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

AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

ObjectiveTo investigate the efficacy and mechanism of Polygoni Cuspidati Rhizoma et Radix （Huzhang） in treating respiratory syncytial virus（RSV） infection by regulating pulmonary surfactant lipid homeostasis through lipidomics. MethodsSixty BALB/c mice were randomly divided into the blank group， model group， positive group（ribavirin group， 46 mg·kg^-1）， and low- and high-dose Huzhang groups（0.75， 2.25 g·kg^-1）， with 12 mice in each group. Except for the blank group， all other groups were infected with RSV via intranasal instillation. The drug intervention groups were given corresponding doses of drug by gavage for 3 consecutive days， while normal saline was used in the blank and model groups. Hematoxylin-eosin（HE） staining was used to observe pathological changes in mouse lung tissue. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect viral loads［RSV-nucleoprotein（N） and RSV-glycoprotein（G） mRNA］ and inflammatory factor levels［interleukin（IL）-1β and tumor necrosis factor（TNF）-α mRNA］ in the lung tissue. Mouse bronchoalveolar lavage fluid was collected to detect the levels of pulmonary surfactant lipids through ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， followed by principal component analysis and differential lipid identification. ResultsCompared with the blank group， the model group exhibited extensive inflammatory cell infiltration， congestion， and tissue damage in the lungs， and the pathological score and lung index of lung tissue significantly increased（P<0.01）， along with significantly elevated mRNA expressions of RSV-N， RSV-G， IL-1β， and TNF-α（P<0.01）. Compared with the model group， different doses of Huzhang and ribavirin significantly reduced the pathological scores of the lung tissue and lung index（P<0.01）. In addition， the mRNA levels of RSV-N， RSV-G and TNF-α in the lungs significantly decreased in the Huzhang high dose group（P<0.01）. Lipidomics analysis identified multiple significantly changed differential metabolites. Compared with the blank group， the model group showed obvious abnormal lipid metabolism， which was manifested by the elevated levels of prostaglandin（PG）， ceramide（Cer）， phosphatidylcholine（PC）， phosphatidylethanolamine（PE）， phosphatidylinositol（PI）， sphingomyelin（SM）， and the decreased levels of diglycerides（DG） and acylethanolamine（NAE）. After the intervention of low dose of Huzhang， the above lipid metabolites showed a significant reversal trend， while the intervention of high dose of Huzhang could regulate levels of PI lipids， PG lipids and PC lipids. ConclusionHuzhang can significantly reduce the viral load of lung tissue and improve lung inflammation in RSV-infected mice. The underlying mechanism may be related to the maintenance of homeostasis in pulmonary surfactant lipids such as PI and PG.

ObjectiveTo investigate the efficacy and mechanism of Polygoni Cuspidati Rhizoma et Radix （Huzhang） in treating respiratory syncytial virus（RSV） infection by regulating pulmonary surfactant lipid homeostasis through lipidomics. MethodsSixty BALB/c mice were randomly divided into the blank group， model group， positive group（ribavirin group， 46 mg·kg^-1）， and low- and high-dose Huzhang groups（0.75， 2.25 g·kg^-1）， with 12 mice in each group. Except for the blank group， all other groups were infected with RSV via intranasal instillation. The drug intervention groups were given corresponding doses of drug by gavage for 3 consecutive days， while normal saline was used in the blank and model groups. Hematoxylin-eosin（HE） staining was used to observe pathological changes in mouse lung tissue. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect viral loads［RSV-nucleoprotein（N） and RSV-glycoprotein（G） mRNA］ and inflammatory factor levels［interleukin（IL）-1β and tumor necrosis factor（TNF）-α mRNA］ in the lung tissue. Mouse bronchoalveolar lavage fluid was collected to detect the levels of pulmonary surfactant lipids through ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， followed by principal component analysis and differential lipid identification. ResultsCompared with the blank group， the model group exhibited extensive inflammatory cell infiltration， congestion， and tissue damage in the lungs， and the pathological score and lung index of lung tissue significantly increased（P<0.01）， along with significantly elevated mRNA expressions of RSV-N， RSV-G， IL-1β， and TNF-α（P<0.01）. Compared with the model group， different doses of Huzhang and ribavirin significantly reduced the pathological scores of the lung tissue and lung index（P<0.01）. In addition， the mRNA levels of RSV-N， RSV-G and TNF-α in the lungs significantly decreased in the Huzhang high dose group（P<0.01）. Lipidomics analysis identified multiple significantly changed differential metabolites. Compared with the blank group， the model group showed obvious abnormal lipid metabolism， which was manifested by the elevated levels of prostaglandin（PG）， ceramide（Cer）， phosphatidylcholine（PC）， phosphatidylethanolamine（PE）， phosphatidylinositol（PI）， sphingomyelin（SM）， and the decreased levels of diglycerides（DG） and acylethanolamine（NAE）. After the intervention of low dose of Huzhang， the above lipid metabolites showed a significant reversal trend， while the intervention of high dose of Huzhang could regulate levels of PI lipids， PG lipids and PC lipids. ConclusionHuzhang can significantly reduce the viral load of lung tissue and improve lung inflammation in RSV-infected mice. The underlying mechanism may be related to the maintenance of homeostasis in pulmonary surfactant lipids such as PI and PG.

AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

Objective To analyze the diagnostic quality of imported malaria in Hubei Province from 2019 to 2022, and to further improve the diagnostic level and consolidate the achievements in eliminating malaria. Methods The samples of reported malaria cases in Hubei were collected by the provincial reference laboratory (PRL) from 2019 to 2022. The microscopy and fluorescent PCR were performed to confirm the infection of plasmodium species of each case．The positive coincidence rate and species coincidence rate were analyzed and compared． Results A total of 257 imported malaria cases were reported in Hubei Province from 2019 to 2022. Among 229 malaria cases were confirmed, the overall coincidence for malaria diagnosis was 91.24% (229/251), and the overall coincidence rate for parasite species identification was 86.03% (197/229). The difference in species coincidence rate among different years was statistically significant (χ²=10.458, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification in different cities (prefectures) of Hubei Province were 71.43% to 100.00% and 50.00% to 100.00%, respectively, with significant differences among different regions (χ²=29.283, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification were 72.73% to 100.00% and 0.00% to 100.00% in different diagnostic institutions, and the coincidence rate of species identification in hospitals (87.61%) was higher than that in Centers for Disease Control institutions (54.55%) (χ²=81.275, P<0.05). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale identification were 91.50%, 88.57%, 80.00%, and 58.06%, respectively (χ²=19.777, P<0.05). Conclusion The quality of the qualitative diagnosis of malaria cases reported online from 2019 to 2022 is generally high. However, the ability of Plasmodium typing needs to be improved. In the future, technical training and quality control should be strengthened to improve the malaria surveillance capability during the post-elimination stage.

Objective Reliability and validity of the Chinese version of disability attitude scales(DAS-CN)toward disabled persons were created and tested to provide an assessment instrument for measuring the attitude of medical staff toward disabled persons in China.Methods Authorised by the author of DAS in August 2020,based on BRISLIN translation model,the English version of DAS was translated into Chinese followed by back translation,cultural debugging and then put it into pre-experiment in September 2020.The reliability and validity of the finalised DAS-CN were further tested in a survey with 400 randomly selected medical staff in rehabilitation from 8 general hospitals in Jinzhou,Panjin,Yingkou and Fushun in Liaoning Province,China by using the convenience sampling method in March 2021.Results A total of 357 surveyees completed the survey.The localised DSA-CN was composed of 4 dimensions with a total of 20 items,including 4 items in clinical knowledge and skills,4 in clinical responsibility,8 in clinical behaviour and 4 in emotional response.The Cronbach α coefficient of the scales was 0.943,with the split-half reliability and test-retest reliability at 0.824 and 0.899,respectively.The Cronbach α coefficient of each dimension was 0.843～0.944,and the split half reliability was 0.854～0.904.The test-retest reliability ranged from 0.701 to 0.913.The KMO value of exploratory factor analysis was 0.921.The Bartrett spherical test value was 5534.981(P<0.01).The total explanatory rate of variation was 73.050%.Conclusion The Chinese version of Disability Attitude Scales(DSA-CN)has good reliability and validity.Therefore,DSA-CN can be used as an instrument in investigation of the current status about the attitudes towards the disabled persons among the medical staff in China.

Objective:To analyze the dietary patterns of Chinese adults and explore the relationship with serum uric acid (SUA) and hyperuricemia (HUA).Methods:A total of 9 358 adults were selected in the 2018 China Health and Nutrition Survey. Dietary intake data were collected by three consecutive 24-hour dietary recalls and weighing method. The social demographic information of the survey subjects was obtained through questionnaire surveys. The dietary patterns were extracted using factor analysis, and the relationship between dietary patterns and SUA was analyzed using multiple linear regression analysis. The correlation between HUA and dietary patterns was analyzed using logistic regression analysis models.Results:Four dietary patterns were identified: northern (high intakes of wheat, other cereals,and tubers); modern (high intakes of fruit, dairy, eggs, and nuts); southern (high intakes of rice and vegetables);animal food-wine (high intake of organ meats, seafood, and wine). The multiple linear regression analysis results showed that the northern pattern was negatively correlated with SUA ( β=-0.438, 95% CI: -0.500--0.376); the modern pattern was negatively correlated with SUA ( β=-0.134, 95% CI: -0.219--0.049); the southern model was significantly correlated with higher SUA ( β=0.146, 95% CI: 0.079-0.214); the animal food-wine pattern was positively correlated with SUA ( β=0.188, 95% CI: 0.123-0.252). Logistic regression analysis showed that compared with the northern model score Q1 group, the risk of developing HUA was reduced in Q3 and Q4 groups, with ORs values of 0.777 (95% CI: 0.650-0.929) and 0.509 (95% CI: 0.423-0.613), respectively; and compared with the modern model score Q1 group, the higher the scores in Q3 and Q4 groups, the HUA was lower, with ORs of 0.793 (95% CI: 0.660-0.953) and 0.768 (95% CI: 0.631-0.934), respectively. Compared with the animal food-wine pattern score Q1 group, the risk of developing HUA was increased in both Q3 and Q4 groups ( Q3 group: OR=1.224, 95% CI: 1.012-1.480; Q4 group: OR=1.312, 95% CI: 1.086-1.584). Conclusions:Dietary patterns are associated with HUA. The northern and modern patterns are related to lower SUA levels and reduced risk of HUA, while the animal food-wine pattern increases the risk of HUA.

The epidermal growth factor receptor(EGFR)gene is the most common driver gene in non-small cell lung cancer(NSCLC).The third generation tyrosine kinase inhibitor(TKIs)targeting EGFR mutations are the preferred first-line treatment choice for EGFR-mutated advanced NSCLC patients.Although third-generation EGFR-TKIs have provided durable survival benefits for patients,the emergence of drug resistance poses significant challenges for subsequent treatment.Currently,the mechanisms of resistance to the third-generation EGFR-TKIs and corresponding treatment strategies are under investigation.The resistance mechanisms to third-generation EGFR-TKIs can be classified into two types:EGFR-dependent and EGFR-independent.EGFR-dependent resistance mechanisms represent acquired EGFR mutations including C797S.EGFR-independent resistance mechanisms include activation of bypass signaling pathways,alterations in cell cycle-related genes,and phenotypic transformation.Researchers are exploring potential post-resistant treatment approaches such as fourth-generation EGFR-TKIs,combination therapy,chemotherapy,and immunotherapy to overcome these resistance mechanisms.Through in-depth study of resistance mechanisms and the exploration of novel treatment strategies,we hope to overcome the resistance to third-generation EGFR-TKIs,providing more treatment options and better clinical outcomes for EGFR-mutated advanced NSCLC patients.