Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

[Objective]To explore the role of estrogen and estrogen receptor (ER) in the pathogenesis and regulation of non-invasive fungal rhinosinusitis (NIFR).[Methods]Totally 60 patients with NIFS who met the inclusion criteria in Fuzhou Second General Hospital from November 2020 to November 2023 were selected as the NIFS group,while 30 healthy volunteers were recruited as the blank control group. Samples of each group were collected. The number of eosinophils and mast cells in each group were detected by HE staining;ER expression was detected by immunohistochemistry and immunofluorescence;mRNA expression levels of NF-κB,IKK and MASPIN were detected by qPCR;and protein expression levels of NF-κB,IKK and MASPIN were detected by immunohistochemistry and Western blot.[Results]In the NIFS group,the counts of eosinophils and mast cells were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01 and P<0.05,respectively). The Estrogen Receptor (ER) score in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.05). Additionally,the average high-density value in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.01). The expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01,P<0.05,and P<0.01,respectively). The mRNA expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased,respectively,compared with those in the control group (P<0.01). Furthermore,the protein expression levels of NF-κB,IKK,and MASPIN in the NIFS group were increased,respectively,and the inter-group differences are statistically significant (P<0.01,P<0.01,and P<0.05,respectively).[Conclusion]Our results show that the significant increase in the number of eosinophils and mast cells,and in the expression levels of ER,NF-κB,IKK and MASPIN may indicate a significant increase in eosinophil and mast cell infiltration in ER positive patients,and suggest the involvement of estrogen and its receptors in the pathogenesis of NIFS.

Objective To investigate the value of interleukin(IL)-6 and kidney injury molecule(Kim)-1 in the early prediction of contrast-induced pnephropathy(CIN)after percutaneous coronary intervention(PCI)in patients with coronary heart disease.Methods A total of 730 patients with coronary heart disease who underwent PCI were retrospectively collected,divided into CIN group(n=46)and non-CIN group(n=684),and the medical records of the two groups were compared,and the relationship between Kim-1 and IL-6 of renal injury and CIN was analyzed by binary regression,and the receiver operating characteristic(ROC)curve was used to explore the predictive value of these two markers on CIN after PCI for coronary heart disease.Results There was no significant difference between two groups in terms of preoperative IL-6(P=0.467)and Kim-1(P=0.643),and 48h and 72h after PCI,IL-6 and Kim-1 in CIN group was higher than that in non-CIN group(P＜0.001),and IL-6 and Kim-1 in CIN group was higher than that in before surgery(P＜0.001).48h postoperative IL-6(OR=1.884,P=0.002),48h postoperative Kim-1(OR=1.409,P＜0.001)and 72h postoperative IL-6(OR=1.377,P＜0.001)and 72 hours postoperative Kim-1(OR=1.092,P=0.004)were independent risk factors for CIN.The ROC curve showed that when used as a diagnostic marker for CIN,the area under the curve(AUC)of IL-6(48h),IL-6(72h)were 0.837,0.782,AUC of 48h Kim-1 and 72h Kim-1 were 0.820 and 0.827,respectively.Conclusion IL-6 and Kim-1 are independent risk factors for CIN after PCI for coronary heart disease.IL-6 and Kim-1 were positively correlated with the occurrence of CIN after PCI for coronary heart disease.IL-6 and Kim-1 have good diagnostic sensitivity and specificity for CIN after PCI for coronary heart disease.

Background: and Purpose The eye-movement examination can be applied as a noninvasive method to identify multiple-system atrophy (MSA). Few studies have investigated eye movements during the early stage of MSA with predominant parkinsonism (MSA-P). We aimed to determine the characteristic oculomotor changes in the early stage of MSA-P. Methods: We retrospectively selected 17 patients with MSA-P and 40 with Parkinson’s disease (PD) with disease durations of less than 2 years, and 40 age-matched healthy controls (HCs).Oculomotor performance in the horizontal direction was measured in detail using videonystagmography. Results: We found that the proportions of patients with MSA-P and PD exhibiting abnormal eye movements were 82.4% and 77.5%, respectively, which were significantly higher than that in the HCs (47.5%, p<0.05). Compared with HCs, patients with MSA-P presented significantly higher abnormal proportions of fixation and gaze-holding (17.6% vs. 0%), without-fixation (47.1% vs. 0%), prolonged latency in reflexive saccades (29.4% vs. 5.0%), memory-guided saccades (93.3% vs. 10.0%), and catch-up saccades in smooth-pursuit movement (SPM, 41.2% vs. 0) (all p<0.05). Compared with those with PD, patients with MSA-P presented a significantly higher proportion of catch-up saccades in SPM (41.2% vs. 2.5%, p<0.001). Conclusions MSA-P presented the characteristic of catch-up saccades in SPM in the early stage, which may provide some value in differentiating MSA-P from PD.

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Radiotherapy, Intensity-Modulated/methods* ; Retrospective Studies ; Lung Injury ; Radiotherapy Dosage ; Radiation Injuries/epidemiology* ; Esophagitis/epidemiology* ; Risk Factors ; Pulmonary Disease, Chronic Obstructive/complications*

Humans ; COVID-19 ; Quarantine ; Renal Dialysis ; SARS-CoV-2 ; Hospitals

Objective To investigate localized regional recurrence after chemotherapy and chest radiotherapy in limited stage small cell lung cancer (LS-SCLC),and explore the relationship between recurrence location and radiotherapy and chemotherapy and its influencing factors.Methods From 2006 to 2014,pathological LS-SCLC treated in CAMS,125 patients had local recurrence,Kaplan-Meier statistical method was used to analyze the survival rate and PFS of each recurrence site.Log-rank was used to compare the survival rate of each group.Univariate analysis includes Chi-squareand t-test for the factors for the recurrence site.Multivariate analysis using Logistic regression.Results The 1-,2-and 5-year overall survival rates were 92.0％,46.4％ and 14.7％,respectively.The median progression time was 12.96 months,The median survival time after progression was 1 1.5 months,and the 1-,2-,and 5-year overall survival rates were 45.0％,23.0％,and 10.0％,respectively.The recurrence sites include intrapulmonary recurrence (67 patients),regional lymph nodes (21 patients),simultaneous intrapulmonary and regional lymph nodes (28 patients),and contralateral or supraclavicular lymph nodes (9 patients).The median survival time were 23.96 months,24.76 months,23.23 months,and 18.66 months,and the 2-year survival rates were 49％,52％,46％,and1 1％,respectively (P=0.000,0.004,0.008).In 6 patients (4.0％),5 patients were located in the supraclavicular region,and 1 patient (0.8％) in the field.Conclusions For LS-SCLC undergoing IMRT and chemotherapy,the local failure location is mainly located in the pulmonary,and further treatment of the split dose and targets requires further clinical exploration.

Objective To compare the clinical efficacy and toxicity between nedaplatin-and cisplatin-based regimens in patients with unresectable locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy.Methods From January,2015 to December,2016,patients with unresectable locally advanced NSCLC receiving concurrent chemoradiotherapy were included in this study.Patients received thoracic radiotherapy (RT) combined with nedaplatin-based concurrent chemotherapy were enrolled in the nedaplatin group (n=38).Those treated with thoracic RT combined with cisplatin-based chemotherapy were allocated into the cisplatin group (n=84).The chemotherapy regime consisted of platinumin combination with paclitaxel or etoposide.Platinum combined with pemetrexed was adopted in patients with adenocarcinoma.Overall,the median age was 58 years old.Most of the patients were male (86.1％),77.0％ of them had a history of smoking and 63.9％ of the patients were pathologically diagnosed with squamous cell carcinoma.Besides,59.0％ of the patients had Ⅲ B NSCLC.Results In the nedaplatin and cisplatin groups,the overall response rate (ORR) was 79％ and 86％,and the disease control rate was 94％ and 94％.The median follow-up time was 20 months.In the nedaplatin group,the 1-and 2-year PFS was 49％ and 23％,and 67％ and 39％ in the cisplatin group (P=0.160).In the nedaplatin group,the 1-and 2-year OS was 91％ and 72％,and 89％ and 68％ in the cisplatin group (P=0.552).Nine patients (24％) had ≥grade 3 adverse events in the nedaplatin group and 25 patients (30％) in the cisplatin group (P=0.488).No statistical significance was found in radiation-induced esophagitis,bone marrow suppression and gastrointestinal toxicity between two groups.One patient in the nedaplatin group presented with grade 3 radiation-induced pneumonitis and 2 patients died of radiation-induced pneumonitis in the cisplatin group.Conclusions Thoracic radiotherapy combined with nedaplatin-based chemotherapy is a promising option for patients with unresectable locally NSCLC.Compared with the cisplatin-based chemotherapy,nedaplatin-based regime yields equivalent clinical efficacy and less adverse events,especially suitable for the elderly patients with poor tolerance.

Objective: To evaluate the effects of the intervention based on WeChat on blood pressure control in patients with essential hypertension. Methods: The databases of CNKI，Wanfang，VIP，PubMed and the Cochrane Library were researched for the literatures about effects of the intervention based on WeChat on blood pressure control in patients with essential hypertension published from 2011 to 2018. These papers were retrieved and evaluated according to inclusion and exclusion criteria. Stata 12.0 software was used for meta analysis. Results: Eleven out of 880 papers were included into meta analysis. There were 1 174 cases，with 587 cases in the experimental group and 587 cases in the control group. The results of the meta analysis showed that compared with traditional health intervention method，the intervention based on WeChat significantly reduced the level of systolic blood pressure（WMD=14.77，95%CI：11.76-17.77）and diastolic blood pressure（WMD=8.17，95%CI：5.67-10.67）of hypertensive patients. Subgroup analysis showed that the longer the intervention，the better the effects（P<0.05）. Conclusion The intervention based on WeChat is more helpful than traditional health intervention for blood pressure control of patients with essential hypertension.

Objective To observe the objective response rate, survival and safety of radiotherapy combined with Iressa for patients with locally advanced non-small cell lung cancer ( NSCLC) unsuitable for surgery or concurrent chemoradiotherapy. Methods The patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy were recruited and received thoracic intensity-modulated radiotherapy ( IMRT) combined with Iressa 250 mg daily. Results A total of 30 patients were enrolled between July 2014 and March 2017. Twenty-nine patients were analyzed. At 1 month after radiotherapy,the complete response (CR) was 0,partial response (PR) was 21(72％),stable disease (SD) was 6(21％), progressive disease (PD) was 2(7％),the disease control rate (CR+PR+SD) was 93％,and the objective response rate was 72％. The median follow-up time was 25 months. Fourteen ( 48％) patients died,and 15 (52％) survived. Twenty-three (79％) patients obtained PD including local progression in 18(62％) and distant metastasis in 14(48％). The median survival time (MST) was 26 months and the median PFS was 11 months. The 1-year OS and PFS were 79％ and 44％,and the 2-year OS and PFS were 55％ and 18％. Univariate analysis demonstrated that smoking history and disease stage were influencing factors for OS ( P=0. 035,0. 031) . Moreover, disease stage, the primary tumor diameter, the volume of GTV and PTV were influencing factors for PFS (P=0. 000,0. 016,0. 039,0. 030). Multivariable analysis revealed that disease stage and the volume of PTV were independent prognostic factors for PFS (P=0. 000,0. 012).Two patients ( 7％) developed grade 3 acute adverse events and 7 ( 24％) experienced grade 2 acute irradiation pneumonitis. Conclusions For patients with locally advanced NSCLC unsuitable for surgery or concurrent chemoradiotherapy,IMRT combined with Iressa yields high objective response rate and well tolerance. The long-term clinical efficacy remains to be validated.