression of NeuN in PLGA/GO/BDNF group was 13.7 ± 2.2,significantly higher than that in injury control group (4.3 ± 2.9) (P <0.05),and the expression of GFAP in PLGA/GO group was (25.6 ± 4.3) % significantly lower than that in injury control group [(38.5 ± 6.2) %] and PLGA/GO group [(36.7 ± 7.3) %] (P < 0.05).Conclusion PLGMGO nanofibers combined with BDNF can effectively promote the proliferation and neuron differentiation of NSCs in vitro and repair spinal cord injury in vivo through orthotopic transplantation at the injury site.
10.Epidemiology and perinatal risk factors of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture
Suying WU ; Fen PENG ; Ting DING ; Hongyan TAN ; Qian WU ; Hongyan LIU ; Xinqiao YU ; Congrong TAN ; Zhiping PAN ; Zuofen YUAN ; Zhenju HUANG ; Shiwen XIA
Chinese Journal of Perinatal Medicine 2019;22(8):575-580
Objective To investigate the incidence and risk factors of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture. Methods Live born infants, including those diagnosed with neonatal asphyxia, were recruited from 16 different hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture from January to December of 2016. The 16 hospitals included four grade A tertiary hospitals (three general hospitals and one traditional Chinese medicine hospital) and 12 grade A secondary hospitals (eight general hospitals, one maternal and child health hospital and three traditional Chinese medicine hospitals). A retrospective investigation was conducted using questionnaire to analyze the basic information, perinatal risk factors and prognosis of those infants. Chi-square test was used for statistical analysis. Results Among 22 294 recruited live born infants, 733 (3.29%) were diagnosed with neonatal asphyxia on discharge, including 627 (85.54%) mild cases and 106 (14.46%) severe cases. And neonatal asphyxia resulted in deaths of 27 cases (3.68%). The risk factors for neonatal asphyxia included multiple pregnancy, pregnancy conceived with assisted reproductive technology, premature infant, low birth weight infant, fetal malposition, congenital malformation, male infant, born during transfer, mother of Tujia nationality, low educational level (primary school or lower), living in rural area, the number of antenatal visits ≤3, history of early threatened abortion, anemia in pregnancy, hypertensive disorders of pregnancy, chorioamnionitis, abnormal pregnancy history and abnormality of umbilical cord, amniotic fluid or placenta. Conclusions The incidence of neonatal asphyxia in Enshi area is obviously higher than the national average. The main risk factors for neonatal asphyxia in this area are related to maternal background and the living condition of the mother during pregnancy, delivery as well as the newborn at birth.

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