ABSTRACT
In recent years, advances in interventional bronchoscopy have led to safer and more effective solutions for the diagnosis and treatment of respiratory diseases. However, the techniques currently used to diagnose and treat peripheral pulmonary lesions (PPL) have certain limitations. Robotic-assisted bronchoscopy (RAB) offers a new solution to these limitations. Currently, three RABs have been approved by the US Food and Drug Administration (FDA) and are successfully marketed, while two domestic RABs are in the research and development stage. This article provided an overview of the advantages and disadvantages of various techniques and introduced five RABs in detail. It also discussed the advantages and disadvantages of RAB technology and future trends in its development.
Subject(s)
Bronchoscopy , Robotic Surgical Procedures , Bronchoscopy/methods , Humans , Robotic Surgical Procedures/methods , Lung Diseases/diagnosisABSTRACT
BACKGROUND: Treatment regimens for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after failure of platinum-based chemotherapy have been illustrated with limited efficacy. PATIENTS AND METHODS: Here, we report a single-arm, multicenter, phase â ¡ study of R/M HNSCC patients treated with a programmed cell death-1 antibody penpulimab (200 mg) and anlotinib (12 mg) after failing at least one line of platinum-based chemotherapy. RESULTS: Of 38 patients in total, 13 (34.21%) patients achieved partial response and 16 (42.11%) patients achieved stable disease. After a median follow-up of 7.06 months (range: 4.14-15.70 months), the independent review committee-assessed objective response rate was 34.21%, the disease control rate was 76.32%. The median progression-free survival was 8.35 months (95% confidence interval 5.95-13.11 months). Twelve patients died and the median overall survival (OS) was not reached. The 12-month OS rate was 59.76%. Grade 3/4 treatment-related adverse events occurred in 47.37% of the patients. CONCLUSION: Penpulimab combined with anlotinib demonstrated promising efficacy and manageable safety in R/M HNSCC patients after failure of platinum-based chemotherapy.
Subject(s)
Head and Neck Neoplasms , Platinum , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Head and Neck Neoplasms/drug therapyABSTRACT
Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Subject(s)
Familial Mediterranean Fever , Hereditary Autoinflammatory Diseases , Male , Child , Female , Humans , Child, Preschool , Receptors, Tumor Necrosis Factor, Type I/genetics , Retrospective Studies , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/genetics , Hereditary Autoinflammatory Diseases/drug therapy , Glucocorticoids/therapeutic use , Biological Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Autoantibodies , Familial Mediterranean Fever/diagnosis , MutationABSTRACT
Pulmonary artery sling in adults is a rare congenital vascular malformation usually accompanied by tracheal and bronchial stenosis. Due to its high mortality risk and relatively poor prognosis, it has rarely been reported in adults. We reported a middle-aged patient who presented with shortness of breath, predominantly after activity, since childhood. He was diagnosed with "tracheal stenosis" in another hospital and received symptomatic treatment. The diagnosis of left pulmonary artery sling with congenital tracheal stenosis was confirmed by multi-slice spiral CT (MSCT), airway examination with flexible bronchoscope and 3D image post-processing system. Data from this case and the related literatures have been summarized and analyzed. This will help clinicians to improve their level of diagnosis and treatment.
Subject(s)
Pulmonary Artery , Vascular Malformations , Male , Middle Aged , Humans , Adult , Infant , Child , Constriction, Pathologic , Vascular Malformations/diagnosisABSTRACT
Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Male , Female , Humans , Chemoradiotherapy , Retrospective Studies , Waiting Lists , Rectal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Treatment OutcomeABSTRACT
OBJECTIVE: This study aims to investigate the CT-DNA (Calf thymus DNA) binding properties and HeLa cell viabilities of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazone (HL2). MATERIALS AND METHODS: A series of metal complexes derived from (E)-2-hydroxy-N'-((thiophen-2-yl)methylene)benzohydrazone (H2L1) and (E)-N'-((thiophen-2-yl)methylene)isonicotinylhydrazonewere (HL2) were synthesized, and their structures were characterized through FT-IR, ESI-MS, elemental analysis, molar conductivities and X-ray diffraction. DNA binding properties between CT-DNA and metal complexes were investigated by UV-Vis spectrophotometry and viscosity titration. The toxicological properties of compounds on HeLa cell were measured in vitro. RESULTS: Ligand H2L1 or HL2 exhibits a tridentate and anion ligand and uses oxygen anion, nitrogen atom and sulfur atom to coordinate with metal ions. When coordinated with metal ions, the unit O=C-NH- of each ligand has been enolized and deprotonated into -O-C=N-. The suggested chemical formulas of metal complexes are: [Co(HL1)2], [Ni(HL1)2], [Cu(HL1)2], [Co(L2)2], [Cu(L2)2], [Zn(L2)2], [ScL2(NO3)2(H2O)2], [Pr(L2)2(NO3)] and [Dy(L2)2(NO3)]. Both ligands and their metal complexes can bind strongly to CT-DNA through hydrogen bond and intercalation with Kb of 104~105 L mol-1 compared to ethidium bromide [classical DNA intercalator, Kb(EB-DNA) = 3.068 × 104 L mol-1]; however, the groove pattern cannot be excluded. The coexistence of multiple binding modes may be a common form of drug binding to DNA. HeLa cell shows lower viabilities in the presence of [Ni(HL1)2] and [Cu(HL1)2] (*p < 0.05) compared to the other compounds, with the LC50 of 2.6 µmol L-1 and 2.2 µmol L-1, respectively. CONCLUSIONS: These compounds, especially [Ni(HL1)2] and [Cu(HL1)2], will be promising for anti-tumor drugs, which should be further studied.
Subject(s)
Coordination Complexes , Humans , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Thiophenes , Cell Survival , HeLa Cells , Ligands , Spectroscopy, Fourier Transform Infrared , DNA/metabolismABSTRACT
AIM: To investigate the predictive value of the combination of DEEPVESSEL-fractional flow reserve (DVFFR) and quantitative plaque analysis using coronary computed tomographic angiography (CCTA) for major adverse cardiac events (MACE). METHOD: In this retrospective study, data from 69 vessels from 58 consecutive patients were collected. These patients who underwent coronary angiography (CAG) with DVFFR were divided into MACE-positive and MACE-negative groups. DVFFR measurements were obtained from CCTA images acquired before CAG, and an FFR or DVFFR value ≤ 0.80 was considered haemodynamically significant. CCTA images were analysed quantitatively using automated software to obtain the following indices: total plaque volume (TPV) and burden (TPB), calcified plaque volume (CPV) and burden (CPB), non-calcified plaque volume (NCPV) and burden (NCPB), low-attenuation plaque (LAP), minimum lumen area (MLA), stenosis grade (SG) and lesion length (LL). Univariate and multivariate logistic regression, correlation, and receiver operating characteristic (ROC) analyses were used for statistical analysis. RESULTS: DVFFR was highly correlated with invasive FFR (R=0.728), and the Bland-Altman plot showed good agreement between DVFFR and FFR (95% CI: -0.109-0.087) on a per-vessel level. DVFFR showed a high diagnostic performance in identifying abnormal haemodynamic vessels, with an area under the ROC curve (AUC) of 0.984. In multivariate analysis, the following biomarkers were predictors of MACE: DVFFR ≤ 0.8, SG, TPB, NCPB, and LL values. The combination of the above independent risk factors yielded the most valuable prediction for MACE (AUC:0.888). CONCLUSIONS: DVFFR was highly correlated with FFR with satisfactory diagnostic accuracy. DVFFR, together with plaque analysis indices, yielded valuable predictions for MACE.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Plaque, Atherosclerotic , Humans , Coronary Angiography/methods , Computed Tomography Angiography/methods , Coronary Stenosis/diagnostic imaging , Retrospective Studies , Predictive Value of Tests , Prognosis , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/complications , Coronary Artery Disease/complicationsABSTRACT
Objective: To analyze the effect of selective bronchial occlusion (SBO) in the treatment of biliary bronchial fistula (BBF). Methods: Eight patients with BBF that without biliary obstruction admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Naval Medical University from January 1, 2015 to December 31, 2021 were included in this study. Bronchial silicone plug (6 cases) and autologous blood+thrombin (2 cases) were used as sealing materials for SBO treatment for the first time. Among the 7 patients who underwent subsequent closure treatment, 5 cases were blocked by bronchial silicone plug, 1 case was blocked by "bronchial silicone plug+bullet-covered stent" and 1 case was blocked by "bronchial silicone plug+bronchial one-way valve". The clinical data related to SBO treatment were collected and patients were followed up, and the therapeutic effect of SBO on BBF was analyzed. Results: The age of BBF onset was (58±9) years old, including 6 males. Among the 6 patients who used bronchial silicone plug as plugging material in the first SBO treatment, 1 case was successfully plugged, 2 cases did not achieve symptoms relief after plugging, 2 cases coughed up the plugging device immediately after surgery, and 1 case developed a new fistula. Autologous blood and thrombin were used as sealing materials in 2 patients, and both failed. Among the 7 patients who received subsequent closure treatment, bronchial silicone plug+bullet-covered stent (1 case) and bronchial silicone plug+bronchial unidirectional valve (1 case) were successful. After 2-6 times of bronchial silicone plug (5 cases), fistula were successfully blocked in 3 cases, and the frequency and volume of bile-like sputum decreased by 50% or more in 2 cases. The main postoperative complications were fever and cough (expectoration) in 7 and 6 cases, respectively. During the follow-up period, 2 patients were lost to follow-up, and the remaining 6 patients were followed up for 2-31 months. During the follow-up period, the effect of closure treatment was basically stable, and there was no death case. Conclusion: SBO therapy provides a safe and feasible palliative treatment for BBF.
Subject(s)
Bronchial Fistula , Male , Humans , Middle Aged , Aged , Bronchial Fistula/etiology , Thrombin , Bronchi , Pneumonectomy/adverse effects , SiliconesABSTRACT
Based on the research methods of literature review and philosophical reflection, this article points out the deficiencies and problems in the current research of brain banks: lack of nature analysis of brain banks and human brains; insufficient discussion of ethical, legal and social issues (ELSI) in the process of brain bank implementation - which has become the main research goal of this article. The article firstly clarifies the formation process of modern brain banks and briefly introduces the current development status of brain banks in the UK, the US and China, as well as the different types of modern brain banks. Next, the nature of brain banks and human brain samples are analyzed through an analogical model. Then, the ELSI issues at different stages are analyzed according to three stages: recruitment of donors, acquisition and storage of human brain tissue samples, and release and use of human brain tissue samples. Last, in the conclusion section, the main ideas of this paper are reiterated and questions for further reflection are presented.
Subject(s)
Brain , Tissue Donors , Biological Specimen Banks , China , HumansABSTRACT
The imbalanced conditions of pronociceptive ON-cells and antinociceptive OFF-cells in the rostral ventromedial medulla (RVM) alter nociceptive transmission and play an important role in the development of chronic pain. This study aimed to explore the neuroplastic mechanisms of the RVM ON-cells and OFF-cells in a male rat model of experimental occlusal interference (EOI)-induced nociceptive behavior reflecting orofacial hyperalgesia and in modified models involving EOI removal at early and later stages. We recorded the mechanical head withdrawal thresholds (HWTs), orofacial operant behaviors, and the activity of identified RVM ON-cells and OFF-cells in these rats. EOI-induced orofacial hyperalgesia could be relieved by EOI removal around postoperative day 3; this effect could be inhibited by intra-RVM microinjection of the kappa-opioid receptor agonist U-69593. EOI removal around postoperative day 8 did not relieve the orofacial hyperalgesia which could however be reversed by intra-RVM microinjection of the NK-1 receptor antagonist L-733060. The activity of ON-cells and OFF-cells did not change during both the initial 3 and 6 days of EOI. When EOI was removed on postoperative day 3, OFF-cell responses decreased, contributing to the reversal of hyperalgesia. When EOI lasted for 8 days or was removed on postoperative day 8, spontaneous activity and stimulus-evoked responses of ON-cell increased, contributing to the maintained hyperalgesia. In contrast, when the EOI lasted for 14 days, OFF-cell responses decreased, possibly participating in the maintenance of hyperalgesia with persistent EOI. Our results reveal that adaptive changes in the RVM were associated with orofacial pain following EOI placement and removal.SIGNIFICANCE STATEMENTA considerable proportion of patients suffered from chronic orofacial pain throughout life despite the therapies given or removal of potential etiological factors. However, current therapies lack effectiveness due to limited knowledge of the chronicity mechanisms. Using electrophysiological recording, combined with a behavioral test, we found that the prevailing descending facilitation in the rostral ventromedial medulla (RVM) participates in the maintenance of orofacial hyperalgesia following late removal of nociceptive stimuli, while the prevailing descending inhibition from the RVM may contribute to the reversal of orofacial hyperalgesia following early removal of nociceptive stimuli. Thus, variable clinical outcomes of orofacial pain may be associated with descending modulation and an optimal window of time may exist in the management of chronic orofacial pain.
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In recent years, with the rapid development of interventional pulmonary diseases, new instruments and new concepts are constantly updated. The increased detection rate of pulmonary nodules increases the demand of patients. These factors jointly promote the continuous progress of bronchoscopy diagnosis and treatment technology. The following techniques including thin/ultrathin bronchoscopes, radial probe endobronchial ultrasound (R-EBUS), and navigation bronchoscopy including virtual navigation bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB), robotic-assisted bronchoscopy (RAB), frozen biopsy for the diagnosis of diffuse lung diseases are particularly prominent and important in clinical practice. This paper reviews the progress and application of bronchoscopy in interventional diagnosis through the review of literature published in 2021.
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Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.
Subject(s)
Aspirin , Platelet Aggregation Inhibitors , Aspirin/therapeutic use , Clopidogrel/therapeutic use , Coronary Artery Bypass/adverse effects , Drug Therapy, Combination , Humans , Isoindoles , Male , Phenylbutyrates , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: No validated biomarkers currently exist for predicting the efficacy outcomes in patients with neuroendocrine tumors (NETs) treated with antiangiogenic therapy. We aimed to evaluate the association between treatment-related adverse events (TRAEs) and efficacy outcomes of surufatinib in patients with advanced NET. PATIENTS AND METHODS: We included patients with NET treated with surufatinib in two multicenter, randomized, double-blind, placebo-controlled, phase III trials (SANET-p and SANET-ep) in this study. The main exposure was the presence of any of the TRAEs including hypertension, proteinuria, and hemorrhage in the first 4 weeks of surufatinib treatment. The primary outcome of the study was investigator-assessed progression-free survival (PFS). PFS outcomes were estimated using the Kaplan-Meier method with the log-rank test. Hazard ratios (HRs) were calculated by using univariable and multivariable Cox proportional hazard regression models. Blinded independent image review committee (BIIRC) assessments and 4-week landmark analysis were also performed as supportive evaluations. RESULTS: During the study period, a total of 242 patients treated with surufatinib were included in the analysis, and 164 (68%) patients had at least one of hypertension, proteinuria, and hemorrhage in the first 4 weeks of treatment. The presence of TRAEs in the first 4 weeks was associated with prolonged median PFS [11.1 versus 9.2 months; HR 0.67, 95% confidence interval (CI) 0.47-0.97; P = 0.036]. In multivariable Cox regression analysis, the presence of TRAEs was also significantly associated with longer PFS (HR 0.65, 95% CI 0.44-0.97; P = 0.035). Similar results were obtained in the BIIRC assessments and 4-week landmark analysis. CONCLUSIONS: Treatment-related hypertension, proteinuria, and hemorrhage could be potential biomarkers to predict antitumor efficacy of surufatinib in patients with advanced NET. Future prospective studies are needed to validate the findings. TRIAL REGISTRATION: ClinicalTrials.govNCT02589821; https://clinicaltrials.gov/ct2/show/NCT02589821 and ClinicalTrials.gov NCT02588170; https://clinicaltrials.gov/ct2/show/NCT02588170.
Subject(s)
Hypertension , Neuroendocrine Tumors , Biomarkers , Female , Humans , Indoles , Male , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Proteinuria , Pyrimidines , SulfonamidesABSTRACT
BACKGROUND: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. PATIENTS AND METHODS: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. RESULTS: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. CONCLUSIONS: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Squamous Cell Carcinoma/chemically induced , Esophageal Squamous Cell Carcinoma/drug therapy , HumansABSTRACT
Bohai Black (BHB) cattle, one of eight representative indigenous breeds in China, is well known for its high resistance to disease, endurance under unfavorable feeding conditions and excellent meat quality. Over recent, the number of BHB cattle has decreased sharply. To investigate the population structure and genetic diversity of this breed, the whole-genome data of 35 individuals from a conservation farm were obtained using the Illumina 150 bp paired-end platform. The results of the genetic structure and diversity analyses showed that BHB cattle had mixed Bos taurus and Bos indicus ancestry, close phylogenic relationships with Jiaxian Red and Luxi cattle and abundant genetic diversity. The bulls tested here could be divided into six families. This study presents a comprehensive evaluation of the genetic structure and diversity of the BHB cattle, and lays the theoretical basis for conservation and utilization of the valuable germplasm resource.
Subject(s)
Cattle/genetics , Genetic Variation , Whole Genome Sequencing/veterinary , Animals , Chromosome Mapping , Female , MaleABSTRACT
OBJECTIVE: To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation. METHODS: Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications. RESULTS: The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group. CONCLUSION: For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.
Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Diskectomy , Endoscopy , Humans , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , China , Humans , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/therapy , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/therapyABSTRACT
OBJECTIVE: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control. DESIGN: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC). RESULTS: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage. CONCLUSIONS: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH.