1.Integrated network pharmacology analysis and cellular evidence reveal the mechanisms of Myristica fragrans against atherosclerosis
Shuxian LU ; Zhiling ZHOU ; Yifeng ZHANG ; Jun YU
Acta Universitatis Medicinalis Anhui 2026;61(4):618-627
ObjectiveTo explore the potential mechanisms by which Myristica fragrans prevents and treats atherosclerosis (AS). MethodsThe major active components of Myristica fragrans and their shared targets with AS were obtained from databases. The shared targets were subjected to pathway enrichment analysis and PPI network construction using the ClusterProfile package and the STRING database. Molecular docking between key targets and major active components was performed using AutoDock. Gene expression data from early and late, as well as stable and unstable AS plaques, were used to validate changes of key targets and major pathways during AS progression. Western blot, flow cytometry, YO-PRO-1/PI staining, and TUNEL staining were applied to verify the main mechanisms. ResultsNine active components of Myristica fragrans interacted with 293 AS-related targets, among which eight components acted on an average of 57.0% of the shared targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the anti-AS effects mainly involved oxidative stress, inflammation, lipid metabolism, fluid shear stress, and apoptosis pathways. PPI network revealed JUN, CASP3, MAPK3, and AKT1 as key targets mainly involved in regulating apoptosis. Molecular docking showed stable binding conformations and high affinities between major components and these targets. Integrated analysis of gene expression in early and late, as well as stable and unstable AS plaques, showed significant enrichment of leukocyte apoptosis pathways in late and unstable plaques. Cell experiments further confirmed that Myristica fragrans significantly reduced Cleaved-CASP3(P=0.04)and p-MAPK3(P=0.000 3)levels, increased p-AKT1(P=0.004)levels, and inhibited macrophage apoptosis. ConclusionMyristica fragrans potentially interferes with AS development by modulating pathways related to oxidative stress, inflammation, lipid metabolism, fluid shear stress, and apoptosis, with CASP3, MAPK3, and AKT1 serving as key targets mediating its anti-apoptotic and anti-AS effects.
2.A single-center analysis of the short-term efficacy and safety of RAPN in 45 patients with non-metastatic pT 3a renal cell carcinoma
Xiangpeng ZOU ; Yunhan LUO ; Zhiling ZHANG ; Zhaohui ZHOU ; Longbin XIONG ; Yulu PENG ; Yixin HUANG ; Xin LUO ; Wensu WEI ; Zhenhua LIU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Urology 2025;46(5):369-375
Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy(RAPN)for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was(54.3±10.7)years,and the average clinical tumor diameter was(4.9±1.8)cm. Of all the patients,35(77.8%)were asymptomatic,7(15.6%)presented with hematuria,and 3(6.7%)presented with lumbar pain. Preoperative imaging assessed 34 patients(75.6%)as having clinical stage T 3a,all suspected of involving the collecting system or perirenal fat invasion;the remaining 11 patients(24.4%)were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0(7.0,10.0). A history of hypertension,diabetes,or chronic kidney disease was present in 18 patients(40.0%). The primary endpoint was progression-free survival,and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method,and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients(71.1%),with a median estimated blood loss of 150.0(50.0,300.0)ml. Seven(15.6%)patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0(4.0,6.0)days. Postoperative complications occurred in 6 patients(13.3%),including 5(11.1%)with mild complications and 1(2.2%)with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients(61.5%),while 3 patients(7.7%)developed surgery-related chronic kidney disease 3 to 12 months postoperatively,but none required dialysis. The median follow-up time was 31.8(22.7,50.9)months,12(26.7%)patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up,3 patients experienced tumor recurrence,the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma,RAPN performed by experienced surgeons is a feasible and safe option,providing excellent short-term oncological outcomes,complication control,and renal function recovery. The long-term efficacy remains to be seen.
3.Identification of in vivo Components and Distribution Characteristics in Rats,Cardiac Tissues of Zhigancao Decoction by UP-LC-Q-TOF/MS
Zhiling TANG ; Yao LI ; Hao ZHI ; Jingyan WANG ; Xueting CAI ; Peng CAO ; Qian ZHOU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):896-903
OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction,a classic tradi-tional Chinese medicine formula,and provide scientific evidence for its rational application and development in modern clinical practice.METHODS Wistar rats were treated with 12.15 g·kg-1 Zhigancao Decoction by gavage.Rat plasma samples were collect-ed at 10 time points(5,15,30,60,120,240,360,480,600 and 720 min after administration)and rat heart(atrial and ventricu-lar)tissue samples were collected at 12 h after administration.Components in the plasma and heart samples were qualitatively identi-fied by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and the distri-bution characteristics of Zhigancao Decoction in vivo were analyzed.At the same time,the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.RESULTS A total of 11 prototype components(Ajugol,Nicotiflorin,Isoschaftoside,4-Hydroxycinnamic acid,Rehmapicrogenin,4-Hydroxybenzoic acid,4′,7-Dihydroxyflavone,Calycosin,3′,4′,7-Trihydroxyflavone,Pinellic acid,Truxillic acid)and 7 metabolites were identified from the plasma samples of Zhigancao Decoction,mainly including flavonoids(flavonoids glycosides),organic acids,and iridoid glyco-sides,etc.Additionally,6 prototype components(Ajugol,Isoschaftoside,Rehmapicrogenin,4′,7-Dihydroxyflavone,Liquiritigenin,3′,4′,7-Trihydroxyflavone)and 3 metabolites were identified from the cardiac samples(the atrium and the ventricle showed the same results).The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.CONCLUSION The prototype compo-nents and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined,providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.
4.Multivue reconstruction technique during mitral valve transcatheter edge-to-edge repair: A case report
Qiuzhe GUO ; Yunfei ZHOU ; Da ZHU ; Shouzheng WANG ; Zhiling LUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(10):1517-1520
Echocardiography is an important imaging technique in mithal valve transcatheter edge-to-edge repair (TEER). During the operation, mitral leaflets capture and clamping have the highest requirements for ultrasound image quality and should be performed under the guidance of high-quality commissural view. However, standard commissural view cannot be obtained in some patients due to cardiac enlargement, transposition or limited esophageal acoustic window. In this condition, the optimal view can be obtained by Multivue technology. This paper reports a male patient aged 67 years with successful mitral valve TEER under the real-time guidance of Multivue technology, and summarizes the key points of this technology.
5.Dose-response relationship between working hours and occupational stress among primary and secondary school teachers
Lei LI ; Cui ZHOU ; Xiaoli LIU ; Sijia LÜQIU ; Yifan ZENG ; Huijia LONG ; Dan YU ; Zhiling YU
China Occupational Medicine 2025;52(5):511-515
Objective To analyze the current status of occupational stress among primary and secondary school teachers, and explore the dose-response relationship between weekly work hours and occupational stress. Methods A total of 1 252 teachers from 13 primary and secondary schools in three prefecture-level cities of a central province of China were selected as the research subjects by the convenience sampling method. The Core Occupational Stress Scale was used to assess occupational stress levels of the teachers. Multivariate logistic regression analysis combined with restricted cubic spline models was applied to study the dose-response relationship between weekly work hours and occupational stress. Results The average weekly work hours were (55.3±15.9) hours, with 78.6% of teachers working more than 40.0 hours per week. The total score of occupational stress was (40.3±8.2) points, and the detection rate of occupational stress was 29.8%. Multivariate logistic regression analysis combined with restricted cubic spline models revealed a linear dose-response relationship in weekly work hours and occupational stress among teachers (P for overall trend <0.05, P for nonlinearity was 0.22). Result of age-stratified analysis showed that weekly work hours had a linear dose-response relationship with occupational stress risk in teachers aged 21-<31 and 31-<46 years (P for overall trend <0.05, P for nonlinearity was 0.71 and 0.27, respectively). However, no association was found between weekly work hours and occupational stress risk among teachers aged ≥46 years (P for overall trend =0.08, P for nonlinearity was 0.09). Conclusion There is a linear dose-response relationship between weekly work hours and occupational stress among primary and secondary school teachers in the province, with younger teachers being more susceptible to suffer occupational stress due to long working hours.
6.Effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome at acute stage.
Mingjun YING ; Min YUAN ; Zhiliang LAI ; Zhiling LV ; Yiming LAI ; Chao LI ; Jingjing ZHOU ; Guiping HE ; Weifang ZHU
Chinese Acupuncture & Moxibustion 2025;45(12):1699-1704
OBJECTIVE:
To investigate the effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome (SHS) at acute stage.
METHODS:
Eighty patients with post-stroke SHS at acute stage were randomized into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case was eliminated). In the control group, the routine medication, basic rehabilitation training, and hyperbaric oxygen therapy were administered. In the observation group, besides the treatment as the control group, relaxing needling was delivered at the contracted sites of meridian-muscle regions. These contracted sites were distributed along three yin meridians of hand and three yang meridians of hand on the affected upper limbs. The intervention was given once daily, 5 times a week and for 4 weeks. Before and after treatment, the scores of visual analogue scale (VAS) for pain, edema degree, modified Barthel index (MBI), and Fugl-Meyer assessment (FMA) for motor function, and the integrated electromyography (iEMG) of surface electromyogram (sEMG) were observed in the two groups. The curative effect was evaluated after treatment and in follow-up of 2 months after treatment in the two groups.
RESULTS:
After treatment, VAS scores and the scores of edema degree were reduced when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). MBI and FMA scores increased after treatment compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05) after treatment. The iEMG values of the biceps brachii, triceps brachii, and wrist extensors were elevated after treatment in comparison with those before treatment (P<0.05) in the two groups, and the values in the observation group were larger than those in the control group after treatment (P<0.05). The total clinical effective rate in the observation group was 92.3% (36/39), which was better than that of the control group (74.4%, 29/39, P<0.05) after treatment; and that of the observation group was 97.4% (38/39), which was better than 82.1% (32/39) in the control group (P<0.05) in follow-up.
CONCLUSION
Relaxing needling at the contracted sites of meridian-muscle regions in treatment of post-stroke SHS at acute stage can attenuate the symptoms such as upper limb pain, swelling and spasm, improve motor function and the activity of daily living of patients.
Humans
;
Male
;
Female
;
Middle Aged
;
Acupuncture Therapy
;
Aged
;
Meridians
;
Stroke/complications*
;
Reflex Sympathetic Dystrophy/etiology*
;
Adult
;
Acupuncture Points
7.Clinical commissioning of Monte Carlo algorithm for synchrotron-based spot scanning proton therapy system
Mei CHEN ; Yuanlin YAN ; Hui ZHOU ; Xuming JIANG ; Yibin ZHANG ; Xiaodong HE ; Lu CAO ; Zhiling CHEN ; Manzhou ZHANG ; Cheng XU ; Jiayi CHEN
Chinese Journal of Radiation Oncology 2025;34(3):275-281
Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.
8.Identification of in vivo Components and Distribution Characteristics in Rats,Cardiac Tissues of Zhigancao Decoction by UP-LC-Q-TOF/MS
Zhiling TANG ; Yao LI ; Hao ZHI ; Jingyan WANG ; Xueting CAI ; Peng CAO ; Qian ZHOU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(7):896-903
OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction,a classic tradi-tional Chinese medicine formula,and provide scientific evidence for its rational application and development in modern clinical practice.METHODS Wistar rats were treated with 12.15 g·kg-1 Zhigancao Decoction by gavage.Rat plasma samples were collect-ed at 10 time points(5,15,30,60,120,240,360,480,600 and 720 min after administration)and rat heart(atrial and ventricu-lar)tissue samples were collected at 12 h after administration.Components in the plasma and heart samples were qualitatively identi-fied by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and the distri-bution characteristics of Zhigancao Decoction in vivo were analyzed.At the same time,the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.RESULTS A total of 11 prototype components(Ajugol,Nicotiflorin,Isoschaftoside,4-Hydroxycinnamic acid,Rehmapicrogenin,4-Hydroxybenzoic acid,4′,7-Dihydroxyflavone,Calycosin,3′,4′,7-Trihydroxyflavone,Pinellic acid,Truxillic acid)and 7 metabolites were identified from the plasma samples of Zhigancao Decoction,mainly including flavonoids(flavonoids glycosides),organic acids,and iridoid glyco-sides,etc.Additionally,6 prototype components(Ajugol,Isoschaftoside,Rehmapicrogenin,4′,7-Dihydroxyflavone,Liquiritigenin,3′,4′,7-Trihydroxyflavone)and 3 metabolites were identified from the cardiac samples(the atrium and the ventricle showed the same results).The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.CONCLUSION The prototype compo-nents and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined,providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.
9.A single-center analysis of the short-term efficacy and safety of RAPN in 45 patients with non-metastatic pT 3a renal cell carcinoma
Xiangpeng ZOU ; Yunhan LUO ; Zhiling ZHANG ; Zhaohui ZHOU ; Longbin XIONG ; Yulu PENG ; Yixin HUANG ; Xin LUO ; Wensu WEI ; Zhenhua LIU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Urology 2025;46(5):369-375
Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy(RAPN)for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was(54.3±10.7)years,and the average clinical tumor diameter was(4.9±1.8)cm. Of all the patients,35(77.8%)were asymptomatic,7(15.6%)presented with hematuria,and 3(6.7%)presented with lumbar pain. Preoperative imaging assessed 34 patients(75.6%)as having clinical stage T 3a,all suspected of involving the collecting system or perirenal fat invasion;the remaining 11 patients(24.4%)were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0(7.0,10.0). A history of hypertension,diabetes,or chronic kidney disease was present in 18 patients(40.0%). The primary endpoint was progression-free survival,and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method,and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients(71.1%),with a median estimated blood loss of 150.0(50.0,300.0)ml. Seven(15.6%)patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0(4.0,6.0)days. Postoperative complications occurred in 6 patients(13.3%),including 5(11.1%)with mild complications and 1(2.2%)with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients(61.5%),while 3 patients(7.7%)developed surgery-related chronic kidney disease 3 to 12 months postoperatively,but none required dialysis. The median follow-up time was 31.8(22.7,50.9)months,12(26.7%)patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up,3 patients experienced tumor recurrence,the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma,RAPN performed by experienced surgeons is a feasible and safe option,providing excellent short-term oncological outcomes,complication control,and renal function recovery. The long-term efficacy remains to be seen.
10.Clinical commissioning of Monte Carlo algorithm for synchrotron-based spot scanning proton therapy system
Mei CHEN ; Yuanlin YAN ; Hui ZHOU ; Xuming JIANG ; Yibin ZHANG ; Xiaodong HE ; Lu CAO ; Zhiling CHEN ; Manzhou ZHANG ; Cheng XU ; Jiayi CHEN
Chinese Journal of Radiation Oncology 2025;34(3):275-281
Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

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