PROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis.

BACKGROUND: Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration. METHODS: The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM. RESULTS: The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01). CONCLUSION: The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.

Effects of the Insect Growth Regulators Azadirachtin, Pyriproxyfen, and Tebufenozide on the Fatty Acid Metabolome of Bactrocera Dorsalis Larvae.

Insects' lipids, including fatty acids, as the second largest constituents in insects, play a variety of fundamental and vital functions. However, there is a lack of reports on the effects of insect growth regulators on fatty acid profiles and metabolic mechanisms. Therefore, in this study, a comparative study of three growth regulators, azadirachtin, pyriproxyfen, and tebufenozide, on fatty acids was carried out using a targeted metabolomics approach to fill this gap. The results showed that when exposed to azadirachtin, pyriproxyfen, and tebufenozide, there were 14, 17, and 11 differentially regulated fatty acids, respectively. The pathway of biosynthesis of unsaturated fatty acids was the common shared pathway, while fatty acid biosynthesis and linoleic acid metabolism were the specific pathways affected by the 3 insect growth regulators. Therefore, the results could be helpful to deepen the effects of azadirachtin and insect growth regulators on terrestrial insects.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.

Clinicians' knowledge and understanding regarding multidisciplinary treatment implementation: a study in municipal public class III grade A hospitals in Southwest China.

BACKGROUND: Previous studies have highlighted several problems in the implementation of multidisciplinary treatment (MDT) from a managerial perspective. However, no study has addressed these issues from clinicians' perspective. Therefore, this study aimed to identify and address the existing problems in MDT by investigating what clinicians know and think about the implementation of MDT. METHODS: A self-designed questionnaire was used to evaluate clinicians' understanding of MDT in municipal public Class III Grade A hospitals in Western China using a cross-sectional questionnaire study. RESULTS: Overall, 70.56% of clinicians knew the scope of MDT, and 63.41% knew the process of MDT. Professional title (P = 0.001; OR: 2.984; 95% CI: 1.590-5.603), participated in MDT (P = 0.017; OR: 1.748; 95% CI: 1.103-2.770), and application for MDT (P = 0.000; OR: 2.442; 95% CI: 1.557-3.830) had an impact on clinicians' understanding of the scope of MDT. Professional title (P = 0.002; OR:2.446; 95% CI: 1.399-4.277) and participation in MDT (P = 0.000; OR: 2.414; 95% CI: 1.581-3.684) influenced clinicians' understanding of the scope of MDT. More than 70% of the respondents thought that MDT was important in medical care. However, less than half of the clinicians who had attended MDT were currently satisfied with the results of MDT. CONCLUSION: Most clinicians agreed that MDT was crucial in clinical care. However, more than a third of clinicians did not fully understand the scope and process of MDT. Appropriate measures are necessary to improve the quality of MDT. Our study suggests that healthcare administration should strengthen MDT education, especially for new and young clinicians.

Factors associated with quality of life in Chinese people with psoriasis: a cross-sectional study.

BACKGROUND: The ultimate goal of medical care is to eradicate disease and restore normality to a person's life. Quality of life (QOL) is a concern as dermatologists and researchers strive to find better drug treatments. However, there have been few reports on the factors associated with QOL among Chinese people with psoriasis. METHODS: A total of 185 people with psoriasis were surveyed to assess their sociodemographic status, disease-related information, psychosocial status, and QOL. The questionnaires included a sociodemographic questionnaire, the Athens Insomnia Scale, the Hospital Anxiety and Depression Scale, the Perceived Social Support Scale, the Psychosocial Adaptation Questionnaire of Chronic Skin Disease and the Dermatology Life Quality Index. Multiple stepwise regression and path analysis were used to study the factors associated with QOL among Chinese people with psoriasis and to analyse the relationship between them. RESULTS: The results showed that the presence of anxiety/depression, lesion area, sleep disorders, psychosocial adaptation, and sex could jointly predict 62.1% of the variance in QOL among Chinese people with psoriasis. According to previous theories and the literature, a path model was established for five variables. Four internal variables could be effectively explained. The values of the explanatory variables were 62.1% (F(1056) = 61.020, p = 0.000) for QOL, 71.8% (F(2433) = 117.370, p = 0.000) for anxiety/depression, 44.0% (F(660) = 36.935, p = 0.000) for sleep disorders, and 66.9% (F(6886) = 93.556, p = 0.000) for psychosocial adaptation. The path analysis confirmed that 9 paths were consistent with the predicted path, and 3 paths were not confirmed. CONCLUSION: To improve QOL among Chinese people with psoriasis, attention should be given to the presence of anxiety/depression, lesion area, sleep disorders, psychosocial adaptation and sex differences. Therefore, health care programs for psoriasis should include physical, psychological and social aspects.

The tigecycline resistance gene tetX has an expensive fitness cost based on increased outer membrane permeability and metabolic burden in Escherichia coli.

Livestock-derived tetX-positive Escherichia coli with tigecycline resistance poses a serious risk to public health. Fitness costs, antibiotic residues, and other tetracycline resistance genes (TRGs) are fundamental in determining the spread of tetX in the environment, but there is a lack of relevant studies. The results of this study showed that both tetO and tetX resulted in reduction in growth and an increased in the metabolic burden of E. coli, but the presence of doxycycline reversed this phenomenon. Moreover, the protection of E. coli growth and metabolism by tetO was superior to that of tetX in the presence of doxycycline, resulting in a much lower competitiveness of tetX-carrying E. coli than tetO-carrying E. coli. The results of RNA-seq showed that the increase in outer membrane proteins (ompC, ompF and ompT) of tetX-carrying E. coli resulted in increased membrane permeability and biofilm formation, which is an important reason for fitness costs. Overall, the increased membrane permeability and metabolic burden of E. coli is the mechanistic basis for the high fitness cost of tetX, and the spread of tetO may limit the spread of tetX. This study provides new insights into the rational use of tetracycline antibiotics to control the spread of tetX.

A Nomogram Based on Atelectasis/Obstructive Pneumonitis Could Predict the Metastasis of Lymph Nodes and Postoperative Survival of Pathological N0 Classification in Non-small Cell Lung Cancer Patients.

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. METHODS: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan-Meier survival analysis were also used in this study. RESULTS: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694-0.704). Moreover, the Cox proportional hazards analysis and Kaplan-Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. CONCLUSION: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC.

Deep Learning Algorithm Trained on Lumbar Magnetic Resonance Imaging to Predict Outcomes of Transforaminal Epidural Steroid Injection for Chronic Lumbosacral Radicular Pain.

BACKGROUND: Transforaminal epidural steroid injections (TFESI) are widely used to alleviate lumbosacral radicular pain. Knowledge of the therapeutic outcomes of TFESI allows clinicians to elucidate therapeutic plans for managing lumbosacral radicular pain. Deep learning (DL) can outperform traditional machine learning techniques and learn from unstructured and perceptual data. A convolutional neural network (CNN) is a representative DL model. OBJECTIVES: We developed and investigated the accuracy of a CNN model for predicting therapeutic outcomes after TFESI for controlling chronic lumbosacral radicular pain using T2-weighted sagittal lumbar spine magnetic resonance (MR) images as input data. STUDY DESIGN: Imaging study using DL. SETTING: At the spine center of a university hospital. METHODS: We collected whole T2-weighted sagittal lumbar spine MR images from 503 patients with chronic lumbosacral radicular pain due to a herniated lumbar disc (HLD) and spinal stenosis. A "good outcome" was defined as a >= 50% reduction in the numeric rating scale (NRS-11) score at 2 months after TFESI vs the pretreatment NRS-11 score. A "poor outcome" was defined as a < 50% decrease in the NRS-11 score at 2 months after TFESI vs pretreatment. RESULTS: In the prediction of therapeutic outcomes after TFESI on the validation dataset, the area under the curve was 0.827. LIMITATIONS: Our study was limited in that we used a small amount of lumbar spine MR imaging data to train the CNN model. CONCLUSIONS: We demonstrated that a CNN model trained, using whole lumbar spine sagittal T2-weighted MR images, could help determine outcomes after TFESI in patients with chronic lumbosacral radicular pain due to an HLD or spinal stenosis.

Marking ground glass nodules with pulmonary nodules localization needle prior to video-assisted thoracoscopic surgery.

OBJECTIVES: To evaluate the efficacy and safety of marking ground glass nodules (GGNs) with pulmonary nodules localization needle (PNLN) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From June 2020 to February 2021, all patients with GGNs who received CT-guided localization using PNLN before VATS were enrolled. Clinical and imaging data were retrospectively analyzed. RESULTS: A total of 352 consecutive patients with 395 GGNs were included in the study. The mean diameter of GGNs was 0.95 ± 0.48 cm, and the shortest distance from nodules to the pleura was 1.73 ± 0.96 cm. All 395 GGNs were marked using PNLNs. The time required for marking was 7.8 ± 2.2 min. The marking success rate was 99.0% (391/395). The marking failure of four nodules was all due to the unsatisfactory position of PNLNs. No marker dislocation occurred. Marking-related complications included pneumothorax in 63 cases (17.9%), hemorrhage in 34 cases (9.7%), and hemoptysis in 6 cases (1.7%). All the complications were minor and did not need special treatment. Localization and VATS were performed on the same day in 95 cases and on different days in 257 cases. All GGNs were successfully removed by VATS. No patient converted to thoracotomy. Histopathological examination revealed 74 (18.7%) benign nodules and 321 (81.3%) malignant nodules. CONCLUSIONS: It is safe and reliable to perform preoperative localization of GGNs using PNLNs, which can effectively guide VATS to remove GGNs. KEY POINTS: • Preoperative localization of GGNs could effectively guide VATS to remove GGNs. • PNLN was based on the marking principle of hook-wire, through the improvement of its material, specially designed to mark pulmonary nodules. • The application of PNLN to mark GGNs had high success rate, good patient tolerance, and no dislocation. Meanwhile, VATS could be performed 2 to 3 days after marking GGNs with PNLN.

Bioconversion of cyanobacteria by black soldier fly larvae (Hermetia illucens L.): Enhancement by antioxidants.

Cyanobacterial blooms have been a global environmental problem for decades. Bioconversion by black soldier fly larvae (BSFL) has been widely reported to be a clean and efficient method to remove organic pollutants. In this study, BSFL bioconversion was used to treat cyanobacterial blooms. Antioxidants (a mixture of l-ascorbic acid [180 mg/kg fresh feed] and α-tocopherol [360 mg/kg fresh feed]) were added to compare bioconversion performance against a non-supplemented group. With increasing proportions of cyanobacteria (0%-25% dry mass), the bioconversion efficiency of the antioxidant group improved significantly compared to the control group, and the survival rate of larvae rose from 96.50-45.50% to 98.00-55.83% with antioxidant addition. The toxic effects of exogenous anti-nutrients could be reduced by the antioxidants through inactivation of trypsin inhibitor and enhancement of the microcystin-LR degradation rate. Overall, the BSFL bioremediation capacity was improved with addition of exogenous antioxidants, verifying both the effects and mechanism of antioxidant addition in promoting the bioconversion of cyanobacteria by BSFL and providing a basis for future application and study.

Delayed diagnosis and comprehensive treatment of cutaneous tuberculosis: A case report.

BACKGROUND: Tuberculosis (TB) is a widespread infectious disease, with an incidence that is increasing worldwide. Cutaneous TB (CTB) occurs rarely, accounting for less than 1% of all TB cases. Due to the clinical presentation and diagnostic difficulties, CTB is often clinically neglected and misdiagnosed. CASE SUMMARY: A 32-year-old man underwent several debridement surgeries and skin flap transplantation after trauma. The wound remained unhealed, accompanied by sinus formation. According to empirical judgment, T-cell spot of TB test, and bacterial culture of pyogenic fluids, he was diagnosed with CTB due to infection with exogenous Mycobacterium tuberculosis. A comprehensive anti-TB regimen that included isoniazid, rifampicin, ethambutol, and pyrazinamide was applied. The sinus was filled with a hydrophilic fiber-containing silver dressing, and wound-protecting sponges were applied to part of the wound. The wound healed after 40 d. No ulceration was found within 2 mo after discharge; further follow-up will be conducted. CONCLUSION: A non-healing wound may be caused by TB infection. Comprehensive treatment of CTB is effective.

Effect of hyperglycemia on microglial polarization after cerebral ischemia-reperfusion injury in rats.

Hyperglycemia has been shown to aggravate ischemic brain damage, in which the inflammatory reaction induced by hyperglycemia is involved in the worsening of cerebral ischemia-reperfusion injury. However, the role of microglial polarization in hyperglycemia-aggravating cerebral ischemia-reperfusion injury remains unknown. The present study investigated whether diabetic hyperglycemia inhibited or activated microglia, as well as microglial subtypes 1 and 2. Rats were used to establish the diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) model. The markers CD11b, CD16, CD32, CD86, CD206, and Arg1 were used to show M1 or M2 microglia. The results revealed increased neurological deficits, infarct volume, and neural apoptosis in rats with hyperglycemia subjected to MCAO for 30 min and reperfused at 1, 3, and 7 days compared with the normoglycemic rats. Microglia and astrocyte activation and proliferation were inhibited in hyperglycemic rats. Furthermore, M1 microglia polarization was promoted, while that of M2 microglia was inhibited in hyperglycemic rats. These findings suggested that the polarization of M1 and M2 microglia is activated and inhibited, respectively, in hyperglycemic rats and may be involved in the aggravated brain damage caused by ischemia-reperfusion in diabetic hyperglycemia.

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy.

OBJECTIVE: To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CT-guided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. RESULTS: All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. CONCLUSION: CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.

CT-guided transthoracic needle biopsy of pulmonary lesions: comparison between the cutting needle and aspiration needle.

OBJECTIVES: To compare CT-guided transthoracic cutting needle biopsy (TCNB) with transthoracic aspiration needle biopsy (TANB) for pulmonary lesions with respect to the diagnostic accuracy and complication rate. METHODS: Of the 859 cases that underwent consecutive CT-guided biopsy of pulmonary lesions, 713 cases confirmed by surgical pathology or clinical follow-up were enrolled. Of these, the first consecutive 275 cases underwent TANB, and the remaining 438 received TCNB. The final diagnosis determined the accuracy of biopsy. Based on the post-biopsy CT and clinical medical records, the presence or absence of biopsy-related complications was determined. The χ2 test was used to compare the differences between TCNB and TANB in terms of diagnostic accuracy and complication rate. RESULTS: Among the 713 biopsy lesions, the final diagnosis was malignant in 411 cases and benign in 302 cases. As compared to TANB, the diagnostic accuracy of TCNB (98.9% vs 93.8%, χ2 = 14.35, p < 0.01), sensitivity to malignant lesions (97.8% vs 90.6%, χ2 = 10.58, p < 0.01), negative predictive value (97.6% vs 84.8%, χ2 = 19.03, p < 0.01), and specific diagnostic rate for benign lesions (73.4% vs 57.9%, χ2 = 7.29, p < 0.01) were improved. On the other hand, a statistical difference was detected between TCNB and TANB with respect to the incidence of pneumothorax (20.6% vs 13.1%, χ2 = 6.46, p = 0.01), hemorrhage (32.2% vs 13.1%, χ2 = 33.03, p < 0.01), and hemoptysis (8.2% vs 3.3%, χ2 = 6.87, p < 0.01). One patient died just several minutes after TCNB due to severe hemorrhage with hemoptysis. CONCLUSIONS: Compared to TANB, CT-guided TCNB improves the diagnostic accuracy of pulmonary lesions, but complication rate increases significantly. ADVANCES IN KNOWLEDGE: In general, TCNB should be recommended, especially for highly suspicious benign lesions. For patients with small lesions adjacent to vessels or vessels within the lesion, TANB should be considered.

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy

Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy

Objective@#To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS). @*Materials and Methods@#Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CTguided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy. @*Results@#All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma. @*Conclusion@#CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.

Clinical value of the emergency department in screening and diagnosis of COVID-19 in China.

Since the global outbreak of severe acute respiratory syndrome (SARS) in 2003, China has gradually built a robust prevention and control system for sudden infectious diseases. All large hospitals have a fever clinic that isolates patients with all kinds of acute communicable diseases as the first line of medical defense. The emergency department, as the second line of medical defense in hospitals, is constantly shouldering the heavy responsibility of screening communicable diseases while also treating all kinds of other non-communicable acute and critical diseases (Zhang et al., 2012; Zhu et al., 2015; Wang et al., 2017; Feng et al., 2018; Lu, 2018; Xu and Lu, 2019). An outbreak of pneumonia of unknown etiology that began in Wuhan city (China) has spread rapidly in China since December 2019 (Huang et al., 2020; WHO, 2020; Zhu et al., 2020). In February 2020, the National Health Commission of China named the disease a novel coronavirus pneumonia (NCP); then, it was formally named the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on Feb. 11, 2020. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses designated this causative virus as SARS coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the ß coronavirus genus, and its pathogenic mechanism has not been clarified, which requires further study. To better understand the clinical characteristics of COVID-19 and more effectively prevent and control this disease, we retrospectively analyzed four representative cases of COVID-19 that had recently been screened and diagnosed in our emergency department.

CT-guided microcoil implantation for localizing pulmonary ground-glass nodules: feasibility and accuracy of oblique approach for lesions difficult to access on axial images.

OBJECTIVE: (1) To evaluate the value of CT-guided microcoil implantation for localizing pulmonary ground-glass nodules (GGNs) before video-assisted thoracoscopic surgery (VATS). (2) To evaluate the feasibility, safety and accuracy of cephalic-caudal oblique approach for lesions difficult to access on axial images owing to overlying bony structures, large vessels or interlober fissures. METHODS: From June 2016 to March 2019, all patients with GGNs resected by VATS after marking using CT-guided microcoil implantation in China-Japan friendship hospital were enrolled and clinical and imaging data were retrospectively analyzed. According to the microcoil marked path, the GGNs were divided into cephalic-caudal oblique group (oblique group) and non-oblique group. The success rate of marking, the time required for marking and the incidence of complications between the two groups were compared. RESULTS: 258 GGNs from 215 consecutive patients were included in this study. The diameter of GGNs was 1.22 ± 0.50 cm, and the shortest distance from GGNs to the pleura was 1.56 ± 1.09 cm. All 258 GGNs were successfully resected by VATS under the guidance of implanted microcoils, and no case was converted to thoracotomy. During CT-guided microcoil implantation, cephalic- caudal oblique approach was taken in 56 GGNs (oblique group) to avoid bone, interlobar fissure and blood vessels. The time required for marking was significantly longer for oblique group compared with non-oblique group (16.6 ± 2.4 vs. 13.1 ± 1.9 min, p<0.01). No significant differences in the success rate of marking (94.6% vs 91.6%), the incidence of pneumothorax (19.6% vs 17.8%), the bleeding rate (10.7% vs 8.9%), and the hemoptysis rate (1.8% vs 1.5%) were observed between the two groups. CONCLUSION: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. For GGNs difficult to access on axial images, CT-guided cephalic-caudal oblique approach is feasible, safe, and accurate. ADVANCES IN KNOWLEDGE: CT-guided microcoil implantation can effectively guide VATS to resect GGNs. The marked path with cephalic-caudal obliquity can effectively avoid bone, interlobar fissure and blood vessels, successfully mark GGNs difficult to access on axial images, while keeping the distance from the pleura to the lesion on the marked path as short as possible at the same time.

Estradiol Alters Hippocampal Gene Expression during the Estrous Cycle.

Estrogen (E2) modulates a wide range of neural functions such as spine formation, synaptic plasticity, and neurotransmission in the hippocampus. Dendritic spines and synapse numbers in hippocampal neurons of female rats cyclically fluctuate across the estrous cycle, but the key genes responsible for these fluctuations are still unknown. In order to address this question, we explore the hippocampal transcriptome via RNA-sequencing (RNA-seq) at the proestrus (PE) and estrus (ES) stages in female rats. At standard fold-change selection criteria, 37 differentially expressed genes (DEGs) were found in PE vs. ES groups (FDR adjusted p-value (q)<0.05). The transcriptional changes identified by RNA-seq were confirmed by quantitative real-time PCR. To gain insight into the function of the DEGs, the E2-regulated genes were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG). Based on GO and KEGG pathways, the identified DEGs of PE vs. ES stages are involved in extracellular matrix formation, regulation of actin cytoskeleton, oxidative stress, neuroprotection, immune system, oligodendrocyte maturation and myelination, signal transduction pathways, growth factor signaling, retinoid signaling, aging, cellular process, metabolism and transport. The profiles of the gene expression in the hippocampus identified at the PE vs. ES stages were compared with the gene expression profiles in ovariectomized (OVX) rats receiving E2 replacement via RNA-seq and qPCR. The profiles of gene expression between the OVX+E2 and the estrous cycle were different and the possible causes were discussed.

Clinical value of the emergency department in screening and diagnosis of COVID-19 in China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Since the global outbreak of severe acute respiratory syndrome (SARS) in 2003, China has gradually built a robust prevention and control system for sudden infectious diseases. All large hospitals have a fever clinic that isolates patients with all kinds of acute communicable diseases as the first line of medical defense. The emergency department, as the second line of medical defense in hospitals, is constantly shouldering the heavy responsibility of screening communicable diseases while also treating all kinds of other non-communicable acute and critical diseases (Zhang et al., 2012; Zhu et al., 2015; Wang et al., 2017; Feng et al., 2018; Lu, 2018; Xu and Lu, 2019). An outbreak of pneumonia of unknown etiology that began in Wuhan city (China) has spread rapidly in China since December 2019 (Huang et al., 2020; WHO, 2020; Zhu et al., 2020). In February 2020, the National Health Commission of China named the disease a novel coronavirus pneumonia (NCP); then, it was formally named the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on Feb. 11, 2020. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses designated this causative virus as SARS coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the β coronavirus genus, and its pathogenic mechanism has not been clarified, which requires further study. To better understand the clinical characteristics of COVID-19 and more effectively prevent and control this disease, we retrospectively analyzed four representative cases of COVID-19 that had recently been screened and diagnosed in our emergency department.