2.Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
ZOU HAI ; ZHANG MENGYU ; YANG XUE ; SHOU HUAFENG ; CHEN ZHENGLIN ; ZHU QUANFENG ; LUO TING ; MOU XIAOZHOU ; CHEN XIAOYI
Journal of Zhejiang University. Science. B 2024;25(9):756-772
Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
3.Comparative study of indigo carmine staining and white light endoscopy in detection rate of right hemicolonic polyp
Ping LIANG ; Yi YANG ; Chuan LIANG ; Weizhen ZHOU ; Ye YANG ; Hai MOU ; Sijing HAN
Chongqing Medicine 2024;53(8):1209-1213
Objective To compare the detection rate of right hemicolonic polyp between indigo carmine staining and white light endoscopy.Methods A total of 1052 patients with colonoscopic examination in Qing-baijiang District People's Hospital of Chengdu City from July 2022 to March 2023 were selected as the study subjects and divided into the indigo carmine staining group and white light endoscopy group,526 cases in each group.The right hemicolon was observed by indigo carmine staining and white light pattern respectively.The difference in the detection rate of right hemicolonic polyp was compared between the two detection methods. Results Compared with the white light endoscopic examination group,the detection rate of the right hemico-lonic polyp (41.6%),detection rate of the right hemicolon adenoma (20.9%),detection rate of wide basal ser-rated lesion (2.1%),detection rate of proliferative polyps (20.3%),detection rate of Paris type 0-Ⅱ (38.0%),detection rate of NICE 1 type (pale lesion,22.2%),detection rate of polyps with a diameter<5 mm (30.5%) and the consistency rate of pathological biopsy (86.4%),specificity (84.7%) and sensitivity (88.2%) in the indigo carmine staining group were higher,and the differences were statistically significant (P<0.05).There was no statistical difference in the duration of mirror withdrawal between the white light endoscopy group and the indigo carmine staining group (t=1.407,P=0.160).Conclusion The endoscopic examination with indigo carmine staining has a higher detection rate for right hemicolonic polyp,and is easier to detect micropolyps and flat polyps with pale color.
4.Curcumin protects against liver cancer in a mouse model by down-regu-lating HO-1/NQO1
Haijun MOU ; Xingxing CHEN ; An'an LIU ; Li ZHANG ; Jiaxin ZHU ; Hai JIN
Chinese Journal of Pathophysiology 2024;40(3):438-443
AIM:To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-ni-trosodiethylamine(DEN)combined with carbon tetrachloride(CCl4),and to explore its mechanism.METHODS:Forty young male C57BL/6J mice were intraperitoneally injected with DEN(25 mg/kg)14 d after birth and randomly divided in-to the following 4 groups at the 4th week(10 in each group):model control group and curcumin(100,200 and 400 mg/kg)groups.Ten male mice of the same age were used as normal control group.The mice in model group and curcumin groups were gavaged with 10%CCl4(5 mL/kg)twice a week from the 8th week on.At the same time,the mice in curcumin groups were gavaged with curcumin,and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks.After administration,the mice were sacrificed,the liver surface was observed,and the number of tumor nodules was compared.The activity of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum was detected by an automatic biochemical instrument.The pathological changes of liver tissues were ob-served by HE staining.The mRNA expression levels of heme oxygenase-1(HO-1)and NAD(P)H-quinone oxidoreductase 1(NQO1)were detected by RT-qPCR,and the protein expression levels of HO-1,NQO1 and Ki67 were detected by Western blot and immunohistochemistry.RESULTS:Compared with normal control group,the body weight of the mice in model group was decreased significantly(P<0.01),the liver index was increased significantly(P<0.01),and the se-rum levels of ALT and AST were increased obviously(P<0.01).There was no significant difference in the mRNA expres-sion levels of HO-1 and NQO1(P>0.05),the protein levels of HO-1 and NQO1 were increased distinctly(P<0.05),and the positive expression rate of Ki67 was increased significantly(P<0.05).After curcumin treatment,the body weight of the mice was significantly increased(P<0.01),the liver index was not changed(P>0.05),and the number of tumor nodules in the liver was decreased significantly(P<0.05 or P<0.01).The serum level of AST was decreased significantly(P<0.01),the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly(P<0.05),and the posi-tive expression rate of Ki67 was decreased significantly(P<0.05).CONCLUSION:Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4,and its mechanism may be related to the inhibition of HO-1 and NQO1 expression.
5.Association of Family Cohesion and Adaptability with Eating Behaviors of Preschoolers
Shi-ya HUANG ; Hai-shan ZHOU ; Chao-yu ZHANG ; Jin-song MOU ; Hong-di LIANG ; Cai-xia ZHANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):439-445
ObjectiveTo examine the current status of preschoolers' eating behaviors and investigate its correlation with family cohesion and adaptability. MethodsA cross-sectional study was conducted involving 21,954 preschoolers and their families from Pingshan District, Shenzhen, between September 2021 and December 2021. A general demographic questionnaire, the Chinese version of Family Adaptability and Cohesion Evaluation Scale Ⅱ (FACESⅡ-CV) and Chinese Preschoolers’ Eating Behavior Questionnaire (CPEBQ) were used to collect the relevant information. Multiple linear regression was used to analyze the association of family cohesion and adaptability with eating behaviors of preschoolers. ResultsTypes of family cohesion and adaptability were significantly correlated with all the 7 dimensions of preschoolers' eating behaviors, including food fussiness (R2=0.252, F=114.457, P<0.001), food responsiveness (R2 = 0.111, F =24.973, P<0.001), eating habit (R2= 0.304, F =139.658, P<0.001), satiety responsiveness (R2 = 0.259, F =105.332, P<0.001), external eating (R2 = 0.182, F =50.150, P<0.001), emotional eating (R2 = 0.234, F =91.084, P<0.001) and initiative eating (R2 = 0.349, F =168.608, P<0.001). After adjusting for confounding factors, our study showed that types of family cohesion and adaptability were independent predictors of preschoolers' eating behaviors (P<0.05). ConclusionsTypes of family cohesion and adaptability have a significant predictive effect on the 7 dimensions of preschoolers' eating behaviors. Higher scores of family cohesion and adaptability imply stronger initiative eating ability and less poor dietary behaviors in preschoolers.
6.Classification system of radical surgery for rectal cancer based on membrane anatomy.
A Jiana LI ; Jia Qi WANG ; Hai Long LIU ; Mou Bin LIN
Chinese Journal of Gastrointestinal Surgery 2023;26(7):625-632
Because the classification system of radical surgery for rectal cancer has not been established, it is impossible to select the appropriate surgical method according to the clinical stage of the tumor. In this paper, we explained the theory of " four fasciae and three spaces " of pelvic membrane anatomy and then combined this theory with the membrane anatomical basis of Querleu-Morrow classification for radical cervical cancer resection. Based on this theory and the membrane anatomy of Querleu-Morrow classification of radical cervical cancer resection, we proposed a new classification system of radical rectal cancer surgery based on membrane anatomy according to the lateral lymph node dissection range of the rectum. This system classifies the surgery into four types (ABCD) and defines corresponding subtypes based on whether the autonomic nerve was preserved. Among them, type A surgery is total mesorectal excision (TME) with urogenital fascia preservation, type B surgery is classical TME, type C surgery is extended TME, and type D surgery is lateral extended resection. This classification system unifies the anatomical terminology of the pelvic membrane, validates the feasibility of using the " four fasciae and three fascial spaces " theory to classify rectal cancer surgery, and lays the theoretical foundation for the future development of a unified and standardized classification of radical pelvic tumor surgery.
Female
;
Humans
;
Uterine Cervical Neoplasms
;
Rectal Neoplasms/pathology*
;
Rectum/anatomy & histology*
;
Pelvis/innervation*
;
Proctectomy
7.Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model.
Yingyu MA ; Zhiwei LIN ; Xiaoyi CHEN ; Xin ZHAO ; Yi SUN ; Ji WANG ; Xiaozhou MOU ; Hai ZOU ; Jinyang CHEN
Chinese Medical Journal 2023;136(9):1089-1097
BACKGROUND:
Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.
METHODS:
First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.
RESULTS:
Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.
CONCLUSIONS
hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.
Animals
;
Humans
;
Rabbits
;
Hair Follicle
;
Achilles Tendon/pathology*
;
Tendinopathy/pathology*
;
Proteomics
;
Collagen Type I
;
Mesenchymal Stem Cells
8."Two spaces" lateral lymph node dissection based on fascia anatomy for low rectal cancer.
Yi CHANG ; Hai Long LIU ; Mou Bin LIN
Chinese Journal of Gastrointestinal Surgery 2022;25(4):315-320
As a treatment of rectal cancer, lateral lymph node dissection (LLND) is still a controversial issue. The argument against LLND is that the procedure is complicated, and consequently results in a high incidence of postoperative urogenital dysfunction. The surgical modality from fascia to space is adopted by lateral lymph node dissection in "two spaces". This operation has significant advantages of clear location of nerves and blood vessels and simplified surgical procedures, so the surgical procedure can be repeated and modulated. The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia constitute the dissection plane for lateral lymph node dissection.Two spaces refer to Latzko's pararectal space and paravesical space. During the establishment of fascia plane, the dissection of external iliac lymph node (No.293), commoniliac lymph node (No.273) and abdominal aortic bifurcation lymph node (No.280) can be performed. While in the "space" dissection, internal iliac lymph node (No.263), obturator lymph node (No.283), lateral sacral lymph node (No.260) and median sacral lymph node (No.270) can be removed. LD2 or LD3 lateral lymph node dissection prescribed by the Japanese Society of Colorectal Cancer can be completed according to the needs of the disease. This article describes the anatomical basis and standardized surgical procedures.
Dissection
;
Fascia/pathology*
;
Humans
;
Lymph Node Excision/methods*
;
Lymph Nodes/pathology*
;
Rectal Neoplasms/surgery*
9.Single oblique lumbar interbody fusion with robot-assisted posterior internal fixation for lumbar degenerative diseases.
Qun-Long PAN ; Hai-Ming YU ; Rong-Mou ZHANG
China Journal of Orthopaedics and Traumatology 2022;35(2):128-131
OBJECTIVE:
To investigate the efficacy of single oblique lumbar interbody fusion(OLIF) with robot-assisted posterior internal fixation for the treatment of lumbar degenerative diseases.
METHODS:
The clinical data of 67 patients with lumbar degenerative diseases treated from September 2019 to December 2020 was retrospectively analyzed. According to different surgical methods, the patients were divided into traditional group and robot group. The traditional group received traditional OLIF with posterior fluoroscopy percutaneous nail fixation, and the robot group received OLIF with robot-assisted posterior internal fixation. There were 33 patients in traditional group, including 13 males and 20 females, aged from 44 to 82 years old with an average of (59.7±9.1) years; and 34 cases in robot group, including 7 males and 27 females, aged from 45 to 81 years old with an average of(61.6±8.8) years. The operation time, fluoroscopy time, intraoperative blood loss, postoperative out of bed time and hospital stay were recorded. The visual analogue scale (VAS) of low back pain and Oswestry Disability Index(ODI) were compared before operation and 3 days, 3 months after operation between two groups. The accuracy of nail placement was evaluated by postoperative CT scan.
RESULTS:
Both groups of patients successfully completed the operation and were followed up for more than 3 months. The operation time, fluoroscopy time, intraoperative blood loss, postoperative out of bed time and hospital stay in traditional group were(299.85±15.79) min, (62.58±10.83) min, (118.33±10.80) ml, (2.5±0.7) d, (9.67±2.13) d;and robot group was(248.53±14.22) min, (19.47±3.51) min, (115.74±9.86) ml, (2.3±0.6) d, (9.44±1.93) d, respectively. The symptoms of postoperative low back pain, lower limb pain and numbness were significantly improved in all patients. The operation time and fluoroscopy time in robot group were significantly less than those of traditional group. There was no significant difference in intraoperative blood loss, postoperative out of bed time, hospital stay, VAS and ODI before and after operation (P>0.05). The accuracy of nail placement in robot group was 98.8% (2/160), which was higher than 89.9% (16/158) in traditional group.
CONCLUSION
Treatment of lumbar degenerative diseases with single body position OLIF with robot-assisted posterior minimally invasive internal fixation has less operation time and fluoroscopy time, high nail placement accuracy and accurate surgical effect, which is worthy to be popularized in clinic.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Lumbar Vertebrae/surgery*
;
Lumbosacral Region
;
Male
;
Middle Aged
;
Retrospective Studies
;
Robotics
;
Spinal Fusion/methods*
;
Treatment Outcome
10.Preparation of CD52-targeted chimeric antigen receptor-modified T cells and their anti-leukemia effects.
Yan LIU ; Yu LIU ; Ke Jing TANG ; Zhao Qi CHEN ; Jun Li MOU ; Ying Xi XU ; Hai Yan XING ; Zheng TIAN ; Qing RAO ; Min WANG ; Jian Xiang WANG
Chinese Journal of Hematology 2022;43(4):279-286
Objective: To construct chimeric antigen receptor (CAR) T cells targeting CD52 (CD52 CAR-T) and validate the effect of CD52 CAR-T cells on CD52-positive leukemia. Methods: A second-generation CD52-targeting CAR bearing 4-1BB costimulatory domain was ligated into a lentiviral vector through molecular cloning. Lentivirus was prepared and packaged by 293 T cells with a four-plasmid system. Fluorescein was used to label cell surface antigens to evaluate the phenotype of CD52 CAR-T cells after infection. Flow cytometry and ELISA were used to evaluate the specific cytotoxicity of CD52 CAR-T cells to CD52-positive cell lines in vitro. Results: ①A pCDH-CD52scFv-CD8α-4-1BB-CD3ζ-GFP expressing plasmid was successfully constructed and used to transduce T cells expressing a novel CD52-targeting CAR. ②On day 6, CD52-positive T cells were almost killed by CD52-targeted CAR-T post lentivirus transduction [CD52 CAR-T (4.48 ± 4.99) %, vs Vector-T (56.58±19.8) %, P=0.011]. ③T cells transduced with the CAR targeting CD52 showed low levels of apoptosis and could be expanded long-term ex vivo. ④The CD52 CAR could promote T cell differentiation into central and effector memory T cells, whereas the proportion of T cells with a CD45RA(+) effector memory phenotype were reduced. ⑤CD52 CAR-T cells could specifically kill CD52-positive HuT78-19t cells but had no killing effect on CD52-negative MOLT4-19t cells. For CD52 CAR-T cells, the percentage of residual of HuT78-19t cells was (2.66±1.60) % at an the E:T ratio of 1∶1 for 24 h, while (56.66±5.74) % of MOLT4-19t cells survived (P<0.001) . ⑥The results of a degranulation experiment confirmed that HuT78-19t cells significantly activated CD52 CAR-T cells but not MOLT4-19t cells[ (57.34±11.25) % vs (13.06± 4.23) %, P<0.001]. ⑦CD52 CAR-T cells released more cytokines when co-cultured with HuT78-19t cells than that of vector-T cells [IFN-γ: (3706±226) pg/ml, P<0.001; TNF-α: (1732±560) pg/ml, P<0.01]. Conclusions: We successfully prepared CD52 CAR-T cells with anti-leukemia effects, which might provide the foundation for further immunotherapy.
CD52 Antigen
;
Cell Line, Tumor
;
Humans
;
Immunotherapy, Adoptive/methods*
;
Lentivirus/genetics*
;
Leukemia
;
Receptors, Antigen, T-Cell
;
Receptors, Chimeric Antigen/genetics*

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