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Abstract The mechanisms underlying the natural control of hepatitis B virus (HBV) infection have long been an intriguing question. Given the wide physiological range of liver stiffness and the growing attention to the role of mechanical microenvironment in homeostasis and diseases, we investigated how physical matrix cues impact HBV replication. High matrix stiffness significantly inhibited HBV replication and activated YAP in primary hepatocyte culture system, a key molecule in mechanosignaling. YAP activation notably suppressed HBV transcription and antigen expression. Several YAP-induced genes exhibited strong anti-HBV effects. Single-cell analysis of liver tissue from male individuals with active HBV replication revealed a strong significant negative correlation between YAP signature activation and HBV transcript levels. Intraperitoneal administration of YAP small molecule agonist potently controls HBV in male mouse models. These findings unveil a mechanism that involves the mechanical environment of hepatocytes and YAP to clear hepatotropic viral infection in the liver, providing new perspectives for HBV cure studies and antiviral development.

BackgroundTreatment of locally advanced unresectable non-small cell lung cancer (NSCLC) is a significant challenge, especially for patients with IIIA/IIIB NSCLC. Patients receiving neoadjuvant chemoimmunotherapy (NCI) show improved pathological responses and disease-free survival (DFS) compared to those receiving Neoadjuvant chemotherapy (NC). However, there is still no consensus on the treatment for potentially resectable stage IIIA/IIIB NSCLC.MethodsThis retrospective study included 71 patients newly diagnosed with stage III NSCLC at our institution between 2017 and 2023: 46 patients received NCI and 25 patients received NC followed by surgical resection. Their clinicopathological characteristics were reviewed and analyzed.ResultsPatients who received NCI had a significantly longer DFS. The median DFS was 15 months in the NC group (hazard ratio: 0.186, 95% confidence interval[CI]: 0.073–0.479; P

Lung enteric-type adenocarcinoma (ETAC) is a rare subtype of non-small cell lung cancer (NSCLC), comprising approximately 0.6% of all primary lung adenocarcinomas. It is characterized by a tendency for early metastasis and a prognosis comparable to that of common lung adenocarcinoma. This case report described a patient with lung-ETAC who developed gastric metastasis. The patient underwent treatment with chemotherapy and a PD-1 inhibitor, resulting in disease remission with a progression-free survival (PFS) of 8 months. The follow-up time was 13 months. This case report was aimed to enhance understanding of the biological behavior of this rare tumor and provide insights into potential future treatment strategies.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Background: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery. Materials and methods: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study. All patients underwent radical resection and systematic mediastinal lymphadenectomy after neoadjuvant treatments. The pathological remission, immunohistochemistry (CD4, CD8, CD20, CD56, FoxP3, CD68, CD163, CD11b tumor-infiltrating lymphocytes, or macrophages), and single-source dual-energy computed tomography (ssDECT) scans were assessed. The IC between imaging remission by CT and pathological remission was investigated. The underlying cause of IC, the correlation between IC and DFS, and prognostic biomarkers were explored. Results: After neoadjuvant immunotherapy, enhanced immune killing and reduced immunosuppressive performance were observed. 70 % of neoadjuvant chemoimmunotherapy patients were in high/medium IC level. Massive necrosis and repair around and inside the cancer nest were the main pathological changes observed 30–45 days post-treatment with PD1/PD-L1 antibody and were the main causes of IC between the pathology and imaging responses after neoadjuvant immunotherapy. High IC and preoperative CD8 expression (H score ≥ 3) indicate a high pathological response rate and prolonged DFS. Iodine material density ssDECT images showed that the iodine content in the lesion causes hyperattenuation in post-neoadjuvant lesion in PCR patient. Conclusions: Compared to chemotherapy and targeted therapy, the efficacy of neoadjuvant immunotherapy was underestimated based on the RECIST criteria due to the unique antitumor therapeutic mechanism. Preoperative CD8+ expression and ssDECT predict this IC and evaluate the residual tumor cells. This is of great significance for screening immune beneficiaries and making more accurate judgments about the timing of surgery.

Abstract Systemic administration of platinum-based drugs has obvious limitations in the treatment of advanced bladder cancer (BC) owing to lower tumor accumulation and uncontrolled release of chemotherapeutics. There is an urgent need for advanced strategies to overcome the current limitations of platinum-based chemotherapy, to achieve maximal therapeutic outcomes with reduced side effects. In this study, self-polymerized platinum (II)-polydopamine nanocomplexes (PtPDs) were tailored for efficient chemo-photoimmunotherapy of BC. PtPDs with high Pt loading content (11.3%) were degradable under the combination of a reductive tumor microenvironment and near-infrared (NIR) light irradiation, thus controlling the release of Pt ions to achieve efficient chemotherapy. In addition, polydopamine promoted stronger photothermal effects to supplement platinum-based chemotherapy. Consequently, PtPDs provided effective chemo-photothermal therapy of MB49 BC in vitro and in vivo, strengthening the immunogenic cell death (ICD) effect and robust anti-tumoral immunity response. When combined with a PD-1 checkpoint blockade, PtPD-based photochemotherapy evoked systemic immune responses that completely suppressed primary and distant tumor growth without inducing systemic toxicities. Our work provides a highly versatile approach through metal-dopamine self-polymerization for the precise delivery of metal-based chemotherapeutic drugs, and may serve as a promising nanomedicine for efficient and safe platinum-based chemotherapy for BC.

Summary: Background: Some locally advanced (IIIA/IIIB) non-small cell lung cancers (NSCLCs) might have surgical options available. However, information regarding the effectiveness of neoadjuvant immunotherapy for potentially resectable IIIA/IIIB NSCLC is limited. The intent of this investigation was to offer a more favourable alternative to the standard approach of chemoradiotherapy (concurrent or sequential chemoradiotherapy) followed by immunotherapy for potentially resectable stage III NSCLC. Methods: This prospective, single-arm, phase 2 clinical trial (NCT04326153) enrolled treatment-naïve patients with ‘potentially resectable’ IIIA/IIIB NSCLC who were deemed unsuitable for complete (R0) resection upon initial diagnosis. The study period was between March 20, 2020, and August 20, 2021. Patients underwent neoadjuvant chemoimmunotherapy (sintilimab combined with nab-paclitaxel and carboplatin) for two to three cycles prior to surgical resection of the lung carcinoma and systematic nodal dissection within 30–45 days. The primary endpoint was the 2-year disease-free survival (DFS) rate, with secondary endpoints encompassing major pathological response (MPR) rate, pathological complete response (pCR) rate, overall survival, objective response rate (ORR), downstaging rate, and adverse events (AEs). Tumour immune cell infiltrates, identified via immunohistochemistry, were assessed as biomarkers at baseline and after surgery. Findings: Among 30 patients who received neoadjuvant chemoimmunotherapy, 20 underwent complete resection. The disease control rate was 96.7% (95% CI: 90.3%–99.99%), with an ORR of 55% (95% CI: 37.2%–72.8%) and a downstaging rate of 80% (95% CI: 65.7%–94.3%). In the subgroup of 20 patients who underwent surgery, the MPR rate was 65% (95% CI: 43.3%–82.9%), and the pCR rate was 40% (95% CI: 21.2%–46.3%). The 2-year DFS rate in the surgical group was 75% (95% CI 56%–94%). Notably, the MPR group demonstrated significantly prolonged DFS compared with the non-MPR group (p = 0.00024). A significant increase in pretreatment CD8 expression correlated with improved DFS (p = 0.00019). Three patients (10%) experienced grade 3 or higher immune-related AEs—one case of grade 3 elevated myocardial enzymes, one case of grade 3 interstitial pneumonia, and one case of grade 5 bronchopleural fistula. Interpretation: Neoadjuvant immunotherapy markedly enhanced the rate of pathological response and 2-year DFS in patients with potentially resectable IIIA/IIIB NSCLC. Overexpression of CD8 before treatment (H score≥3) may serve as a potential predictive biomarker for DFS. Consequently, the treatment landscape for potentially resectable IIIA/IIIB NSCLC could undergo changes. Funding: This study did not receive any financial support.

Dermatomyositis represents an autoimmune disorder characterized by notable skin and muscular manifestations. The annual incidence of dermatomyositis stands at approximately (5~10)/1 million individuals. Notably, patients with malignant tumors exhibit an elevated risk of developing dermatomyositis compared to the general population. However, in cases where dermatomyositis co-occurs with malignancy, the efficacy of hormone therapy alone tends to be suboptimal. Moreover, reports addressing the correlation between tumor treatment and the management of dermatomyositis are scarce. A 60-year-old male patient presented with dermatomyositis, initially manifesting through symptoms such as rash, muscle weakness, and dysphagia. Despite undergoing standard hormone therapy, there was no discernible improvement in the dermatomyositis symptoms. Considering the patient’s concomitant troublesome cough, further investigations were conducted, including CT, PET-CT, and pathological biopsy. These assessments confirmed the diagnosis of limited-stage small cell lung cancer (T1cN3M0 IIIB). Notably, in this patient, dermatomyositis was suspected to be a paraneoplastic syndrome associated with small cell lung cancer. Standard chemotherapy and radiotherapy were employed to treat the small cell lung cancer, resulting in partial remission after two treatment cycles. As the malignancy regressed, a notable improvement in dermatomyositis symptoms was observed, subsequently leading to a gradual reduction in the prescribed hormone dosage. In conclusion, we present a comprehensive case study of dermatomyositis as a paraneoplastic syndrome throughout the treatment process. The response to tumor therapy coincided with the amelioration of dermatomyositis symptoms. Therefore, diligent malignancy screening is imperative for patients diagnosed with dermatomyositis.

Abstract Introduction Currently, only a few options are available for the treatment of patients with small‐cell lung cancer (SCLC) after the failure of first‐line platinum‐based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second‐line treatment of advanced SCLC. Patients and Methods This prospective clinical trial recruited patients treated with apatinib plus second‐line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression‐free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second‐line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3–4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance. Conclusion Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second‐line therapy in SCLC.

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a rare malignant tumor that arises from a primary or recurrent benign pleomorphic adenoma (PA). Ca ex PA has an aggressive behavior and poor prognosis. To date, there are no standardized therapeutic methods. Herein, we reported a case of a 57-year-old Chinese female with Ca ex PA of the submandibular gland. After surgery, cervical lymph nodes recurred, and multiple distant metastases were detected. During the treatment, she received multiple chemotherapies and radiotherapy but suffered from multidrug resistance and repeated disease progression. Hence, PD-1 inhibitor (sintilimab), in combination with anlotinib, was administered, which resulted in better control of pulmonary metastases compared to the other treatment regimens. This provided an alternative treatment option for Ca ex PA of the submandibular gland patients with failed multiple therapies.

Abstract Background Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings. Methods In this retrospective study, ALK-positive NSCLC patients with brain metastases (BM) or leptomeningeal metastases (LM) from six hospitals in China were divided into three cohorts based on the treatment history before the administration of alectinib. ALK-TKI-naive patients were enrolled in cohort 1, cohort 2 included patients who experienced intracranial progression with or without extracranial progression after treatment with crizotinib, and cohort 3 included patients who developed progression only in CNS following treatment with other second-generation ALK-TKIs. The definition and evaluation of intracranial and extracranial lesions were based on Response Evaluation Criteria in Solid Tumors version 1.1. Results Sixty-five patients were eligible and included in our study (cohort 1: 20, cohort 2: 32, cohort 3: 13). For the overall population and patients with uncontrolled CNS metastases, similar intracranial response in CNS target lesions was observed: cohort 1: 81.8% and 80%; cohort 2: 76.5% and 86.7%; cohort 3: 42.8% and 33.3%. For patients in these three cohorts, 75% (6/8), 78.6% (11/14), and 83.3% (5/6) were reported to have significant improvement in CNS-related symptoms respectively. The number of patients who were in need of mannitol or corticosteroids decreased remarkably after the treatment of alectinib (p

Abstract Background There is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC. Methods The medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. Results A total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population. Conclusion Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.

This pilot study (NCT03958097; https://www.clinicaltrials.gov/ct2/show/NCT03958097) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIB/IIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×109 NK cells every 3 weeks. 20 patients were enrolled, median follow up time was 22.6 months. The median PFS was 11.6 months, ORR was 45%. Median OS was 17.7 months, 6-month OS rate and 12-month OS rate was 95.0% and 80.0%. Unexpected adverse events were not observed. 2 patients reported grade 3 adverse events (hypertriglyceridemia, neutropenia and increased creatine kinase). The autologous NK cells did not add extra adverse events to the ICI treatment. Autologous NK plus sintilimab showed promising antitumor activity and an acceptable safety profile in advanced driven-mutation negative NSCLC who failed on the first line treatment.

Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS.

Background: Nivolumab has been approved in China as second-line treatment for advanced non-small-cell lung cancer (NSCLC) via weight-based infusion, based on the CheckMate 078 study. We investigated the safety and efficacy of 240 mg flat-dose nivolumab in patients with advanced NSCLC, including those with hepatitis B virus (HBV) and epidermal growth factor receptor ( EGFR ) mutation/ALK receptor tyrosine kinase ( ALK ) translocation due to high prevalence in China. Methods: CheckMate 870 was a single-arm, open-label, phase IIIb trial in Asian (primarily Chinese) patients with previously treated advanced NSCLC. Patients received flat-dose nivolumab 240 mg every 2 weeks (Q2W) for up to 2 years. The primary endpoint was the incidence and severity of treatment-related select adverse events (TRsAEs) in non-HBV patients; secondary and exploratory endpoints included severity of high-grade TRsAEs in HBV-infected patients, and safety, efficacy and patient-reported outcomes (PROs) in the whole population. Results: Out of 404 patients enrolled, 400 received treatment. Median (standard deviation) age was 60.5 (8.68) years and the majority were male (78.5%). At a median follow-up of 37.6 months, no Grade 5 TRsAEs were reported, and the frequency of Grade 3–4 TRsAEs was low (0.0–5.9%) in non-HBV and HBV NSCLC patients. Median overall survival (OS) and progression-free survival (PFS) in all treated patients were 14.7 (12.3–18.1) and 3.6 (2.3–3.8) months, respectively. Median OS was 14.2 (12.3–18.1) and 22.3 (10.0–NA) months for non-HBV and HBV-infected patients, 19.3 (11.2–31.7) and 13.7 (11.5–18.1) months for EGFR -positive and wild-type subgroups, and 19.3 (12.9–23.5) and 13.3 (10.9–17.7) months for those with programmed death-ligand 1 (PD-L1) expression ⩾1% and

Abstract Impulse control disorders (ICD) in Parkinson’s disease (PD) might be attributed to misestimate of rewards or the failure to curb inappropriate choices. The mechanisms underlying ICD were reported to involve the lateralization of monoamine network. Our objective was to probe the significant role of lateralization in the pathogenesis of ICD. Twenty-one PD patients with ICD (PD-ICD), thirty-three without ICD (PD-no ICD), and thirty-seven healthy controls (HCs) were recruited and performed T1-weighted, diffusion tensor imaging (DTI) scans and resting state functional magnetic resonance imaging (rs-fMRI). By applying the Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer, we evaluated participants’ synchronicity of functional connectivity and structural changes between hemispheres. Also, tract-based spatial statistics (TBSS) was applied to compare fiber tracts differences. Relative to PD-no ICD group, PD-ICD group demonstrated reduced VMHC values in middle frontal gyrus (MFG). Compared to HCs, PD-ICD group mainly showed decreased VMHC values in MFG, middle and superior orbital frontal gyrus (OFG), inferior frontal gyrus (IFG) and caudate, which were related to reward processing and inhibitory control. The severity of impulsivity was negatively correlated with the mean VMHC values of MFG in PD-ICD group. Receiver operating characteristic (ROC) curves analyses uncovered that the mean VMHC values of MFG might be a potential marker identifying PD-ICD patients. However, we found no corresponding asymmetrical alteration in cortical thickness and no significant differences in fractional anisotropy (FA) and mean diffusivity (MD). Our results provided further evidence for asymmetry of functional connectivity in mesolimbic reward and response inhibition network in ICD.

Abstract Acquired BRAF V600E mutation can occur in tumors with EGFR mutation and is suspected as a resistance mechanism to third‐generation EGFR‐tyrosine kinase inhibitors (TKIs). However, the treatment strategy for the coexistence of EGFR and acquired BRAF mutation with heterogeneity in lung cancer has not been systematically established. Here, we report a patient in whom BRAF V600E and EGFR 19del mutation in a metastatic lesion followed by disease progression on osimertinib was detected. Treatment with single‐agent vemurafenib was effective for treatment of the metastatic lesion in this patient but the primary lesion progressed. A concurrent combination of vemurafenib and osimertinib was therefore administered and a partial response of both primary and metastatic lesions was achieved with progression‐free survival (PFS) of 7 months. The concurrent combination treatment was well tolerated by the patient through dosing modification and supportive medical care. This case highlights the consideration of heterogeneity between different lesions and provides a successful example of the concurrent therapy with vemurafenib and osimertinib for triggering regression of osimertinb resistance induced by BRAF mutation.

Abstract Multiple primary lung cancer (MPLC) refers to the simultaneous occurrence of two or more lung primary malignant tumors in one individual. The detection rate of MPLC has increased significantly in recent years, and the distinction between MPLC and lung metastasis has strong clinical significance. Whole exome sequencing (WES) can clearly identify the heterogeneity between MPLC nodules. Here, we report a case of a 50‐year‐old Asian female without a history of smoking. She underwent a lung computed tomography (CT) scan and three ground‐glass nodules (GGNs) were found which were pathologically confirmed as atypical adenomatous hyperplasia (AAH), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA), respectively. We performed WES on the three pulmonary nodules and analyzed the sequencing results. We believe that this is the first published report of a case of “three phases” of lung adenocarcinoma analyzed by WES. Under the same genetic background and internal environment, these three nodules showed significant genetic differences and developed into “three phases” of lung adenocarcinoma. Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets. Key points Significant findings of the study We used WES to analyze the gene mutation status of three tumors in one individual. We found that even if under the same genetic background, AAH, MIA and IA showed significant genetic differences and developed into “three phases” of lung adenocarcinoma. What this study adds Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets.

Immune checkpoint inhibitors have made remarkable breakthroughs in the treatment of lung cancer, bringing significant survival benefits to the patients. A number of adverse events aggravated by immunotherapy in patients with pre-existing autoimmune diseases have been reported in the past, especially skin toxicity, such as rash, pruritus, erythema, and vitiligo. However, whether the exacerbated autoimmune disease is reversible and when it will return to its original state after immunotherapy discontinuation is still inconclusive. In our report, we described a patient diagnosed with non-small cell lung cancer whose vitiligo was stable for about 10 years. We followed up and observed the patient’s skin depigmentation for the complete time window, from aggravation of application anti-programmed cell death-1 receptor antibody (anti-PD-1 antibody) to recovery after the withdrawal. We presented the objective images at particular time points using reflectance confocal microscopy and wood’s light. We found that the use of anti-PD-1 antibody aggravated in skin toxicity, but it was reversible, the time window from the beginning to recovery status was approximately 9 months. We used this real case scenario to explain the relationships between immunotherapy and autoimmune diseases.

Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.

Background: Convalescent plasma (CP) has been used successfully to treat many types of infectious disease, and has shown initial effects in the treatment of the emerging 2019 coronavirus disease (COVID-19). However, its curative effects and feasibility have yet to be confirmed by formal evaluation and well-designed clinical trials. To explore the effectiveness of treatment and predict the potential effects of CP with COVID-19, studies of different types of infectious disease treated with CP were included in this systematic review and meta-analysis. Methods: Related studies were obtained from databases and screened according to the inclusion criteria. The data quality was assessed, and the data were extracted and pooled for analysis. Results: 40 studies on CP treatment for infectious diseases were included. Our study found that CP treatment could reduce the risk of mortality, with a low incidence of adverse events, promote the production of antibodies, lead to a decline in viral load, and shorten the disease course. A meta-analysis of 15 controlled studies showed that there was a significantly lower mortality rate in the group treated with CP (pooled OR = 0.32; 95% CI = 0.19–0.52; p

In this paper, based on a 2015 social accounting matrix (SAM) for China elaborated by us, we conducted a comprehensive analysis of the structure of China’s economic system using the impact multiplier model. Having this analysis as a background, we focused on the tax reform China completed in 2016, moving from a bifurcated system based on a business tax (BT) and Value Added Tax (VAT) to an entirely VAT-based system. The effects of this reform remain under observation and discussion, regarding not only the reduction in the tax burden on the industrial and service sectors but also economic improvements. Nonetheless, currently, an analysis of the existing literature on the topic indicated consensus that the reform had positive effects in both respects. Given this context, it would be interesting to analyse what effects a selective reduction in the VAT rate would have on China’s economy under this new VAT-based system. To the best of our knowledge, no such analysis has been performed. We attempted to fill this gap and, based on the above purpose-built SAM, we conducted an impact multiplier analysis of the aforementioned effects. Several results have been achieved. From the estimation of the industry-level endogenous coefficients there is evidence of a considerable average degree of integration among the industries and of the key role of “Manufacturing” in China’s production structure. Moreover, the significant orientation of the industries to the production of value added is highlighted. The analysis of the impact of the indirect tax reform have demostrated that making the central government the sole operator of indirect taxes is a general advantage. Overall, there is evidence that the economic system strongly reacts—by a nearly 4% increasing—to an average VAT cut of 1.2% for 6 industries, thus highlighting its elasticity to this kind of exogenous shocks.

A 61‐year‐old Chinese man with a history of tuberculosis was found to have a large mass in the left lower lobe and multiple ground‐glass nodules (GGNs) on lung computed tomography (CT). Post‐operative pathology showed lung squamous carcinoma in the left lower lobe and mediastinal lymph node metastases, which were confirmed as lung adenocarcinoma. Multiple gene sequencing was performed, and no relationship was observed between the two primary sites. Chemotherapy consisting of four cycles of gemcitabine plus cisplatin were prescribed for this patient after the operation. After a period of two‐year follow‐up, the lung adenocarcinoma was found to have progressed with new metastases in the right cervical lymph nodes which had the same pathology and gene mutation as the metastatic mediastinal lymph nodes removed two years previously. Meanwhile, a primary lesion was found following PET‐CT scan, and the tuberculosis scar was determined as its point of origin. In conclusion, we have found that a tuberculosis scar is a risk factor of lung cancer, especially adenocarcinoma, and more attention should be paid to close monitoring and follow‐up by clinicians.

Multiple primary lung cancers (MPLCs) refers to two or more primary malignant tumors that occur simultaneously or successively in the lung of the same patient. Distinguishing MPLCs from intrapulmonary metastases is important for treatment strategy and prognosis. MPLCs have been considered as having different origins and clonal evolutionary processes. Whole genome sequencing (WGS) and whole exome sequencing (WES) are regarded as an effective way to identify the relationship and differentiation among MPLC nodules. Here, we report the case of a 63‐year‐old MPLC male patient who smoked for 40 years. Two nodules were found on chest computed tomography (CT) scan, which were further confirmed by pathology to be lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC), respectively. WES of the two different nodules was performed, and the results showed that there was a significant genetic difference between the two nodules. Further analysis of the tumor mutation burden (TMB) of the two tumor lesions showed that the TMB of the squamous cell carcinoma was higher than that of the adenocarcinoma, indicating that the squamous cell carcinoma had a higher mutation frequency. According to the pathology and WES sequencing results, MPLCs for this case were regarded as independent of each other, with different origins and clonal evolutionary processes. In this case report, we emphasize that WES should play an important role in determining the origin of MPLC clones, and also make some explorations for the further discovery of new potential driver genes and therapeutic targets.

Multicolor fluorescence of mixed halide perovskites enormously enables their applications in photonics and optoelectronics. However, it remains an arduous task to obtain multicolor emissions from perovskites containing single halogen to avoid phase segregation. Herein, a fluorescent composite containing Eu-based metal-organic frameworks (MOFs), 0D Cs4PbBr6, and 3D CsPbBr3 is synthesized. Under excitations at 365 nm and 254 nm, the pristine composite emits blue (B) and red (R) fluorescence, which are ascribed to radiative defects within Cs4PbBr6 and 5D0→7FJ transitions of Eu3+, respectively. Interestingly, after light soaking in the ambient environment, the blue fluorescence gradually converts into green (G) emission due to the defect repairing and 0D-3D phase conversion. This permanent and unique photochromic effect enables anticounterfeiting and microsteganography with increased security through a micropatterning technique. Moreover, the RGB luminescence is highly stable after encapsulation by a transparent polymer layer. Thus, trichromatic light-emitting modules are fabricated by using the fluorescent composites as color-converting layers, which almost fully cover the standard color gamut. Therefore, this work innovates a strategy for construction of tunable multicolor luminescence by manipulating the radiative defects and structural dimensionality.

Background Tyrosine kinase inhibitors (TKIs) can significantly prolong overall survival for patients with advanced non‐small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐mutation or anaplastic lymphoma kinase (ALK)‐rearrangement. However, the real‐world evaluation status of ALK/EGFR in China remains unclear. Methods We conducted a prospective study including 1134 patients with cytologically or histologically confirmed advanced NSCLC (stage IIIb–IV) at 12 Chinese hospitals. Results The most common evaluation methods were amplification‐refractory mutation system for EGFR status and immunohistochemistry targeting D5F3 for ALK status. Among patients with non‐squamous, the EGFR mutation rate was 44.1% and the ALK rearrangement rate was 10.0%. Among patients with squamous cell carcinoma, the EGFR mutation rate was 8.3% and the ALK rearrangement rate was 3.7%. Among all patients, gender (HR = 1.7, 95%CI = 1.2–2.4, P = 0.006), smoking history (HR = 1.8, 95%CI = 1.3–2.7, P = 0.001), histology (HR = 5.0, 95%CI = 2.4–10.1, P < 0.001), and brain metastases (HR = 1.5, 95%CI = 1.1–2.2, P = 0.017) were independent predictors of EGFR mutation, while age (HR = 2.6, 95%CI = 1.7–4.1, P < 0.001) was an independent predictor of ALK rearrangement. The median time from tumor diagnosis to EGFR or ALK status confirmation was 7 and 5 days, respectively. Targeted therapy rate was 73.8% in EGFR‐positive patients and 51.4% in ALK‐positive patients. There was a negative correlation between the first‐line targeted therapy rate and the EGFR mutation detection period (r = −0.152, P = 0.02), while no significant correlation among patients with ALK rearrangement (r = −0.179, P = 0.076). Conclusion Squamous NSCLC patients should also be routinely tested to determine their EGFR/ALK statuses. The first‐line targeted therapy rate remains low in Chinese patients with NSCLC.

The morbidity and mortality of lung cancer is the first in the world, immunotherapy has become a important treatment strategy in addition to chemotherapy, radiotherapy and targeted therapy. In recent years, the US Food and Drug Administration (FDA) has successively approved immunological checkpoint inhibitors as standard programs for non-small cell lung cancer (NSCLC) in second-line or first-line treatment. The National Comprehensive Cancer Network (NCCN) also recommends immunological checkpoint inhibitors as the standard treatment for small cell lung cancer (SCLC). Now, the treatment for lung cancer has entered the era of precision treatment, it is very important to select effective and reliable biomarker for the dominant populations of lung cancer to receive immunotherapy. A large number of researchs indicated that tumor mutation burden (TMB) may be an independent predicted biomarker for immunotherapy, but with limitations. This article reviewed the predictive value of TMB and its limitations in the field of immunotherapy for lung cancer.

The ErbB family is composed of four cell membrane receptors: ErbB-1 (epidermal growth factor receptor or human epidermal growth factor receptor [HER]1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). All members of the ErbB family play a critical role in regulating cell growth, proliferation and migration of tumours. Afatinib is an irreversible ErbB family inhibitor that is approved for second-line treatment of advanced squamous cell carcinoma (SqCC) that has progressed following platinum-based chemotherapy. Here we describe the case of a 56-year-old male Chinese patient with SqCC who had previously failed chemotherapy and radiotherapy and was subsequently enrolled in the LUX-Lung 8 study. The patient responded well to treatment with afatinib (40 mg/day). His disease stabilised after 8 weeks and a complete response was achieved after 12 weeks of treatment. Follow-up of this patient is ongoing; he is still alive and has not experienced disease progression in the 7 years since initiation of afatinib. The long-term response and prolonged survival in this patient provide additional evidence for second-line treatment with afatinib in patients with SqCC.

The discovery of epidermal growth factor receptor ( EGFR ) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have altered the therapeutic prospects of advanced non-small-cell lung cancer (NSCLC). G719X and S768I are uncommon mutations, and they often exist as compound mutations. A few reports have described the efficacy of first- and second-generation EGFR-TKIs. However, the efficacy of osimertinib in patients with these uncommon compound mutations is unknown. In this study, we reported the postoperative outcome of a patient with NSCLC and uncommon compound EGFR G719X and S768I mutations. After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.

Objective: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p

Abstract Background The incidence of ocular metastasis from lung cancer is reported to be 0.1–7%, with adenocarcinoma and small cell lung cancer accounting for the highest proportions of these cases. The majority of cases involves metastasis to more than one other distal organ in addition to the eye. Here, we report for the first time, a case of lung squamous cell carcinoma with solitary symptomatic ocular metastasis as the initial manifestation that was managed by a multidisciplinary treatment (MDT). Case presentation A woman presented at the ophthalmology department of hospital with a 1-week history of left eye pain and blurred vision. Systemic examination led to the diagnosis of central lung cancer in the right lower lobe with ocular metastasis. After consultations with an MDT, including specialists from the surgery, internal medicine, ophthalmology, radiotherapy and imaging departments, the patient underwent surgery and chemotherapy. Her eye symptoms disappeared, and the ocular lesion was well controlled without any specific ocular treatment. The patient demonstrated a prolonged progression-free survival. Conclusion This is the first report of a rare case with solitary ocular metastasis as the initial manifestation of lung squamous cell carcinoma. This rare patient was treated based on evidence-based medicine, indicating the importance of cooperation within an MDT. The successful treatment of this case was reported as a new therapeutic reference for clinicians who encounter similar cases in the future.

Background and objective The significant efficacy of tyrosine kinase inhibitors (TKIs) has been approved for advanced non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations. No clear evidence exists that EGFR-L861Q is sensitive to TKIs, and the best treatment for NSCLC patients with EGFR-L861Q mutation is undetermined. This study aims to discuss the best treatment for advanced NSCLC patients with EGFR-L861Q mutation by analyzing the differences among the structures of wild-type EGFR, activating mutant EGFR-L858R, and EGFR-L861Q mutation. Method The protein structures of wild-type EGFR were reconstructed. EGFR-L858R and EGFR-L861Q mutation were activated. The differences among the three kinds of protein conformation were analyzed using homologous modeling technique. Results The structure of EGFR-L858R and wild-type EGFR exhibited notable distinctions. The structure of EGFR-L861Q mutation was different compared with wild-type EGFR and activating mutant EGFR-L858R protein conformations. NSCLC patients with EGFR-L861Q mutation were given chemotherapy as the first-line of therapy, and TKIs were applied to maintain treatment when the tumor is unchanged. Effect evaluation result was improved when the lung computed tomography lesions were reviewed. Conclusion The analysis of the protein conformation of EGFR-L861Q mutation and the curative effect of chemotherapy with TKIs could help predict the sensitivity of EGFR-L861Q to TKIs. Combining the analysis with a clinical case, maintenance treatment with TKIs may achieve satisfactory curative effect in advanced NSCLC patients who have achieved disease control after first-line chemotherapy.