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

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Objective:To analyze the genetic evolution characteristics of hemagglutinin (HA) and neuraminidase (NA) of influenza B virus in Tongling during 2019-2022 surveillance years.Methods:Twenty-two strains of Victoria influenza B virus isolated from our laboratory during 2019-2022 were selected for whole genome sequencing. The sequence comparison and phylogenetic analysis were conducted by using bioinformatic analysis software.Results:During 2019-2022, seasonal influenza in Tongling City was predominantly caused by influenza B Victoria lineage viruses, which fell within the V1A.3 branch. Among these, 14 strains isolated in the 2021-2022 season were further classified into the V1A.3a.2 sub-branch. Compared with vaccine strains, multiple amino acid mutation sites were detected in both HA and NA proteins of the 22 influenza B Victoria lineage viruses. Notably, all four major antigenic sites (120-loop, 150-loop, 160-helix, and 190-helix regions) in the HA protein exhibited variations. Although no mutations were detected at resistance sites on the NA protein, a change occurred in the glycosylation site at position 197 NETQ in the HA protein.Conclusions:The main amino acid sites of the HA protein of the influenza B Victoria lineage viruses in Tongling City from 2019 to 2022 have undergone significant variation, which may lead to antigenic drift. Therefore, it is essential to strengthen the monitoring of influenza virus mutations.

Objective To analyze the influence of different processing methods,including frying,ginger frying,and salt frying,on the volatile components of A.fructus.Methods The volatile components in different processed products of A.fructus were detected and analyzed by gas chromatography-mass spectrometry(GC-MS)based on multivariate statistical analysis.After OPLS-DA analysis,the different components were screened under the conditions of VIP＞1.5 and P＜0.05 and were qualitatively searched using the NIST 11 spectral library.Results A total of 49 different components were identified,with 14 components only changing in the seed mass and 22 components changing in the peel.The content of camphor could be significantly reduced in the seed mass after A.fructus was processed and the content of bornyl acetate significantly increased in the peel of frying A.fructus.Salt frying had a great influence on the alkanes in A.fructus,and ginger processing did not only increase the volatile components in ginger,which reflected the complexity of the processing mechanism.Conclusion At present,the specific processing mechanism is not clear,but the experimental results provide theoretical data for the "detoxification and efficiency enhancement" effect of A.fructus processing,reflecting the scientific nature of the processing,enriching the processing theory of A.fructus,and providing a reference for further in-depth research on the activity of different processed products of A.fructus.

Objective To analyze the effect of Mortality and Morbidity Conferences(MMC)in the prevention and treatment of hospital-related venous thromboembolism(VTE),and to provide a reference forthe implementation of prevention and treatment measures of VTE in hospitals.Methods Two MMC implemented in August-September 2023 at a tertiary genera l hospita l in Beijing were selected,and rainstorming and root cause analysis were used to profile two cases selected at the meetings that were highly suspected to have died from acute pulmonary embolism.Results Insufficient awareness of VTE,insufficient sensitivity to the diagnosis of VTE,inadequate management of adverse events and failure to establish a VTE risk assessment process are the root causes of hospital-related VTE events.Conclusion Hospitals should establish a management organisational structure for the prevention and treatment of VTE,carry out VTE training on a regular basis,set up a VTE information system,define a standardised VTE risk assessment process,and enhance the sensitivity of the medical staff to the patient's abnormalities.

Objective:To investigate the diagnostic value of nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry（MALDI-TOF MS）in sputum smear-negative patients with nontuberculous Mycobacterial（NTM）pulmonary disease.Methods:Clinical data of 123 patients suspected of NTM pulmonary disease admitted in Public Health Clinical Center Affiliated to Shandong University between July 2022 and November 2023 were retrospectively analyzed. Bronchoalveolar lavage fluid（BALF）specimens were collected for MALDI-TOF MS assay and MGIT 960 culture. The diagnostic efficacy of MALDI-TOF MS for NTM pulmonary disease in patients with negative sputum smears for acid-fast bacilli was evaluated with receiver operating characteristic（ROC）curve. Statistical analysis was performed using SPSS 26.0 software and MedCalc statistical software.Results:Diagnosis of NTM pulmonary disease was finally confirmed in 66 out of the 123 suspected patients. It took 8 to 24 h for MALDI-TOF MS to identify NTM species and resistance. By MALDI-TOF MS，72 NTM strains were identified，with the Mycobacterium avium complex being the most prevalent（34 strains，47.22%），followed by the Mycobacterium abscessus complex（13 strains，18.06%）；resistance to macrolides was detected in 6 cases，while no resistance to aminoglycosides was found. It took 9 to 45 days for BALF MGIT 960 culture to identify NTM，and took 7 to 15 days for NTM typing and drug sensitivity testing. By BALF MGIT 960 culture，28 NTM strains were identified；and 1 case was found to be resistant to macrolides. Using confirmed diagnosis as the gold standard，MALDI-TOF MS demonstrated higher sensitivity，negative predictive value，and agreement rate compared to MGIT 960 culture（84.85% vs. 42.42%，81.13% vs. 56.32%，80.49% vs. 62.60%， χ2=25.667，8.998，9.664， P<0.05 or <0.01）. The area under ROC curve（AUC）for MALDI-TOF MS was significantly higher than that of MGIT 960 culture（0.801 vs. 0.642， Z=3.300， P=0.001）. Conclusion:Compared to MGIT 960 culture，MALDI-TOF MS exhibits superior diagnostic efficiency in detecting NTM pulmonary disease in patients with acid-fast bacilli smear-negative sputum，with advantage of rapidly identifying NTM species and resistance.

Objective To analyze the effect of Mortality and Morbidity Conferences(MMC)in the prevention and treatment of hospital-related venous thromboembolism(VTE),and to provide a reference forthe implementation of prevention and treatment measures of VTE in hospitals.Methods Two MMC implemented in August-September 2023 at a tertiary genera l hospita l in Beijing were selected,and rainstorming and root cause analysis were used to profile two cases selected at the meetings that were highly suspected to have died from acute pulmonary embolism.Results Insufficient awareness of VTE,insufficient sensitivity to the diagnosis of VTE,inadequate management of adverse events and failure to establish a VTE risk assessment process are the root causes of hospital-related VTE events.Conclusion Hospitals should establish a management organisational structure for the prevention and treatment of VTE,carry out VTE training on a regular basis,set up a VTE information system,define a standardised VTE risk assessment process,and enhance the sensitivity of the medical staff to the patient's abnormalities.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Objective To analyze the effect of Mortality and Morbidity Conferences(MMC)in the prevention and treatment of hospital-related venous thromboembolism(VTE),and to provide a reference forthe implementation of prevention and treatment measures of VTE in hospitals.Methods Two MMC implemented in August-September 2023 at a tertiary genera l hospita l in Beijing were selected,and rainstorming and root cause analysis were used to profile two cases selected at the meetings that were highly suspected to have died from acute pulmonary embolism.Results Insufficient awareness of VTE,insufficient sensitivity to the diagnosis of VTE,inadequate management of adverse events and failure to establish a VTE risk assessment process are the root causes of hospital-related VTE events.Conclusion Hospitals should establish a management organisational structure for the prevention and treatment of VTE,carry out VTE training on a regular basis,set up a VTE information system,define a standardised VTE risk assessment process,and enhance the sensitivity of the medical staff to the patient's abnormalities.