Optogenetic manipulation of lysosomal physiology and autophagy-dependent clearance of amyloid beta.

Lysosomes are degradation centers of cells and intracellular hubs of signal transduction, nutrient sensing, and autophagy regulation. Dysfunction of lysosomes contributes to a variety of diseases, such as lysosomal storage diseases (LSDs) and neurodegeneration, but the mechanisms are not well understood. Altering lysosomal activity and examining its impact on the occurrence and development of disease is an important strategy for studying lysosome-related diseases. However, methods to dynamically regulate lysosomal function in living cells or animals are still lacking. Here, we constructed lysosome-localized optogenetic actuators, named lyso-NpHR3.0, lyso-ArchT, and lyso-ChR2, to achieve optogenetic manipulation of lysosomes. These new actuators enable light-dependent control of lysosomal membrane potential, pH, hydrolase activity, degradation, and Ca2+ dynamics in living cells. Notably, lyso-ChR2 activation induces autophagy through the mTOR pathway, promotes Aß clearance in an autophagy-dependent manner in cellular models, and alleviates Aß-induced paralysis in the Caenorhabditis elegans model of Alzheimer's disease. Our lysosomal optogenetic actuators supplement the optogenetic toolbox and provide a method to dynamically regulate lysosomal physiology and function in living cells and animals.

Experimental study of erodible bed scoured by the debris flow in the narrow-steep gully.

In recent years, debris flows have frequently erupted in the narrow-steep gully of the earthquake-hit Wenchuan region, displaying high flow velocities and powerful scouring abilities. However, few scouring studies in the narrow-steep gully have been conducted. A model experiment simulated the debris flow scouring process in a narrow-steep flume, in which several important physical parameters, including the debris flow density (ρ), flume slope (θ), and grain size of the sediment (D), were varied to investigate their influences on the erodible strength. The experimental flows were composed of 50 L of water and grains, which scoured 2.3 m of erodible bed down a steeply inclined flume. A high-speed camera photographed the scouring processes, while a 3D laser device captured the final bed shapes. The experiments show that the debris flow first collides with the sediment at the head of the gully to form a pit, which is enlarged by continuous impact; the velocity of the debris flow out of the pit is significantly reduced due to the change in flow direction, resulting in a much lesser scouring effect after the pit; and finally, the gully bed presents the shape of a pit at the entrance and a groove in the middle and rear. The critical scour slope, where the gully bed shows scouring, increases with increasing debris flow density but decreases with increasing grain size of sediment. Following scouring, the maximum scouring depth is further positively correlated with the flume slope. In narrow-steep gullies, the gully bed is extremely susceptible to scouring by debris flow with a low density, and even headward erosion appears, at which the maximum scouring depth only increased from 148.04 to 149.97 mm, but the erosion amount had a significant increase of 36.9%. The research results have an important significance for revealing the disaster-causing phenomena and mechanisms of debris flows in the narrow-steep gully.

The effect of COVID-19 outbreak on urological procedures for urinary stones: data from three high-volumes centers in China.

China has been the first country to be affected by the COVID-19 outbreak. The pandemic resulted in significant disruption of Health Care Services worldwide, and this effect on treatments for urinary stones is currently unclear. This is the first retrospective study involving three tertiary referral centers for urolithiasis across China. We evaluated surgical volumes and peri-operative outcomes of procedures delivered for upper urinary tract stones. We compared trimester prior to restrictions for COVID-19 (October 1st, 2019 to December 31st, 2019, period A), during restrictions (February 1st, 2020 to March 31st, 2020, period B), and afterword (April 1st, 2020 to June 31st, 2020, period C). A total of 2,543 procedures have been carried out. We observed a loss of 743 cases during period B (-29.2%) and 201 during period C (-7.9%). Percutaneous surgery showed the worst reduction, with 507 mini-PCNLs delivered in period A, 168 in period B (-60.8%), and 389 (-18.3%) in period C (p = 0.001). A worst trend was shown for standard PCNLs with 84 procedures carried out in period A, 5 in period B (-95.2%), and 9 (-89.2%) in period C (p = 0.001). Retrograde surgery also decreased, from 420 cases in period A to 190 cases in period B (-54.8%). An increment was however seen in period C when 468 cases have been carried out (+ 11.4%, p = 0.008). In term of SFRs, a difference was noticed for RIRSs, being 69.2%, 80.5%, and 69.3% during three periods (p = 0.045) and semirigid ureteroscopies (90.3%, 97.1%, and 84.8%, p = 0.013). Charlson's Comorbidity Score could not show any difference between groups as well as no differences in term of post-operative complications have been noticed.

[Comprehensive Analysis of the Relationship between m6A Methylation Patterns and Immune Microenvironment in Lung Adenocarcinoma].

BACKGROUND: m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD. METHODS: LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases. RESULTS: The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues. CONCLUSIONS: m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.

[Single-versus Two-port Video-assisted Thoracic Surgery in Thymoma: 
A Propensity-matched Study].

BACKGROUND: In recent years, with the advancement of minimally invasive techniques, thoracoscopic thymoma resection has experienced a development process from three-port video-assisted thoracic surgery (VATS) to two-port (TP) and single-port (SP) variants. However, the feasibility and safety of SP-VATS have not been generally recognized. This study intends to explore the safety and feasibility of SP-VATS in thymoma resection, in order to provide a reference for clinical surgicalselection. METHODS: The clinical data of 197 patients who underwent thoracoscopic thymoma resection in Beijing Tongren Hospital from January 2018 to September 2021 were retrospectively analyzed. The patients were divided into SP-VATS group (n=42) and TP-VATS group (n=155). After matching propensity scores, there is no statistically significant difference in preoperative baseline data between SP-VATS group and TP-VATS group. Among them, there were 17 males and 25 females with an average age of 28-72 (48.00±9.43) years in the SP-VATS group, and 20 males and 22 females with an average age of 30-75 (50.38±9.83) years in TP-VATS group. The clinical effects of the two groups were compared. RESULTS: The operation was successfully completed in both groups, and there was no conversion to thoracotomy or increased surgical incisions. Compared with the TP-VATS group, the chest drainage time and hospital stay in the SP-VATS group were shorter [(2.95±0.76) d vs (3.33±0.85) d; (4.57±0.83) d vs (5.07±1.13) d], and the visual pain score at 24 h and 72 h after surgery were lower [(3.64±0.85) points vs (4.05±0.66) points; (2.33±0.75) points vs (3.07±0.68) points] (P<0.05). There was no statistically significant difference between the two groups in operation time [(130.00±26.23) min vs (135.24±27.03) min], intraoperative blood loss [(69.52±22.73) mL vs (82.38±49.23) mL] (P>0.05). CONCLUSIONS: SP-VATS in thymoma is a safe, feasible, and less invasive procedure, with less postoperative pain and faster recovery than multi-port VATS.

As-Built Inventory and Deformation Analysis of a High Rockfill Dam under Construction with Terrestrial Laser Scanning.

The construction of large earth/rock fill dams, albeit its remarkable progress, still relies largely on past experiences. Therefore, a comprehensive yet dependable monitoring program is particularly beneficial for guiding the practice. However, conventional measurements can only produce limited discrete data. This paper exploits the potential of the terrestrial laser scanning (TLS) for an accurate inventory of as-built states of a concrete-faced rockfill dam under construction and for a full-field analysis of the 3D deformation pattern over its upstream face. For the former, a well-designed 3D geodetic system, with a particular consideration of the topography, promises a regulated acquisition of high-quality and blind-zone-free point cloud at field and also eases the cumbersome data registration process while maintaining its precision in house. For the latter, a problem-tailored processing pipeline is proposed for deformation extraction. Its core idea is to achieve a highly precise alignment of the point clouds with Iterative Closed Point algorithms from different epochs in datum areas that displays a featured, undeformed geometry at stable positions across epochs. Then, the alignment transformation matrix is applied to the point clouds of respective upstream face for each epoch, followed by pairwise comparisons of multiple adjusted point clouds for deformation evaluation. A processing pipeline is used to exploit the peal scene data redundancy of the GLQ dam acquired at six different epochs. Statistical analysis shows that satisfactory accuracy for deformation detection can be repeatably achieved, regardless of the scanner's positioning uncertainties. The obtained 3D deformation patterns are characterised by three different zones: practically undeformed, outward and inward deformed zones. Their evolutions comply well with real construction stages and unique 3D valley topography. Abundant deformation results highlight the potential of TLS combined with the proposed data processing pipeline for cost-efficient monitoring of huge infrastructures compared to conventional labor-intense measurements.

Low-pressure Pneumoperitoneum With Abdominal Wall Lifting Versus Standard Pressure Pneumoperitoneum in Laparoscopic Fundoplication for Gastroesophageal Reflux Disease: A Propensity Score-matched Analysis.

OBJECTIVE: The objective of this study was to compare the treatment results of low-pressure pneumoperitoneum with abdominal wall lifting (AWL+LP, 6 mm Hg) versus standard pressure pneumoperitoneum (SP, 12 mm Hg) during laparoscopic fundoplication for gastroesophageal reflux disease (GERD), using propensity score matching (PSM). MATERIALS AND METHODS: A retrospective analysis was made of 362 patients, 123 in the AWL+LP group and 239 in the SP group, who underwent laparoscopic fundoplication for GERD from January 2010 to December 2017. Perioperative and prognostic outcomes were compared after PSM with 1:1 match. RESULTS: After PSM, 107 matched pairs were obtained. Compared with the SP group at 30 and 60 minutes after pneumoperitoneal initiation, the AWL+LP group showed significantly lower end-tidal carbon dioxide value (P<0.001, <0.001, respectively), lower partial pressure of carbon dioxide value (P<0.001, 0.016, respectively) and significantly higher pH value (P<0.001, <0.001, respectively). However, postoperative shoulder pain, abdominal pain, and arrhythmia in the AWL+LP group were less than those in SP group (P=0.01, 0.017, 0.005, respectively). There was no significant difference in operative time (106.54±27.80 vs. 107.38±24.78 min), blood loss [15 mL (interquartile range: 12.5 to 20 mL) vs.15 mL (interquartile range: 10 to 20 mL)], length of stay (4 vs. 4 d), the wound ecchymosis [2 (1.87%) vs. 3 (2.80%)] and rates of recurrence [8 (7.48%) vs. 5 (4.67%)] between AWL+LP group and SP group. CONCLUSION: AWL+LP resulted in comparable perioperative and prognostic outcomes with less impact on changes in cardiorespiratory function compared with SP approaches of laparoscopic fundoplication for GERD.

[Analysis of Influencing Factors for Postoperative Venous Thromboembolism 
of Thymic Malignancies].

BACKGROUND: The previous study has indicated that the incidence of venous thromboembolism (VTE) after thoracic surgery is high. The purpose of this study was to analyze the incidence and risk factors of postoperative VTE in thymic malignancy patients. METHODS: This was a single-center study. Patients undergoing resection for thymic malignancy between December 2017 and February 2021 in Department of Thoracic Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. In addition to the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower extremity ultrasound before and after surgery. Patients did not receive any prophylactic anticoagulant therapy before and after surgery. All patients received modified caprini risk assessment. According to whether VTE occurred after operation, patients were divided into VTE group and control group. The clinical data of the two groups were compared. The occurrence time and possible high risk factors of VTE after operation were analyzed. RESULTS: A total of 169 patients with thymic malignant tumor were enrolled, including 94 males and 75 females, aging from 22 to 76 years. A total of 95 patients underwent thoracoscopic surgery and 74 patients underwent median sternotomy. The total incidence of VTE was 12.4%. The median time for diagnosis of VTE was 4 days (2 days-15 days) after operation. According to the modified caprini score, the incidence of VTE in low risk patients (Caprini score≤4 points), moderate risk patients (Caprini score 5 to 8 points) and high risk patients (Caprini score≥9 points) were 0% (0/7), 7.0% (8/115) and 27.7% (13/47), respectively (Z=1.670, P=0.008). Univariate analysis showed that there were significant differences between VTE group and control group in age, operation method, operation time, indwelling central venous catheter, postoperative bed rest time more than 72 hours (P<0.05). Multivariate analysis showed that over 60 years old, operation method and operation time were independent risk factors for VTE after resection for thymic malignancies. CONCLUSIONS: Over 60 years old, operation method and operation time are independent risk factors for VTE. Modified caprini assessment can effectively screen high-risk patients.

[Survival Analysis of 76 Cases of Head and Neck Adenoid Cystic Carcinoma
with Lung Metastasis].

BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck often develops lung metastasis. At present, there are not many research reports on ACC lung metastasis, little is known about its exact clinical features and treatment results, and there is no consensus on the best treatment strategy. This study explored the effective treatment strategies, clinical outcomes and long-term prognosis of head and neck ACC lung metastases. METHODS: The clinical and follow-up data of 76 patients with head and neck ACC lung metastases were retrospectively analyzed. According to the initial treatment of patients, they are divided into 4 groups: surgery, surgery+chemotherapy or radiotherapy, chemotherapy or radiotherapy and supportive treatment. The patients were staged according to the International Registry of Lung Metastases Staging System (IRLM). Kaplan-Meier method and Log-rank test were used to compare the statistical differences of overall survival (OS) and progression-free survival (PFS) of patients with different treatment methods and different IRLM stages. RESULTS: The OS and PFS of patients undergoing surgery are better than those of supportive therapy or radiotherapy and/or chemotherapy (OS: P<0.000,1; PFS: P<0.000,1). The OS and PFS of patients with low stage IRLM are better than those with high stage (OS: P<0.000,1; PFS: P<0.000,1). Patients with single lung metastasis and without pleural effusion have better OS and PFS. CONCLUSIONS: The long-term prognosis of patients with lung metastasis of head and neck ACC who undergo surgery is better than other treatments, which is related to higher OS and PFS. For patients with ACC lung metastases who are operationally eligible, the significance of complete surgical resection should be higher than other treatment options.

Case Report: MDM4 Amplified in a Thymoma Patient With Autoimmune Enteropathy and Myocarditis.

Introduction: Thymoma is a type of mediastinal malignant tumors which always associated with autoimmune diseases. Although surgery is the predominant treatment method for thymoma, the pathogenesis of thymoma and thymoma-associated autoimmune diseases is still unknown. However, the case study here provided a possible pathogenesis and treatment to cure the thymoma with autoimmune enteropathy and myocarditis. Case presentation: A thymoma case with autoimmune enteropathy and myocarditis undergoing surgery was reported. The symptoms and laboratory results of the patient had dramatically fluctuated after tumor resection and gradually alleviated. The whole exome sequencing found MDM4 amplified in tumor cells. Immunohistochemistry indicated that thymoma cells were positive for MDM4. The result of drug sensitivity tests showed thymoma cells were highly sensitive to Nutlin-3a. Conclusion: MDM4 could play an important role in the pathogenesis of this thymoma case with autoimmune enteropathy and myocarditis. This discovery may provide a novel idea of pathogenesis and treatment for thymoma and autoimmune diseases.

Cloud model-based evaluation of landslide dam development feasibility.

As natural backwater structures, landslide dams both threaten downstream human settlement or infrastructure and contain abundant hydro-energy and tourism resources, so research on their development feasibility is of great significance for permanently remedying them and effectively turning disasters into benefits. Through an analysis of the factors influencing landslide dam development and utilization, an index system (consisting of target, rule, and index layers) for evaluating development feasibility was constructed in this paper. Considering uncertainty and randomness in development feasibility evaluation, a cloud model-improved evaluation method was proposed to determine membership and score clouds based on the uncertainty reasoning of cloud model, and a cloud model-improved analytic hierarchy process (AHP-Cloud Model) was introduced to obtain weights. Final evaluation results were obtained using a hierarchical weighted summary. The improved method was applied to evaluate the Hongshiyan and Tangjiashan landslide dams and the results were compared with the maximum membership principle results. The results showed that the cloud model depicted the fuzziness and uncertainty in the evaluation process. The improved method proposed in this paper overcame the loss of fuzziness in the maximum membership principle evaluation results, and was capable of more directly presenting evaluation results. The development feasibility of the Hongshiyan landslide dam was relatively high, while that of the Tangjiashan landslide dam was relatively low. As suggested by these results, the evaluation model proposed in this paper has great significance for preparing a long-term management scheme for landslide dams.

Placing covered self-expanding metal stents by suspension laryngoscope in benign tracheal stenosis.

BACKGROUND: Tracheobronchial stent placement for malignant airway strictures has been proved to improve respiratory function, but experience for benign tracheobronchial stenoses is limited. The purpose of our study is to investigate the efficacy of covered expandable metallic stents, inserted through a suspension laryngoscope, treating tracheal stenosis following intubation or tracheostomy. METHODS: From 2010 to 2018, 67 adult patients with the benign tracheal stenosis, underwent stent placement, using a suspension laryngoscope. According to the date of stent placement and stent caliber, these patients have been subdivided into two groups: Group 1 (from 2010 to 2013, stent caliber ranging from 16 to 20 mm) and Group 2 (from 2014 to 2018, stent caliber ranging from 18 to 22 mm). Complications, related reinterventions, and long-term prognosis were retrospectively evaluated. RESULTS: Primary successful stent placement was achieved and symptoms were improved in all patients. Complications occurred in 27 (40.3%) cases. Among these, there were 14 (20.9%) cases with stent migration, 10 (14.93%) with granulation tissue formation and 3 (4.48%) with pneumonia. Stent migration in Group 1 was nearly 30% higher than that in Group 2 (P = 0.002). Five of the 8 patients who had placement of 16 mm stents had stent migration, more often than with 20 mm stents (P = 0.002). Ten patients' trachea had slight narrowing but without any symptoms. Six patients still had granulation tissue but without any growth at least two-year follow-up (2 patients whose stents were removed more than 1 year after placement). Even without tracheal narrowing and granulation tissue, 5 patients felt persistent shortness of breath. 92.5% of the patients reported to be satisfied with significant improvement in symptoms. CONCLUSIONS: Patients with tracheal obstruction secondary to intubation or tracheostomy can benefit from tracheal stents. Placing 16 mm stents might lead to stent migration more easily than 20 mm stents. Tracheal stents placed by a suspension laryngoscope provide a reasonable alternative to open surgery for patients with benign tracheal stenosis or obstruction.

Surgical feasibility and long-term outcome of superior vena cava replacement for advanced thymoma in patients undergoing preoperative chemotherapy or chemoradiotherapy.

BACKGROUND: The aim of this study was to investigate the long-term outcome of superior vena cava (SVC) replacement after chemotherapy or chemoradiotherapy for advanced thymoma. METHODS: The medical information of patients with advanced thymoma who underwent thymoma resection and SVC replacement in Beijing Tongren Hospital from 2002 to 2017 were reviewed. We compared surgical outcomes, postoperative complications and long-term prognosis in the chemoradiotherapy + surgery group (CRT + surgery group, 19 cases) and the surgery group (26 cases). RESULTS: The operation time (486.05 ± 148.01 vs. 370.77 ± 124.32 min; p = 0.007) and intraoperative blood loss (1400 ml [IQR 1125-2105 ml] vs. 855 ml [IQR 555-1682.5 ml], p = 0.036), poor wound healing (three cases [15.79%] vs. zero cases [0.0%], p = 0.036) in the CRT + surgery group were significantly higher than those of the surgery group. There was no significant difference between the CRT + surgery group and the surgery group in postoperative chest tube drainage time, hospitalization time, postoperative arrhythmia and incidence of pneumonia. Kaplan Meier analysis showed that the recurrence-free survival (RFS) curves of the CRT + surgery group patients were better than those of the surgery group (p = 0.031). However, overall survival (OS) between the two groups was not significantly different (p = 0.069). CONCLUSIONS: Thymoma resection and SVC replacement is feasible for patients undergoing preoperative induction chemotherapy or chemoradiotherapy for advanced thymoma. Although patients in the CRT + surgery group had a longer operation time and increased intraoperative bleeding, the RFS rate seemed to be better than that in the surgery group.

Application of Percutaneous Holmium Laser Lithotripsy in the Treatment of Bladder Calculi with Lower Urinary Tract Obstruction or Pelvic Joint Disease.

OBJECTIVE: The aim was to summarize the experience of percutaneous holmium laser lithotripsy in the treatment of bladder calculi with lower urinary tract obstruction or pelvic joint disease in our hospital, explore its efficacy and safety, and improve the minimally invasive surgical technique for bladder calculi. METHODS: The clinical data of 61 patients with bladder calculi combined with lower urinary tract obstructive diseases, including urethral stricture, benign prostatic hyperplasia, and bladder neck contracture or pelvic joint diseases in our hospital from 2017 to 2019 were retrospectively analyzed. All patients with bladder stones measuring 1.5-9 cm were placed in supine or lithotomy position. B-scan was conducted to locate the puncture above the pubic symphysis, establishing a 16-30 Fr bladder channel, and Lumenis holmium laser lithotripsy was subsequently performed through a Li Xun Nephroscope. The crushed stones were flushed out through the percutaneous bladder channel or taken out with foreign body forceps. After surgery, the cystostomy tube was indwelled for 3 days. RESULTS: All the 61 cases were operated successfully with an average lithotripsy time of 25 min, and there was no conversion to open surgery. Postoperative reexamination showed neither residual calculi nor complications such as severe infection, massive hemorrhage, and intestinal injury. CONCLUSION: Percutaneous holmium laser lithotripsy is an improved minimally invasive surgical technique for the treatment of bladder calculi with the advantages of clear surgical field, high stone removal efficiency, less trauma, low-pressure bladder perfusion, and low incidence of accessory injury and infection. For patients with lower urinary tract obstructive disease resulting in obstruction of transurethral surgery and patients with pelvic joint disease resulting in difficult lithotomy position placement, this procedure is more advantageous than transurethral surgery. It is also suitable for bladder calculus with a long diameter >5 cm or multiple calculi.

Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis.

BACKGROUND: Our study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma. METHODS: From 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools. RESULTS: After surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene-MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis. CONCLUSION: Our study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis.

Venous thromboembolism after adult thymus or thymic tumor resection: A single-center experience.

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the VTE incidence after major thoracic surgery is high. However, there have been no exclusive data after thymectomy thus far. To investigate the incidence of postoperative VTE, we conducted a single-center, prospective cohort study. METHODS: Patients who underwent thymectomy between December 2017 and January 2020 were enrolled. None of the patients received any prophylaxis perioperatively. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥9). Occurrence of VTE events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), were identified by imaging. RESULTS: There were 192 patients who underwent thymectomy enrolled into the study. The overall VTE incidence was 8.9%. All the patients were diagnosed with DVT, and none were diagnosed with PE. The VTE incidence was 4.6% in patients with benign thymic diseases and 14.5% with malignant diseases. The VTE incidence was 4.7% in patients undergoing thoracoscopic surgery and 22.7% undergoing median sternotomy. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 10.3% and 37.5%, respectively. In patients with thymic malignancy, the VTE incidence in the moderate and high risk groups were 8.8% and 31.8%, respectively. CONCLUSIONS: VTE occurred frequently in patients after thymectomy without VTE prophylaxis. The median sternotomy procedure and malignant tumor may be the major risk factors for the development of VTE. Aggressive VTE screening/treatment protocols should be implemented in patents after thymectomy.

Evaluating the effectiveness of chemotherapy for thymic epithelial tumors using the CD-DST method.

BACKGROUND: Thymic epithelial tumors (TET) are frequently eligible for curative-intent surgical resection. For locally advanced TETs, chemotherapy has been used to both reduce the tumor burden and achieve prolonged disease control. However, effective therapy for this disease largely remains to be determined. Here, we report the chemosensitivity of 100 patients with TETs determined by the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). METHODS: A total of 100 patients with TETs underwent surgical resection. The efficacy of antitumor agents on TET cells was tested by CD-DST. RESULTS: Thymic epithelial tumors were pathologically confirmed after surgery: two cases were type A thymoma, 17 were type AB, 12 were type B1, 44 were type B2, 12 were type B3, and there were 13 cases with thymic carcinoma. A total of 36% patients with TETs were sensitive to different types of chemotherapeutic agents. There was no significant differences in age, histological type, clinical staging, or association with autoimmune diseases between sensitive and nonsensitive cases. Type B1 and B2 thymoma were relatively more sensitive to chemotherapeutic agents (6/12 and 18/44, respectively), while sensitivity of type B3 cases to chemotherapeutic agents was much lower (only 2/12). Cases with type A thymoma were not sensitive to any antitumor drugs. Among 11 chemotherapeutic agents tested in our study, the sensitivity of TETs to EPI was the highest (16%). No patients with thymoma were sensitive to Alimta (Pemetrexed). CONCLUSIONS: Our work illuminates the effectiveness of chemotherapy for TETs and provides important clues for choosing antitumor drugs with relatively high drug sensitivity to TETs in advance.

Temporal and Spatial Evolution of Vegetation Coverage in the Mianyuan River Basin Influenced by Strong Earthquake Disturbance.

The 2008 Wenchuan earthquake caused significant economic losses and degradation of regional ecosystems, including the terrestrial vegetation. Since the vegetation root system can enhance the soil's anti-erosion capacity and therefore mitigate the occurrence of slope instabilities, it is beneficial to study the spatial and temporal evolution of vegetation for a long-term assessment of co-seismic secondary disasters. The Mianyuan River Basin, an uninhabited area passing through an active fault located in the earthquake-affected region, was selected as the study area. The Normal Difference Vegetation Index (NDVI) was calculated using remote sensing images from 1994 to 2017 to analyze the process of vegetation growth, loss, fluctuation and recovery. Statistical results suggest that the area in the middle and lower reaches, near the river network, and with a slope of 30 to 40 degrees were variable regions, showing more significant vegetation destruction during the earthquake and faster repair after the seismic event. Besides, vegetation near the fault was damaged more severely after the earthquake, but the active fault did not play an essential role in the vegetation recovery period. In the Mianyuan River Basin, vegetation experienced a volatility period (5 plus or minus one year) before entering the recovery period. In 8 to 9 years after the earthquake, the surficial vegetation could recover to the state before the earthquake.

Successful treatment of thymic carcinoma with dermatomyositis and interstitial pneumonia: A case report.

Here, we report a rare case of thymic carcinoma (TC) associated with dermatomyositis (DM) and interstitial pneumonia (IP) in a 68-year-old man. The patient presented with the characteristic features of a skin rash with Gottron's papules and increased serum levels of muscle-associated enzymes. Computed tomography (CT) showed the presence of an anterior mediastinal soft tissue mass with IP, which was diagnosed as TC by CT-guided tumor biopsy. The patients DM and IP disappeared completely after radical resection of the tumor. After a 20-month follow-up period, the patient was in good clinical condition without disease recidivism.

Integration of Terrestrial Laser Scanning and NURBS Modeling for the Deformation Monitoring of an Earth-Rock Dam.

A complete picture of the deformation characteristics (distribution and evolution) of the geotechnical infrastructures serves as superior information for understanding their potential instability mechanism. How to monitor more completely and accurately the deformation of these infrastructures (either artificial or natural) in the field expediently and roundly remains a scientific topic. The conventional deformation monitoring methods are mostly carried out at a limited number of discrete points and cannot acquire the deformation data of the whole structure. In this paper, a new monitoring methodology of dam deformation and associated results interpretation is presented by taking the advantages of the terrestrial laser scanning (TLS), which, in contrast with most of the conventional methods, is capable of capturing the geometric information at a huge amount of points over an object in a relatively fast manner. By employing the non-uniform rational B-splines (NURBS) technology, the high spatial resolution models of the monitored geotechnical objects can be created with sufficient accuracy based on these point cloud data obtained from application of the TLS. Finally, the characteristics of deformation, to which the geotechnical infrastructures have been subjected, are interpreted more completely according to the models created based on a series of consecutive monitoring exercises at different times. The present methodology is applied to the Changheba earth-rock dam, which allows the visualization of deformation over the entire dam during different periods. Results from analysis of the surface deformation distribution show that the surface deformations in the middle are generally larger than those on both sides near the bank, and the deformations increase with the increase of the elevations. The results from the present application highlight that the adhibition of the TLS and NURBS technology permits a better understanding of deformation behavior of geotechnical objects of large size in the field.