1.Repair of sciatic nerve defect in rats by adipose tissue decellularized matrix hydrogel
Yan LI ; Zhaoyang CHEN ; Youbai CHEN ; Jing REN ; Zehao NIU ; Wenwen PU ; Yan HAN
Chinese Journal of Microsurgery 2021;44(3):292-297
Objective:To observe the effect of adipose tissue decellularized matrix hydrogel (DAT-gel) on the repair of sciatic nerve defect in rats.Methods:From April, 2019 to April, 2020, aseptic granular adipose tissue was collected from healthy adult women who underwent thigh or abdominal liposuction in the Department of Plastic Surgery, the First Medical Centre of the PLA General Hospital. Decellularisation and enzymatic digestion of adipose tissue were performed to prepare DAT-gel. Scanning electron microscope (SEM) was used to observe the ultrastructure of the hydrogel, and rheology was employed to test the gel dynamics and viscoelasticity of the hydrogel. A rat model of sciatic nerve defect was established and randomly divided into 3 groups: simple chitin catheter group (Chitin group), DAT-gel plus chitin catheter group (DAT-gel group) and autologous nerve reverse connection group (Autograft group) with 10 rats in each group. At the 12th week after surgery, the general view, function and morphology of the regenerated nerve were observed to evaluate the repairing status of the injured nerve. One-way analysis of variance (one-way ANOVA) was used for data analysis. If the difference between the groups was statistically significant, the Turkey method was further used for pairwise comparison. P<0.05 was considered as statistically significant. Results:The results of SEM showed that the DAT-gel had a three-dimensional structure in porous fibre network. The results of rheological test results showed that the complex viscosity of the hydrogel at 4 ℃ and 37 ℃ were 148.91 mPa·s and 801.29 mPa·s, respectively. DAT-gel underwent a sol-gel phase transition when the temperature had been increased. The results showed that DAT-gel had a good temperature-sensitive effect, and its critical point of sol-gel phase transition was similar to the internal temperature of rat. The results of animal experiments showed that the morphology and function of the regenerated nerve in the DAT-gel group were superior to Chitin group at 12 weeks after surgery, according to macroscopic view of the regenerated nerve, electrophysiology of the nerve, the morphology of the new axon and the target muscle, etc.. There was statistically significant between groups ( P<0.05). Conclusion:DAT-gel can significantly promote a repair of sciatic nerve defects in rats.
2.Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes
Xin LI ; Zehao LI ; Lin LI ; Tong LIU ; Cheng QIAN ; Yanlv REN ; Zhigao LI ; Kejin CHEN ; Dongchen JI ; Ming ZHANG ; Jinsong WANG
Cancer Research and Treatment 2024;56(1):134-142
Purpose:
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods:
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results:
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.
3.Growth Inhibitory and Pro-Apoptotic Effects of Hirsuteine in Chronic Myeloid Leukemia Cells through Targeting Sphingosine Kinase 1
Shan GAO ; Tingting GUO ; Shuyu LUO ; Yan ZHANG ; Zehao REN ; Xiaona LANG ; Gaoyong HU ; Duo ZUO ; Wenqing JIA ; Dexin KONG ; Haiyang YU ; Yuling QIU
Biomolecules & Therapeutics 2022;30(6):553-561
Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.
4.SingHealth Radiology Archives pictorial essay Part 1: cardiovascular, respiratory and neurological cases.
Mark Bangwei TAN ; Kim Ping TAN ; Joey Chan Yiing BEH ; Eugenie Yi Kar CHAN ; Kenneth Fu Wen CHIN ; Zong Yi CHIN ; Wei Ming CHUA ; Aaron Wei-Loong CHONG ; Gary Tianyu GU ; Wenlu HOU ; Anna Chooi Yan LAI ; Rebekah Zhuyi LEE ; Perry Jia Ren LIEW ; May Yi Shan LIM ; Joshua Li Liang LIM ; Zehao TAN ; Eelin TAN ; Grace Siew Lim TAN ; Timothy Shao Ern TAN ; Eu Jin TAN ; Alexander Sheng Ming TAN ; Yet Yen YAN ; Winston Eng Hoe LIM
Singapore medical journal 2020;61(12):633-640
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in 2020 in commemoration of the 20th anniversary of the formation of SingHealth, the 55th National Day of Singapore, and the 125th anniversary of the International Day of Radiology. This pictorial essay comprises cardiovascular, respiratory and neurological cases from the archives.
5.SingHealth Radiology Archives pictorial essay Part 2: gastroenterology, musculoskeletal, and obstetrics and gynaecology cases.
Mark Bangwei TAN ; Kim Ping TAN ; Joey Chan Yiing BEH ; Eugenie Yi Kar CHAN ; Kenneth Fu Wen CHIN ; Zong Yi CHIN ; Wei Ming CHUA ; Aaron Wei-Loong CHONG ; Gary Tianyu GU ; Wenlu HOU ; Anna Chooi Yan LAI ; Rebekah Zhuyi LEE ; Perry Jia Ren LIEW ; May Yi Shan LIM ; Joshua Li Liang LIM ; Zehao TAN ; Eelin TAN ; Grace Siew Lim TAN ; Timothy Shao Ern TAN ; Eu Jin TAN ; Alexander Sheng Ming TAN ; Yet Yen YAN ; Winston Eng Hoe LIM
Singapore medical journal 2021;62(1):8-15
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.