Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*

Small cell lung cancer(SCLC)is a highly malignant neuroendocrine tumor,which is prone to metastasis and is associated with a very poor prognosis.SCLC was previously regarded as a homogeneous disease that lacked individualized treatment strategies.In recent years,molecular typing studies have revealed the high heterogeneity of SCLC.However,issues such as inconsistent typing standards,the dy-namic transformation of subtypes,and complex drug resistance mechanisms restrict the clinical translation of the results.This article sys-tematically expounds the research progress of SCLC molecular typing,summarizes its potential and challenges in driving precision treatment,and aims to provide ideas for the development of precise medical treatment plans and promote the clinical translation of the"typing-guided treatment"model for SCLC.

Objective:To investigate the impact of virtual navigation bronchoscopy on perioperative information in patients undergoing thoracoscopic pulmonary resection.Methods:Employed three distinct propensity score matching models to effectively address the baseline data disparities among patients undergoing thoracoscopic pulmonary resection. Categorized the patients into two groups: pulmonary wedge resection and pulmonary segmentectomy. Compared the disparities in clinical characteristics, intraoperative lesion resection, and postoperative recovery between patients who underwent virtual navigation bronchoscopy assisted localization prior to surgery and those who did not employ any specific localization methods.Results:This reserch included a total of 127 patients who underwent localization assisted by virtual navigation bronchoscopy, and 122 patients who did not undergo specialized localization. After propensity score matching, the navigation group demonstrated a statistically significant reduction in intraoperative blood loss[model 3, 40(20, 50) ml vs. 50(20, 100) ml, P=0.027], drainage volume on the first day post-surgery[model 3, 100(50, 175) ml vs. 150(100, 220) ml, P=0.023], and incidence of residual pleural effusion(model 3, 31 cases vs. 38 cases, P=0.046) compared to the non-positioning group among patients undergoing pulmonary wedge resection. In the pulmonary segmentectomy group, we observed a reduction in intraoperative blood loss[model 3, 50(30, 100) ml vs. 100(50, 100) ml, P=0.003] and incidence of residual pneumothorax(model 3, 18 cases vs. 28 cases, P=0.012) in patients who underwent navigation-assisted procedures compared to those without specialized positioning. Conclusion:The utilization of virtual navigation bronchoscopy for preoperative localization assistance in thoracoscopic sublobectomy(including wedge resection and segmental resection) may represent a viable approach to mitigate intraoperative injury and facilitate postoperative recovery.

Small cell lung cancer(SCLC)is a highly malignant neuroendocrine tumor,which is prone to metastasis and is associated with a very poor prognosis.SCLC was previously regarded as a homogeneous disease that lacked individualized treatment strategies.In recent years,molecular typing studies have revealed the high heterogeneity of SCLC.However,issues such as inconsistent typing standards,the dy-namic transformation of subtypes,and complex drug resistance mechanisms restrict the clinical translation of the results.This article sys-tematically expounds the research progress of SCLC molecular typing,summarizes its potential and challenges in driving precision treatment,and aims to provide ideas for the development of precise medical treatment plans and promote the clinical translation of the"typing-guided treatment"model for SCLC.

Objective:To investigate the impact of virtual navigation bronchoscopy on perioperative information in patients undergoing thoracoscopic pulmonary resection.Methods:Employed three distinct propensity score matching models to effectively address the baseline data disparities among patients undergoing thoracoscopic pulmonary resection. Categorized the patients into two groups: pulmonary wedge resection and pulmonary segmentectomy. Compared the disparities in clinical characteristics, intraoperative lesion resection, and postoperative recovery between patients who underwent virtual navigation bronchoscopy assisted localization prior to surgery and those who did not employ any specific localization methods.Results:This reserch included a total of 127 patients who underwent localization assisted by virtual navigation bronchoscopy, and 122 patients who did not undergo specialized localization. After propensity score matching, the navigation group demonstrated a statistically significant reduction in intraoperative blood loss[model 3, 40(20, 50) ml vs. 50(20, 100) ml, P=0.027], drainage volume on the first day post-surgery[model 3, 100(50, 175) ml vs. 150(100, 220) ml, P=0.023], and incidence of residual pleural effusion(model 3, 31 cases vs. 38 cases, P=0.046) compared to the non-positioning group among patients undergoing pulmonary wedge resection. In the pulmonary segmentectomy group, we observed a reduction in intraoperative blood loss[model 3, 50(30, 100) ml vs. 100(50, 100) ml, P=0.003] and incidence of residual pneumothorax(model 3, 18 cases vs. 28 cases, P=0.012) in patients who underwent navigation-assisted procedures compared to those without specialized positioning. Conclusion:The utilization of virtual navigation bronchoscopy for preoperative localization assistance in thoracoscopic sublobectomy(including wedge resection and segmental resection) may represent a viable approach to mitigate intraoperative injury and facilitate postoperative recovery.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

{L-End}Objective To analyze the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) and their influencing factors among workers in the chemical pharmaceutical industry. {L-End}Methods A total of 563 workers from three chemical pharmaceutical factories in Guangzhou City were selected as the research subjects using the judgment sampling method. The prevalence of multi-site WMSDs in the past 12 months was investigated using the electronic questionnaire of Chinese Version of Musculoskeletal Disorders Questionnaire. {L-End}Results The prevalence of multi-site WMSDs in the research subjects was 30.0% (169/563). The results of multivariable logistic regression analysis showed that workers who smoked regularly/frequently and those who had their hands above shoulder level for long periods of time had a lower risk of multi-site WMSDs than those who never/occasionally smoked (all P≤0.05). Workers with a high school, secondary specialty, college degree, or above had a lower risk of multi-site WMSDs than those with a middle school education or below (all P<0.05). The longer the daily working hours, the higher the risk of multiple WMSDs (all P<0.05). Workers with regular/frequently work shifts had a lower risk of multi-site WMSDs than those with none/occasional work shifts (P<0.05). {L-End}Conclusion The prevalence of multi-site WMSDs among workers in the chemical pharmaceutical industry is relatively high. The influencing factors are individual factors, unreasonable work organization and poor ergonomics factors.

Objective To investigate the combined effect of noise and hand-transmitted vibration on hearing loss in male noise-exposed workers. Methods A total of 952 male noise-exposed workers from an automobile manufacturing enterprise were selected as the research subjects using judgment sampling method. Occupational epidemiological surveys, assessments of occupational hazards in workplace, and pure-tone audiometry tests were conducted on the research subjects, and they were divided into low-level noise group, low-level combined group, high-level noise group, and high-level combined group according to whether the noise exposure level exceeded the national standard and whether they were jointly exposed to hand-transmitted vibration. The joint effects of noise and hand-transmitted vibration on hearing loss were analyzed. Results The detection rate of hearing loss in 952 noise-exposed workers was 21.7%. The detection rate of hearing loss of four groups, from high to low, was as follows： high-level combined group, high-level noise group, low-level combined group, and low-level noise group (44.9% vs 32.7% vs 12.9% vs 5.7%, P<0.01). The results of multivariate logistic regression analysis showed that the risk of hearing loss in the low-level noise group, the low-level combined group, the high-level noise group and the high-level combined group increased sequentially after adjusting for the confounding factors such as age, education level, smoking, drinking, listening to music with headphones, frequency of wearing noise-blocking earplugs and body mass index. The risk of hearing loss in the high-level noise group was 8.62 times more than that of the low-level noise group (P<0.01). The risk of hearing loss in the low-level noise combined group was 2.50 times more than that of the low-level noise group (P<0.01). The risks of hearing loss in the high-level combined group were 5.76 and 1.67 times more than that of the low-level combined group and the high-level noise group. Conclusion Combined exposure to noise and hand-transmitted vibration can increase the risk of hearing loss in male noise-exposed workers, and the higher the noise intensity, the greater the synergistic effect. Hand-transmitted vibration is a synergistic risk factor for occupational noise-induced hearing loss.

Objective:To investigate the spectrum of amino acid, organic acid, and fatty acid oxidative metabolic diseases in children diagnosed by detecting urinary organic acid levels using gas chromatography-mass spectrometry.Methods:From January 2005 to December 2021, clinical data of 2 461 children diagnosed with inherited metabolic diseases (IMD) by gas chromatography-mass spectrometry, in combination with tandem mass spectrometry and genetic testing in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed.Results:Among 2 461 children, 1 446 were male and 1 051 were female. A total of 32 types of IMD were detected among 2 461 patients, which included 10 amino acid disorders in 662 cases (26.9%), 6 common diseases were hyperphenylalaninemia, citrin deficiency, ornithine carbamoyltransferase deficiency, maple syrup urine disease, alkaptonuria, and tyrosinemia-I, 17 types of organic acidemias in 1 683 cases (68.4%), 6 common diseases were methylmalonic acidemia, propionic acidemia, valeric acidemia-type Ⅰ, isovaleric acidemia, 3-methylcrotonyl-CoA carboxylase deficiency and multiple carboxylase deficiency and 5 fatty acid β oxidative defects in 116 cases (4.7%), 2 common diseases were multiple acyl-CoA dehydrogenase deficiency and short-chain acyl-CoA dehydrogenase deficiency).Conclusion:Among the diseases diagnosed by analyzing urinary organic acid profiling with gas chromatography-mass spectrometry, the most common are organic acidemias, followed by amino acid disorders and fatty acid oxidation defects.

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75％ of the lesions in the CRT group were reduced compared with 34％ in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100％ and 98％.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33％,significantly higher compared with 26％ in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.