1.Study on mechanism of berberine inhibiting tumor stem cells proliferation and its in vivo safety evaluation
Jinjin XIE ; Yan CHEN ; Xin DU ; Yuke LI ; Mengnan ZHAO ; Sanjun SHI
China Pharmacy 2024;35(12):1443-1450
OBJECTIVE To investigate the in vitro inhibitory mechanism of berberine on the proliferation of tumor stem cells and evaluate its in vivo safety. METHODS Flow cytometry was used to select tumor stem cells from mouse skin melanoma B16F10 cells; CD44, CD133, Nanog homologous box protein (NANOG) and octamer-binding transcription factor 4 (OCT4) were used as indicators to characterize tumor stem cells. Tumor stem cells were divided into control group, all-trans retinoic acid (ATRA) group, and berberine group, and the CCK-8 method was used to detect the effects of berberine on the viability of tumor stem cells; flow cytometry was adopted to detect cell apoptotic rate, the proportion of CD44+/CD133+ and the positive cell rate of sex determining region Y box protein 2 (SOX2); the morphological changes of tumor balls were recorded after treatment with berberine; the morphology of cell pyroptosis in each group was recorded, and the release rate of lactate dehydrogenase (LDH) was detected; Western blot assay was adopted to detect the expressions of pyroptosis-related protein gasdermin E (GSDME), GSDME- N, caspase-3 and cleaved caspase-3. Preliminary evaluation of in vivo safety of berberine was conducted by using zebrafish embryo toxicity experiments. RESULTS Compared with B16F10 cells, the proportion of CD44+/CD133+ cells in tumor stem cells and the fluorescence intensity of NANOG and OCT4 were significantly increased (P<0.000 1). The half-inhibitory concentration of berberine to tumor stem cells was 50.98 μmol/L. Compared with the control group, the apoptotic rate of cells in the berberine group was significantly increased, while the proportion of CD44+/CD133+ cells and the rate of SOX2 positive cells were reduced significantly (P<0.000 1); tumor stem cell spheroids were atrophied, with partial cell death. After treatment with berberine, tumor stem cells exhibited swelling in their outermost layer, the release rate of LDH of cells was significantly increased and the release rate of LDH increased with increasing dose; the protein expressions of GSDME-N and cleaved-caspase-3 of cells in berberine 20, 40 μmol/L groups were significantly increased, and the protein expressions of GSDME and caspase-3 were significantly reduced (except for berberine 20 μmol/L group, P<0.05). The embryonic development of zebrafish treated with berberine was almost unaffected, and the survival rate of embryo reached 100%, with no obvious abnormalities observed. CONCLUSIONS Berberine has good activity against the proliferation of tumor stem cells, and its mechanism of action may be related to activating GSDME and promoting cell pyroptosis; berberine has good in vivo safety.
2.Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis.
Mengnan ZHAO ; Rujing WANG ; Kunmeng YANG ; Yuhong JIANG ; Yachen PENG ; Yuke LI ; Zhen ZHANG ; Jianxun DING ; Sanjun SHI
Acta Pharmaceutica Sinica B 2023;13(3):916-941
RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.
3.Efficacy of percutaneous compression plate for femoral neck fractures in elderly patients
Huanxiang BAO ; Haifeng LI ; Sanjun GU ; Qudong YIN ; Li CHENG ; Dehong FENG ; Weiya ZHANG
Chinese Journal of Orthopaedic Trauma 2021;23(6):477-483
Objective:To investigate the advantages and disadvantages of percutaneous compression plate (PCCP) for femoral neck fractures in the elderly patients.Methods:A retrospective study was conducted of the 31 elderly patients with femoral neck fracture who had been treated with PCCP from January 2012 to December 2018 at Orthopaedic Department, The First People's Hospital of Yancheng, Orthopaedic Department, The Ninth People's Hospital of Wuxi and Department of Orthopaedics, The People's Hospital of Wuxi. They were 16 men and 15 women, aged from 65 to 80 years (average, 70.5 years). By the Garden classification, 7 cases were type Ⅱ, 15 cases type Ⅲ and 9 cases type Ⅳ; by the Singh index, 4 cases were level Ⅲ, 11 cases level Ⅳ, 10 cases level Ⅴ and 6 cases level Ⅵ. The time from injury to operation ranged from 3 to 14 days (average, 5.8 days). The operation time, intraoperative blood loss, fracture reduction, fracture union time, complications and functional recovery of the hip were observed.Results:The operation time averaged 73.4 min and intraoperative blood loss 116.4 mL. At one week after operation, the Garden alignment index was level Ⅰ in 25 cases and level Ⅱ in 6. Superficial incision infection was noted in one case intraoperatively. Follow-ups for the 31 patients ranged from 12 to 47 months (mean, 18.9 months). All the fractures united after 4.9 months on average (from 4 to 8 months). Delayed union occurred in 2 cases, neck shortening in 12 cases, and avascular necrosis of femoral head in 3 displaced subcranial fractures 2 of which were high shear ones. The necrosis of femoral head was treated by arthroplasty in 2 and by conservative treatment in one. The Harris hip scores at the last follow-up for the 31 patients averaged 90.9 (from 75 to 100), giving 15 excellent, 12 good and 4 fair cases and an excellent to good rate of 87.1% (27/31).Conclusions:In treatment of femoral neck fractures in the elderly patients, PCCP has advantages of allowing early weight-bearing after operation, a high rate of fracture union, limited complications and quick and fine functional recovery of the hip. However, it should be used with caution in patients with severe osteoporosis, displaced subcranial or high shear fracture.
4.Treatment of traumatic lesions of popliteal artery by staged stretching
Jianbing WANG ; Sanjun GU ; Qudong YIN ; Kelin XU ; Haifeng LI ; Zhenzhong SUN ; Yongjun RUI
Chinese Journal of Orthopaedic Trauma 2019;21(1):81-84
Objective To investigate the clinical effects of treating traumatic lesions of the popliteal artery by staged stretching.Methods From July 2011 to March 2016,29 patients with traumatic lesion of the popliteal artery underwent staged stretching after direct end to end anastomosis at Department of Orthopaedics,The 9th People's Hospital of Wuxi.They were 19 males and 10 females,with a mean age of 38.3 years (range,from 16 to 61 years).The average length of popliteal artery lesions was 3.7 cm (range,from 2 to 5 cm).After the keen joint was immobilized at flexion by external fixation,direct end to end anastomosis was performed with a proper segmental vascular freedom.From 4 weeks after operation,the popliteal artery was stretched stage by stage to its original length by gradual adjustment of the external fixation till the knee joint was fully extended.The color,skin temperature,pulp tension and capillary reaction of the toes were closely observed after surgery.CT angiography (CTA) was performed 6 months after surgery.The active range of motion was assessed at 12 months after surgery for the knee and ankle joints on the injured limb.Results All the patients were available for an average follow-up of 2 years (range,from 1 to 3 years).Blood supply was good for all the affected limbs.The staged stretching of the popliteal artery resulted in no rupture of any anastomotic stoma or no thrombus.CTA at 6 months after surgery showed fine patency of the popliteal artery and no formation of false aneurysm or arteriovenous fistula.At 12 months after surgery,the knee function was excellent in 15 cases,good in 10 and fair in 4;the ankle function was excellent in 18 cases,good in 8 and fair in 3.Conclusion Staged stretching is a safe,convenient and effective treatment of traumatic lesions of the popliteal artery.
5. Recombinant human interleukin-11 for chemotherapy-induced thrombocytopenia of acute leukemia: a multi-center study
Xinyu CUI ; Hong ZHOU ; Yinghua LI ; Li ZHENG ; Lian BAI ; Na LIU ; Yanzhang QU ; Libo JIANG ; Sanjun CHEN
Journal of Leukemia & Lymphoma 2018;27(5):276-279
Objective:
To explore the efficacy and safety of recombinant human interleukin-11 (rhIL-11) in treatment of chemotherapy-induced thrombocytopenia of acute leukemia.
Methods:
Acute leukemia patients with chemotherapy-induced thrombocytopenia [Platelets (Plt) < 50×109/L] in 6 centers nationwide from February 2016 to July 2016 were treated with rhIL-11 (2 mg/time, twice per day) by subcutaneous injection. Treatment lasted 7 days or at least until Plt≥ 50×109/L. The Plt recovery was observed during treatment.
Results:
A total of 112 patients were enrolled, and 2 patients decided to drop out of study. The efficacy population consisted of 110 patients, and the total response rate reached 74.5% (82/110). The average variation of Plt during treatment was (70±54)×109/L, and recovery average time of Plt for the patients with favorable efficacy was (8.7±3.0) days. In treatment with severe thrombocytopenia, rhIL-11 alone could shorten the recovery time compared with rhIL-11 combined with Plt transfusion [(8.0±2.6) d vs. (9.6±3.5) d,
6.Changes of serum IL-6 and IL-8 levels in patients with gastric cancer and the clinical relationships with Helicobacter pylori infection
Sanjun DU ; Qibin LYU ; Duo LI ; Huibin GAO ; Jinku SHEN
Journal of Chinese Physician 2017;19(2):250-252,256
Objective To explore the changes of serum interleukin-6 (IL-6),and interleukin-8 (IL-8) in patients with gastric cancers and the clinical relationships with Helicobacter pylori (Hp) infection.Methods Totally 62 cases of patients who were diagnosed gastric cancer in our hospital from January 2013 to September 2015 were selected as the study group,who did not accept anti-tumor therapy.The patients were divided into the Hp positive group (with 53 cases) and Hp negative group (with 9 cases) according to whether the merger of Hp infection.Another 60 normal healthy volunteers of the same age in our hospital for health examination during the same period were selected as the control group.The serum IL-6 and IL-8 levels were detected,and the changes of the factors in the study group and control group were compared and analyzed,as well as the U values of Hp infection.The clinical relationships between the expression levels of the two in patients with gastric cancer and the U values of Hp infection were confirmed.Results The serum IL-6 and IL-8 levels and the U values of Hp infection of the study group were significantly higher than those of the control group (P < 0.05),which in the Hp positive group were significantly higher than those in the Hp negative group (P < 0.05).The levels of serum IL-6 and IL-8 in patients with gastric cancer showed positive correlations with the U value of Hp infection (r =0.457,0.531,P < 0.05).Conclusions The serum IL-6 and IL-8 levels in patients with gastric cancer are much higher than those in normal healthy people,and there are significant positive relationship with Hp infection.It can improve the curative effect of gastric cancer patients by improving the eradication rate of Hp.
7.Arthroscopy-assisted minimally invasive treatment of posterior tibial plateau fractures
Sanjun GU ; Haifeng LI ; Yongjun RUI ; Jianbing WANG ; Qudong YIN ; Kelin XU ; Yu LIU
Chinese Journal of Orthopaedic Trauma 2016;18(4):351-354
Objective To explore the therapeutic efficacy of arthroscopy-assisted minimally invasive treatment for posterior tibial plateau fractures.Methods From July 2010 to June 2014,10 posterior tibial plateau fractures were treated at our department by arthroscopy-assisted minimally invasive treatment with percutaneous lag screws.They were 8 men and 2 women,with a median age of 31 years (from 18 to 52 years).All the fractures were closed and fresh,including 3 posteromedial tibial plateau ones,5 posterolateral tibial plateau ones,and 2 posteromedial and posterolateral tibial plateau ones.They were followed up periodically by radiological examinations.At the final follow-up,their knee functions were evaluated by Rasmussen scoring system,and their pain was evaluated by the visual analogue scale(VAS).Subjective factors included swelling,stairs climbing,joint stability,job participation and satisfaction with recovery.Results The follow-ups averaged 18 months (from 12 to 24 months).All fractures healed within 3 months postoperatively,with no infection or serious complications like implant failure.At 12 months postoperation,the mean Rasmussen score was 26 points (from 19 to 30 points).Eight cases were rated as excellent,one as good,and one as fair.Their mean VAS score was 1.2 points (from 0 to 4 points).Conclusion Arthroscopy-assisted minimally invasive management of posterior tibial plateau fractures with cannulated screw fixation is feasible,because it results in limited invasion,satisfactory reduction,reliable fixation,quick functional recovery and a low rate of complications.
8.Can the weekday of surgery influence the prognosis of colorectal cancer patients? A retrospective study based on a single-center of large sample.
Yaqi LI ; Wencheng YU ; Weixing DAI ; Qingguo LI ; Sanjun CAI ;
Chinese Journal of Gastrointestinal Surgery 2016;19(10):1129-1132
OBJECTIVETo investigate the impact of the weekday of surgery on the prognosis of patients with colorectal cancer.
METHODSA retrospective analysis was conducted in patients with colorectal cancer who underwent radical resection in Fudan University Shanghai Cancer Center(FUSCC) between January 2007 and December 2013, and 4 971 patients were identified eligible. Statistical analyses were carried out between patients who received surgery on Monday to Thursday and those who received surgery on Friday. Chi-square test was used to analyze the relationship between clinicopathological parameters and day of surgery. T test was used to compare continuous variables between groups. The 5-year overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method, and compared by log-rank test.
RESULTSThere were no statistically significant differences between two groups in age, gender and pathological grade et al (all P>0.05). However, the number of dissected lymph node was higher in patients who received surgery on Monday to Thursday (median 16) compared with patients who received surgery on Friday (median 14), with statistically significant difference (P=0.038). The 5-year OS and DFS in all eligible patients were 78.0% and 55.0%, respectively. 5-year OS of patients in Monday to Thursday surgery group and Friday surgery group was 79.6% and 77.2%, while 5-year DFS in two groups was 57.8% and 50.4%. There were no significant differences in OS and DFS between two group, with P=0.882 and P=0.210, respectively. Subgroup analyses were conducted according to different pathological stages. 5-year OS of patients at stage I( in Monday to Thursday surgery group and Friday surgery group was 94.7% and 90.6% (P=0.742) and 5-year DFS was 85.1% and 78.2% (P=0.765). 5-year OS of patients at stage II( in two groups was 85.5% and 83.7% (P=0.496) and 5-year DFS was 72.7% and 62.8% (P=0.121). 5-year OS of patients at stage III( in two groups was 69.7% and 69.4%(P=0.354) and 5-year DFS was 41.8% and 37.4% (P=0.976). No statistically significant differences manifested in subgroup analyses.
CONCLUSIONPatients with colorectal cancer undergoing surgery on Monday to Thursday have similar long-term prognosis with those on Friday.
Adult ; China ; Colorectal Neoplasms ; surgery ; Disease-Free Survival ; Female ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Time Factors
9.Establishment of three-dimensional computational fluid dynamics model of upper airway in patients with obstructive sleep apnea-hypopnea syndrome
Sanjun LI ; Yibo LI ; Yongming LI
Chinese Journal of Tissue Engineering Research 2015;19(20):3211-3215
BACKGROUND:The analysis of gas flow in upper respiratory tract of patients with obstructive sleep apnea-hypopnea syndrome contributes to further understanding the correlation of anatomical structure and function of upper respiratory tract so as to know the pathogenesis of obstructive sleep apnea-hypopnea syndrome. OBJECTIVE:To establish the three-dimensional computational fluid dynamics model of upper airway in patients with obstructive sleep apnea-hypopnea syndrome, to study the characteristics of airflow dynamics in upper respiratory tract in above patients, and to lay the foundation for further exploring the pathogenesis of obstructive sleep apnea-hypopnea syndrome. METHODS:CT scan of the upper airway was performed with a moderate obstructive sleep apnea-hypopnea syndrome patient. Data stored in DICOM format were imported in Mimics 10.01 software, and processed, and then computational fluid dynamics model was built. ANSYS ICEM CFD14.0 was used to perform the grid division of the three-dimensional model. The internal flow of upper respiratory tract was simulated by ANSYS 14.0-Fluid Dynamics, and relevant information on airflow field of upper airway was obtained. RESULTS AND CONCLUSION: The three-dimensional computational fluid dynamics model of upper airway wasestablished with 1 751 940 elements and 303 981 nodes of upper airway. The flow rate was 11.087 m/s in the lower bound of pharyngopalatiae, which was the most narrowed areas of upper airway in patients with obstructive sleep apnea-hypopnea syndrome. The three-dimensional computational fluid dynamics model of upper airway has accurately simulated biomechanical feature of human, which provides a foundation for further studying the airflow dynamics of upper respiratory tract of patients with obstructive sleep apnea-hypopnea syndrome.
10.New fixation set-up designed for micro-tensile test
Shuai LU ; Sanjun ZHAO ; Yong SUN ; Peng LI ; Jihua CHEN
Journal of Practical Stomatology 2015;(4):455-459
Objective:To introduce a new fixation set-up for micro-tensile test.Methods:Dentin-composite were bonded with AdperTM Single Bond 2 (SB2)and sectioned into stick-shaped specimens.Specimens from each tooth(n =6)were equally divided into Ciucchi's jig and the designed set-up(Control and experimental)groups for micro-tensile bond test according to the utilized fixa-tion set-up.The bonding interface failure mode was examined with field-emission scanning electron microscope (FESEM).Three-dimensional models of the two set-ups and the specimen were developed,stress distribution was analyzed by finite element analysis (FEA).Results:The bond strength(MPa)of experimental and control group was 32.76 ±7.43 and 43.58 ±4.72(P <0.05),the ratio of mixed failure was 28 /36 and 20 /36(P <0.05)respectively.FEA showed that the designed set-up for fixing the sticks pro-vided a uniform stress distribution along the long axis of the specimen.FEA and failure mode analysis confirmed such uniform distri-bution was also concentrated at the bonding interface.Conclusion:The new set-up is feasible for micro-tensile test.

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