With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

At present, fatigue state monitoring of upper limb movement generally relies solely on surface electromyographic signal (sEMG) to identify and classify fatigue, resulting in unstable results and certain limitations. This paper introduces the sEMG signal recognition and motion capture technology into the fatigue state monitoring process and proposes a fatigue analysis method combining an improved EMG fatigue threshold algorithm and biomechanical analysis. In this study, the right upper limb load elbow flexion test was used to simultaneously collect the biceps brachii sEMG signal and upper limb motion capture data, and at the same time the Borg Fatigue Subjective and Self-awareness Scale were used to record the fatigue feelings of the subjects. Then, the fatigue analysis method combining the EMG fatigue threshold algorithm and the biomechanical analysis was combined with four single types: mean power frequency (MPF), spectral moments ratio (SMR), fuzzy approximate entropy (fApEn) and Lempel-Ziv complexity (LZC). The test results of the evaluation index fatigue evaluation method were compared. The test results show that the method in this paper has a recognition rate of 98.6% for the overall fatigue state and 97%, 100%, and 99% for the three states of ease, transition and fatigue, which are more advantageous than other methods. The research results of this paper prove that the method in this paper can effectively prevent secondary injury caused by overtraining during upper limb exercises, and is of great significance for fatigue monitoring.
Electromyography/methods* ; Fatigue ; Humans ; Muscle Fatigue ; Muscle, Skeletal ; Upper Extremity

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: To investigate the characteristics of acute myocardial infarction caused by spontaneous coronary artery dissection(SCAD) in young female patients. Methods: In this casecontrolstudy,127 young(≤55 years) female patients with acute myocardial infarction onset within 1 week in Nanjing first hospital, Xuzhou central hospital, affiliated hospital of Xuzhou medical university, and Lianyungang first people's hospital were enrolled between January 2013 and February 2017,and the clinical data were retrospectively analyzed. According to their clinical manifestations and coronary angiography(CAG) results,the patients were divided into coronary atherosclerosis disease(CAD) group(CAG evidenced atherosclerosis, n=83) and SCAD group(CAG detected coronary artery dissection,n=44).The SCAD patients were subdivided into definite group (the results affirmed from intravenous ultrasound or optical coherence tomography, n=21) and probable group (the CAG results highly confirmed to characteristics of SCAD,but no intravenous ultrasound or optical coherence tomography image affirmation,n=23). Then, according to the different treatment strategies, the SCAD patients were subdivided into conservative treatment group(treated with drugs,n=19) and interventional therapy group(treated with percutaneous coronary intervention,n=25). Results: (1)Compared to CAD group, patients in the SCAD group had less risk factors, such as hypertension history (25.0% (11/44) vs. 45.8% (38/83) , P=0.022) and diabetes history (6.8% (3/44) vs. 21.7% (18/83) , P=0.043),and had lower levels of fasting blood glucose (5.34(4.59,5.87) mmol/L vs. 7.12(5.18,8.60)mmol/L, P=0.001),total cholesterol((3.94±1.14) mmol/L vs. (4.91±1.50) mmol/L, P=0.001),triglyceride(1.42 (0.91,1.64) mmol/L vs. 1.89 (1.23,2.45) mmol/L, P=0.005),and low density lipoprotein cholesterol ((2.24±0.91) mmol/L vs. (2.94±1.16) mmol/L, P=0.001),CAG results showed that patients in the SCAD group had more single vessel lesion (88.6% (39/44) vs. 39.8% (33/83) , P=0.001), and their target lesion stenosis was less severe ( (79.2±22.4) % vs. (91.5±12.1) %, P=0.001). (2) The clinical risk factors such as hypertension history, diabetes history, smoking history, family history of cardiology disease, fasting blood glucose,total cholesterol,triglyceride and low density lipoprotein cholesterol were similar between definite group and probable group (all P>0.05). CAG results showed that prevalence of single vessel lesion (100% (21/21) vs. 78.3% (18/23) , P=0.050) and percent of target lesion stenosis ( (76.9±20.6) % vs. (81.2±24.1) %, P=0.529) were similar between definite group and probable group.(3)There were no significant difference in single vessel(84.0% (21/25) vs. 94.7% (18/19) , P=0.370), target lesion stenosis(85.0(70.0,100.0)% vs. 75.0(50.0,90.0)%, P=0.186),and survival rates in hospital(96.0% (24/25) vs. 100% (19/19) , P=1.000) between interventional therapy group and conservative treatment group. Conclusions Prevalence of SCAD is highin young female patients with acute myocardial infarction. Acute myocardial infarction patients with less risk factors of CAD and with CAG showing smooth lesion of narrowing segment and normal finding in the other vessels, are more likely to be diagnosed with SCAD.Acute myocardial infarction patients caused by SCAD have high survival rate either receiving percutaneous coronary intervention or drug treatment.

Objective: To improve the accuracy of diagnosis and to reduce the misdiagnosis rate of nasopharyngeal carcinoma by analyzing the characteristics of such masses. Methods: Clinical data from 55 patients with suspicion of nasopharyngeal carcinoma diagnosed and treated between March 2016 and September 2017 were analyzed. All patients were followed up regularly. Results: With following-up of 12 to 25 months, 6 (10.9%) of 55 cases were identified as nasopharyngeal malignant tumors, including 4 cases of nasopharyngeal carcinoma and 2 cases of lymphoma, and 49 cases (89.1%) were diagnosed with nasopharyngeal benign masses, including 29 (59.2%) cases for nasopharyngeal lymphoid proliferation, 15 (30.6%) for adenoid hypertrophy, 2 (4.1%) for nasopharyngeal cyst, 1 (2.0%) for polyp, 1 for papilloma and 1 for nasopharyngeal pharyngeal cyst. Small nasopharyngeal malignant tumor and masses with benign hyperplasia showed the overlap of images on the enhanced MRI/CT and Fibro-nasopharyngoscopy, but all 6 patients with nasopharyngeal malignant tumors presented with moderately enhanced multiple enlarged lymph nodes. Conclusions Fibro-nasopharyngoscopy and enhanced MRI/CT have some value on evaluation of nasopharyngeal masses, but biopsy is a golden standard for diagnosis. Follow-up is necessary for the patients with negative biopsy and benign nasopharyngeal hyperplasia indicated by fibro-nasopharyngoscopy and enhanced MRI/CT.

OBJECTIVETo compare the difference of intra-abdominal infection between intracorporeal anastomosis (IA) and extracorporeal anastomosis (EA) in patients undergoing laparoscopic right hemicolectomy within postoperative 30 days.

METHODSClinical date of right colon cancer patients undergoing laparoscopic right hemicolectomy at the Department of Colorectal Surgery, PUMCH from January 1st, 2013 to October 31st, 2016 were retrospectively analyzed. Patients with stage IV cancers which could not be radically resected, emergency operation and conversion to open surgery were excluded. The intracorporeal anastomosis and extracorporeal anastomosis were compared in the items of operation time, postoperative infection and postoperative hospital stay.

RESULTSA total of 194 patients were enrolled in the study, including 73 patients with IA and 121 patients with EA. No significant differences were found in gender, age, previous operation history, tumor site and T stage of the tumor between two groups (all P>0.05). There were also no significant differences in mean operative time (162.4 minutes vs. 167.7 minutes, P=0.257), time to first flatus (3.3 days vs. 3.4 days, P=0.744), number of harvested lymph nodes (30.3 nodes vs. 33.8 nodes, P=0.071) and postoperative hospital stay (7 days vs. 7 days, P=0.067) between two groups. The incidence of intra-abdominal infection in patients with IA was significantly higher than that in those with EA [13.7%(10/73) vs. 1.7%(2/121), P=0.001], while the differences of the incidence of wound infection [1.4%(1/73) vs. 3.3%(4/121), P=0.652], respiratory infection [1.4%(1/73) vs. 3.3%(4/121), P=0.652] and urinary tract infection [2.7%(2/73) vs. 0.8%(1/121), P=0.558] were not significant.

CONCLUSIONCompared with EA, IA may increase the risk of intra-abdominal infection in patients undergoing laparoscopic right hemicolectomy.

Objective To explore the safety and cosmetic effect of nipple-sparing modified radical mas tectomy and immediate tissue expander implantation with single circumaereolar incision.Methods 30 patients were enrolled in Peking Union Medical College Hospital between Jan.2014 and Dec.2015.All the patients were categorized according to surgical incision (single circumaereolar incision group vs double incisions group).Data on clinicopathological parameters,average hospital stay,complications and overall cosmetic effect were retrospectively collected.Data was performed with Chi-square test,Fisher exact test and t-test.Statistical significance was defined as P＜0.05.Results 19 patients were enrolled in single circumaereolar incision group,and 11 patients in double incisions group.There was no significant difference for operation duration (P=0.093) and average hospital stay (P=0.339).After follow-up for 19.1 months,ranging from 8 to 31 months,no patients developed seroma or arm lymphedema.There was no statistical significance between the two groups in terms of sensation in nippleaereolar area (P=0.973),bilateral symmetry (P=0.650) and overall cosmesis (P=0.483).Conclusion single circumaereolar incision nipple-sparing modified radical mastectomy and immediate tissue expander implantation can be one of the preferable surgical procedures with benefits of minimal invasiveness,reliable oncological safety and decent cosmetic effect.

A 48-year-old middle aged male presented swelling lymph nodes and mass in neck for 5 years. Physical examination shows swollen mass in head and neck regions. The masses could be touched in bilateral parotids and neck with a little movement and moderate tenderness. The level of IgG was normal, but Eosinophi count was high. The function of heart liver and kidney was normal. The result of B-mode ultrasonography reveals bilateral parotids and subcutaneous near parotids were widely swollen and several swollen lymph nodes in neck. pathological examination displays features of a large number of lymph follicles hyperplasia, acidophilic granulocyte infiltration, capillary hyperplasia and fibrosis of different level. The disease were eventually diagnosed by pathological examination. Method of treatment includes glucocorticoid drug therapy, surgical resection and local radiotherapy. The last treatment of patients with Kimura's disease should be combined with the clinical manifestation of them to determine the individualized treatment, so as to improve the quality of life of patients.
Angiolymphoid Hyperplasia with Eosinophilia ; diagnosis ; pathology ; therapy ; Glucocorticoids ; therapeutic use ; Humans ; Lymph Nodes ; pathology ; Male ; Middle Aged ; Neck ; Parotid Gland ; pathology

OBJECTIVE: To investigate the influence of nasal septal deviation on the incidence of bilateral sinusitis. METHOD: Two thousand and seventy-four cases of nasal septal deviation with chronic sinusitis available from January 2006 to March 2012 were reviewed retrospectively. RESULT: Of these 2074 cases, 1 687 (81.3%) patients had sinusitis in narrow side and 1582 (76.3%) in wide side, the difference was statistically significant (P < 0.01) and the relative risk value in narrow side (1.4) was higher than wide side (0.7) associated with the incidence of sinusitis. There was significant difference (P < 0.05) between the two group counting datas analyzed by rank sum test, and the mean rank order in narrow side was 1656.396, significantly greater than wide side (1 612.184). The incidence of sinusitis in men was 50.6% (1049/2074), in women was 49.4% (1025/2074), and there was no significant difference between them. Deviating leftward was 1148 cases (55.4%), deviating rightward was 926 cases (44.6%), and the difference was statistically significant (P < 0.05). Anatomic variations in narrow side and wide side were uncinate process hypertrophy (7.0%, 27.0%), middle turbinate hypertrophy (7.8%,38.0%), ethmoidal bulla hypertrophy (26.2%, 39.0%), paradoxical middle turbinate (5.4%, 15.5%), hypertrophic inferior turbinate (52.9%, 67.0%) and mucosa pachynsis (0.5%, 2.8%), respectively. CONCLUSION Sinusitis incidence in narrow side is higher than wide side. There is no significant difference between the incidence of sinusitis in men and women. The majority of nasal septum deviate leftward. Higher incidence of sinusitis in wide side is the result of compensatory mechanism. Only septoplasty may not restore the normal venting function in nasal cavity. Hypertrophic inferior turbinate are closely correlated with sinusitis.
Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Nasal Cavity ; Nasal Septum ; abnormalities ; Paranasal Sinuses ; Retrospective Studies ; Sinusitis ; epidemiology ; Turbinates ; abnormalities ; Young Adult

Summary: The regulation of hypoxic response elements on the expression of vascular endothelial growth factor (VEGF) gene transfected to primary cultured rat skeletal myoblasts under hypoxic environment was investigated, pEGFP-C3-9HRE-CMV-VEGF vector was constructed with molecular biology technique and transfected to primary cultured rat skeletal myoblasts by lipofectamine in vitro. Gene expression of transfected myoblasts was detected by RT-PCR, Western blot and fluorescence microscope under different oxygen concentrations and different hypoxia time. The results showed that in hypoxia group, the VEGF gene bands were seen and with the decrease of oxygen concentrations and prolongation of hypoxia time, the expression of VEGF mRNA was obviously increased.Under hypoxic environment, the expression of VEGF protein in the transfected myoblasts was significantly increased. EGFP was expressed only under hypoxic environment but not under normoxic environment. It was concluded that hypoxia promoter could be constructed with HRE and regulate the expression of VEGF gene under hypoxic and normoxic environment, which could enhance the reliability of gene therapy.