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 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 This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.

Nuclear receptors are transcriptional regulators involved in almost all biological processes such as cell growth, differentiation, apoptosis, substance metabolism and tumor formation, and they can be regulated by small molecules that bind to them. Autophagy is a special way of programmed cell death and it is a highly conserved metabolic process. Once autophagy defects or excessive autophagy occur, the disease will develop. In recent years, numerous studies have shown that nuclear receptors are related to autophagy. Therefore, this paper mainly reviews the research progress on nuclear receptors involved in the regulation of autophagy, and focuses on the mechanism of several nuclear receptors involved in the regulation of autophagy, aiming at understanding the molecular basis of how nuclear receptors participate in regulating autophagy, as well as providing possible ideas and strategies for the treatment of corresponding diseases.

Objective To investigate the temporal expression patterns of the related transcription factors and target genes in cardiomyocyte hypertrophy,and provide valuable clues for further researches on cardiomyocyte hypertrophy.Methods Isoproterenol (ISO) was used to induce ventricular myocytes hypertrophy in neonatal mice.The survival rate of cardiomyocyte was detected by CCK-8,and the average diameters and surface areas of cells were measured by computer photograph analysis system.The mRNA and protein expression levels of related genes were respectively measured by RT-PCR and Western blotting.Results The model of cardiomyocyte hypertrophy stimulated by ISO was constructed successfully.The expression levels of GATA4,MEF2C,GATA5,BNP and ANP increased 24 hours after ISO treatment,the expression levels of P300,α-MHC and TBX5 increased 12 hours after ISO treatment,and of SRF and β-MHC mRNA increased 6 hours after ISO treatment (P＜0.05).The expression levels of GATA4,α-MHC,β-MHC,SRF and P300 mRNA increased firstly,and then decreased in cardiomyocytes induced by ISO.The expression levels of GATA4,SRF,α-MHC,β-MHC and P300 mRNA were still higher than normal (P＜0.05),but of MEF2C decreased to normal (P＞0.0S) 72 hours after ISO treatment.The expression levels continuously elevated of GATA5,TBX5,ANP and BNP mRNA than that of controls (P＜0.05),while no fluctuation was found in NKX2.5 mRNA expression (P＞0.05).The expression of GATA4 protein increased,while of HEY2 protein decreased 48 hours after ISO treatment (P＜0.05).Conclusions In hypertrophic cardiomyocytes,the expression pattern of MEF2C is similar to,but the patterns of GATA5,GATA4,TBX5 and SRF are different with that in the development of heart,implying these genes are important during the process from compensatory stage to decompensation stage.The expression patterns of GATA4,MEF2C and SRF are similar to that of acetylase P300,implying the temporal expressions could be regulated by P300 in cardiomyocyte hypertrophy.

Objectives To explore the clinical characteristics and prognosis of different degrees of noncompaction of ventricular myocardium (NVM) in children and to investigate the clinical significance of the ratio of the thickness of the non-compact myocardium to the dense myocardium (N/C). Methods The clinical data of the children with NVM were analyzed retrospectively. The differences between children with N/C > 2.0 and children with N/C 1.4~2.0 were compared. Results There were 26 children in each of the two groups. There was no significant difference in age, sex, the ratios of low birth weight and malnutrition, heart disease, and complication (P all > 0.05). When discharged, 8 cases were improved, 15 cases has no obvious improvement, and 3 cases died in N/C>2.0 group; while 18 cases were improved, 8 cases has no obvious improvement, and none died in N/C 1.4~2.0 group, and the effective rate of treatment between two groups was statistically difference (χ2=7.69,P=0.006). In 8 years of follow-up, the mortality rate in N/C > 2.0 group was higher than that in N/C 1.4~2.0 group, and the difference was statistically different (χ2=6.993, P=0.008). Conclusions The treatment efficiency was lower and the prognosis was worse when the N/C value was higher in children with NVM.

Objective To explore the effect of SFI in radiation-induced mice brain injury after 20 Gy cranial radiation.Methods The mice were divided into three groups:(1) control group,(2) RT-only group:the whole brain was irradiated with a dose of 20 Gy,(3) RT and SFI group:SFI at 20 ml/kg/d from 4 weeks after 20 Gy cranial radiation theraty(CRT).Results Morris water maze test showed that the latency of the irradiated group was longer than control group and SFI improved the cognitive function of mice (t =6.34,6.70,P ＜0.05).The expression of TNF-α reached to the highest level at 3 h after irradiation,and then it decreased but got the second higher level again at 4 weeks after irradiation.The expression of IL-1 β reached to the highest level at 72 h after irradiation and decreased until 4 weeks after irradiation.SFI decreased both expressions of TNF-α (t =11.34,9.70,6.07,P ＜ 0.05) and IL-1 β (t =12.27,5.70,7.52,P ＜ 0.05).Immune florescence staining showed that SFI reduced the number of activated microglia (t =12.35,8.64,7.82,P ＜ 0.05)and inhibited the translocation of p65 of microglia after irradiation.Conclusions Findings suggest that SFI may decrease microglial activation and suppress the expression of TNF-α and IL-1β by inhibiting the translocation of NF-κB p65 and then attenuate irradiation-induced brain injury.

Objective To investigate the clinical pathological characteristics, diagnosis and treatment of breast rhabdomyosarcoma, and to enhance the awareness of malignancy infiltration to bone marrow (BM). Methods The data of one case of Rhabdomyosarcoma of breast were analyzed retrospectively. BM aspirate and biopsy, morphology, immunology, cytogenetics, molecular biology (MICM) in different parts of BM, peripheral blood smear, fine puncture of breast mass, final biopsy of breast mass by Mammotome System and whole body PET-CT were performed. The immunochemistry stain of specimen of breast mass was used. Results The peripheral blood smear of this patient showed immature erythrocytes, leucocytes and classification of unknown cells which were consistent with BM morphology. The results of BM aspirate and biopsy depicted a hypercellular specimen with disseminated unknown cells infiltration. Unknown cells were positive for CD56 and negative for any hematopoietic markers by flow cytometry. The whole body PET-CT showed that uptake of 18F-FDG of bilateral breast and whole BM was increased, whereas the mass of breast was not presented by CT. PET-CT suggested a probable malignant hematologic disease. The enough specimen of breast mass got from Mammotome System showed embryonal rhabdomyosarcoma, and the tumor cells were positive for MyoD1, Vimentin and Desmin. Conclusions It is a challenge for early diagnosis of solid sarcoma with unknown origin which diffusely infiltrating into BM. Negative expression of hematopoietic markers by flow cytometry plays a role on differential diagnosis in this setting, whereas PET-CT only provides a valuable reference. Enough specimen and immunohistochemical staining could provide solid evidences of diagnosis.

Objective To detect the effect of ox‐LDL on self‐renewal and Oct‐4 express of MSCs in vitro .Methods MSCs cul‐tured in vitro were divided into 4 groups :blank control(no reagents in culture system ) ,ox‐LDL (1 ,5 ,10 ,20 μg/mL ox‐LDL were added into culture system) ,ox‐LDL+NAC(corresponding ox‐LDL were added into culture system after NAC treatment ) ,negative control(corresponding nLDL were added into culture system ) .Growth curve were drawn at different time ,Oct‐4 ,a stem cell special marker ,were detected by real‐time PCR ,the production of ROS (reactive oxygen species ,ROS) in culture system were measured with electron paramagnetic resonance spectroscopy .Results proliferation of MSCs was inhibited by ox‐LDL ,when concentration of ox‐LDL was more than 5μg/mL ;apoptosis of MSCs appeared as well as attenuated expression of Bcl‐2 ,ox‐LDL generated a signifi‐cant amount of ROS in the culture system ,which was completely prevented by NAC .Conclusion The proliferation and Oct‐4 ex‐pression of MSCs were inhibited by ox‐LDL ,which may be related to increase of ROS in culture system .

Objective To evaluate the impact of low dietary glycemic index on the risk of coronaryheart disease (CHD).Methods We searched the Cochrane Database of Systematic Reviews,JBI Database of Systematic Reviews,MEDLINE,EMbase,CBMdisk,and CNKI to collect cohort studies from 2000 to 2011.The quality of cohort studies was critically appraised and data were extracted by 4 reviewers independently.Meta-analysis were conducted for the eligible cohort studies using RevMan 5.0.Results Five cohort studies were included,and 128 911 samples were researched.The result of meta analysis indicated that low dietary glycemic index was a protective factor of CHD,RR value was 1.25,95％ CI was (1.13,2.15).Further more,the result was only effective to female,RR value was 1.35,95％ CI was (1.16,1.57),but not to male,RR value was 0.96,95％CI was (0.76,1.31).Conclusions Low dietary glycemic index can decrease the risk of CHD,but it is still to be proved whether it is suitable to male.