1.Thermal proteome profiling (TPP) reveals NAMPT as the anti-glioma target of phenanthroindolizidine alkaloid PF403.
Fangfei LI ; Zhaoxin ZHANG ; Qinyan SHI ; Rubing WANG ; Ming JI ; Xiaoguang CHEN ; Yong LI ; Yunbao LIU ; Shishan YU
Acta Pharmaceutica Sinica B 2025;15(4):2008-2023
Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD+) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.
2.Clinical Efficacy of Balloon Stent Kissing Technique and Jailing Wire Technique in Patients With True Bifurcation Lesions of the Left Anterior Descending Branch-diagonal Branch of the Coronary Artery
Shuo WANG ; Liu LI ; Guoying LIU ; Yonggang SUI ; Rubing WU ; Jie MI
Chinese Circulation Journal 2025;40(2):131-137
Objectives:To explore the therapeutic efficacy of balloon stent kissing technique(BSKT)and jailing wire technique(JWT)in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch of the coronary artery,and to observe the impact of these two interventional procedures on the lumen area,angina symptoms,cardiac function,myocardial injury,and myocardial perfusion of patients.Methods:A retrospective analysis was conducted in 203 patients with true bifurcation lesions of the left anterior descending branch-diagonal branch who underwent BSKT and JWT procedures and completed a 6-month follow-up in the Department of Cardiovascular Medicine at Shijiazhuang People's Hospital from January 2022 to January 2024.Patients were randomly assigned to the BSKT group(n=107)or the JWT group(n=96).The safety,efficacy,and myocardial perfusion indicators of the two groups were compared.Results:The minimum lumen area measured by intravascular ultrasound immediately after procedure,the Canadian Cardiovascular Society angina classification at 6 months post-intervention,the total score of resting+stress myocardial perfusion at 6 months post-intervention,the total number of segments with resting+stress myocardial ischemia,and the abnormal myocardial perfusion area in both the BSKT group and JWT group were significantly improved compared to baseline values(all P<0.05).In the BSKT group,87 cases(81.3%)achieved immediate success in stent placement,whereas in the JWT group,64 cases(66.7%)achieved immediate success in stent placement.The BSKT group significantly outperformed the JWT group.In terms of the myocardial injury and cardiac function indicators assessed on postoperative day 1,the cardiac troponin I level([0.22±0.13]ng/ml vs.[0.45±0.27]ng/ml,P<0.001),creatine kinase MB([35.24±13.15]U/L vs.[42.39±21.66]U/L,P=0.004),and B-type natriuretic peptide([133.52±25.62]pg/ml vs.[167.22±22.04]pg/ml,P<0.001)were all significantly lower in the BSKT group than in the JWT group.In terms of the myocardial perfusion indicators at 6 months post-intervention,the number of ischemic segments under stress(3.23±1.54 vs.3.87±1.62,P=0.004),the total score of stress perfusion(4.18±2.21 vs.4.97±2.96,P=0.031),and the abnormal myocardial perfusion area([7.04±3.27]%vs.[8.24±3.69]%,P=0.014)were all significantly lower in the BSKT group than in the JWT group.Conclusions:Both BSKT and JWT procedures can significantly improve the lumen area of the left anterior descending branch,angina symptoms,and myocardial perfusion in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch.The BSKT procedure provides more adequate protection for the bifurcation vessels compared to the JWT procedure.
3.Efficacy of intracoronary injection of adenosine and sodium nitroprusside before PCI in patients with attenuated plaques
Shuo WANG ; Liu LI ; Zhichao GAO ; Hong GENG ; Lei XU ; Rubing WU
Journal of China Medical University 2025;54(9):786-790
Objective To investigate the efficacy of preprocedural intracoronary injections of adenosine and sodium nitroprusside in patients with intravascular ultrasound-attenuated plaques(AP).Methods In total,200 patients with AP detected using intravascular ultrasound(IVUS)at Shijiazhuang People's Hospital from January 1,2022,to January 1,2024,were selected and randomly divided into conventional treatment and pretreatment groups,with 100 patients in each group.The conventional treatment group underwent standard percutaneous coronary intervention(PCI)procedures,whereas the pretreatment group underwent intracoronary injection of sodium nitro-prusside and adenosine through a guiding catheter prior to PCI.The observation parameters included intraoperative no-reflow(NR)inci-dence,post-PCI TIMI myocardial perfusion frame count(TMPFC),perioperative myocardial infarction(PMN),and 6-month major adverse cardiac and cerebrovascular events(MACCE).Results The pretreatment group exhibited a significantly lower intraoperative NR inci-dence,reduced postoperative TMPFC,and attenuated PMN severity than the conventional treatment group(P<0.05).Conclusion Pre-procedural intracoronary administration of adenosine and sodium nitroprusside through a guiding catheter can effectively reduce PCI-re-lated NR occurrence,improve post-PCI TMPFC,and mitigate PMN in patients with AP,although no significant improvement in MACCE incidence can be observed at the 6-month follow-up.
4.Clinical Efficacy of Balloon Stent Kissing Technique and Jailing Wire Technique in Patients With True Bifurcation Lesions of the Left Anterior Descending Branch-diagonal Branch of the Coronary Artery
Shuo WANG ; Liu LI ; Guoying LIU ; Yonggang SUI ; Rubing WU ; Jie MI
Chinese Circulation Journal 2025;40(2):131-137
Objectives:To explore the therapeutic efficacy of balloon stent kissing technique(BSKT)and jailing wire technique(JWT)in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch of the coronary artery,and to observe the impact of these two interventional procedures on the lumen area,angina symptoms,cardiac function,myocardial injury,and myocardial perfusion of patients.Methods:A retrospective analysis was conducted in 203 patients with true bifurcation lesions of the left anterior descending branch-diagonal branch who underwent BSKT and JWT procedures and completed a 6-month follow-up in the Department of Cardiovascular Medicine at Shijiazhuang People's Hospital from January 2022 to January 2024.Patients were randomly assigned to the BSKT group(n=107)or the JWT group(n=96).The safety,efficacy,and myocardial perfusion indicators of the two groups were compared.Results:The minimum lumen area measured by intravascular ultrasound immediately after procedure,the Canadian Cardiovascular Society angina classification at 6 months post-intervention,the total score of resting+stress myocardial perfusion at 6 months post-intervention,the total number of segments with resting+stress myocardial ischemia,and the abnormal myocardial perfusion area in both the BSKT group and JWT group were significantly improved compared to baseline values(all P<0.05).In the BSKT group,87 cases(81.3%)achieved immediate success in stent placement,whereas in the JWT group,64 cases(66.7%)achieved immediate success in stent placement.The BSKT group significantly outperformed the JWT group.In terms of the myocardial injury and cardiac function indicators assessed on postoperative day 1,the cardiac troponin I level([0.22±0.13]ng/ml vs.[0.45±0.27]ng/ml,P<0.001),creatine kinase MB([35.24±13.15]U/L vs.[42.39±21.66]U/L,P=0.004),and B-type natriuretic peptide([133.52±25.62]pg/ml vs.[167.22±22.04]pg/ml,P<0.001)were all significantly lower in the BSKT group than in the JWT group.In terms of the myocardial perfusion indicators at 6 months post-intervention,the number of ischemic segments under stress(3.23±1.54 vs.3.87±1.62,P=0.004),the total score of stress perfusion(4.18±2.21 vs.4.97±2.96,P=0.031),and the abnormal myocardial perfusion area([7.04±3.27]%vs.[8.24±3.69]%,P=0.014)were all significantly lower in the BSKT group than in the JWT group.Conclusions:Both BSKT and JWT procedures can significantly improve the lumen area of the left anterior descending branch,angina symptoms,and myocardial perfusion in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch.The BSKT procedure provides more adequate protection for the bifurcation vessels compared to the JWT procedure.
5.Efficacy of intracoronary injection of adenosine and sodium nitroprusside before PCI in patients with attenuated plaques
Shuo WANG ; Liu LI ; Zhichao GAO ; Hong GENG ; Lei XU ; Rubing WU
Journal of China Medical University 2025;54(9):786-790
Objective To investigate the efficacy of preprocedural intracoronary injections of adenosine and sodium nitroprusside in patients with intravascular ultrasound-attenuated plaques(AP).Methods In total,200 patients with AP detected using intravascular ultrasound(IVUS)at Shijiazhuang People's Hospital from January 1,2022,to January 1,2024,were selected and randomly divided into conventional treatment and pretreatment groups,with 100 patients in each group.The conventional treatment group underwent standard percutaneous coronary intervention(PCI)procedures,whereas the pretreatment group underwent intracoronary injection of sodium nitro-prusside and adenosine through a guiding catheter prior to PCI.The observation parameters included intraoperative no-reflow(NR)inci-dence,post-PCI TIMI myocardial perfusion frame count(TMPFC),perioperative myocardial infarction(PMN),and 6-month major adverse cardiac and cerebrovascular events(MACCE).Results The pretreatment group exhibited a significantly lower intraoperative NR inci-dence,reduced postoperative TMPFC,and attenuated PMN severity than the conventional treatment group(P<0.05).Conclusion Pre-procedural intracoronary administration of adenosine and sodium nitroprusside through a guiding catheter can effectively reduce PCI-re-lated NR occurrence,improve post-PCI TMPFC,and mitigate PMN in patients with AP,although no significant improvement in MACCE incidence can be observed at the 6-month follow-up.
6.Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis
Ninghua LI ; Zulong WANG ; Chenming ZHANG ; Xiao LI ; Rubing CHEN ; Qi ZHANG ; Zhong HUA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):77-82
ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia (BPH) in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups, with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets, and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks, the international prostate symptom score (IPSS), quality of life (QOL) score, residual urine volume (RUV), maximum urinary flow rate (Qmax), TCM syndrome score, TCM symptom score, electrocardiogram, and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment, the total response rate in the control group was 63.64% (28/44), which was lower than that (84.44%, 38/45) in the observation group (χ2=5.026, P<0.05). The clinical efficacy in the observation group was higher than that in the control group (Z=-2.17, P=0.030). The treatment in both groups decreased the IPSS, QOL score, RUV, and TCM syndrome scores and increased the Qmax (P<0.05). Moreover, the observation group had lower IPSS, QOL score, RUV, and TCM syndrome score (P<0.05) and higher Qmax than the control group after treatment (P<0.05). The treatment in the observation group decreased all the TCM symptom scores (P<0.05), while that in the control group only decreased the frequency of urination at night and the scores of dysuria, weak urine stream, and post-urinary drainage (P<0.05). After treatment, the observation group had lower frequency of urination at night and lower scores of mental fatigue, cold limbs, lower abdominal discomfort, and loose stool than the control group (P<0.05). No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life, being a safe and reliable choice for clinical application.
7.Effect of Wuwei Fuzheng Yijing Decoction on Sperm DNA Integrity in Male Infertility Patients
Panpan ZHAO ; Zulong WANG ; Rubing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):127-132
ObjectiveTo observe the effect of Wuwei Fuzheng Yijing decoction on sperm DNA integrity in male infertility patients. MethodOne hundred male infertility patients with sperm DNA damage (spleen and kidney Qi deficiency and blood stasis) that met the inclusion criteria were randomly divided into an observation group (Wuwei Fuzheng Yijing decoction) and a control group (L-carnitine oral solution), with 50 cases in each group. After 12 weeks of treatment, the DNA fragmentation index (DFI) and traditional Chinese medicine (TCM) syndrome score, progressive sperm motility (PR), sperm survival rate, and sperm concentration of the two groups before and after treatment were observed and compared. ResultThe total effective rate of the observation group was 89.80% (44/49) higher than 62.50% (30/48) of the control group (P<0.05). Compared with the conditions before treatment, the DFI and TCM syndrome score of the two groups were reduced after treatment, while the PR, sperm survival rate, and sperm concentration were increased (P<0.05), and the observation group was superior to the control group in terms of the above indexes (P<0.05). ConclusionWuwei Fuzheng Yijing decoction obviously repairs sperm DNA of male infertility patients and improves sperm quality, with high safety.
8.Progress in the application of patch materials in cardiovascular surgery.
Rubing SHAO ; Jiehua LI ; Lunchang WANG ; Xin LI ; Chang SHU
Journal of Central South University(Medical Sciences) 2023;48(2):285-293
The cardiovascular patch, served as artificial graft materials to replace heart or vascular tissue defect, is still playing a key role in cardiovascular surgeries. The defects of traditional cardiovascular patch materials may determine its unsatisfactory long-term effect or fatal complications after surgery. Recent studies on many new materials (such as tissue engineered materials, three-dimensional printed materials, etc) are being developed. Patch materials have been widely used in clinical procedures of cardiovascular surgeries such as angioplasty, cardiac atrioventricular wall or atrioventricular septum repair, and valve replacement. The clinical demand for better cardiovascular patch materials is still urgent. However, the cardiovascular patch materials need to adapt to normal coagulation mechanism and durability, promote short-term endothelialization after surgery, and inhibit long-term postoperative intimal hyperplasia, its research and development process is relatively complicated. Understanding the characteristics of various cardiovascular patch materials and their application in cardiovascular surgeries is important for the selection of new clinical surgical materials and the development of cardiovascular patch materials.
Cardiac Surgical Procedures/methods*
;
Tissue Engineering
;
Heart Ventricles
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Heart Atria
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Treatment Outcome
9.The predictive value of TIMP-2 and IGFBP7 in delayed renal function recovery after DCD renal transplantation
Xiaobo CUI ; Zhouji SHEN ; Yimeng ZHU ; Yina WANG ; Chao ZHANG ; Xiaoren ZHANG ; Rubing LI ; Sinian ZHENG
Chinese Journal of Urology 2021;42(8):620-626
Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.
10.Epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in 2013-2017
Chinese Journal of School Health 2019;40(3):336-338
Objective:
To understand the epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in recent 5 years, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures.
Methods:
The two stage sampling method was used to survey 3 junior middle school schools randomly selected from Shunyi District, Beijing, in November 2013, December 2015 and November 2017. The number of students surveyed each year was 1 520, 1 404 and 1 467 respectively.
Results:
A total of 4 500 questionnaires were distributed and 4 391 questionnaires were valid, with an effective rate of 97.6%. The current smoking rate and the attempting smoking rate in Shunyi District junior high school students increased substantially, the difference was statistically significant(χ2=9.15, 11.54, P<0.01). The exposure rate of second-hand smoke among junior high school students in Shunyi District is increasing year by year. The current smoking rate and the attempting smoking rate of second-hand smoke at home and in public places were higher than those of non-exposed ones. The differences in the current smoking rates of junior high school students (χ2=25.86, 37.61, P<0.01) and the attempting smoking rate (χ2=49.51, 63-86, P<0.01) were statistically significant. The influence of Shunyi District junior high school students through different tobacco information access channels on the current smoking rate of junior high school students increased year by year. Different tobacco information access channels have significant difference in the influence of the junior middle school students’ attempting smoking rate(P<0.05).
Conclusion
The overall tobacco use of junior high school students in Shunyi District of Beijing is increasing by year. The exposure of second-hand smoke is not optimistic, and the supervision of tobacco information acquisition channels is urgent to be strengthened.


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