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BACKGROUND: RNA 3'-terminal phosphate cyclase-like protein (Rcl1) is involved in pre-rRNA processing, but its implication in cancers remains unclear. METHODS: RCL1 expressions in 21 malignancies was examinated through GEPIA website portal. Clinical implication data related to RCL1 level in Hepatocellular Carcinoma (HCC) samples were downloaded through TCGA, ICGC, GEO databases. Survival analysis and gene function enrichment analyses were performed through R software. The correlation between RCL1 expression and tumor immune infiltration was assessed via the TIMER2.0 database. The effects of Rcl1 overexpression or knockdown on cell growth and metastasis was evaluated by CCK8, transwell, and cell cycle assays. RESULTS: RCL1 expression is commonly down-regulated in HCC. The lower expression of RCL1 is associated with higher tumor stage, higher AFP level, vascular invasion, and poor prognosis. RCL1 expression has a significant correlation with immune cells infiltration in HCC, especially myeloid-derived suppressor cell (MDSC). Moreover, it was further identified that Rcl1 expression was reduced in HCC cell lines and negatively correlated with invasion of HCC cell lines. Immunofluorescence (IF) analysis revealed that the level of Rcl1 expression in the cytoplasm of HCC cells is significantly lower than that in the cytoplasm of L-02 cell. Moreover, both gain- and loss-of-function studies demonstrated that Rcl1 inhibited the growth and metastasis of HCC cells and regulated cell cycle progression in vitro. CONCLUSIONS: Rcl1 may serve as a novel tumor suppressor in HCC, and its biological effect needs further study.
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Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.
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The laccase (PpLAC) gene family members in peach fruit were identified and the relationship between their expression pattern and chilling induced browning were investigated. The study was performed using two varieties of peaches with different chilling tolerance, treated with or without exogenous γ-aminobutyric acid (GABA) during cold storage. Twenty-six genes were screened from the peach fruit genome. These genes were distributed on 6 chromosomes and each contained 5-7 exons. The PpLAC gene family members shared relatively similar gene structure and conserved motifs, and they were classified into 7 subgroups based on the cluster analysis. Transcriptome sequencing revealed that the expression levels of PpLAC7 and PpLAC9 exhibited an increasing pattern under low temperature storage, and displayed a similar trend with the browning index of peach fruit. Notably, GABA treatment reduced the degree of browning and inhibited the expression of PpLAC7 and PpLAC9. These results suggested that PpLAC7 and PpLAC9 might be involved in the browning of peach fruit during cold storage.
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Food Storage , Fruit/genetics , Laccase/genetics , Prunus persica/geneticsABSTRACT
Objective To analyze the efficacy and safety of PD-1 inhibitor combined with anlotinib on advanced neuroendocrine carcinoma. Methods We collected the data of patients with advanced neuroendocrine carcinoma who had failed the first-line standard chemotherapy and treated with PD-1 inhibitor combined with anlotinib from the First Affiliated Hospital of Zhengzhou University. Results A total of 45 patients, including 24 males and 21 females, were included. The median age was 57 years old. The primary tumor sites were lung (23 cases, 51.1%), esophagus (8 cases, 17.8%), pancreas (7 cases, 15.6%) and rectum (7 cases, 15.6%). Eighteen cases (40%) had failed the first- and second-line treatments, and 27 cases (60%) had failed the third-line and above treatments. All patients received 2-15 cycles of treatment, 3 cases died due to disease progression, overall objective response rate was 11.1%, disease control rate was 53.5%, median progression-free survival was 5.8 months, and 10-month progression-free survival rate was 25.5%. Adverse events were mainly grade 1-2 myelosuppression and digestive tract reactions. Conclusion PD-1 combined with anlotinib show better efficacy and good tolerance on advanced neuroendocrine carcinoma. It can be used as a choice after the failure of standard first-line treatment of advanced neuroendocrine carcinoma.
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Objective:To investigate the clinical feasibility of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in the quantitative assessment of blood perfusion of hepatocellular carcinoma (HCC).Methods:Between January 2020 and August 2021, 36 HCC patients (39 lesions in total) confirmed by pathology and clinical diagnosis without any treatment from Zhongshan Hospital, Fudan University were enrolled and underwent both 2D-CEUS and 3D-CEUS examinations. Each examination last for 150 s and all images were recorded, and then the data were analyzed. A region of interest was manually drawn along the margin of the whole tumor and then the time-intensity curve (TIC) generated. The following perfusion parameters were extracted: peak intensity (PI), peak time (TTP), ascending slope (AS), mean transit time (MTT) and area under the curve (AUC). After calculating the quality of fit (QOF) of the curve, the intraobserver agreement of the 3D-CEUS quantitative parameters obtained by the same doctor between two times were assessed, and the consistency of the 3D-CEUS and 2D-CEUS quantitative parameters was evaluated when QOF>75%. The differences of the quantitative parameters between different groups (divided by depth of 8 cm and necrosis rate of 50%, respectively) in 3D-CEUS were compared.Results:There were 38 lesions (97.4%, 38/39) with QOF>75% in 3D-CEUS. The intraobserver agreement was excellent, the intraclass correlation efficient(ICC) values was 0.85-0.99. The consistency of the time quantitative parameters (TTP and MTT) were high (the ICC values of 0.87 and 0.91), and the correlation of intensity quantitative parameters were substantial, the rs values were 0.71, 0.72 and 0.71. The differences in 3D-CEUS quantitative parameters of the two groups of lesions with different depths were statistically significant (all P<0.05); but there were no significant differences in quantitative parameters between the two groups with different necrosis rate (all P>0.05). Conclusions:Quantitative 3D-CEUS is an useful and creditable tool in evaluating the blood perfusion of HCC, especially when the depth of lesion was less than 8 cm.
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Since the outbreak of Corona Virus Disease 2019 (COVID-19) in December 2019, the number of new confirmed cases in Wuhan has been increasing, and medical resources are in short supply. Under this grim situation, makeshift hospitals have been used to treat patients with mild symptoms and achieved the largest capacity. Under the model of concentrated admission in makeshift hospitals with limited medical resources, the frontline surgeons adopt strict disease observation and treatment strategies, actively carry out psychological counseling for patients, and organize multidisci-plinary teams to deal with chronic and emergency surgical diseases of patients with COVID-19. Combined with their own clinical practices, the authors summarize a series of clinical experiences for the treatment of patients with COVID-19.
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Objective:To explore the clinical characteristics and risk factors of incomplete endoscopy of small intestine capsule.Methods:From August 2015 to February 2019, the data of 282 patients with small intestine examination by capsule endoscopy in Affiliated Hospital of Xuzhou Medical University were analyzed retrospectively.The clinical and laboratory examination data were statistically analyzed.The risk factors of incomplete small intestine examination were analyzed by multivariate logistic regression.Results:In all 282 patients, 45 cases did not complete the examination, the incomplete rate was 16.0% (45/282). Multivariate analysis showed that male ( OR=3.261, 95% CI1.084-9.815, P=0.035), age (64.78±13.23) years ( OR=1.046, 95% CI1.007-1.086, P=0.020), intragastric time (59.78 (27.89, 108.67)) min ( OR=1.014, 95% CI1.005-1.024, P=0.004), gastrointestinal bleeding ( OR=3.017, 95% CI1.025-8.880, P=0.045), abdominal operation history ( OR=4.902, 95% CI1.553-15.470, P=0.007) were risk factors for incomplete examination.Hemoglobin (95.20±26.16) g/L( OR=0.977, 95% CI0.957-0.998, P=0.033), albumin (35.73±7.11) g/L( OR=0.871, 95% CI0.790-0.961, P=0.006) were protective factors for incomplete examination. Conclusion:Male, age, intragastric time, gastrointestinal hemorrhage and abdominal operation history were risk factors for incomplete small bowel examination with capsule endoscopy, and hemoglobin and albumin were protective factors.Before capsule endoscopy, patients should not only evaluate the intestinal stenosis, but also pay attention to the nutritional status and clinical symptoms of patients, so as to improve the completion rate of patients.
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Wuhan is the city with the most serious outbreak of corona virus disease 2019 (COVID-19) in China. The outbreak of community has exhausted the current medical resources. With integrating local and support medical resources from other province, Wuhan City has rapidly rebuilt a new emergency medical system of classified treatment, and effectively responded to the overload medical demand after the outbreak in the community.
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Objective To investigate the effects of glutamate (Glu) injected into hypothalamic pa-raventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possi-ble mechanism. Methods Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th,10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group),CVH + injection of saline into PVN group (NS group),CVH+ injection of Glu into PVN (3,6,and 12 μg Glu,namely G3,G6,and G12,respectively),6 rats in each group,and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold,abdominal withdrawal reflex (AWR) score,and abdominal external ob-lique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL. Results Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups in-creased,and the AWR scores and EMG amplitudes decreased. The differences were statistically significant (Pain threshold:t=7. 65,16. 31,24. 78,both P<0. 05;AWR scores:t=-2. 98,-4. 77,-7. 29,both P<0. 05;EMG amplitudes:t=-3. 06,-5. 75,-8. 92,both P<0. 05). Compared with the Sham group,the expression of AVP in PVN of the CVH group and NS group decreased ((42. 63±5. 20) %,(18. 67±2. 94) %,(17. 53± 2. 47) %; t=6. 95,t=7. 56,both P<0. 05). The expression of AVP was increased after different doses of Glu into PVN,and the AVP level in G12 group ((18. 15±6. 49)%) was higher than that of NS group,the difference was statistically significant (t=-4. 21,P<0. 05). Compared with the Sham group,the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65. 48±1. 68) %,(18. 39± 1. 67) %,(17. 69±1. 68) %;t=34. 35,t=34. 80,both P<0. 05). The expression of PCNA was increased after different doses of Glu injected into PVN,and the PCNA level in G12 group ((59. 91±5. 63)%) was higher than that of NS group,the difference was statistically significant (t=-12. 44,P<0. 05). Compared with the Sham group,the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23. 38±11. 40)%,(83. 79± 3. 57)%,(80. 91± 2. 47)%;t=-8. 77,t=-8. 54,both P<0. 05). The expression of apoptotic cells was decreased after different doses of Glu into PVN,and the G12 group was ((18. 15±6. 49) %). Compared with NS group,the difference was statistically significant ( t=15. 65,P<0. 05). Conclusion Injection of Glu into hypothalamic PVN can alleviate the visceral pain be-haviors in CVH rats,and its mechanism may be related to arginine vasopressin.
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Objective@#To investigate the effects of glutamate (Glu) injected into hypothalamic paraventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possible mechanism.@*Methods@#Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th, 10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group), CVH + injection of saline into PVN group (NS group), CVH+ injection of Glu into PVN (3, 6, and 12 μg Glu, namely G3, G6, and G12, respectively), 6 rats in each group, and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold, abdominal withdrawal reflex (AWR) score, and abdominal external oblique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL.@*Results@#Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups increased, and the AWR scores and EMG amplitudes decreased. The differences were statistically significant(Pain threshold: t=7.65, 16.31, 24.78, both P<0.05; AWR scores: t=-2.98, -4.77, -7.29, both P<0.05; EMG amplitudes: t=-3.06, -5.75, -8.92, both P<0.05). Compared with the Sham group, the expression of AVP in PVN of the CVH group and NS group decreased ((42.63±5.20) %, (18.67±2.94) %, (17.53±2.47) %; t=6.95, t=7.56, both P<0.05). The expression of AVP was increased after different doses of Glu into PVN, and the AVP level in G12 group ((18.15±6.49)%) was higher than that of NS group, the difference was statistically significant (t=-4.21, P<0.05). Compared with the Sham group, the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65.48±1.68) %, (18.39±1.67) %, (17.69±1.68) %; t=34.35, t=34.80, both P<0.05). The expression of PCNA was increased after different doses of Glu injected into PVN, and the PCNA level in G12 group ((59.91±5.63)%) was higher than that of NS group, the difference was statistically significant (t=-12.44, P<0.05). Compared with the Sham group, the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23.38±11.40)%, (83.79±3.57)%, (80.91±2.47)%; t=-8.77, t=-8.54, both P<0.05). The expression of apoptotic cells was decreased after different doses of Glu into PVN, and the G12 group was ((18.15±6.49) %). Compared with NS group, the difference was statistically significant (t=15.65, P<0.05).@*Conclusion@#Injection of Glu into hypothalamic PVN can alleviate the visceral pain behaviors in CVH rats, and its mechanism may be related to arginine vasopressin.
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Objective To investigate the safety and feasibility of intraluminal brachytherapy using iodine-125 seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice.Methods Clinical data of 17 consecutive patients,from January 2010 to February 2015,diagnosed with pancreatic ductal adenocarcinoma (4 cases of T4 N0 M0 and 13 of T4 N1M0) with obstructive jaundice and received intraluminal brachytherapy using iodine-125 seed strand were collected and analyzed retrospectively.Liver function was evaluated using paired-samples t test.The iodine-125 seed strand radiation doses were calculated using iodine-125 radiation field distribution calculation software (version 0.1,Institute of Radiation Medicine,Fudan University,Shanghai,China) based on the American Association of Physicists in Medicine TG43U1 brachytherapy formula.Obstruction free survival and overall survival were calculated using the Kaplan-Meier method.Complications were assessed according to the CTCAE 4.0 criteria.Results The estimated mean accumulating dose (r =5 mm,240 days) was 167.2Gy,from 164.19Gy to 170.05Gy.The mean and median obstruction free survival time were (9.62 ± 1.47) months (95％CI:6.73-12.50) and (7.26 ± 1.71) months (95 ％CI:3.90-10.62).The mean and median overall survival time were (9.89 ± 1.59) months (95％CI:6.78-13.00) and (7.26 ± 1.71) months (95 ％ CI:3.90-10.62),retrospectively.Total bilirubin and conjugated bilirubin decreased significantly after the therapy.Two patients had adverse event of Grade 3,one of Grade 4.Stent dysfunction occurred in 1/17 (5.9 ％) patients.Conclusions Intraluminal brachytherapy using iodine-125 seed strand might be considered as a safe treatment option for the locally advanced pancreatic duct adenocarcinoma complicated by obstructive jaundice.
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Objective To evaluate the safety and efficacy of brachytherapy with 125I seed strand in treating implanted main portal vein tumor thrombus (MPVTT) in experimental rabbits.Methods VX2 tumor cell line was implanted in the main portal vein (MPV) of 32 New Zealand white rabbits to establish MPVTT models.The rabbits were randomly divided into the treatment group (group T,n=16) and the control group (group C,n=16).125I seed strand was implanted in the MPVTT of the rabbits of group T,while blank seed strand was implanted in the MPVTT of the rabbits of group C.After the implantation,the changes in general condition,body weight and laboratory testing results were recorded.Two weeks after the treatment,every 8 rabbits from each group were sacrificed,and the specimens were collected and sent for pathological examination.The remaining rabbits were fed till they died,and then autopsy was conducted.Multi-slice spiral CT manifestations,histopathological findings,Ki-67 labeling index and apoptosis index were used to assess the curative effect,and the results were compared between the two groups.Results At each observation time point after brachytherapy,the weight loss of the experimental rabbits was more obvious in group C than in group T.No statistically significant differences in liver functions and white blood cell count existed between the two groups (P＞0.05).The mean MPVTT volume of group T and group C were (565.40±220.90) mm3 and (2 269.90±437.00) mm3 respectively (P＜0.001);the Ki-67 labeling indexes were (4.14±1.84)％ and (33.82± 6.07)％ respectively (P=0.001);the median survival days were (39.50±2.37) d and (27.38±1.22) d respectively (P=0.001).Conclusion For the treatment of implanted MPVTT in experimental rabbits,brachytherapy with 125I seed strand is safe and effective.
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Objective To evaluate the efficacy and safety of therapeutic drug monitoring (TDM ) based vancomycin dose adjustment in patients with gram‐positive infections .Methods A cohort study was designed with 128 inpatients undergoing TDM in Huashan Hospital from January 2005 to September 2014 .The clinical data of these patients were used to analyze the efficacy and safety of vancomycin therapy by Cox model and survival analysis .Results The patients undergoing TDM‐based dose adjustment had a higher daily dose and blood trough concentration ,which may lead to better bacteriological efficacy and overall efficacy .Cox proportional hazards model analysis showed that TDM‐based dose adjustment is a protective factor .No safety‐related risk factor was found .Conclusions TDM‐based vancomycin dose adjustment is important for patients to achieve better outcomes in fighting gram‐positive infections .
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Objective To analyze the risk factors of post-operative respiratory failure in elderly cardiac carcinoma patients.Methods 28 elderly patients with respiratory failure (respiratory failure group) after the resection of cardiac carcinoma and 56 controls (control group) were studied.Preoperative respiratory function,the other complications,the site of incision,intravenous infusion,age of patients and smoking between two groups were compared by Logistic regression.Results Univariate risk factors included MVV<50% ,RV/TLC>50% ,FEV1<1.5L,PEF<70% ,DLCO<80% ,V75<70% ,the venous input,incision at chest.Multivariate logistic regression analysis identified that MVV<50% ,RV/TLC>50% ,FEV,<1.5 L,DLCO<80% were risk factors.Conclusion These results suggested that the patients with risk factors described above need more careful pre and post operative surveillance and management.
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BACKGROUND: At present, genetic recombinant technique has been utilized to express recombinant human bone morphogenetic protein-2 (rhBMP-2)and to induce either orthotopic or ectopic regenerated bone successfully. But,because that osteoblastic activity induced by rhBMP-2 is lower than that by natural BMP-2, the perfect vectors have not been discovered yet.OBJECTIVE: BMP recombinant adenovirus (rAdV) was constructed so as to provide feasible vector for the basic treatment of bone defect.DESIGN: Single sample was designed in the experiment.SETTING: Experimental Center of Molecular Biology in First Hospital of Xi'an Jiaotong University.MATERIALS: PACCMV-PLPA plasmid, PJM17 plasmid, 293-cell line.METHODS: The experiment was performed in Experimental Center of Molecular Biology in First Hospital of Xi'an Jiaotong University from September 2001 to June 2002. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to clone the whole-length gene of BMP-2 and construct AdV vector. DNA-calcium phosphate coprecipitation was used to transfect accessory plasmid PJM17 into 293cell and homologous recombination was used to construct rAdV. The titer was assayed and CsC1 density gradient centrifugation and purification were applied.construction of rAdV.binant plasmid is named as pGEM-T/hBMP2, (3 015+1 213)bp in size.It was indicated in agar gel electrophoresis that the practical value was in BMP2 shuttle plasmid: The plasmid was about 10 Kbp in size. Since PACCMV-PLPA plasmid multiclone sites belonged to PUC plasmid series,EcoR Ⅰ enzyme digestion was used to linerarizate recombinant plasmid,10 Kbp in size. 8.8 Kb and 1.2 Kbp visible fragments were obtained durtion of rAdV: PCR technique was used to identify rAdV. The target fragment 1.2Kbp that was amplified by BMP2 specific primer of the whole length was in conformity completely with the theoretic value.CONCLUSION: Successful construction of BMP2 rAdV lays a foundation for the feasible genetic treatment with vector of bone defect.
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Objective Acute spinal injury(ASI) is a kind of disease commonly seen in the orthopedic department, with secondary pathological injury causing the delayed damage of tissue structure. This study is focused on finding the injury mechanism of endothelin and the relation with calcium in SCI, and developing an effective treatment of SCI through animal experiment for clinic application in the future. Methods ASI animal model with radioimmuolo gical techniques are applied to examine the level of endothelin, and to find the pathological changes under microscope and electron-microscope. Results The quantity of endothelin and calcium in the cell with 1, 4-dihydropyridine calci um channel inhibitor is decreased, as a result, depolarization was lightened. The mechanism delays the development of secondary injury significantly. Conclusion This type of treatment may be used in emergency for spinal cord injury in order to protect the function and to gain much precious opportunity for spinal recovery and other treatment.
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Objective To investigate the protective mechanisms of nerve growth factor (NGF) on spinal cord injury.Methods The spinal cord injury (SCI) of Wistar rats was performed by a 10g×2.5cm impact on the posterior T12 spinal cord.The experimental animals received NGF liquid by subarachnoid space tube.The radioimmunological techniques were applied to examine the level of endothelin.Results The level of endothelin was significantly increased after the injury as compared with that in control group(P＜0.01).The level of endothelin in NGF group as obviously lowered as compared with that in normal saline group 4 h after injury (P＜0.01).Conclusion NGF can protect spinal cord against injury in vivo.One of the mechanisms is that NGF could inhibit endothelin-induced vicious circle.