1.Network pharmacological analysis on Balanophora involucrata Hook.f.in treatment of hyperuricemia and its therapeutic effect on hyperuricemia cell model and hyperuricemia model mouse
Li LIU ; Linsheng HUANG ; Yongheng ZHAO ; Wenjie CAO ; Yongshuai QIAN ; Huifan YU ; Fei LI
Journal of Jilin University(Medicine Edition) 2024;50(1):58-70
Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.
2.The application of endoscopic tubular musculoskeletal tumor surgery in the treatment of spinal tumors
Guowen WANG ; Yan ZHANG ; Yao XU ; Chengliang ZHAO ; Xiuxin HAN ; Chao ZHANG ; Jinyan FENG ; Yongheng LIU ; Yuxiang SHEN ; Zhe FENG
Chinese Journal of Orthopaedics 2024;44(20):1339-1348
Objective:To explore the effect and safety of endoscopic tubular musculoskeletal tumor surgery (ETMS) technology in spinal tumors.Methods:Clinical data were retrospectively collected from 18 spinal tumor patients who were treated with ETMS technology at Tianjin Medical University Cancer Institute and Hospital ( n=16) or the Affiliated Hospital of Qingdao University ( n=2) from November 2022 to December 2023. The total cohort included 11 males and 7 females, with the age at 60.3±8.6 years (range of 41-76). Two cases were diagnosed with benign tumors, four patients were diagnosed with spinal hematologic malignancies while other 12 cases were patients with spinal metastases. After localization under the C-arm X-ray machine, the spinal endoscopic channel is established using dilators. Soft tissue is dissected under endoscopic guidance to create an artificial cavity. Subsequently, the saline medium relied upon by the spinal endoscopic technique is removed, and posterior decompression and tumor curettage are performed using tubular techniques. Frankel grade classification and paraplegia index were used to evaluate the improvement of postoperative function and the VAS score was performed in pain scoring. The surgical complications and tumor evaluation were observed by postoperative outpatient and telephone follow-up. Results:The ETMS technology was successfully completed in all 18 patients with the mean operation time of 240.3±80.2 min. The median of intraoperative bleeding was 200.0(172.5, 350.0) ml and the mean postoperative drainage was 131.4±69.5 ml. The median value of postoperative hospitalization days was 6.0(4.0, 10.25) d. The paraplegia index decreased from 1.5(0, 3.0) preoperatively to 0(0, 1.25) postoperatively ( Z=-2.599, P=0.009). All the patients presented an improvement in Frankel grading after surgery except for one patient (downgrading from grade E to grade D). There was significantly difference in Frankel grading between preoperative and postoperative groups ( Z=2.812, P=0.005). The median value of preoperative VAS score was up to 5.5(4.0, 7.0) while the median value at postoperative, one month after surgery and three months after surgery were 1.5(1.0, 2.25), 1.0(0, 1.0) and 0(0, 1.0), respectively (χ 2=44.641, P<0.001). The 3-month postoperative VAS improvement rate was 91.2% (range 75%-100%). During a mean follow-up period of 7.6±6.2 months, none of the 18 patients presented surgical complications or tumor recurrence at surgical region. Only one patient died at 3.2 months after surgery until the last follow-up due to respiratory failure after lung tumor progression. The mean survival of the total cohort was up to 13.3 [95% CI (11.5, 15.0)] months. The 16 cases with spinal metastases or spinal hematological malignancies had a mean survival of 13.2 [95% CI (11.3, 15.0)] months. Conclusion:The ETMS technology presented good efficacy and safety in treatment of spinal tumors with low blood supply and with diameter less than 5cm.
3.Prognosis of epilepsy after operation for low-grade insular glioma
Panjie SHI ; Yongheng WANG ; Yingjie HAN ; Jianhua ZHAO ; Zhiguang HAN ; Ying HAN
Journal of Clinical Surgery 2023;31(11):1023-1026
Objective To explore the influencing factors and prognosis of epilepsy after operation for insular low-grade gliomas.Methods The clinical data of 120 patients with insular low-grade gliomas with pre-operative seizure symptoms in the Chinese glioma Genome Atlas Project(CGGA)database from July 2008 to June 2014 were retrospectively analyzed.The seizure control and survival prediction information of the patients were followed up one year after operation.The risk factors affecting post-operative seizures were analyzed by Logistic multiple factor regression analysis,Kapla-Meier curve was used to analyze the effect of postoperative epilepsy control factors on progression free survival(PFS)and overall survival(OS).Results Before operation,36 cases(30.0%)had simple focal seizures,53 cases(44.2%)had focal seizures with different degrees of cognitive impairment,and 31 cases(25.8%)had generalized seizures.During the follow-up after one year of surgical treatment,72 patients(60%)had a complete improvement in epilepsy symptoms(Engel grade Ⅰ),33 patients(27.5%)had a significant improvement(Engel grade Ⅱ),11 patients(9.2%)had a significant improvement(Engel grade Ⅲ),and 4 patients(3.3%)had no improvement or deterioration(Engel grade Ⅳ).Larger tumor resection degree,no putamen involved,IDH1 mutation are favorable factors for postoperative control of epilepsy.Improvement of seizures was a favorable prognostic factor for PFS and OS.Conclusion Epilepsy is the most common symptom of insular gliomas.The improvement of postoperative epilepsy symptoms is related to the degree of tumor resection,involvement of putamen and IDH1 mutation status.Complete improvement of epilepsy symptoms can prolong the progression free survival time and overall survival time of patients.
4.Effect of single nucleotide variation of OPG gene on osteoporosis in patients with gestational diabetes mellitus
Lina MA ; Cong WANG ; Guixiang MEN ; Yongheng ZHAO ; Shuai SHAO
Chinese Journal of Endocrine Surgery 2023;17(2):209-213
Objective:To investigate the effect of single nucleotide variation of osteoprotegerin (OPG) gene on the occurrence of osteoporosis (OP) in patients with gestational diabetes mellitus (GDM) .Methods:From Apr. 2018 to Apr. 2022, 276 pregnant women with GDM who underwent prenatal examination and gave birth in Linyi People’s Hospital were collected for analysis, general data were collected and bone mineral density was tested. According to the bone mineral density test results, they were divided into normal group and OP group. The OPG genotype was tested, and the general information, OPG genotype and allele frequency of the two groups were compared. The differences in bone mineral density among different genotypes of OPG were compared, and the genotypes affecting the risk of OP in GDM patients were analyzed.Results:There was no significant difference in the general data of the two groups of patients (all P>0.05). The allelic distribution of the rs3134069 and rs2073618 loci of the OPG gene in the two groups of patients conformed to the Hardy-Weinberg equilibrium law (all P>0.05). There was a statistically significant difference in the frequency of the AC genotype at rs3134069 between the two groups ( χ2=7.75, P=0.005). Taking patients with the AA genotype as a reference, patients with the AC genotype had a lower risk of developing OP ( OR=0.15, 95% CI: 0.03-0.59). There was a statistically significant difference in the frequency of CC genotype at rs2073618 between the two groups ( χ2=11.30, P=0.001). Taking patients with GG genotype as a reference, patients with CC genotype had a higher risk of developing OP ( OR=7.42, 95% CI: 2.19-27.18). Comparing rs3134069 and rs2073618 loci, there was no significant difference in bone mineral density at each part of the three genotypes (all P>0.05). The multivariate Logistic regression model showed that the AC genotype of rs3134069 ( OR=0.18, 95% CI: 0.03-0.70, P=0.029) was a protective factor for the induction of OP, while GC genotype of rs2073618 ( OR=6.86, 95% CI: 1.57-27.15, P=0.007) were the risk factors for OP in GDM patients. Conclusion:The CC genotype of rs2073618 is significantly positively correlated with the susceptibility to OP in GDM patients.
5.Personalized quantitative evaluation of the quality of radiotherapy plans based on dose prediction
Bingzhi WU ; Zhao PENG ; Yongheng YAN ; Jieping ZHOU ; Xie XU ; Xi PEI
Chinese Journal of Radiological Medicine and Protection 2022;42(3):188-193
Objective:To develop a dose prediction-based quantitative evaluation method of the quality of radiotherapy plans, and to verify the clinical feasibility and clinical value of the method .Methods:The 3D U-Netwas trained using the radiotherapy plans of 45 rectal cancer cases that were formulated by physicists with more than five years of radiotherapy experience. After obtaining 3D dose distribution using 3D U-Net prediction, this study established the plan quality metrics of intensity modulated radiotherapy(IMRT) rectal cancer radiotherapy plans using dose-volume histogram(DVH) indexes of dose prediction. Then, the initial scores of rectal cancer radiotherapy plans were determined.Taking the predicted dose as the optimization goal, the radiotherapy plans were optimized and scored again. The clinical significance of this scoring method was verified by comparing the scores and dosimetric parameters of the 15 rectal cancer cases before and after optimization.Results:The radiotherapy plans before and after optimization all met the clinical dose requirements. The total scores were(77.21±9.74) before optimization, and (88.78±4.92) after optimization. Therefore, the optimized radiotherapy planswon increased scores with a statistically significant difference( t=-4.105, P<0.05). Compared to the plans before optimization, the optimized plans show decreased Dmax of all organs at risk to different extents. Moreover, the Dmax, V107%, and HI of PTV and the Dmax of the bladder decreased in the optimized plans, with statistically significant differences ( t=2.346-5.771, P<0.05). There was no statistically significant difference in other indexes before and after optimization ( P>0.05).The quality of the optimized plans were improved to a certain extent. Conclusions:This study proposed a dose prediction-based quantitative evaluation method of the quality of radiotherapy plans. It can be used for the effective personalized elevation of the quality of radiotherapy plans, which is beneficial to effectively compare and review the quality of clinical plans determined by different physicists and provide personalized dose indicators. Moreover, it can provide great guidance for the formulation of clinical therapy plans.
6.A kidney donor with brain death from wild mushroom poisoning: a case report and literature review
Qian YANG ; Yongheng ZHAO ; Chao LI ; Xun SUN ; Wei HU ; Hongren XU ; Li LI
Chinese Journal of Organ Transplantation 2020;41(5):297-300
Objective:To report a pediatric organ donor with brain death due to wild mushroom poisoning to examine whether or not brain death caused by mushroom poisoning might become a potential organ donor and how to evaluate donated organs.Methods:Strict clinical observations, laboratory tests and biopsy were performed for potential donor.Results:This donor's clinical changes were consistent with toxic hepatitis. Gross morphology, laboratory examinations and pathological biopsy of two kidneys were generally normal during organ acquisition. Two kidneys were assigned to two adult recipients and liver was discarded. After a follow-up period of 6 months, one recipient recovered well while another gradually recovered after delayed graft function.Conclusions:This extraordinary case provides some references for selecting potential donors of mushroom poisoning. When the donor's relevant laboratory tests are normal, there is no pathological contraindication, sufficient time is available for estimating the type of mushroom poisoning, observing the trends of organ damage and waiting for the toxin clearance, donor with brain death from wild mushroom poisoning may donate organ.
7.Pedicled bridge transplantation for soft tissue defects at the contrallateral leg with medial leg skin flap and medial hemi-soleus muscle flap
Gonglin ZHANG ; Fugui SHI ; Jun HU ; Tiejun GONG ; Yongheng WANG ; Laixu ZHAO ; Junlin YANG ; Jianhua ZHOU ; Qinyi XUE
Chinese Journal of Orthopaedic Trauma 2020;22(2):162-165
Objective:To evaluate the pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap for the treatment of soft tissue defects at the contrallateral leg.Methods:Between January of 2012 and January of 2016, 8 patients with soft tissue defects at the leg were treated at Department of Orthopedic Surgery, Hand and Foot Surgery Hospital of Lanzhou. They were 5 men and 3 women, aged from 19 to 50 years (mean, 35 years). All of them were treated by bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap pedicled with posterior tibial artery. The size of the defects ranged from 10 cm×9 cm to 13 cm×8 cm. The immediate coverage of the muscle flaps and vessel pedicle was repaired by a meshed split-thickness skin graft. The donor site was closed directly. The therapeutic efficacy was assessed at the final follow-up according to the criteria by Iowa for tibial fractures.Results:All the skin flaps and muscle flaps survived without any vascular crisis. One case developed necrosis of small skin graft at the distal muscle flap which spontaneously healed after dressing change for 2 weeks. Their follow-up ranged from 2.5 to 4.5 years (mean, 3.8 years). A good contour was confirmed at the recipient area. By the Iowa criteria at the final follow-up, 3 cases were excellent, 4 good and one fair.Conclusion:Pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap is a good treatment for soft tissue defects at the contrallateral leg which has only one major blood vessel, reducing damage to the donor site.
8.Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial
Lin WANG ; Yiming ZHAO ; Tingting SUN ; Yuanlian XU ; Shijie LI ; Xiaoyan ZHANG ; Yong CAI ; Yongheng LI ; Zhongwu LI ; Pengju CHEN ; Yifan PENG ; Weihu WANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2020;23(3):258-265
Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.
9.Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial
Lin WANG ; Yiming ZHAO ; Tingting SUN ; Yuanlian XU ; Shijie LI ; Xiaoyan ZHANG ; Yong CAI ; Yongheng LI ; Zhongwu LI ; Pengju CHEN ; Yifan PENG ; Weihu WANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2020;23(3):258-265
Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.
10. Applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou
Yanshan CAI ; Yuzhou GU ; Fei ZHONG ; Lirui FAN ; Yuteng ZHAO ; Yefei LUO ; Yongheng LU ; Weiyun HE ; Weibin CHENG ; Huifang XU
Chinese Journal of Epidemiology 2019;40(10):1212-1216
Objective:
This article was to evaluate the applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou. Hopefully, the results could be used to improve the existing HIV testing services and to support the implementation and scale-up of HIV self-testing programs.
Methods:
Data were collected from a survey on HIV testing preferences among the Internet-using MSM in April to June, 2015. Univariate and multivariate logistic regression analysis were applied to identify factors associated with the use of HIV self-testing service provided by Lingnanzhun. Information related to the users of Lingnanzhun during September 2014 and December 2018 was also collected.
Results:
769 MSM were recruited as participants. Of them, age distribution was 16-77(28.6±6.8) years old, 88.3

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