Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

The epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is a rare subtype of mutations in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC carrying the EGFR ex20ins mutation tend to have poor responses to traditional EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and immunotherapy, leading to a poor clinical prognosis. Significant progress has been made in the development of new drugs targeting the EGFR ex20ins mutation. The research on new drugs targeting EGFR ex20ins mutations has made significant progress. The main ones include new EGFR-TKIs (such as sunvozertinib, mobocertinib, and furmetinib, etc.), bispecific antibodies (such as amivantamab, JMT101, and GB263T, etc.), and emerging drugs such as AUY922. These agents have demonstrated promising efficacy in clinical trials, improving the objective response rate and progression-free survival of patients, and are expected to improve overall survival. An in-depth analysis of the mechanism of action and clinical trial progress of these novel targeted drugs for EGFR ex20ins-mutated NSCLC can offer new therapeutic strategies for patients with EGFR ex20ins-mutated NSCLC.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.

Objective To investigate the correlations of computed tomography (CT), clinical, and pathological features in patients with invasive lung adenocarcinoma positive and negative for spread through air spaces (STAS). Methods A total of 236 patients with invasive lung adenocarcinoma confirmed by surgery and pathology were selected, including 118 patients in STAS-positive group and 118 patients in STAS-negative group. The clinical data, CT signs, and pathological features of the two groups were collected and analyzed. Results There was a correlation between age and the occurrence of STAS. The age of the positive group was higher than that of the negative group. Smoking history and family history of tumor had no correlation with the occurrence of STAS. CT features signs such as nodule type and shape, tumor-lung interface, lobulation sign, spiculation sign, vacuole/cavity, air-bronchogram, pleural indentation sign, vascular changes, mean diameter of tumor, mean diameter of solid component, and the percentage of tumor solid components were significantly different between patients with and without STAS. The incidence of STAS in patients with solid nodules and partial solid nodules was significantly higher than that in patients with ground glass nodules. Multivariate analysis showed that the percentage of tumor solid components, air-bronchogram sign, lobulation sign, and tumor-lung interface were independent risk factors for predicting the occurrence of STAS. Conclusion The clinical data and CT signs of patients with invasive lung adenocarcinoma are related to the occurrence of STAS. CT signs such as the percentage of tumor solid components, air-bronchogram, lobulation sign, and tumor-lung interface are of great significance to STAS prediction. Our findings provide an important basis for selection of personalized clinical treatment plans.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infections have raged globally for more than 2 years.China has always adopted scientific and effective prevention and control measures to achieved some success.However, with the continuous variation of SARS-CoV-2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex.With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS-CoV-2 infection in children in China.Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis, and according to the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of effective prevention and treatment of SARS-CoV-2 infection in children in China.

Objective To investigate the correlation between the features of multimodal magnetic resonance imaging (MRI) and the expression of human epidermal growth factor receptor-2 (HER-2) in ductal carcinoma in situ (DCIS). Methods A total of 53 patients with DCIS confirmed by surgery and pathology in Dezhou Second People’s Hospital from September 2018 to June 2021 were analyzed retrospectively. The patients were divided into HER-2 positive group (29 cases) and HER-2 negative group (24 cases). MRI features were compared between the two groups. Results There were significant differences in the internal enhancement characteristics, microvascular sign, and time-intensity curve type between the two groups (P < 0.05). There were no significant differences in lesion morphology, non-mass-like enhancement pattern, and apparent diffusion coefficient value (P > 0.05). The HER-2 positive group showed clumped enhancement (65.5%), type Ⅱ (48.1%) andtype Ⅲ (29.6%) time-intensity curves, and microvascular sign (89.7%). The HER-2 negative group showed clusteredring enhancement (50.0%), type Ⅱ (45.8%) and type I (54.2%) time-intensity curves, and microvascular sign (54.2%). A combination of clumped enhancement, microvascular sign, and type Ⅲ time-intensity curve showed 100% specificity and 100% positive predictive value for the diagnosis of HER-2 positive DCIS. Conclusion Clumped enhancement, microvascular sign, and type Ⅱ or Ⅲ time-intensity curve on MRI can largely reflect the expression of HER-2 in DCIS. The three can be used in combination to improve the diagnostic efficiency of HER-2 positive DCIS.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.