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Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.
Subject(s)
Aged , Aged, 80 and over , Aortic Valve , Aortic Valve Stenosis/surgery , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation , Humans , Male , Prospective Studies , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.
Subject(s)
Acupuncture Points , Animals , Asthma/drug therapy , Drugs, Chinese Herbal , Immunity, Innate , Lymphocytes , Mice , Network PharmacologyABSTRACT
Objective:To study the epidemiological features of local influenza A(H1N1)pdm09 epidemic strains through analyzing the changes in lineages and to analyze how well the vaccine strains were matched to the circulating strains in Hangzhou.Methods:Of 1 112 clinical specimens from laboratory-confirmed A(H1N1)pdm09 infections in Hangzhou in consecutive seasons from 2009 to 2020, 208 (18.7%) with high viral load (Ct value <30) were randomly selected from 10 influenza epidemics for full-length hemagglutinin gene ( HA) gene sequencing. Genetic variation, evolution and lineage changes of these representative local strains were analyzed by comparison with vaccine strains and reference strains. Results:Since the 2009 pandemic, A(H1N1)pdm09 had become one of the predominant viruses causing seasonal influenza and been reported to co-circulate with influenza A(H3N2) and influenza B viruses in Hangzhou in the past decade. It caused 10 local influenza epidemics in the 12 consecutive seasons from 2009 to 2020. HA gene sequencing revealed complex sources and rapid variation of the local A(H1N1)pdm09 strains. The main epidemic strains often genetically drifted from the recommended northern hemisphere vaccine strains due to lineage changes. Conclusions:This study suggested that it was essential to update the recommended vaccine strains year by year. Besides, enhanced periodic monitoring of influenza A(H1N1)pdm09 strains circulating in the region was important for the prevention and control of influenza A(H1N1)pdm09 infection in the next epidemic season.
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Tuberculous meningitis (TBM) is one of the most serious and lethal diseases in neurology. The early diagnosis and treatment of TBM still faces severe challenges. Acid-fast staining of cerebrospinal fluid and culture of Mycobacteriumtuberculosis are the "gold standard" for the diagnosis of TBM, but lack sensitivity. With the application of metagenomic next-generation sequencing technology, significant advances have been made in the early diagnosis of TBM. The optimal treatment regimen for TBM remains to be further explored and studied. This article intends to provide an overview of the pathogenesis, pathology, clinical manifestations, diagnosis and treatment advancement of TBM, and provide guidance for clinical practice.
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Objective:To evaluate the clinical outcomes of patients with borderline developmental dysplasia of the hip (BDDH) and cam-type femoroacetabular impingement syndrome (FAIS) after hip arthroscopy.Methods:Data were retrospectively reviewed for patients with BDDH and cam-type FAIS who underwent hip arthroscopy surgery from June 2017 to December 2019. A total of 32 patients were enrolled, with a mean age of 36.13±8.67 years (range, 20-50 years), including 15 males and 17 females. The preoperative lateral center-edge angle was 22.3°±1.6° (range 20.1°-24.7°), while the preoperative α angle was 64.1°±4.6° (range, 56.0°-69.8°). All patients were treated with arthroscopic limited acetabular plasty, labral repair, femoral osteoplasty, and capsular plication after excluding from external hip diseases by ultrasound-guided hip blocking test. The visual analogue scale (VAS), modified Harris Hip Scores (mHHS) and International Hip Outcome Tool-12 (iHOT-12) scores were used to evaluate the clinical effects.Results:All patients were followed up, and the mean follow-up time was 2.5±0.8 years (range, 2.0-4.7 years). The VAS score decreased from 6.07±1.56 to 1.96±0.92 at 1 year and to 1.86±1.01 at 2 years after operation ( F=112.64, P<0.001); the mHHS score increased from 53.87±13.04 to 86.12±8.64 at 1 year and to 88.71±8.15 at 2 years after operation ( F=101.70, P<0.001); the iHOT-12 score was improved from 40.00±7.33 to 76.27±9.50 at 1 year and to 78.67±10.31 at 2 years after operation ( F=134.91, P<0.001). The α angle improved to 40.27°±4.52° (range, 34.8°-49.7°) with significant difference ( t=9.24, P<0.001). Conclusion:Hip arthroscopy can achieve satisfied short-term outcomes in treating BDDH and cam-type FAIS with few complications and less trauma.
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Objective:To investigate the radiosensitization effect of low-dose sulfasalazine (SAS) on colorectal cancer (CRC) cells.Methods:Proliferation inhibition effect of SAS on CRC cells was detected by CCK-8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK-8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results:High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non-lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer-1). Low dose of SAS combined with radiotherapy significantly down-regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion:Our findings suggest that low-dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.
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It is still at the initial stage for basic-level military doctors to participate in the standardized residency training. While, their professional backgrounds and training objectives are significantly different from those civilian residents, it is necessary to explore the standardized training methods in line with the military career demands for those basic-level military doctors. Based on the actual needs of grass-roots troops and military medicine, this study makes significant progress in the integration of standardized residency training and field surgery training methods, making the basic-level military doctors achieve the goal of field surgery training in the course of clinical practice of residents. Not only the surgical capability of basic-level military doctors, but also the medical support capability in grass-roots troops has been improved. This article summarizes the application methods and experience of field surgery teaching in the standardized residency training of military medical residents at the grass-roots level.
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Objective:To investigate the influences of age-adjusted Charlson comorbidity index (ACCI) on prognosis of patients undergoing laparoscopic radical gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 242 gastric cancer patients who underwent laparoscopic radical gastrectomy in 19 hospitals of the Chinese Laparoscopic Gastrointestinal Surgery Study Group-04 study, including 54 patients in Fujian Medical University Union Hospital, 32 patients in the First Hospital of Putian City, 32 patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 31 patients in Zhangzhou Affiliated Hospital of Fujian Medical University, 17 patients in Nanfang Hospital of Southern Medical University, 11 patients in the First Affiliated Hospital with Nanjing Medical University, 8 patients in Qinghai University Affiliated Hospital, 8 patients in Meizhou People′s Hospital, 7 patients in Fujian Provincial Hospital, 6 patients in Zhongshan Hospital of Fudan University, 6 patients in Longyan First Hospital, 5 patients in the First Affiliated Hospital of Xinjiang Medical University, 5 patients in the First Hospital Affiliated to Army Medical University, 4 patients in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 4 patients in West China Hospital of Sichuan University, 4 patients in Beijing University Cancer Hospital, 3 patients in the First Affiliated Hospital of Xiamen University, 3 patients in Guangdong Provincial People′s Hospital, 2 patients in the First Affiliated Hospital of Xi′an Jiaotong University, from September 2016 to October 2017 were collected. There were 193 males and 49 females, aged 62(range, 23?74)years. Observation indicators: (1) age distribution, comorbidities and ACCI status of patients; (2) the grouping of ACCI and comparison of clinicopathological characteristics of patients in each group; (3) incidence of postoperative early complications and analysis of factors affecting postoperative early complications; (4) follow-up; (5) analysis of factors affecting the 3-year recurrence-free survival rate of patients. Follow-up was conducted using outpatient examination or telephone interview to detect postoperative survival of patients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametric rank sum test. The X-Tile software (version 3.6.1) was used to analyze the best ACCI grouping threshold. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-Rank test was used for survival analysis. The Logistic regression model was used to analyze the factors affecting postoperative early complications. The COX proportional hazard model was used for univariate and multivariate analyses of factors affecting the 3-year recurrence-free survival rate of patients. Multivariate analysis used stepwise regression to include variables with P<0.05 in univariate analysis and variables clinically closely related to prognosis. Results:(1) Age distribution, comor-bidities and ACCI status of patients. Of the 242 patients, there were 28 cases with age <50 years, 68 cases with age of 50 to 59 years, 113 cases with age of 60 to 69 years, 33 cases with age of 70 to 79 years. There was 1 patient combined with mild liver disease, 1 patient combined with diabetes of end-organ damage, 2 patients combined with peripheral vascular diseases, 2 patients combined with peptic ulcer, 6 patients combined with congestive heart failure, 8 patients combined with chronic pulmonary diseases, 9 patients with diabetes without end-organ damage. The ACCI of 242 patients was 2 (range, 0-4). (2) The grouping of ACCI and comparison of clinicopathological characteristics of patients in each group. Results of X-Tile software analysis showed that ACCI=3 was the best grouping threshold. Of the 242 patients, 194 cases with ACCI <3 were set as the low ACCI group and 48 cases with ACCI ≥3 were set as the high ACCI group, respectively. Age, body mass index, cases with preoperative comorbidities, cases of American Society of Anesthesiologists classification as stage Ⅰ, stage Ⅱ, stage Ⅲ, tumor diameter, cases with tumor histological type as signet ring cell or poorly differentiated adenocarcinoma and cases with tumor type as moderately or well differentiated adenocarcinoma, cases with tumor pathological T staging as stage T1, stage T2, stage T3, stage T4, chemotherapy cycles were (58±9)years, (22.6±2.9)kg/m 2, 31, 106, 85, 3, (4.0±1.9)cm, 104, 90, 16, 29, 72, 77, 6(4,6) in the low ACCI group, versus (70±4) years, (21.7±2.7)kg/m 2, 23, 14, 33, 1, (5.4±3.1)cm, 36, 12, 3, 4, 13, 28, 4(2,5) in the high ACCI group, showing significant differences in the above indicators between the two groups ( t=-14.37, 1.98, χ2=22.64, Z=-3.11, t=-2.91, χ2=7.22, Z=-2.21, -3.61, P<0.05). (3) Incidence of postoperative early complications and analysis of factors affecting postoperative early complications. Of the 242 patients, 33 cases had postoperative early complications, including 20 cases with local complications and 16 cases with systemic complica-tions. Some patients had multiple complications at the same time. Of the 20 patients with local complications, 12 cases had abdominal infection, 7 cases had anastomotic leakage, 2 cases had incision infection, 2 cases had abdominal hemorrhage, 2 cases had anastomotic hemorrhage and 1 case had lymphatic leakage. Of the 16 patients with systemic complications, 11 cases had pulmonary infection, 2 cases had arrhythmias, 2 cases had sepsis, 1 case had liver failure, 1 case had renal failure, 1 case had pulmonary embolism, 1 case had deep vein thrombosis, 1 case had urinary infection and 1 case had urine retention. Of the 33 cases with postoperative early complications, there were 3 cases with grade Ⅰ complications, 22 cases with grade Ⅱ complications, 5 cases with grade Ⅲa complications, 2 cases with grade Ⅲb complications and 1 case with grade Ⅳ complica-tions of Clavien-Dindo classification. Cases with postoperative early complications, cases with local complications, cases with systemic complications were 22, 13, 9 in the low ACCI group, versus 11, 7, 7 in the high ACCI group, respectively. There were significant differences in cases with postoperative early complications and cases with systemic complications between the two groups ( χ2=4.38, 4.66, P<0.05), and there was no significant difference in cases with local complications between the two groups ( χ2=2.20, P>0.05). Results of Logistic regression analysis showed that ACCI was a related factor for postoperative early complications of gastric cancer patients undergoing laparoscopic radical gastrectomy [ odds ratio=2.32, 95% confidence interval ( CI) as 1.04-5.21, P<0.05]. (4) Follow-up. All the 242 patients were followed up for 36(range,1?46)months. During the follow-up, 53 patients died and 13 patients survived with tumor. The 3-year recurrence-free survival rate of the 242 patients was 73.5%. The follow-up time, cases died and cases survived with tumor during follow-up, the 3-year recurrence-free survival rate were 36(range, 2-46)months, 29, 10, 80.0% for the low ACCI group, versus 35(range, 1-42)months, 24, 3, 47.4% for the high ACCI group. There was a significant difference in the 3-year recurrence-free survival rate between the two groups ( χ2=30.49, P<0.05). (5) Analysis of factors affecting the 3-year recurrence-free survival rate of patients. Results of univariate analysis showed that preoperative comorbidities, ACCI, tumor diameter, histological type, vascular invasion, lymphatic invasion, neural invasion, tumor pathological TNM staging, postoperative early complications were related factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy [ hazard ratio ( HR)=2.52, 3.64, 2.62, 0.47, 2.87, 1.90, 1.86, 21.77, 1.97, 95% CI as 1.52-4.17, 2.22-5.95, 1.54-4.46, 0.27-0.80, 1.76-4.70, 1.15-3.12, 1.10-3.14, 3.01-157.52, 1.11-3.50, P<0.05]. Results of multivariate analysis showed that ACCI, tumor pathological TNM staging, adjuvant chemotherapy were indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy ( HR=3.65, 11.00, 40.66, 0.39, 95% CI as 2.21-6.02, 1.40-86.73, 5.41-305.69, 0.22-0.68, P<0.05). Conclusions:ACCI is a related factor for post-operative early complications of gastric cancer patients undergoing laparos-copic radical gastrectomy. ACCI, tumor pathological TNM staging, adjuvant chemotherapy are indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy.
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Objective To explore the mechanism of puerarin inhibiting the proliferation,invasion,and migration of non-small cell lung cancer cells. Methods A549 cells were cultured and treated with different concentrations of puerarin.The inhibition rate (IR) on cell proliferation was detected by CCK-8,and qRT-PCR was performed to detect the mRNA levels of miR-490 and denticleless E3 ubiquitin protein ligase(DTL).Double luciferase reporter assay was employed to identify the targets of miR-490 and DTL based on the establishment of NC mimic group,miR-490 mimic group,NC inhibitor group,and miR-490 inhibitor group.The cells treated by 20 μmol/L puerarin were classified into six groups:DMSO,puerarin,puerarin+NC inhibitor,puerarin+miR-490 inhibitor,puerarin+miR-490 inhibitor+Si-NC,and puerarin+miR-490 inhibitor+Si-DTL.Transwell was used to detect cell migration and invasion.Western blotting was performed to detect the protein levels of epithelial-mesenchymal transition-related markers E-cadherin,N-cadherin,and Vimentin. Results With the increase in puerarin concentration,the IR gradually elevated (F=105.375,P<0.001),miR-490 expression gradually increased (F=32.919,P<0.001),and DTL expression gradually decreased (F=116.120,P<0.001).Compared with NC mimic group,miR-490 mimic group had decreased luciferase activity (t=7.762,P=0.016),raised miR-490 mRNA level (t=13.319,P<0.001),and declined DTL mRNA level (t=7.415,P=0.002).Compared with those in NC inhibitor group,miR-490 demonstrated decreased mRNA level (t=9.523,P=0.001) and DTL presented increased mRNA level (t=11.305,P<0.001) in miR-490 inhibitor group.Western blotting showed that the protein level of DTL was higher in NC mimic group (t=7.953,P=0.001) than in miR-490 mimic group and higher in miR-490 inhibitor group than in NC inhibitor group (t=10.552,P<0.001).Compared with DMSO group,puerarin group showed up-regulated mRNA level of miR-490 (t=10.255,P=0.001) while down-regulated mRNA level of DTL (t=6.682,P=0.003).Compared with those in puerarin+NC inhibitor group,the mRNA level of miR-490 declined (t=10.995,P<0.001) while that of DTL raised (t=12.478,P<0.001) in puerarin+miR-490 inhibitor group.The mRNA level of miR-490 had no significant difference between puerarin+miR-490 inhibitor+Si-NC group and puerarin+miR-490 inhibitor+Si-DTL group (t=1.081,P=0.341),and that of DTL was lower in the latter group (t=14.321,P<0.001).The protein level of DTL was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=11.423,P<0.001),and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=12.080,P<0.001).Compared with DMSO group,puerarin group showed inhibited cell proliferation (F=129.27,P<0.001).The activity of cell proliferation was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (F=75.12,P<0.001),and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (F=52.59,P<0.001).Compared with DMSO group,puerarin group had suppressed cell migration (t=8.963,P=0.001).The cell migration ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=12.117,P<0.001) and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (t=12.934,P<0.001).Puerarin group showed weakened cell invasion ability compared with DMSO group (t=4.710,P=0.009).The cell invasion ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=13.264,P<0.001) and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=13.476,P<0.001).Compared with DMSO group,puerarin group showed up-regulated protein level of E-cadherin (t=7.137,P=0.002) while down-regulated protein levels of N-cadherin (t=8.828,P=0.001) and vimentin (t=6.594,P=0.003).Compared with those in puerarin+NC inhibitor group,the protein level of E-cadherin (t=12.376,P<0.001) decreased while those of N-cadherin (t=13.436,P<0.001) and vimentin (t=11.467,P<0.001) increased in puerarin+miR-490 inhibitor group.Compared with puerarin+miR-490 inhibitor+Si-NC group,puerarin+miR-490 inhibitor+Si-DTL group up-regulated the protein level of E-cadherin (t=13.081,P<0.001) while down-regulated the protein levels of N-cadherin (t=10.835,P<0.001) and vimentin (t=11.862,P<0.001). Conclusion Puerarin could inhibit the proliferation,invasion,and migration of non-small cell lung cancer cells by up-regulating miR-490 and down-regulating DTL.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Isoflavones/pharmacology , Lung Neoplasms , MicroRNAs/metabolism , Ubiquitin-Protein Ligases/metabolismABSTRACT
Objective:To investigate the characteristics of gene mutations in colorectal cancer(CRC)patients by using next-generation generation sequencing(NGS).Methods:Blood and tissue samples were collected from 90 CRC patients admitted to Beijing Hospital between August 5, 2016 and December 29, 2020.Analysis of driver gene mutations was performed by using a 1021-gene NGS panel.Results:There were 43 tissue samples and 83 blood samples.Also, 36 patients had both tissue and blood samples.The frequency rates of KRAS and BRAF mutations were 51.2%(22/43)and 20.9%(9/43)in tissue samples, and 3 rare concomitant KRAS/ BRAF mutations were detected.The frequency rates of KRAS and BRAF mutations were 26.5%(22/83)and 10.8%(9/83)in blood samples.In patients with tissue and blood samples, the rates of KRAS and BRAF mutations were 52.8%(19/36)and 10.8%(8/36). Conclusions:The rate of KRAS mutations in tissue samples from colorectal cancer patients is similar to rates reported in the literature, but the rate of BRAF mutation and the rate of rare KRAS and BRAF co-mutations are higher than those reported from other countries.
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Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.
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OBJECTIVE@#To investigate and compare the clinical efficacies of remnant-preserving and remnant-non-preserving, remnant-non-preserving remnant segment preserving and remnant root preserving with anterior cruciate ligament reconstruction.@*METHODS@#From March 2014 to December 2017, 204 patients with anterior cruciate ligament (ACL) injuries were treated by single-bundle ACL reconstruction with hamstring tendon autograft. According to the different methods of remnant preservation, the procedures were divided into remnant segment preserving group (A), remnant root preserving group (B), and remnant-non-preserving group (C). There were 37 males and 39 femalesin group A aged from 16 to 43 years old with an average of (28.80±5.41) years old. The time from injury to operation ranged from 2 to 11 weeks with an average of (3.68±1.04) weeks. In group B, there were 39 males and 25 females aged from 18 to 41 years old with an average of (28.42±5.60) years old. The time from injury to operation ranged from 2 to 10 weeks with an average of (3.36±1.68) weeks. In group C, there were 37 males and 27 females aged from 18 to 43 years old with an average of (29.10±6.11) years old. The time from injury to operation ranged from 3 to 11 weeks with an average of (3.54±1.46) weeks. The range of motion (ROM) of the knee was used to assess the range of extension and flextion of the knee at pre-operation and 24 months after operation. Lysholm score and the international knee documentation committee (IKDC) score were used to assess the knee function. The differences among three procedures were judged by comparing among the three groups at 6, 12 and 24 months postoperatively.@*RESULTS@#All incisions got a one stage healing, and no complications, such as vascular injury, nerve damage and articular infect or the like, occurred. All the patients were followed up, and the follow-up duration of group A ranged from 24.00 to 45.96 months with a mean of (35.52±14.40) months;the follow up duration of group B ranged from 27.96 to 48.00 months with a mean of (37.56±10.68) month;and the follow up duration of group C ranged from 24.00 to 66.00 months with a mean of (37.08±13.44) month. There were no significant differences in follow up time among three groups (@*CONCLUSION@#Compared with remnant-non-preserving group, the residual tissue of anterior cruciate ligament is preserved, which is conducive to promote the healing and remodeling of tendon graft and accelerate the recovery of joint function. Proper fixation of residual tissue and restoration of its tension are the key factors affecting the postoperative efficacy.
Subject(s)
Adolescent , Adult , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction , Arthroscopy , Case-Control Studies , Female , Humans , Knee Joint/surgery , Male , Treatment Outcome , Young AdultABSTRACT
The incidence of posterior instability of shoulder joint was significantly lower than that of anterior instability, but the clinical diagnosis and treatment was difficult, and the misdiagnosis and missed diagnosis rate were high. Its etiology, clinical manifestation and treatment strategy are totally different from the anterior instability. Therefore, the deep understanding of the anatomical structure around the shoulder joint, the mastery of the examination method, and the classification of the shoulder instability based on the anatomy and injury mode are of great importance to improve the accuracy of diagnosis. CT three-dimensional reconstruction is helpful to evaluate the defect of humeral head and glenoid bone, and MRA is helpful for the accurate diagnosis of posterior glenoid lip and joint capsule. The treatment was divided into conservative treatment and surgical treatment. Conservative treatment is recommended for muscular instability. Surgical treatment is recommended for traumatic and dysplastic instability. Different operative methods should be performed according to the injury of glenoid side or humeral head side. According to the condition of bone defect, soft tissue operation, bone grafting or osteotomy were performed to reconstruct the posterior stable structure of the glenoid injury; according to the area of the anterior bone defect, bone grafting or subscapular muscle packing were performed to the head of humerus defect. The former has the advantages of short learning curve and firm fixation, while the latter has the advantages of minimally invasive operation and the ability to observe the lesions from multiple angles and accurately control the location of bone masses. This paper summarizes the above problems.
Subject(s)
Humans , Humeral Head , Joint Instability/surgery , Scapula , Shoulder , Shoulder Dislocation , Shoulder Joint/surgeryABSTRACT
Pancreatic cancer is highly malignant, and surgical resection is the only cure method at present. In recent years, neoadjuvant therapy has enabled some patients to be successfully downgraded with surgical treatment, which increased the R0 surgical resection rate and prolonged the survival time of patients, has become an important part in the treatment of pancreatic cancer. However, the applicability and standardization of neoadjuvant therapy for pancreatic cancer still need more advanced evidence. This article reviews whether neoadjuvant therapy should be used for resectable pancreatic cancer, the choice of neoadjuvant chemotherapy, and the progress, advantages and disadvantages of neoadjuvant chemoradiotherapy.
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OBJECTIVE@#To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma.@*METHODS@#36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis.@*RESULTS@#The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis.@*CONCLUSION@#The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , B-Lymphocytes , Disease-Free Survival , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, Non-Hodgkin/therapy , Retrospective Studies , Transplantation Conditioning , Transplantation, Autologous , Treatment OutcomeABSTRACT
OBJECTIVE@#To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562.@*METHODS@#CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC@*RESULTS@#ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05).@*CONCLUSION@#The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.
Subject(s)
Animals , Cell Proliferation , Humans , K562 Cells , Leukemia , Mice , Mice, Nude , Phosphodiesterase 4 Inhibitors/pharmacologyABSTRACT
As the diagnosis rate of early gastric cancer is increasing annually, the current hot spot in the treatment of early gastric cancer is how to better preserve the anatomical structure and physiological function of the stomach and improve the quality of life of patients after surgery under the premise of tumor eradication. Therefore, function-preserving gastrectomy has been the trend of surgical treatment for early gastric cancer. It is not just a modified gastrectomy, but a better combination of improved surgical techniques and the concept of function-preserving treatment, rather than being limited to traditional surgical treatments. Currently, the routine function-preserving gastrectomy mainly includes pylorus-preserving gastrectomy, proximal gastrectomy and partial gastrectomy combined with endoscopy. In addition, with the deeper understanding of metastasis pattern of gastric cancer and the development and popularization of minimally invasive techniques, laparoscopic and endoscopic cooperative surgery is gradually gaining attention. The application of laparoscopic and endoscopic hybrid surgery combined with sentinel lymph node navigation is anticipated in the treatment of early gastric cancer.
Subject(s)
Gastrectomy , Humans , Laparoscopy , Lymph Node Excision , Pylorus , Quality of Life , Stomach Neoplasms/surgeryABSTRACT
Objective@#To investigate whether silencing UCP2 can sensitize cervical cancer cell line Siha to radiation.@*Methods@#Siha cells were transfected with UCP2 siRNA and then irradiated by X-ray. The radiosensitivity of Siha cells was verified by colony formation, CCK-8, apoptosis and immunofluorescence assays. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were detected to further explore the related mechanism.@*Results@#RT-PCR and Western blot assays showed that the expression of UCP2 in Siha cells was increased after irradiation and the UCP2 siRNA successfully silenced the expression of UCP in cells. According to the survival curves, the D0, Dq, N and SF2 were 1.54, 1.31, 2.31 Gy and 0.52 for siUCP2 group, 2.50, 3.64, 4.30 Gy and 0.83 for blank control group, and 3.34, 2.16, 1.91 Gy and 0.69, for siNC group, respectively. The radiosensitivity enhancement ratio of silent group was 0.62 and 0.46, compared with blank control group and negative control group, respectively. The proliferative activity of cells in the silent group was lower than that in the control group (t=13.2, P<0.05). Apoptosis levels in the silent group were significantly higher than those in the control group after irradiation(t=3.14, P<0.05). At 4 h after irradiation, the ROS production in the silent group was significantly higher than that in the control group (t=19.10, P<0.05). At 24 h after irradiation, the mitochondrial membrane potential of Siha cells in the silent group was significantly lower than that in the control group (t=4.18, P<0.05).@*Conclusions@#The radiosensitivity of Siha cells is enhanced after UCP2 silencing, and thus UCP2 may applicable as a new target for radiosensitization of cervical cancer cells.
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Objective@#To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy.@*Methods@#The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis.@*Results@#There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m2. (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ2=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D1 lymph lode dissection, D2 lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ2=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ2=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05).@*Conclusions@#The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.
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OBJECTIVE@#To explore the effects of single anterior approach under shoulder arthroscopy in the treatment of Bankart injury, and to provide a scheme to overcome the difficulties and simplify the operation process.@*METHODS@#From July 2016 to January 2019, 62 patients with recurrent dislocation caused by Bankart leision were treated under shoulder arthroscopy, including 50 males and 12 females, ranging in age from 19 to 44 years old with an average age of (26.5±6.1) years old. There were 25 cases of left shoulder and 37 cases of right shoulder. The patients were divided into two groups according to the operation mode, 35 patients in the front modified single approach group (experimental group) and 27 patients in the traditional double approachgroup (control group). The results of the operation were evaluated by assessing the preoperative and postoperative ASES scores of the shoulder joint, and the time of the approach establishment and the overall operation process was recorded to evaluate whether the operation time of the experimental group was shortened.@*RESULTS@#Three patients were lost during the follow-up after operation, and except for one case of re-dislocation, all patients achieved satisfactory results without neurovascular injury and other complications. The patients were followed up before operation and 3, 6, 12 months after operation, and the ASES scores were significantly enhanced at the latest follow-up compared with those of before operation. The time of establishing surgical approach in the experimental group was (7.5±1.5) minutes, which was shorter than that of control group (13.7±1.2) minutes.@*CONCLUSION@#The improved technique of single-channel anterior approach has the advantages of reducing the surgical incision and shortening the operationtime while ensuring the quality of the operation, which is worthy of popularization and application.