BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective:To discuss the role of M2 macrophages in epithelial-mesenchymal transition(EMT)and cisplatin(DDP)resistance in the non-small cell lung cancer(NSCLC),and to clarify the regulatory mechanism of nuclear factor κB(NF-κB)signaling pathway.Methods:The human monocytic leukemia THP-1 cells were selected and differentiated into M0 macrophages by phorbol myristate acetate(PMA)induction,followed by M2 macrophage polarization through interleukin(IL)-4 and IL-13 stimulation.Western blotting and immunofluorescence methods were used to detect the protein expression levels of CD163,CD86,and arginase-1(Arg-1)in M0 and M2 macrophages.The human NSCLC A549 cells were co-cultured non-contactly with M0 or M2 macrophages in Transwell chambers,and the cells were divided into A549+M0 group(A549 cells co-cultured with M0 macrophages),A549+M2 group(A549 cells co-cultured with M2 macrophages),and A549+M2+BAY11-7082 group(A549 cells co-cultured with M2 macrophages and treated with 10 mmol·L-1 NF-κB inhibitor BAY11-7082).Wound healing assay was used to detect the wound healing rate of the A549 cells in various groups;Transwell assay was used to detect the number of invasion A549 cells in various groups;cell counting kit-8(CCK-8)assay was used to detect the inhibitory rate of proliferation and half maximal inhibitory concentration(IC50)value of the A549 cells after treated with DDP in the co-culture system;Western blotting method was used to detect the expression levels of vimentin,E-cadherin,N-cadherin,transcription factor Snail,phosphorylated P65(p-P65),P-glycoprotein(P-gp),and programmed death-ligand 1(PD-L1)proteins in the A549 cells in various groups.Results:The Western blotting results showed that compared with M0 group,the expression levels of CD163 and Arg-1 proteins in the macrophages in M2 group were significantly increased(P<0.05),while the expression level of CD86 protein was significantly decreased(P<0.05).The immunofluorescence results showed that compared with M0 group,the expression of CD163 protein in the macrophages in M2 group was enhanced and the expression of CD86 protein was weakened.The wound healing assay results showed that at 24 and 48 h of culture,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the wound healing rate of the A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the wound healing rate of the A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05).The Transwell assay results showed that compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05);compared with A549+M2 group,the number of invasion A549 cells in A549+M2+BAY11-7082 group was significantly decreased(P<0.05);in the co-culture system,compared with A549+M0 group,the number of invasion A549 cells in A549+M2 group was significantly increased(P<0.05).The CCK-8 assay results showed that after treated with 2.50,5.00,10.00,20.00,and 40.00 mg·L-1 DDP,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);in the co-culture system,compared with A549+M0 group,the inhibitory rate of proliferation of the A549 cells in A549+M2 group was significantly decreased(P<0.05 or P<0.01),and the IC50 value was significantly increased(P<0.01);compared with A549+M2 group,the inhibitory rate of proliferation of the A549 cells in A549+M2+BAY11-7082 group was significantly increased(P<0.05),and the IC50 value was significantly decreased(P<0.05).The Western blotting results showed that compared with A549+M0 group,the expression level of E-cadherin proteins in the A549 cells in A549+M2 group was significantly decreased(P<0.05),while the expression levels of N-cadherin,vimentin,and Snail proteins were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of vimentin,Snail,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05),while the expression level of E-cadherin proteins was significantly decreased(P<0.05);compared with A549+M2 group,the expression levels of vimentin,N-cadherin,and p-P65 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05),while the expression level of E-cadherin proteins was significantly increased(P<0.05);compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);in the co-culture system,compared with A549+M0 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2 group were significantly increased(P<0.05);compared with A549+M2 group,the expression levels of P-gp and PD-L1 proteins in the A549 cells in A549+M2+BAY11-7082 group were significantly decreased(P<0.05).Conclusion:The M2 macrophages can regulate EMT in the NSCLC cells to promote the invasion and metastasis of tumor,and modulate the expressions of P-gp and PD-L1 to enhance DDP resistance,which is associated with the NF-κB signaling pathway.

Objective To explore the application of bundled nursing care for recurrent obstruc-tive esophageal cancer treated by photodynamic therapy.Methods Thirty patients with recurrent ob-structive esophageal cancer were administered with photosensitizer hematoporphyrin derivative injec-tion.After 24 hours,an optical fiber was introduced under endoscopic guidance,and 630 nm laser was used to irradiate the tumor locally.The degree of relief in dysphagia,improvement in perform-ance status,changes in body mass index,and treatment-related adverse reactions were recorded.Bundled nursing strategies were implemented,including preoperative assessment,education,prepara-tion,postoperative positioning,observation,prevention of complications,and light protection meas-ures.Results After treatment,the median diameter of the narrowest esophageal lesion was increased[(8.92±0.64)mm versus(4.77±0.60)mm],the Karnofsky Performance Status(KPS)score was improved[(77.69±5.99)versus(84.62±6.60)],BMI was increased[(17.17±1.66)kg/m2 ver-sus(18.08±1.60)kg/m2],and the Stooler dysphagia grade was decreased compared with treatment be-fore.The main treatment-related adverse reactions were retrosternal pain and fever.Conclusion Photo-dynamic therapy for recurrent obstructive esophageal cancer has a rapid onset of action and mild ad-verse reactions,and ensures the smooth implementation of PDT and patients'safety.

Objective:To quantitatively evaluate left ventricular myocardial work in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) by pressure strain loop (PSL) technique.Methods:A total of 103 T2DM patients diagnosed at the Heping Hospital Affiliated to Changzhi Medical College from April 2022 to May 2023 were selected. They were divided into three groups based on their fatty liver ultrasound findings: group A (34 cases without NAFLD), group B (37 cases with mild NAFLD), and group C (32 cases with moderate to severe NAFLD). All patients underwent routine echocardiography, which measured the end diastolic left ventricular diameter (LVIDd), end systolic left ventricular diameter (LVIDs), end diastolic interventricular septum (IVSTd), left ventricular posterior wall thickness (LVPWTd), and end systolic left atrial diameter (LAD). The biplane Simpson method was used to measure left ventricular ejection fraction (LVEF), end diastolic left ventricular volume (LVEDV), and end systolic left ventricular volume (LVESV). PSL technology was applied to analyze the overall longitudinal strain (GLS), global work index (GWI), global effective work (GCW), global ineffective work (GWW), and overall work efficiency (GWE) of the left ventricular myocardium. We compared the conventional echocardiography parameters and myocardial work parameters among three groups, and analyzed the correlation between myocardial work parameters and GLS and glycosylated hemoglobin (HbA 1c). Results:The differences in body mass index (BMI), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between group B and group A were statistically significant (all P<0.05); There was a statistically significant difference in BMI, HbA 1c, and low density lipoprotein cholesterol (LDL-C) between group C and group B (all P<0.001); The differences in BMI, HbA 1c, ALT, AST, triglyceride (TC), high density lipoprotein cholesterol (HDL-C), and LDL-C between group C and group A were statistically significant (all P<0.05). The GWI and GCW in group B were lower than those in group A (all P<0.05), while the absolute GLS, GCW, GWI, and GWE in group C were lower than those in group A, and GWW was higher than those in group A (all P<0.05); The absolute values of GLS, GCW, GWI, and GWE in group C were lower than those in group B ( P<0.05). The correlation analysis results showed that GLS and HbA 1c were negatively correlated with GCW and GWI ( r=-0.571, -0.533, -0.273, -0.223, P<0.05). Conclusions:PSL technology can quantitatively evaluate left ventricular myocardial work in patients with T2DM combined with NAFLD, and can detect early impairment of left ventricular systolic function in patients. It has clinical reference value in evaluating overall and local cardiac function.

Objective To establish a prognostic model for lung adenocarcinoma (LUAD) based on genes associated with the disulfidptosis (DS) pathway, and to elucidate its potential biological mechanisms. Methods LUAD-related gene sequencing and clinical information were sourced from public databases.The correlation between results of gene set variation analysis (GSVA) and mRNA expression in The Cancer Genome Atlas (TCGA) dataset was used to screen genes that were significantly active in the disulfur death (DS) pathway.The Least Absolute Shrinkage and Selection Operator (LASSO) analysis and Random Forest (RF) algorithm were employed to screen out DS pathway prognosis-related genes (DPRGs) and multivariate Cox regression analysis was used to construct risk score (RS) model, which was validated using external GEO datasets.The samples were divided into high and low-risk groups based on the median score of RS.A protein-protein interaction (PPI) network corresponding to 7 DPRGs was established, with LDHA identified as the protein with the most interactions, thereby further investigating its function and expression patterns. Results In this study, 7 DPRGs were screened, including SLC2A1, LDHA, SNAI2 and ACO2, FGF12, ANP32B and ST13.The prognostic model constructed based on these genes exhibited high validation efficiency.Kaplan-Meier survival analysis revealed significant differences in overall survival of patients between high-risk group and low-risk group in four datasets.Differential expression gene enrichment analysis between the high-risk and low-risk groups showed that these genes were enriched in pathways such as the p53 signaling pathway and cell cycle. Results of real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry indicated that LDHA expression levels were elevated in LUAD tissue compared to normal tissues. Conclusion The LUAD model established based on DPRGs can effectively predict patients'prognosis, potentially offering insights into the treatment and prognosis of LUAD patients.

Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective To evaluate the expression of FUNDC1 and its clinical significance in non-small cell lung cancer. Methods We used TCGA database to analyze the difference of mitochondrial receptors (DRP1, BNIP3, FUNDC1, NIX, RHEB, LC3, OPA1 and MFN1) expression between normal and NSCLC tissues, as well as its effect on the prognosis of NSCLC patients. Immunohistochemistry was used to detect FUNDC1 expression. The correlations between FUNDC1 expression and clinicopathological characteristics, prognosis were evaluated by SPSS 22.0 statistical software. Results FUNDC1 expression was increased in NSCLC tissues, compared with normal tissues. FUNDC1 expression was related to the degree of differentiation and lymph node metastasis, but not to gender, age, pathological type, distant metastasis or TNM classification. The Cox regression analysis showed that FUNDC1 protein expression, lymph node metastasis, differentiation degree were independent prognostic factors of NSCLC. Increased FUNDC1 expression was related to decreased OS and PFS (P < 0.01). Conclusion The up-regulation of FUNDC1 expression can affect the prognosis of patients with NSCLC. It may be a new potential target for treating with NSCLC.

Objective To analyze the mortality risk and evaluate the curative effects of surgery and non-surgery on NSCLC with diameter > 7.0 cm. Methods We collected the data of NSCLC patients with diameter > 7.0 cm from 2010 to 2015 from the SEER database. The 1, 2, 3-year survival rates were analyzed by life table method. Overall survival curve was estimated by Kaplan-Meier method. Univariate and multivariate Cox regression models were used to analyze the independent prognostic factors. Results The 1, 2, 3-year survival rates were 51.8%, 33.0% and 25.0%, respectively. In univariate and multivariate analyses, tumor size, N stage and treatment were the independent prognostic factors (P < 0.001). Conclusion Surgery is benefited for the prognosis of stage N0-N1 NSCLC patients with diameter > 7.0 cm. And for stage N2 NSCLC patients with diameter 7.0-9.0 cm, surgical treatment has advantages in improving the prognosis. Surgical and non-surgical patients with tumor diameter ≥9.0 cm or lymph node N3 stage have no statistically significant differences in prognosis. In addition, palliative treatment does not improve the prognosis of patients.

Objective To analyze the factors affecting the prognosis of patients with pulmonary sarcomatoid carcinoma (PSC) and construct a nomogram prediction model for the prognosis of PSC patients. Methods Based on the SEER database, 1671 patients diagnosed as PSC from 1988 to 2015 were collected and divided into modeling group and validation group according to the ratio of 7:3. Univariate and multivariate Cox regression analysis were performed in the modeling group to explore independent risk factors affecting the prognosis and construct a nomogram survival prediction model. The consistency index and calibration curve were used for verification in the modeling group and the test module respectively. Results Age, gender, histological type, TNM stage, tumor diameter > 50mm, surgery, radiotherapy and chemotherapy were independent factors that affected the prognosis of PSC patients. The nomogram prediction model was constructed and verified based on independent factors. The C indexes of the modeling group and the test model were 0.790 (95%CI: 0.776-0.804) and 0.781 (95%CI: 0.759-0.803), respectively. The calibration curves of the modeling group and the test model indicated that the predicted survival rate was basically the same as the actual survival rate. Conclusion The nomogram prediction model constructed based on the results of multivariate analysis can predict the prognosis of PSC patients, and has high accuracy and consistency.