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OBJECTIVE: To explore the potential action mechanism of Huotu Jiji Pellets (HJP) in the treatment of erectile dysfunction (ED) based on network pharmacology and molecular docking. METHODS: We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine (TCMIP) and the therapeutic target genes of ED from the databases of Genecards. Then we obtained the common targets of HJP and ED using the Venny software, constructed a protein-protein interaction (PPI) network of HJP acting on ED, and screened out the core targets with the Cytoscape software. Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software. RESULTS: A total of 64 effective compounds, 822 drug-related targets, 1 783 disease-related targets and 320 common targets were obtained in this study. PPI network analysis showed that the core targets of HJP for ED included ESR1, HSP90AA1, SRC, and STAT3. GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus, positive regulation of kinase activity, and positive regulation of MAPK cascade. KEGG pathway enrichment analysis suggested that PI3K-Akt, apoptosis, MAPK, HIF-1, VEGF, autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED. Molecular docking prediction exhibited a good docking activity of the key active molecules of HJP with the core targets. CONCLUSION: This study showed that HJP acted on ED through multi-components, multi-targets and multi-pathways, which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.
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Medicamentos de Ervas Chinesas , Disfunção Erétil , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Masculino , Disfunção Erétil/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Transdução de SinaisRESUMO
OBJECTIVE: To explor the potential mechanisms of ferroptosis involvement in non-obstructive azoospermia based on bioinformatics and machine learning methods. METHODS: To obtain disease-related datasets and ferroptosis-related genes, we utilized the GEO database and FerrDb database, respectively. Using the R software, the disease dataset was subjected to normalization, differential analysis, and GO and KEGG enrichment analysis. The differentially expressed genes from the disease dataset were then intersected with the ferroptosis-related genes to identify common genes. Core genes were selected using three machine learning algorithms, namely LASSO, SVM-RFE, and random forest. Further analysis included exploring immune infiltration correlation, predicting target drugs, and conducting molecular docking simulations. RESULTS: The differential analysis of the GSE45885 dataset yielded 1751 differentially expressed genes, while the GSE145467 dataset yielded 4358 differentially expressed genes. The intersection of these two gene sets resulted in a disease-related gene set consisting of 508 genes. Taking the intersection of the disease-related gene set and the ferroptosis-related gene set, we obtained 17 disease-related ferroptosis genes. After machine learning-based screening, three core genes were identified: GPX4, HSF1, and KLHDC3. CONCLUSION: The mechanism underlying the involvement of ferroptosis in non-obstructive azoospermia may be linked to the downregulation of GPX4, HSF1, and KLHDC3 expression. This finding provides a basis for subsequent in-depth mechanistic and therapeutic studies.
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Azoospermia , Ferroptose , Masculino , Humanos , Azoospermia/genética , Ferroptose/genética , Simulação de Acoplamento Molecular , Biologia Computacional , Aprendizado de MáquinaRESUMO
OBJECTIVES: Proximal migration is one of the complications after pancreatic duct stenting. This study aimed to determine the incidence of proximal migration and to analyze the rescue methods. MATERIALS AND METHODS: A search was performed in MEDLINE/Embase database. The literatures included were reviewed and analyzed. Retrieval tools were classified into the following 3 classes: class A works by indirectly contacting the outer surface of the stent. Class B works by directly contacting the outer surface. Class C works by directly contacting the inner surface. RESULTS: 416 literatures were retrieved from 1983 to 2021. 15 literatures were included. The incidence of proximal migration of pancreatic stents was 4.7% (106/2246). The success rate of endotherapy was 86.6% (214/247), and the surgical conversion rate of it was 9.3%. Among the 214 cases in which the displaced stents were successfully removed under endoscopy, 49 cases (22.9%) used class A methods, 154 cases (72.0%) used class B methods, and 11 cases (5.1%) used class C methods. The overall rate of postoperative complication was 12.1%, including postprocedure pancreatitis (9.1%, 18/247), followed by bleeding (1.5%), perforation (1.0%), and biliary infection (0.5%). CONCLUSIONS: Endoscopy is an effective method for the treatment of proximal displacement of pancreatic stents with acceptable complication rate.
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Migração de Corpo Estranho , Ductos Pancreáticos , Stents , Humanos , Stents/efeitos adversos , Ductos Pancreáticos/cirurgia , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Remoção de Dispositivo/métodos , Remoção de Dispositivo/estatística & dados numéricos , Resultado do Tratamento , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodosRESUMO
Background: Endoscopic pancreatic stenting is an effective way to relieve the stricture of the pancreatic duct. However, proximal stent migration presents a threat to the patient and a challenge to the doctor. The limited space in the pancreatic duct often prevents the operation of suitable devices for stent removal. Case presentation: A 34-year-old man with painful chronic pancreatitis received endoscopic retrograde cholangiopancreatography (ERCP) and insertion of a pancreatic plastic stent, with 8.5 Fr in diameter and 12 cm in length. A year later, radiography revealed that the proximal end of the stent rested in the pancreatic tail while the distal end rested in the branch duct. Both balloon and rat-tooth forceps were used but failed to retrieve the stent. A week later, a second ERCP was performed. After dilation with a 10-mm balloon, a small amount of bleeding was noticed and a crack appeared in the wall of the branch duct. Consequently, the distal end of the stent was released. Then, rat-tooth forceps was used to grasp the distal end, and the stent was pulled out successfully. Conclusions: For a proximally migrated pancreatic stent stuck at both ends, a strategy of maximum dilation can be used cautiously to retrieve the stent.
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Bimodal classification of idiopathic chronic pancreatitis (ICP) into early-onset (<35 years) and late-onset (>35 years) ICP was proposed in 1994 based on a study of 66 patients. However, bimodal distribution wasn't sufficiently demonstrated. Our objective was to examine the validity and relevance of the age-based bimodal classification of ICP. We analyzed the distribution of age at onset of ICP in our cohort of 1633 patients admitted to our center from January 2000 to December 2013. Classify ICP patients into early-onset ICP(a) and late-onset ICP(a) according to different cut-off values (cut-off value, a = 15, 25, 35, 45, 55, 65 years old) for age at onset. Compare clinical characteristics of early-onset ICP(a) and late-onset ICP(a). We found slightly right skewed distribution of age at onset for ICP in our cohort. There were differences between early-onset and late-onset ICP with respect to basic clinical characteristics and development of key clinical events regardless of the cut off age at onset i.e. 15, 25, 35, 45 or even higher. The validity of the bimodal classification of early-onset and late-onset ICP could not be established in our large patient cohort and therefore such a classification needs to be reconsidered.
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Pancreatite Crônica/classificação , Adolescente , Adulto , Idade de Início , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/patologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/terapia , Radioterapia/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estudos Prospectivos , Taxoides/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety. RESULTS: Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control. CONCLUSION: Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/cirurgia , Adulto , Idoso , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/radioterapia , Mucosite/etiologia , Náusea/induzido quimicamente , Estudos Prospectivos , Radioterapia/efeitos adversos , Radioterapia/métodos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: To observe the effect of epidermal growth factor receptor's monoclonal antibody(MAB225) on radiosensitivity of salivary gland adenoid cystic carcinoma cell. METHODS: Bi-fluorescence stain ,MTT test and fluorescence flow cytometry(FCM) were used to observe the apoptosis rate and radiosensitizing effect for MAB225 on ACC-2 cell.SPSS11.0 software package was used for data analysis. RESULTS: Through bi-fluorescence stain, MTT test and fluorescence flow cytometry(FCM),it was found that MAB225 combined with radiation treatment produced a 3-fold induction of apoptosis rate, whereas exposure to radiation alone induced apoptosis only 1 fold, compared to the control group. CONCLUSION: MAB225 enhanced radiosensitivity and decreased survival rates of ACC-2 cell in vitro after radiation.
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Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Apoptose , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Tolerância a Radiação , Glândulas Salivares , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: To study the influence of radiotherapy on immediate reconstruction with the titanium plate after resection of mandible in oral cancer patients. METHODS: Fifty-eight cases (radiation group, 30 patients and control group, 28 patients) with titanium plate for immediate reconstruction of mandibular defects were observed from January, 1997 to May, 2002. The patients of radiation group underwent radiotherapy with total doses of 4,050 - 6,540 cGy (mean 5,495 cGy). The titanium plate was in radiation fields and was irradiated during the radiation therapy. RESULTS: Local infection and fistula accounted for 6 cases and plate exposure accounted for 5 in radiation group. Local infection and plate exposure happened in 4 and 3 patients in control group respectively. Titanium plates were taken in six cases in radiation group and 4 cases in control group by re-surgery 4 - 15 months after primary surgery because of local infection. The success rates of immediate reconstruction with the titanium plate were 80.0% (24/30) in radiation group and 85.7% (24/28) in control group (P > 0.05). CONCLUSIONS: The cases of immediate reconstruction with the titanium plate after resection of mandible in oral cancer patients can accept postoperative radiotherapy.
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Mandíbula/cirurgia , Neoplasias Bucais/radioterapia , Titânio/uso terapêutico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Mandíbula/patologia , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia PlásticaRESUMO
OBJECTIVE: The purpose of this study was to invest the effect of epidermal growth factor receptor monoclonal antibody MAb225 on radiosensitivity of tongue squamous cell carcinoma cell Tca8113. METHODS: Tca8113 cells were treated with different concentrations of MAb225. Radiation dose survival curve was generated from clonogenic survival assay. SERPD0 and survival faction (SF2) was analysed by single hit multi-target (SHMT) radiobiological model using RADMEDIC software. Nude mice with Tca8113 tumor xenografts were treated with MAb225, radiation treatment or both of them. Tumor responses were assessed by tumor growth delay, and t test was used for statistical analysis. RESULTS: MAb225 enhanced the radiosensitivity of Tca8113 cells. SERD0 of Tca8113 cells treated with 0.5 mg/L MAb225 was 1.23. The survival fraction of cells treated with MAb225 was significantly decreased. Tumor radioresponse could be enhanced by MAb225 (P < 0.05). CONCLUSION: MAb225 could enhance radiosensitivity of tongue squamous cell carcinoma cell.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Animais , Anticorpos Monoclonais , Humanos , Camundongos , Camundongos Nus , Tolerância a RadiaçãoRESUMO
PURPOSE: The objective of this study was to investigate the mechanism of MAb225 regulating radiosensitivity of Tca8113 cells. METHODS: Tca8113 cells were treated with MAb225 of different concentrations. The apoptosis rate was analysed by FCM and bi-fluorescence stain, the repair of DNA damage after radiation was analysed by single cell gel electrophoresis, cells redistribution in each phase of cell cycle was analysed by FCM, and GSH level of cell were assessed by spectrophotometer. RESULTS: Radiation alone (6 Gy) and MAb225 alone (0.5 microg/ml) produced a 2-fold induction of apoptosis respectively, whereas exposure to MAb225 (0.5 microg/ml) combination with 6 Gy of radiation induced apoptosis 5-6 fold, compared to untreated controls (F test). The length of comet tail of cells which treated with MAb225 was significantly longer than that of the control cells (t test, P<0.05). The percentage of cells in S phase was significantly decreased in MAb225 treated cells. Intracellular GSH level of MAb225 treated cells was significantly lower than that of untreated cells (t test, P<0.05). CONCLUSION: MAb225 increased the radiosensitivity of Tca8113 cells by enhancing radiation-induced apoptosis, downregulating S phase percentage, inhibiting DNA repair after radiation and decreasing GSH level.
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Anticorpos Monoclonais , Linhagem Celular Tumoral , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral , Apoptose , Ciclo Celular , Dano ao DNA , Reparo do DNA , Glutationa , HumanosRESUMO
OBJECTIVE: To analyse the clinical characteristic, evolution and prognosis of undifferentiated carcinoma with lymphoid stroma(malignant lymphoepithelial lesions, MLEL) in salivary gland. METHODS: During 1989 and 1997, 21 cases of MLEL in salivary gland were treated. The primary site was parotid in 18 cases, palate minor salivary gland in 2 cases and submandibular gland in 1 case. There were 5 men and 16 women with an age range of 31 to 74 years (median, 41 years). For stage II, III, mass dissection and superficial or total parotidectomy were adopted. The facial nerve was preserved when it had not been invaded. 3 to 25 lymph nodes were subjected to exam in pathology for every neck dissection specimen. For stage IV, neck dissection may be included, when necessary. All patients were irradiated on primary site or including ipsilateral neck 2 to 9 weeks after operation, except 2 cases irradiated after recurrence. Tumor doses were 52.03Gy in average. RESULTS: There were 3/21 patients with recurrent benign lymphoepithelial lesion history (BLEL). The shortest duration from the recurrence to specific diagnosis was 6 months, and the longest was 2 years. The II, III, IV stage cases were 8(42.9%), 3 (14.3%), 10 (47.6%), respectively. All of II, III stage cases were N0. The cases with positive lymph nodes were 10/21(47.61%). The 5-year survival rate was 70.66%, for II, III, IV stage was 86.68%, 66.67%, 33.3%, respectively, analyzed by Life Table. And test with Wilcoxon (Gehan) statistic, P=0.2789, means there was no specific difference among each group. In the group, 5 patients dead and 2 lost follow up (counted in dead); mortality was 33.31%, all of them were IV stage. Superior and middle deep cervical metastasis were found in 4 of those patients with parotid MLEL, and neck dissection and ipsilateral neck irradiation were adopted. Recurrence was found in 7/21(33.3%), 5 of 7 cases were IV with N2 or N3, 2 of 7 were palate MELE in early or middle stage. There were 6/7 recurrence occurred on neck. The duration from first treatment to recurrence was 20.7m in median, the shortest was 5 months and the longest was 65 months, among them the recurrence occurred shorter than 20 months in 5 cases. After comprehensive treatment, 3 patients were alive and 3 cases dead. Metastasis occurred in 4 patients in IV stage (T4N2M0), with positive middle cervical lymph nodes in 3 cases treated by neck dissection before. CONCLUSION: Recurrent BLEL intends to develop to malignant lesion. Superior and middle deep cervical lymph nodes metastasis were not unusual in IV stage patients. Neck, dissection and irradiation should be carried out on these patients, especially for those with N2. The peak time of recurrence was 2 years after the first treatment, and during the time, the tumor proliferated rapidly. Active comprehensive treatment should be carried out on recurrent patients. For patients with positive middle deep cervical lymph nodes, chemotherapy or other methods should be adopted to prevent distant metastasis.