Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.

Objective:To investigate the differences in programmed death-ligand 1 (PD-L1) expression and immune cell infiltration characteristics in different molecular subtypes of endometrial cancer.Methods:A retrospective case series study was conducted. Ninety primary treated EC patients who underwent surgery without preoperative neoadjuvant therapy at the Second Hospital of Tianjin Medical University from November 2016 to May 2022 were collected. The surgical paraffin-embedded tissues were selected, and the molecular subtypes of endometrial cancer were classified according to 2020 World Health Organization (WHO) molecular subtypes using POLE gene Sanger sequencing and immunohistochemical staining. The expression of PD-L1, CD3, CD4, CD8, CD68, and CD20 proteins were detected by immunohistochemistry. Stained slides were digitally scanned for quantitative analysis of PD-L1 and immune cell infiltration density. The PD-L1-related scores were evaluated, including tumor cell score (TCS, the percentage of PD-L1 positive tumor cells among total tumor cells ≥1% was TCS positive, <1% was TCS negative), immune cell score (ICS, the percentage of PD-L1 positive tumor-associated lymphocytes and macrophages among total tumor-associated lymphocytes and macrophages ≥1% was ICS positive, <1% was ICS negative) and combined positive score [CPS, PD-L1 positive stained cells (including tumor cells, lymphocytes and macrophages)/total number of viable tumor cells ×100 ≥ 1 was CPS positive, < 1 was CPS negative]. Clinicopathological characteristics, PD-L1 scores and immune cell infiltration densities among different molecular subtypes were analyzed. Kaplan-Meier method was used to plot disease-free survival (DFS) curves for molecular subtypes, PD-L1 scores and immune cell infiltration densities, with subgroup comparisons using log-rank test. Cox proportional hazards models were used for univariate and multivariate analyses of poor DFS in endometrial cancer patients.Results:The median age of 90 patients was 58 years old (range: 33-72 years old); endometrioid carcinoma was present in 78 cases (86.7%), and non-endometrioid carcinoma was present in 12 cases (13.3%). Molecular subtyping identified POLE-mutated subtype in 6 cases (6.7%), mismatch repair deficient (MMRd) subtype in 23 cases (25.6%), p53 abnormal subtype in 14 cases (15.6%), and non-specific molecular profile (NSMP) subtype in 47 cases (52.2%). Significant differences were observed among the 4 molecular subtypes in International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, morphological subtype, tertiary lymphoid structures, estrogen receptor expression, and progesterone receptor expression (all P < 0.05). Among the 90 cases, 18 cases (20.0%) were positive for TCS, 31 cases (34.4%) were positive for ICS, and 39 cases (43.3%) were positive for CPS. Significant differences were found among the 4 molecular subtypes in PD-L1 + cell density, distribution of patients with ICS positivity, and distribution of patients with CPS positivity (all P < 0.01), but not in distribution of patients with TCS positivity ( P = 0.090); compared to NSMP subtype, the proportions of ICS-positive patients in POLE-mutated and MMRd subtypes were higher, the proportion of CPS-positive patients and PD-L1 + cell density in MMRd and p53 abnormal subtypes were higher, and the differences were statistically significant (all P < 0.05). Significant differences in immune cell densities were observed among the 4 molecular subtypes (all P < 0.01); compared to NSMP subtype, POLE-mutated, MMRd and p53 abnormal subtypes had higher densities of CD3 + and CD8 + cells, MMRd subtype had higher CD4 + cell density, and POLE-mutated and MMRd subtypes had higher CD68 + and CD20 + cell densities (all P < 0.05). The median follow-up was 43 months (range: 7-75 months). Among the molecular subtypes, p53 abnormal patients had the worst DFS, and POLE-mutated patients had the best DFS, and the difference in DFS among the 4 subtypes was statistically significant ( P = 0.046). Grouping according to the median density of immune cells in the entire group, patients with high CD8 + cell density (45 cases) had better DFS than those with low density (45 cases) ( P = 0.010), PD-L1 ICS-positive patients had worse DFS than negative patients ( P = 0.019), and NSMP subtype patients with high CD4 + cell density (24 cases) had better DFS than those with low density (23 cases) ( P < 0.001). There was no statistically significant difference in DFS among patients grouping with other PD-L1 scoring modes and other immune cell infiltration density (all P > 0.05). Cox regression analysis indicated that high CD8 + cell density ( HR = 0.335, 95% CI: 0.113-0.990, P = 0.048) was an independent protective factor for poor DFS in endometrial cancer patients, and high CD4 + cell density was an independent protective factor for poor DFS in NSMP subtype patients ( HR = 0.035, 95% CI: 0.003-0.345, P = 0.004). Conclusions:There are significant differences in PD-L1 expression and immune cell infiltration density among the different molecular subtypes of endometrial cancer, which are correlated with the prognosis of patients, and may provide reference for the selection of immunotherapy strategies and prognosis judgment.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. METHODS: We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. RESULTS: The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. CONCLUSION We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.
Humans ; Thymoma ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; China ; Thymus Neoplasms/pathology* ; Prognosis ; Neuroendocrine Tumors/pathology* ; Mutation/genetics*

Objective:To investigate the effect of different scanning centers on eye lens dose, image quality, and the dose reduction rate when using the organ dose modulation (ODM) technique in head CT.Methods:The porus acusticus externus of the head phantom was considered the scanning isocenter. The ODM was initiated and the spiral scans were performed at the scanning centers with the height of porus acusticus externus and its upper and lower 2, 4, and 6 cm, respectively. The scanning range was from the top of the head to the base of the head. Three thermoluminescent dosimeters (TLD) were placed on the surface of two eyes at each scan and the average measurement value was regarded as the radiation dose to the eye lens. The volume CT dose index (CTDI vol) and dose length product (DLP) were recorded. The scans were repeated with no ODM and the dose reduction rates at each scanning center were calculated. The regions of interest (ROI) in each group of images with ODM were drawn and the noise (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated. Results:Compared with the isocenter, the maximum change rates of CTDI vol and DLP in each scanning center were 2.46% and 2.43%, respectively. The eye lens dose increased as the scanning centre moving upwars (i.e. the bed dropping) by 39.02% at the position of 6 cm above the isocenter and decreased by 35.91% at the position of 6 cm below the isocenter. With the seven groups of scanning centers, the reduction rates of CTDI vol and DLP caused by ODM were 7.95%-8.61%, 7.91%-8.61% respectively, and the difference in the reduction rate of each dose value was not statistically significant( P>0.05). The reduction rate for eye lens dose ranged from 18.09% to 26.14%, with the highest reduction rate at the position of 4 cm above the isocentre and the second rate at the isocentre (24.73%). The difference in the rate of reduction at each scanning center was statistically significant( t=0.13, P<0.05). As the scanning center moved up, the SD of the eye region decreased and the SNR increased, and the highest CNR at the isocentre was 239.79. The SD and SNR of the brain parenchyma region were 6.85-7.96 and 3.08-4.19 respectively, and the highest CNR at the isocentre was 244.79. Conclusions:When ODM technique is used in head CT, the scan centre has a significant effect on the eye lens dose and image quality. Meanwhile, the reduction rate of the eye lens dose caused by ODM is also affected. Therefore, porus acusticus externus is recommended as the scanning center in head CT.

Objective Aiming at solving the problem of poor accuracy for numerical solution of traditional finite element method (FEM) in numerical analysis on piezoelectric effects of bone remodelling, a model with an edge-based smoothed FEM (ES-FEM) was proposed. Methods The bone model was discretized by triangular elements, and the smoothing domain was constructed based on edges of the existing mesh element. Based on gradient smoothing technique, the smoothed strain gradient and the smoothed electric field gradient were obtained, and the discrete equations of the system were constructed under the framework of smoothed Galerkin weakform. Results The changes of bone mineral density (BMD) and the distributions of electric potential under piezoelectric effects in the process of bone remodelling were reflected by using the above model. Compared with FEM, ES-FEM could improve the accuracy of simulation result for bone remodelling to a certain extent. Conclusions The proposed ES-FEM can simulate the process of bone remodelling more accurately. The accurate prediction for piezoelectric effect of bone reconstruction by this method provides an effective theoretical basis for clinical research of bone diseases.

Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2022 edition) has been published this year. The 2022 edition has been updated in the aspects of lung cancer screening, pathology, standards of thoracic surgery, treatment of metastatic lung cancer. In this study, we tried to introduce those updated aspects in the guideline of 2022 edition.

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
Humans ; Lung Neoplasms/drug therapy* ; Treatment Outcome ; Neoplasm Recurrence, Local/chemically induced* ; Quinolines/adverse effects*

Objective : To investigate the effect of hypoxic preconditioning (HPC) on mitochondrial energy metabolism in mouse hippocampal HT22 cells and its possible mechanism. Methods : In this paper, mouse hippocampal nerve cells HT22 were divided into control group, hypoxia group, HPC group, and the levels of adenosine triphosphate (ATP) and reactive oxygen species (ROS) in each group were measured for observing the effect of HPC on cell mitochondrial metabolism. Western blot was used to detect the expression of target of rapamycin ( mTOR), phosphorylated mTOR protein and autophagy substrate P62 protein; cellular immunofluorescence was used to detect phosphorylated mTOR, and LysoTrackerTM probe was used to detect lysosomes. Results : Compared with the control group, the ATP level was significantly decreased and the ROS level was increased in the hypoxia group. Exposed to HPC, the ATP level was increased and the ROS level was decreased. Compared with the control group, the expression of phosphorylated mTOR was down⁃regulated and the expression of autophagy substrate P62 was down⁃regulated in the HPC group. Conclusion HPC may affect the energy metabolism of HT22 cells through the mTOR/autophagy signaling pathway, thereby exerting a protective effect on the HT22 cells.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To compare the predictive values between 4 risk assessment scales for deep venous thrombosis (DVT) in patients with pelvic or acetabular fracture.Methods:The clinical data of 235 patients with pelvic or acetabular fracture were retrospectively analyzed who had been admitted to Xi'an Honghui Hospital from July 2014 to July 2018. They were 168 males and 67 females, aged from 18 to 90 years (average, 43.5 years). They were divided into a DVT group and a DVT-free group according to the results of vein ultrasongraphy. The RAPT, Caprini, Wells, and Autar scales were used respectively to assess the risk of DVT in the patients. The 2 groups were compared in terms of the scores of the 4 scales. After the receiver operating characteristic curve (ROC) was drawn and the area under the ROC curve (AUC) was calculated, the predictive values of the 4 scales were evaluated for lower limb DVT in the patients with pelvic or acetabular fracture.Results:Of the 235 patients, 104 (44.3%) had DVT. There was no statistically significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The DVT group scored significantly higher in RAPT, Wells and Autar scales than the DVT-free group( P<0.05). The AUCs for the RAPT, Caprini, Wells, and Autar scales were respectively 0.84±0.02, 0.65±0.05, 0.81±0.02 and 0.72±0.03, showing significant differences ( F=1.254, P=0.031). The AUCs for RAPT and Wells scales were significantly higher than those for Caprini and Autar scales, and the AUS for Autar scale was significant higher than that for Caprini ( P<0.05). The sensibilities for RAPT, Caprini, Wells and Autar scales were respectively 94.0%, 65.0%, 90.6% and 84.0% while the specificities for them 62.1%, 51.8%, 67.2% and 32.5%. Conclusion:Although all the 4 scales have a certain predictive value for the DVT risk in patients with pelvic or acetabular fracture, RAPT and Wells scales are more valuable.