1.Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics"
Hong-qian KUI ; Chuan-xin LIU ; Qiang WANG ; Hai-feng ZHAI ; Jian-mei HUANG
Acta Pharmaceutica Sinica 2024;59(2):336-349
Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.
2.Polyfoliate anterolateral thigh perforator flap in reconstruction of large soft tissue defects around ankle: a study on 11 cases
Tao LIANG ; Jinming TANG ; Junhua PAN ; Zunwen LIN ; Rong YUAN ; Kui DENG ; Gendong HUANG ; Huizhi DENG
Chinese Journal of Microsurgery 2024;47(1):22-27
Objective:To evaluate the viability and clinical effect of polyfoliate anterolateral thigh perforator flap (ALTPF) in reconstruction of large soft tissue defect around ankle.Methods:From June 2019 to October 2022, large soft tissue defects around ankle of 11 patients were reconstructed with ALTPF in the Department of Orthopaedics of the First Affiliated Hospital of Nanchang University. The causes of injury were traffic accident in 8 patients and heavy objects in 3 patients. All wounds were large defects (15.0 cm×14.0 cm-30.0 cm×20.0 cm) and combined with various degrees of infection. Intraoperatively, polyfoliate ALTPFs sized 16.0 cm×14.5 cm-23.0 cm×18.5 cm were used in reconstruction of the defects. Deep dead spaces were filled with antibiotic bone cement, and direct suture was performed to close the donor sites or by skin grafting repair. Postoperative follow-ups were scheduled at 1, 3 and 6 months, and 6 monthly thereafter at outpatient clinics and via telephone interviews. The appearance and colour of the flaps and healing of donor sites were recorded together with evaluation of the recovery of ankle motor function according to the ankle-hindfoot rating scale of American Orthopaedic Foot and Ankle Society (AOFAS).Results:All flaps survived. No haematoma or secondary infection occurred at the recipient site after surgery. All donor sites healed primarily. One patient had venous occlusion at the distal end of the polyfoliate ALTPF. The flap survived completely at 1 week after distal venous bloodletting. Postoperative follow-ups lasted 6-24 (15.27±5.21) months. All flaps had good blood supply with satisfactory appearance, similar colour and texture to the recipient sites, and without obvious bloat nor ulceration. Only a linear scar or few skin graft scar was left at the flap donor sites in concealed locations. The mean AOFAS ankle-hindfoot score was (88.36±10.21) point. There were 6 cases of excellent, 4 cases of good, and 1 case of fair.Conclusion:A polyfoliate ALTPF is an ideal flap for reconstruction of soft tissue defects around ankle by converting the length of a flap to the width.
3.Evaluation of Potential Donors With Different Causes of Brain Death for Adult Heart Transplantation:a Bedside Echocardiographic Study
Xin SUN ; Jie LIU ; Zhongkai LIAO ; Kui XU ; Sheng LIU ; Jie HUANG ; Zhe ZHENG ; Hao WANG ; Zhenhui ZHU
Chinese Circulation Journal 2024;39(5):484-489
Objectives:To investigate the feasibility of using bedside echocardiography on the evaluation of potential donors with different causes of brain death for adult heart transplantation. Methods:Bedside echocardiographic and clinical data of consecutive potential donors for adult heart transplantation evaluated by the team of our institution from February 2018 to December 2020 were retrospectively analyzed.Based on different causes of brain death,the potential donors were divided into stroke(ischemic or hemorrhagic,n=398)and non-stroke(head trauma,brain tumor,anoxia,n=272)groups.The clinical and echocardiographic features were compared between the two groups.A total of 350 donors were assigned to our hospital by the China Organ Transplant Response System and met the inclusion criteria for donor selection.There were 195 cases in the stroke group and 155 in the non-stroke group.Retrieval operations were performed and the retrieval rate of hearts for transplantation in stroke donors was compared to that in non-stroke donors. Results:(1)Among the 670 potential heart donors,compared with the non-stroke group,donors in the stroke group were significantly older,had higher body mass index,larger left ventricular end-diastolic diameter,thicker interventricular septum,higher rates of echocardiographic abnormalities,higher prevalence of hypertension(all P<0.001).Among the 670 potential heart donors,17.5%(117 cases)did not meet the echo selection criteria,the common causes were left ventricular hypertrophy(59 cases,50.4%),left ventricular ejection fraction<50%(27 cases,23.1%),wall motion abnormalities(21 cases,17.9%),and left ventricular dilation(14 cases,12.0%).(2)Among the 350 donors who had met the selection criteria and assigned to our hospital by the China Organ Transplant Response System and underwent retrieval operation,70.3%(246 cases)were successfully procured,110 cases(44.7%)in the stroke group and 136 cases(55.3%)in the non-stroke group.The retrieval rate of stroke donors(110/195,56.4%)was lower compared with that of non-stroke(136/155,87.7%,P<0.001),104 cases(29.7%)were not retrieved,and the leading cause of unsuccessful organ retrieval was the occlusion of at least one major coronary artery(91 cases,87.5%). Conclusions:Bedside echocardiography is of great value as a screening tool for cardiac donors.Cardiac structures of the potential donor with stroke as the cause of brain death were different from those with non-stroke causes.The retrieval rate of stroke donors was lower than that of non-stroke donors,even if the initial criteria for donor selection were fulfilled.
4.Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions
Teng-Fei TIAN ; Fu-Hao MO ; Hao-Yang SU ; Can HUANG ; Hui ZHAO ; Jun LIU ; Bo SHANG ; Kui LI ; Jin-Long QIU
Chinese Journal of Traumatology 2024;27(4):235-241
Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.
5.Research progress on inflammatory mechanism and treatment in aneurysmal subarachnoid hemorrhage
Ming ZHANG ; Xiao-Wei SONG ; Xiao-Kui GAN ; Yi-Ming FANG ; Bao-Sheng HUANG
Medical Journal of Chinese People's Liberation Army 2024;49(11):1336-1342
Aneurysmal subarachnoid hemorrhage(aSAH),primarily caused by the rupture of intracranial aneurysms with bleeding into the subarachnoid space,is an acute neurological disease associated with high disability and mortality.Brain injury after aSAH results from a combination of injury mechanisms,with early brain injury(EBI)occurring within 72 hours post-onset,laying the foundation for subsequent pathophysiological changes in the brain and poor prognosis of patients.Among them,the brain immunoinflammatory response,involving the interaction of various immune cells and active substances,plays a significant role in post-aSAH EBI,and is related to delayed brain injury and long-term prognosis.Systemic inflammatory response following aSAH can also affect the prognosis and outcome of patients.This review summarizes the role of local and systemic immune inflammatory responses in the occurrence and progression of aSAH,as well as the research progress on related inflammatory biomarkers and therapeutic prospects,aiming to provide a theoretical reference for new treatment for aSAH.
6.Angelica Sinensis polysaccharide promoting hematopoietic reconstruction in receptor mice after bone marrow transplantation
Ting YANG ; Kui LIAO ; Cai-Hong HUANG ; Han WEI ; Cheng WANG ; Kun-Hang DU ; Zi-Ling WANG ; Lu WANG ; Ya-Ping WANG
Acta Anatomica Sinica 2024;55(5):556-564
Objective To explore the mechanism of Angelica Sinensis polysaccharide(ASP)promoting donor bone marrow transplantation(BMT)to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells(BMSCs).Methods Bone marrow mononuclear cells(BMMNCs)of male C57BL/6J mice aged 8-10 weeks were separated,purified and transplanted into female receptor mice of the same age.On the ninth day,receptor mice BMMNCs were separated,purified and transplanted again into female receptor mice.The transplanted receptor mice were divided into control group:sham irradiation;Irradiation(IR)group:a whole-body irradiation with a total dose of 8.0 Gy X-ray;BMT group:the receptor mice treated in the same way as the IR group and transplanted BMMNCs(5×106 cells)from male donor via the tail vein;BMT+ASP group:the receptor mice treated in the same way as the BMT group,and injected ASP[100 mg/(kg·d)×9]by intraperitoneal route from the first day of transplantation.Changes in body weight and survival rate of mice were recorded during modeling,receptor mice BMMNCs were collected to detect sex-determining region of Y(SRY)gene after building model,peripheral blood indexes,the number of BMMNCs in femur and histopathology of bone marrow were detected;BMSCs in receptor mice was separated and purified,BMSCs adhesion ability was observed,proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in BMSCs were detected;The levels of granulocyte-macrophage colony-stimulating factor(GM-CSF),stem cell factor(SCF),insulin-like growth factor 1(IGF-1)in culture supernatant of BMSCs were determined,CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes(Notch1,Jagged1,Hes1)in BMMNCs were measured by Real-time PCR.Results All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious.The SRY gene was detected in the receptor female mice BMMNCs.Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced.ASP promoted the proliferation of BMSCs,decreased the contents of ROS and MDA,and increased the activity of SOD in BMSCs.ASP promoted the secretion of SCF,GM-CSF and IGF-1 in BMSCs,and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs.ASP increased the expression of Notch1,Jagged1 and Hes1 mRNA in BMMNCs.Conclusion The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment,improving the secretion of hematopoietic growth factors in BMSCs,and regulating Notch signaling pathway.
7.Image-guided Strategy of Intensity-modulated Radiotherapy in Helical Tomography for Nasopharyngeal Carcinoma
Meng-xue HE ; Pei-xun XU ; Hong HUANG ; Xuan-guang CHEN ; Hui-lang HE ; Zi-xian ZHANG ; Hui LIU ; Sen-kui XU ; Wen-yan YAO
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):131-137
ObjectiveThis study aimed to analyze the difference in setup error before and after correction of systematic error. To determine the most appropriate image-guided strategy during HT treatment, we use different scanning ranges and image-guidance frequencies in patients with nasopharyngeal carcinoma (NPC) treated with helical tomotherapy (HT). MethodsFifteen patients with NPC who received HT treatment in Sun Yat-sen University Cancer Center from October 2019 to February 2020 were selected. Megavoltage computed tomography (MVCT) scanning was performed before each treatment. After five times of radiotherapy, system-error correction was performed to adjust the setup center. The setup errors before and after the correction of systematic errors, as well as the setup errors of different scanning ranges and different scanning frequencies, were collected for analysis and comparison. ResultsWhen comparing the setup errors before and after the correction of systematic error, the differences in setup errors in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions were statistically significant (P<0.05).The different scanning ranges of "nasopharynx + neck" and "nasopharynx" were compared, and a statistically significant difference was found in yaw rotational errors (P<0.05). In the comparison of daily and weekly scan frequency after system-error correction, a significant difference was found in AP direction (P<0.05). ConclusionDuring radiotherapy for NPC, the systematic error can be corrected according to the first five setup errors, and then small-scale scanning was selected for image-guided radiotherapy every day.
8.Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity
Chih-Hsin LIN ; Yu-Shao HSIEH ; Ying-Chieh SUN ; Wun-Han HUANG ; Shu-Ling CHEN ; Zheng-Kui WENG ; Te-Hsien LIN ; Yih-Ru WU ; Kuo-Hsuan CHANG ; Hei-Jen HUANG ; Guan-Chiun LEE ; Hsiu Mei HSIEH-LI ; Guey-Jen LEE-CHEN
Biomolecules & Therapeutics 2023;31(1):127-138
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
9.An analysis of the investigation results of radionuclide content in food in Chongqing, China
Qiang HUANG ; Wei LI ; Kui LI
Chinese Journal of Radiological Health 2023;32(4):433-437
Objective To investigate the radionuclide content in food in Chongqing, China by conducting a survey on the radioactivity in food. Methods A total of 114 samples of vegetables, grain, milk powder, and tea were collected in Chongqing. The samples were dried, pulverized into powder, added into Marinelli beakers, and then measured for radionuclides using a high-purity germanium gamma spectrometer (GEM40P4-765). Results The mean activity concentrations of natural radionuclides 238U, 232Th, 226Ra, and 40K in food in Chongqing were (0.396 ± 0.510), (0.199 ± 0.296), (0.140 ± 0.209), and (119.250 ± 105.470) Bq/kg, respectively. The contents of radionuclides in different foods were significantly different (P < 0.05). The mean activity concentration of the artificial radionuclide 137Cs was (0.091 ± 0.308) Bq/kg, and the mean activity concentration of 90Sr measured in nine tea samples was (1.243 ± 0.860) Bq/kg. Conclusion The contents of radionuclides in food in Chongqing are lower than the national standard limits, but the safety of radioactivity in food still needs to be taken seriously, and long-term surveillance of radioactivity in food is needed.
10.Smart Hip Ultrasound Technology in Screening for Infant Developmental Dysplasia of the Hip
Ying XU ; Hong-kui YU ; Xiao-ying LIN ; Yang ZHAO ; Xing-yi YANG ; Zi-yin HUANG ; Xiao XU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(5):870-877
ObjectiveTo develop a deep learning system for early ultrasound screening of developmental dysplasia of the hip (DDH), a new smart-hip ultrasound technique (S-hip), and to validate its clinical application. MethodsWe selected 11,100 annotated and reviewed coronal ultrasound images of infant hips between November 2021 and August 2022, 8,100 of which were used for the training set and 3,000 for the test set, to build a S-hip deep learning system. To verify the consistency between the automated measurement by S-hip and the manual measurements by sonographers, 174 standard coronal ultrasound images of 87 infants' bilateral hips were acquired, then α angle, β angle and femoral head coverage (FHC) were measured by S-hip, an ultrasound expert and a resident. The measurement data and the time required for the measurements were recorded and statistically analyzed. Another 100 standard coronal ultrasound images of the hips were randomly selected and measured twice respectively by the ultrasound expert and resident to assess the intra-sonographer repeatability. ResultsThe intraclass correlation coefficient (ICC) (95% CI) values of α angle, β angle and FHC results measured by S-hip and ultrasound expert were 0.799 (0.738, 0.847), 0.798 (0.737, 0.846) and 0.934 (0.954, 0.975), respectively. Those values measured by the ultrasound expert and resident were 0.725 (0.645, 0.789), 0.674 (0.583, 0.748) and 0.931 (0.908, 0.949), respectively. The mean absolute errors (MAE) of α angle, β angle and FHC results between measurements by S-hip and ultrasound expert were 2.69 °, 4.43 ° and 2.47%, respectively. The time required for measurements by S-hip, ultrasound expert and resident was (1.59±0.36) s, (18.76±2.23) s and (19.45±2.76) s, respectively. The automated measurement by S-hip cost much shorter time than the manual measurements by sonographers and the difference was statistically significant (P<0.001). The ICC (95% CI) values of α angle, β angle and FHC results between two measurements by the ultrasound expert were 0.943 (0.916, 0.961), 0.959 (0.940, 0.972), and 0.981 (0.971, 0.987), respectively. Those values by the ultrasound resident were 0.884 (0.833, 0.921), 0.921 (0.884, 0.946), and 0.962 (0.944, 0.974). ConclusionThe S-hip based on a deep learning system is a highly reliable automated technique to accurately measure α angle, β angle and FHC. Compared with ultrasound residents, S-hip allows for a more simplified and significantly quicker measurement, which may enhance the widespread use of hip ultrasound screening in infants.

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