1.Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples
Zhaoxia LI ; Honglei DUAN ; Wei LIU ; Ruifang ZHU ; Jie LI
Chinese Journal of Medical Genetics 2024;41(1):1-7
Objective:To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies.Methods:A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups.Results:Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 ( χ2= 85.216, P<0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2= 5.530, P<0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2= 49.440, P<0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group ( P<0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%和60% vs. 23.53%, P<0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. Conclusion:The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45, X was lower than 47, XXX, 47, XYY or 47, XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.
2.Changes in C3,HMGB1 and GPX4 expression in rats after cerebral ischemia-reperfusion injury
Hanting ZHU ; Ruifang XIONG ; Chengyi LI ; Xihai ZHAO ; Xiaoping TANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):699-703
Objective To investigate the changes in the expression of complement C3,high mobility group protein B1(HMGB1),and glutathione peroxidase 4(GPX4)in brain tissue at different time points after cerebral ischemia-reperfusion injury in rats.Methods A total 72 SPF male SD rats were randomly divided into a sham operation group(36 rats)and a model group(36 rats).A rat model of middle cerebral artery occlusion was established using thread occlusion,and then the rats from the model group were further assigned into 4 subgroups with reperfusion time for 3,6 and 24 h and 3 d,respectively,with 9 rats in each subgroup.Zea Longa scoring was used to assess neu-rological function.R2StarMap imaging,diffusion-weighted imaging(DWI),T1 weighted imaging,and T2 weighted imaging were performed on all the rats.The volume of abnormal DWI signals were detected and the volume of cerebral infarction was measured.The original R2StarMap images were post-processed to generate R2*pseudo color images,and then the R2*values of the areas with blood supply from bilateral middle cerebral artery were measured to detect iron deposition in the brain.The protein expression of C3,HMGB1,and GPX4 was detected by Western blotting.Results The sham operation group showed no neurological damage,while the model group had a significant increase in neurological function scores at 3,6 and 24 h and 3 d after modeling when compared to the sham surgery group(P<0.05).While the size of right cerebral infarct was in-creased significantly at 3,6 and 24 h and 3 d in the rats of the model group(P<0.05).The R2*value of the area with blood supply from the right middle cerebral artery in the model group was significantly higher than that in the left side at 3,6 and 24 h and 3 d(P<0.05,P<0.01),and it was also obviously higher than that in the right side of the sham operation group at these time points(P<0.05,P<0.01).The R2*ratio of the right and left blood supply areas in the model group at 3,6 and 24 h and 3 d was also statistically higher than that in the sham operation group at corresponding time points(1.82±0.82 vs 1.12±0.31,P<0.05;1.31±0.26 vs 1.04±0.14,P<0.05;1.94±0.74 vs 1.06±0.10,P<0.01;1.99±0.39 vs 1.02±0.11,P<0.01).Compared with the sham operation group,the expression levels of C3 and HMGB1 was significantly increased in the model group at 3,6 and 24 h and 3 d,while that of GPX4 was notably reduced(P<0.01).Conclu-sion Cerebral ischemia-reperfusion injury impairs the neurological function of rats and signifi-cantly affects the cerebral expression of complement C3,HMGB1,and GPX4.
3.Progress of selenium and its compounds in leukemia
Shuwen ZHANG ; Ruifang ZHU ; Hongwei WANG
Journal of Leukemia & Lymphoma 2024;33(5):313-316
Selenium is one of the essential trace elements in human body, which plays an important role in regulating human growth and physiological function. Selenium deficiency can lead to a variety of diseases, such as Kashin-Beck disease, Keshan disease, thyroid disease and increase the incidence of cancer. It was found that serum selenium level decreased significantly in patients with leukemia, and it was associated with poor prognosis. Selenium can play a dual role in the treatment of leukemia: on the one hand, it can play a synergistic anti-leukemia effect with chemotherapy drugs, and on the other hand, it can reduce the side effects of chemotherapy drugs. In recent years, nano-selenium, as a new type of elemental selenium, has higher bioavailability, stronger bioactivity and lower toxicity than organic and inorganic selenium. This article reviews the progress of selenium and its compounds in leukemia.
4.Clinical and magnetic resonance imaging features of Trousseau's syndrome with acute cerebral infarction
Ruifang XIONG ; Chengyi LI ; Hanting ZHU ; Xiaoping TANG
Academic Journal of Naval Medical University 2024;45(11):1444-1449
Objective To investigate the clinical and magnetic resonance imaging(MRI)features of Trousseau's syndrome(TS)with acute cerebral infarction,so as to improve the accuracy of diagnosis of this disease.Methods Fifty-three cases of TS with clinically confirmed acute multiple brain infarction(AMBI)and 52 cases of TS without AMBI were enrolled,and the head MRI,primary tumor imaging and clinical data of the patients were retrospectively analyzed.The clinical and MRI features and thrombus types of the 2 groups were compared.Results There were significant differences in the types of thrombus between the 2 groups(P=0.001),while there were no significant differences in gender,age,whether they had hypertension,diabetes mellitus,hyperlipidemia,basic cardiovascular diseases or not,preventive medication use,abnormal coagulation function,or D-dimer level(all P>0.05).The primary tumor type of 105 TS patients was mainly adenocarcinoma.MRI of the head of 53 TS with AMBI patients showed that the distribution area of acute and subacute infarct foci was bilateral anterior circulation in 16 cases,bilateral anterior circulation+bilateral posterior circulation in 17 cases,bilateral anterior circulation+unilateral posterior circulation in 4 cases,and unilateral anterior circulation in 16 cases.Enhancement scans were performed in 23 cases,of which 11 cases showed some infarct foci appeared enhanced and 12 cases did not show significant enhancement.Twenty-eight cases did not show meaningful stenosis of the cerebral arteries,4 cases showed stenosis occlusion of the cerebral arteries,and all lesions did not conform to cerebrovascular distribution.Twenty-four cases of arterial thrombosis(10 cases of carotid artery thrombosis,3 cases of lower-extremity arterial thrombosis,5 cases of cerebral arterial ring thrombosis,1 cases of pulmonary artery thrombosis,1 case of renal artery thrombosis,and 4 cases of subclavian artery thrombosis)and 3 cases of venous thrombosis(deep vein thrombosis of the lower extremities)were found among the patients with visualized thrombosis.The D-dimer level was increased in different degrees.Conclusion Multiple speckled and patchy acute anterior and posterior cerebral infarcts involving bilateral cerebral and cerebellar cortex,subcortical areas and hemi-oval centers with lesions not conforming to cerebrovascular distribution are the characteristic manifestations of MRI of the head in the combination of malignant tumors with TS.Adenocarcinoma is the main malignant tumor,and the combination of D-dimer index can improve the accuracy of diagnosis.
5.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
6.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
7.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
8. Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway
Ruifang ZHU ; Dongkai GUO ; Hui ZHI ; Yiguo JIANG ; Yueling ZHANG ; Xiaoping QIAN ; Shiliang JI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(11):1219-1226
AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.
9.Traditional Chinese Medicine Treats Ulcerative Colitis by Intervening in Mitochondrial Quality Control: A Review
Lingfeng YANG ; Ying ZHU ; Bin YU ; Ruifang LIN ; Yin XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):245-252
Ulcerative colitis (UC), a chronic inflammatory bowel disease with the accumulation of colorectal mucosa and submucosa, has a risk of developing into cancer. In recent years, the incidence of UC has been on the rise worldwide. However, its pathogenesis has not been fully elucidated by modern medicine, and even the remission rate of the latest drugs is lower than 50%, which seriously affects the patients' work and quality of life. Mitochondria, as the "power station" of eukaryotic cells, are involved in a variety of physiological processes such as the production of reactive oxygen species and the production of adenosine triphosphate by oxidative phosphorylation, and their dysfunction can lead to a series of diseases. Mitochondrial quality control (MQC) is an important way to maintain the stability of mitochondrial form, quantity, and quality. Studies have shown that MQC disorders characterized by low mitochondrial biogenesis, excessive mitochondrial oxidative stress, mitochondrial autophagy defects, mitochondrial dynamics disorders, and calcium regulation abnormalities are closely related to the occurrence and development of UC. Although progress has been achieved in the treatment of UC by traditional Chinese medicine (TCM) which can regulated MQC in a multi-pathway and multi-target manner in recent years, a review on the treatment of UC by TCM via the intervention in MQC remains to be carried out. Therefore, this paper summarized the TCM treatment of UC by regulating MQC, aiming to provide new ideas for the clinical treatment of UC by TCM.
10.Application of magnetic resonance imaging in nerve fiber tract analysis in a mouse model of stroke
Yifu MA ; Jianguo XING ; Yanxi CHEN ; Tingting LIU ; Xin TIAN ; Wenrong ZHENG ; Zixin ZHU ; Ruifang ZHENG ; Wen WANG ; Fangling SUN
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(4):296-301
Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.