Genomic heterogeneity of multiple synchronous lung cancers in Chinese population.

INTRODUCTION: It is clinically challenging to infer the phylogenetic relationship between different tumor lesions of patients with multiple synchronous lung cancers (MSLC), whether these lesions are the result of independently evolved tumor or intrapulmonary metastases. METHODS: We used the Illumina X10 platform to sequence 128 stage I lung cancer samples collected from 64 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference. RESULTS: We detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including, EGFR, ERBB2, TP53, BRAF, and KRAS. Other putative driver mutations identified were enriched in RTK-RAS signaling, TP53 signaling, and cell cycle. Also, we found some interesting cases, two cases that carried EGFR L858R and T790M co-mutation in one tumor and another tumor with only EGFR 19del, and 1 case with two KRAS hotspots in the same tumor. Due to the short follow-up time and early stage, further investigation is needed to determine whether this unique mutation profile will affect their progression-free survival (PFS) and overall survival (OS). Regarding genetic evolution analysis among 64 tumor samples, 50 of them display distinct mutational profiles, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. On the other hand, six patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. CONCLUSION: In summary, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profiles in different tumor lesions, and we could distinguish MSLC from intrapulmonary metastases via clonality estimation.

LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells.

Exosomes are vital mediators for intercellular communications in the tumor microenvironment to accelerate colon cancer progression. Leucine-rich repeat-containing 8A (LRRC8A), the core component of the volume-regulated anion channel, is closely associated with acquiring heterogeneity for tumor cells. However, the role of LRRC8A in the exosomes remains largely unknown. Here, we reported that LRRC8A was one of the compositions in the exosomes released from colon cancer HCT116 cells. Down-regulation of LRRC8A proteins inhibited ex vivo cell growth and induced apoptosis. Consistently, chloride channel blockers DCPIB and NPPB inhibited cell growth and induced cell apoptosis in a time or concentration-dependent manner. Interestingly, the total amounts and proportions of different diameter exosomes released in 6 h were not altered by the treatment of DCPIB and NPPB in HCT116 cells. In contrast with the inhibition of LRRC8A, overexpression of LRRC8A proteins in HCT116 cells released significantly more distinct populations of exosomes. Importantly, the switches of ratios for exosomes in a hypotonic challenge were eliminated by DCPIB treatment. Collectively, our results uncovered that LRRC8A proteins were responsible for the exosome generation and sorted into exosomes for monitoring the volume regulation.

Anatomical type analysis of right interlobar artery based on chest thin-slice CT scan and three-dimensional reconstruction.

PURPOSE: To analyse and summarize branching pattern types of the interlobar portion of right pulmonary arteries (RPA) through chest thin-slice CT scans and three-dimensional reconstruction. METHODS: A total of 179 patients (58 males and 121 females, with an average age of 53.9 years) at the Thoracic Surgery Department of Ningbo First Hospital were retrospectively included from December 2020 to December 2021. All patients completed preoperative thin-slice CT scans and three-dimensional reconstructions of the chest. The clinical data and branching patterns were collected. Data were analysed using SPSS 21.0. RESULTS: The branching pattern types of the interlobar portion of RPA were divided into 4 types according to the order and number of branches: Type I (145/179, 81.0%), Asc. A2, MA, A6; Type II (28/179, 15.6%), Asc. A2 deletion, MA, A6; Type III (5/179, 2.8%), Asc. A2, A6, MA; and Type IV (1/179, 0.6%), MA, Asc. A2, A6. Type I was the most common pattern. Furthermore, according to the number of branches of MA and A6, this pattern can be subdivided into 15 subcategories. CONCLUSION: Chest thin-slice CT scans and 3D reconstructions can provide surgeons with accurate lung anatomy, which helps surgeons perform preoperative planning and complete surgery successfully.

Detection and Application of Wearable Devices Based on Internet of Things in Human Physical Health.

In order to improve the detection function of wearable intelligent devices in the Internet of things and facilitate people to control a variety of information such as heart rate, exercise state, blood oxygen saturation, and so on, the scientific detection of human physical health based on wearable devices based on Internet of things technology is proposed. Through the combination of software- and hardware-related functional modules, the real-time detection of human physical health information can be effectively realized. Firstly, the detection principle of optical capacitance product pulse wave signal and the waveform characteristics of pulse wave are introduced, and then the application scenarios and advantages of wearable devices are further introduced; then, the convolutional neural network for pulse wave signal denoising and the basic principle of self-encoder are introduced; finally, the regression prediction method and support vector machine method for pulse wave signal feature extraction are introduced in detail. The pulse wave based on optical capacitance product is removed to improve the waveform quality of pulse wave signal. Firstly, the system software development environment is briefly described. Then, the software design of watch terminal master device based on MSP432 and belt terminal slave device based on MSP430 are described in detail, and the detailed program implementation flow of each key technology in the system is given. In addition, the fall detection algorithm based on threshold discrimination is studied, and the program implementation of the algorithm is also described in detail. Finally, the system is tested. The results show that normal state mainly include normal walking, jogging, and fast sitting, and the accuracy rate is 97%, 95%, and 93%, respectively. For fall state, the experimenter needs to simulate various possible fall states, and the accuracy rate is 95%, 93%, and 95%, respectively, which verifies the detection accuracy of the algorithm. The system can automatically turn on the satellite positioning function when the user's physical sign parameters are abnormal or the user's current fall dangerous situation occurs, and send the current position information and alarm content information through the GSM module, so that the dangerous situation can be found and handled at the first time.

CircRNA SOD2 motivates non-small cell lungs cancer advancement with EMT via acting as microRNA-2355-5p's competing endogenous RNA to mediate calmodulin regulated spectrin associated proteins-2.

Circular RNAs (circRNAs) are closely linked with human cancer development such as non-small-cell lung cancer (NSCLC). However, the characteristics and specific functions of most circRNAs in NSCLC remained unknown. Previous studies have suggested that circRNA SOD2 (CircSOD2) expression was upregulated in a number of cancers. This study aimed to explore the functions of circSOD2 in NSCLC advancement with epithelial-mesenchymal transition (EMT). Expression profile analysis of circSOD2, miR-2355-5p, and calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) was detected by real-time quantitative PCR (RT-qPCR). Transwell assay, cell migration assay, CCK8, ELISA, RIP assay, RNA pull-down assay, and Western blot analysis were performed to evaluate the functions of circSOD2, miR-2355-5p, and CAMSAP2. We found elevated expression of circSOD2 and CAMSAP2 while reduced expression of miR-2355-5p in NSCLC tumor tissues. Silencing or overexpression of CircSOD2 resulted in increased or decreased expression of miR-2355-5p, respectively. Mechanically, we showed that silencing of CircSOD2 and overexpression of miR-2355-5p resulted in the reduced rate of NSCLC cell proliferation. Inhibition of miR-2355-5p reversed the changes induced via silencing of CircSOD2. MiR-2355-5p binds to the CircSOD2 promoter and triggered its stimulation, which further activated circSOD2 expression. CircSOD2 suppression impaired lung cancer cell growth, cell migration, prohibited cell cycle progression, and in vivo tumor growth by targeting miR-2355-5p expression in NSCLC tissues. Meanwhile, increased expression of CAMSAP2 reversed the changes stimulated by the elevated level of miR-2355-5p in NSCLC progression. This innovative signaling axis CircSOD2/miR-2355-5p/CAMSAP2 illustrated the new horizon to investigate NSCLC tumorigenesis and provided new prognosis and treatment of NSCLC.

High-fat diet impairs ferroptosis and promotes cancer invasiveness via downregulating tumor suppressor ACSL4 in lung adenocarcinoma.

BACKGROUND: Long-chain acyl-CoA synthetase-4 (ACSL4) is involved in fatty acid metabolism, and aberrant ACSL4 expression could be either tumorigenic or tumor-suppressive in different tumor types. However, the function and clinical significance of ACSL4 in lung adenocarcinoma remain elusive. RESULTS: ACSL4 was frequently downregulated in lung adenocarcinoma when analyzing both the TCGA database and the validation samples, and the lower ACSL4 expression was correlated with a worse prognosis. Using gene set enrichment analysis, we found that high ACSL4 expression was frequently associated with the oxidative stress pathway, especially ferroptosis-related proteins. In vitro functional studies showed that knockdown of ACSL4 increased tumor survival/invasiveness and inhibited ferroptosis, while ACSL4 overexpression exhibited the opposite effects. Moreover, high-fat treatment could also inhibit erastin-induced ferroptosis by affecting ACSL4 expression. The anti-tumor effects of ferroptosis inducers and the anti-ferroptosis effects of the high-fat diet were further validated using the mouse xenograft model. CONCLUSIONS: ACSL4 plays a tumor-suppressive role in lung adenocarcinoma by suppressing tumor survival/invasiveness and promoting ferroptosis. Our study provided a theoretical reference for the application of ferroptotic inducers and dietary guidance for lung adenocarcinoma patients.

The need for immunotherapy when neoadjuvant chemoradiotherapy achieves pathologic complete response in stage IIIB non-small cell lung cancer: a case report.

The 5-year survival rate of patients with stage IIIB non-small cell lung cancer (NSCLC) range is 26%. Pathological complete response (pCR) is the best outcome after treatment for stage IIIB NSCLC. For patients with stage IIIB NSCLC, concurrent chemoradiotherapy with a curative intent is currently the standard treatment. For patients who respond to treatment, this is followed by consolidation immunotherapy with durvalumab. However, because of the complex and diverse nature of stage IIIB NSCLC, standard treatment is not necessarily suitable for all patients; rather, individualized and precise treatment can maximize the benefits of patients. Herein, we report a case of a patient with stage IIIB lung squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiotherapy after receiving all 6 cycles of treatment, the patient underwent video-assisted thoracoscopic surgery (VATS) right upper lobectomy, right middle partial lobectomy, right lower partial lobectomy, and systematic mediastinal lymph node dissection. Postoperative pathological section results showed a pCR. The patient did not continue to use immunotherapy as a consolidation treatment after surgery. He remained disease free until the latest follow-up a half year later. This case has led us to doubt whether immunotherapy with durvalumab is still needed for patients with pCR. However, more clinical trials are needed to provide stronger evidence.

Aspirin-targeted PD-L1 in lung cancer growth inhibition.

BACKGROUND: Aspirin is a classic anti-inflammatory drug and its anticancer effect has been previously explored in many types of cancer including colorectal cancer therapy. Programmed cell death-ligand 1 (PD-L1) is widely expressed in tumor cells and displays an inhibitory role in antitumor immunity. This study aimed to clarify the role of PD-L1 in aspirin-suppressed lung cancer. METHODS: The inhibitory effect of aspirin on lung cancer cell proliferation was assessed using an MTT cell viability assay. The role of aspirin in the modulation of PD-L1 expression was analyzed by western blot or RT-PCR assays. In lung cancer cells, the influence of aspirin on PD-L1 promoter activity was detected using a luciferase reporter assay. The interaction of TAZ with PD-L1 promoter in the cells, with or without aspirin administration, was tested via chromatin immunoprecipitation (ChIP) analysis. The function of PD-L1 in aspirin-mediated growth inhibition of lung cancer was examined using a cell viability assay. RESULTS: Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin was able to markedly decrease the expression of PD-L1 at the mRNA and protein levels in lung cancer cells. For the mechanism study, we found that the promoter of PD-L1 was inactivated by aspirin via TAZ transcriptional coactivator in the cells. With regard to the functional investigation, aspirin was capable of resisting cell proliferation and PD-L1 overexpression abolished aspirin-depressed cell proliferation in lung cancer. CONCLUSIONS: Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD-L1 axis.

Pan-cancer analysis reveals synergistic effects of CDK4/6i and PARPi combination treatment in RB-proficient and RB-deficient breast cancer cells.

DNA damage results in mutations and plays critical roles in cancer development, progression, and treatment. Targeting DNA damage response in cancers by inhibiting poly-(ADP-ribose) polymerases (PARPs) offers an important therapeutic strategy. However, the failure of PARP inhibitors to markedly benefit patients suggests the necessity for developing new strategies to improve their efficacy. Here, we show that the expression of cyclin-dependent kinase 4/6 (CDK4/6) complex members significantly correlates with mutations (as proxies of DNA damages), and that the combination of CDK4/6 and PARP inhibitors shows synergy in both RB-proficient and RB-deficient breast cancer cells. As PARPs constitute sensors of DNA damage and are broadly involved in multiple DNA repair pathways, we hypothesized that the combined inhibition of PARPs and DNA repair (or repair-related) pathways critical for cancer (DRPCC) should show synergy. To identify druggable candidate DRPCC(s), we analyzed the correlation between the genome-wide expression of individual genes and the mutations for 27 different cancer types, assessing 7146 exomes and over 1,500,000 somatic mutations. Pathway enrichment analyses of the top-ranked genes correlated with mutations indicated "cell cycle pathway" as the top candidate DRPCC. Additionally, among functional cell-cycle complexes, the CDK4/6 complex showed the most significant negative correlation with mutations, also suggesting that combined CDK4/6 and PARP inhibition might exhibit synergy. Furthermore, combination treatment showed synergy in not only RB-proficient but also RB-deficient breast cancer cells in a reactive oxygen species-dependent manner. These findings suggest a potential therapeutic strategy to improve the efficacy of PARP and CDK4/6 inhibitors in cancer treatment.

Clinical analysis of 56 cases of simultaneous bilateral video-assisted thoracoscopic surgery for bilateral synchronous multiple primary lung adenocarcinoma.

BACKGROUND: Bilateral synchronous multiple primary lung adenocarcinoma (BSMPLA) is a rapidly increasing disease for which timely and accurate treatment is required. We describe our experience which we hope to establish optimal therapeutic options for patients with BSMPLA. METHODS: This study aimed to explore the feasibility and safety of simultaneous bilateral video-assisted thoracoscopic surgery (VATS) in 56 patients who received histological diagnoses of BSMPLA at our hospital between January 2016 and January 2018. In this retrospective analysis of clinical outcomes, we observed no serious postoperative complications or perioperative death. RESULTS: Four and 28 patients respectively underwent bilateral lobectomy and lobectomy with contralateral sublobar resection, whereas the remaining 24 patients underwent bilateral sublobar resection. Sublobar resection means anatomical segmentectomy or wedge resection. The mean postoperative hospital stay duration was 5.39±2.67 days. Postoperative complications comprising persistent air leakage for more than 5 days was observed in 8 (14.2%) of 56 patients. No severe postoperative complications or deaths occurred. CONCLUSIONS: Our results suggest that simultaneous bilateral VATS is feasible, safe, and reproducible. This therapeutic strategy appears to confer considerable benefits on patients with BSMPLA.

Systematic review and meta-analysis: Tai Chi for preventing falls in older adults.

OBJECTIVE: It remains unclear whether Tai Chi is effective for preventing falls in older adults. We undertook this systematic review to evaluate the preventive effect of Tai Chi by updating the latest trial evidence. DESIGN: Systematic review and meta-analysis. METHODS: The Cochrane Library, MEDLINE and EMBASE were searched up to February 2016 to identify randomised trials evaluating Tai Chi for preventing falls in older adults. We evaluated the risk of bias of included trials using the Cochrane Collaboration's tool. Results were combined using random effects meta-analysis. OUTCOME MEASURES: Number of fallers and rate of falls. RESULTS: 18 trials with 3824 participants were included. The Tai Chi group was associated with significantly lower chance of falling at least once (risk ratio (RR) 0.80, 95% CI 0.72 to 0.88) and rate of falls (incidence rate ratio (IRR) 0.69, 95% CI 0.60 to 0.80) than the control group. Subgroup analyses suggested that the preventive effect was likely to increase with exercise frequency (number of fallers: p=0.001; rate of falls: p=0.007) and Yang style Tai Chi was likely to be more effective than Sun style Tai Chi (number of fallers: p=0.01; rate of falls: p=0.001). The results might be influenced by publication bias as the funnel plots showed asymmetry. Sensitivity analyses by sample size, risk of bias and comorbidity showed no major influence on the primary results. CONCLUSIONS: Tai Chi is effective for preventing falls in older adults. The preventive effect is likely to increase with exercise frequency and Yang style Tai Chi seems to be more effective than Sun style Tai Chi.

Surgical Template to Minimize the Damage of Tooth Buds in Young Children With Mandibular Distraction Osteogenesis.

BACKGROUND: Mandibular distraction osteogenesis has become one of the most powerful reconstructive techniques for the treatment of mandibular deformities in young children. Damage to the tooth buds is often cited as a complication of it. The purpose of this study was to precisely design the osteotomy line and avoid the damage of tooth buds at the mandibular angle area with the help of surgical template. METHODS: Six patients aged from 6 to 10 years were selected in this study. Three-dimensional computed tomography data was put into Mimics software for preoperative planning the osteotomy line and the accurate placement of the distractor based on the exact position of tooth follicle. And then the surgical template was manufactured by a three-dimensional printer with rapid prototyping technique. The surgeons were guided to perform the osteotomy aided with the prefabricated template through an intraoral approach. Distraction began 7 days postoperation with a rate of 1 mm/d and the distractor was removed after a 6 to 8 months consolidation period. The tooth buds were observed through radiographs that were performed at 5 time intervals: before distraction, at the end of latency, at the end of distraction, at the end of consolidation and 2 years of the postoperation to remove the distractor. RESULTS: The average follow-up time is 24 months. Facial appearance and occlusal plane of all the young patients were greatly improved without complications. From the radiological observation, the tooth buds was intact after the surgery and the second molar normally erupted after removing the distractor. CONCLUSIONS: The surgical template was considered to be helpful in improving the surgical accuracy and avoiding the tooth buds damage during mandibular distraction osteogenesis.

The influence of gait speed on the stability of walking among the elderly.

Walking speed is a basic factor to consider when walking exercises are prescribed as part of a training programme. Although associations between walking speed, step length and falling risk have been identified, the relationship between spontaneous walking pattern and falling risk remains unclear. The present study, therefore, examined the stability of spontaneous walking at normal, fast and slow speed among elderly (67.5±3.23) and young (21.4±1.31) individuals. In all, 55 participants undertook a test that involved walking on a plantar pressure platform. Foot-ground contact data were used to calculate walking speed, step length, pressure impulse along the plantar-impulse principal axis and pressure record of time series along the plantar-impulse principal axis. A forward dynamics method was used to calculate acceleration, velocity and displacement of the centre of mass in the vertical direction. The results showed that when the elderly walked at different speeds, their average step length was smaller than that observed among the young (p=0.000), whereas their anterior/posterior variability and lateral variability had no significant difference. When walking was performed at normal or slow speed, no significant between-group difference in cadence was found. When walking at a fast speed, the elderly increased their stride length moderately and their cadence greatly (p=0.012). In summary, the present study found no correlation between fast walking speed and instability among the elderly, which indicates that healthy elderly individuals might safely perform fast-speed walking exercises.

Treatment protocols for growth hormone-secreting pituitary adenomas combined with craniofacial fibrous dysplasia: A case report of atypical McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder, characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone and café-au-lait macules. The most common endocrine dysfunction is gonadal hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders, although the majority of cases have been reported in young females. Atypical presentations of MAS, with only one or two of the classic symptoms, have been previously described, but remain particularly challenging due to the lack of a diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the gene of the α-subunit of the stimulatory G-protein is limited; thus, diagnosis is based on clinical judgment. In the present study, a male with polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with atypical MAS, was reported. The pituitary adenoma was effectively treated with radiotherapy and the patient underwent surgery for the polyostotic fibrous dysplasia, with marked improvements observed in appearance.

Treatment protocol and surgical techniques for macrogenia.

BACKGROUND: This study focused on the treatment protocol for macrogenia and surgical techniques of the semicircular ostectomy of the mandibular inferior border. METHODS: Seven patients with macrogenia were treated following our treatment protocol including a preoperative assessment (the Delaire analysis), an operative design (three-dimensional reconstruction and simulation), operation techniques (semicircular ostectomy of the mandibular inferior border), and a postoperative evaluation. RESULTS: Our treatment procedure provided an overall harmonizing effect on the lower facial contour. All 7 patients were satisfied with their aesthetic results. A few complications such as numbness and submental soft-tissue excess were observed, but they improved to different extent as time went by. CONCLUSIONS: Our treatment protocol for macrogenia is of great use to make the surgeries to be precisely and safely done with satisfactory results.

Screening method based on walking plantar impulse for detecting musculoskeletal senescence and injury.

No consensus has been reached on how musculoskeletal system injuries or aging can be explained by a walking plantar impulse. We standardize the plantar impulse by defining a principal axis of plantar impulse. Based upon this standardized plantar impulse, two indexes are presented: plantar pressure record time series and plantar-impulse distribution along the principal axis of plantar impulse. These indexes are applied to analyze the plantar impulse collected by plantar pressure plates from three sources: Achilles tendon ruptures; elderly people (ages 62-71); and young people (ages 19-23). Our findings reveal that plantar impulse distribution curves for Achilles tendon ruptures change irregularly with subjects' walking speed changes. When comparing distribution curves of the young, we see a significant difference in the elderly subjects' phalanges plantar pressure record time series. This verifies our hypothesis that a plantar impulse can function as a means to assess and evaluate musculoskeletal system injuries and aging.

Bone surface mapping method.

Bone shape is an important factor to determine the bone's structural function. For the asymmetrically shaped and anisotropically distributed bone in vivo, a surface mapping method is proposed on the bases of its geometric transformation invariance and its uniqueness of the principal axes of inertia. Using spiral CT scanning, we can make precise measurements to bone in vivo. The coordinate transformations lead to the principal axes of inertia, with which the prime meridian and the contour can be set. Methods such as tomographic reconstruction and boundary development are employed so that the surface of bone in vivo can be mapped. Experimental results show that the surface mapping method can reflect the shape features and help study the surface changes of bone in vivo. This method can be applied to research into the surface characteristics and changes of organ, tissue or cell whenever its digitalized surface is obtained.