Objective:To explore the efficacy of different second-line treatment strategies in the real world after progression of first-line immunotherapy and its combination therapies in patients with driver gene-negative advanced non-small cell lung cancer (NSCLC) .Methods:A retrospective analysis was conducted on the clinical data of 93 driver gene-negative advanced NSCLC patients who received first-line immunotherapy and its combination therapies from January 1, 2018 to December 31, 2023 at the First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital. Patients were categorized into immune checkpoint inhibitors (ICIs) -resistant ( n=43) and ICIs-responsive ( n=50) groups according to whether progression free survival (PFS) exceeded 6 months after first-line treatment. Patients were categorized into ICIs-treated ( n=55) and non-ICIs-treated ( n=38), anti-angiogenic-treated ( n=51) and non-anti-angiogenic-treated ( n=42) groups according to the different second-line treatment strategies after progression of first-line immunotherapy and its combination therapies. The median PFS2 (mPFS2) and median overall survival (mOS) 2 after second-line treatment of each group were compared. The Kaplan-Meier method was used for survival analysis. Results:The mPFS2 and mOS2 of 93 advanced NSCLC patients who progressed after first-line ICIs treatment were 4.9 months (95% CI: 4.1-5.7 months) and 14.7 months (95% CI: 11.2-18.2 months). The mPFS2 of patients in the first-line ICIs-responsive and ICIs-resistant groups were 6.0 and 3.8 months, respectively, with no statistically significant difference ( χ2=2.00, P=0.157), and the mOS2 were 25.3 and 11.3 months, respectively, with a statistically significant difference ( χ2=12.13, P<0.001). The mPFS2 of patients in the second-line ICIs-treated group and the non-ICIs-treated group were 5.2 and 4.6 months, respectively, with no statistically significant difference ( χ2=0.16, P=0.687). The mOS2 were 15.1 and 12.7 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.930). The mPFS2 of patients in the second-line anti-angiogenic-treated and non-anti-angiogenic-treated groups were 4.5 and 6.0 months, respectively, with no statistically significant difference ( χ2=0.41, P=0.525), the mOS2 were 14.7 and 16.8 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.943) . Conclusions:After progression of first-line ICIs therapy in patients with driver gene-negative advanced NSCLC, first-line ICIs-responsive patients have significantly longer OS after second-line treatment compared with ICIs-resistant patients. The efficacy of second-line therapy in patients after progression of first-line ICIs therapy does not show significant differences due to the type of treatment strategies.

Objective To rvaluate the therapeutic efficacy of balloon-dilatation covered stents in the treatment of renal artery stenosis(RAS).Methods The clinical data of 30 patients with RAS,who received intravascular ultrasonography(IVUS)-guided LifeStream balloon-dilatation covered stent implantation at the Affiliated Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)of China from August 2022 to December 2023,were retrospectively analyzed.The various parameters of the lumen and the stent were measured,and the performance of the stent was evaluated.Results The minimum original blood vessel diameter below the base of the stenotic segment plaque was 5.40(5.17,5.80)mm and the maximum blood vessel diameter was 6.20(5.80,6.93)mm,which became 6.00(5.80,6.00)mm and 7.90(6.00,8.00)mm respectively after stent release,the differences were statistically significant(both P＜0.05).Before stent release the luminal eccentricity index was(14.72±9.37)％,which was(1.54±9.16)％after stent release,the difference was statistically significant P＜0.05).The instant stent symmetry after stent release was(82.69±14.61)％,and the stent expansion factor was(99.81±10.70)％.Ideal narrow coverage rate was obtained.During operation,poor stent adhesion occurred in 2 patients and renal artery rupture with bleeding occurred in one patient,which were solved after immediate re-expansion treatment.Spearman's correlation analysis showed that stent symmetry,stent expansion factor,and stent eccentricity index did not linearly correlate with the lumen cross-sectional area stenosis rate and the plaque eccentricity index(all P＞0.05).Conclusion For the treatment of RAS,the LifeStream balloon-dilatation covered stent is clinically safe,feasible,and effective with satisfactory immediate clinical outcomes.

Objective:To develop a nomogram model for predicting the risk of ventilator-associated pneumonia (VAP) in patients with mechanical ventilation (MV) and to validate the stability of the prediction performance of the model.Methods:The patients with MV admitted to the Department of Critical Care Medicine of General Hospital of Ningxia Medical University from January 2019 to December 2022 were retrospectively selected according to the order of admission. The patients with MV were divided into the non-VAP group and the VAP group according to whether VAP occurred. The clinical data of the two groups, including general information, disease, medication, condition, and operation-related indicators were collected as candidate predictors of the model for comparison. Multivariate logistic stepwise forward regression analysis was used to screen the predictors that finally entered the model, and a nomogram model was constructed. The model discrimination was evaluated by the area under the receiver operating characteristic curve (AUC), the diagnostic test results of the model at the predicted threshold were calculated, the Hosmer-Lemeshow test was used to evaluate the model fit, and the Bootstrap resampling was used 1 000 times for internal validation, and model calibration and clinical applicability were evaluated by calibration curve and decision analysis curve, respectively.Results:A total of 1 250 patients with MV were included, including 1 102 patients in the non-VAP group and 148 patients in the VAP group, and the prevalence of VAP was 11.8%. The detection of multidrug-resistant organisms, chronic kidney disease, brain injury, oxygenation index, the place of tracheal intubation, reintubation, use of bronchoscopy, use of antibiotics, and MV duration were model predictors of VAP. The AUC of the nomogram model was 0.917 (95% CI: 0.895-0.939), the maximum Youden index of 0.697 corresponded to a prediction threshold of 0.096. The model accuracy, sensitivity and specificity were 0.836, 0.865, and 0.832, respectively. The positive predictive value and the negative predictive value were 0.409 and 0.979, respectively. The Hosmer- Lemeshow test indicated that the model fit well ( P=0.938). The results of the internal validation of the model showed that the predicted risk of the calibration curve was generally consistent with the actual risk, and the decision threshold probability of the decision analysis curve ranged from 2% to 90%. Conclusions:The nomogram model developed in this study is simple, convenient and has relatively stable prediction performance, which can be externally validated to evaluate the extrapolation of the model, and provide a basis for individualized clinical prediction of the risk of VAP in patients with MV.

Objective Sleep spindles play an important role in promoting cognition.This paper discusses the influencing factors of sleep spindles and provides objective evidence for clinical intervention and regulation of spindles to improve sleep and cognition.Methods Fifty patients with poor sleep quality were monitored overnight by sleep monitoring system,and physiological parameters of sleep structure,electroencephalography power spectrum,cardiovascular and respiratory function were obtained.The correlations between the parameters,age,sex and the spindle index and characteristics(frequency,duration and amplitude)of non rapid-eye-movement sleep(NREM)Ⅱphase were calculated.In Poincare diagram,SD1 represents the positive index of parasympathetic nerve activity,and SD2 represents the negative index of sympathetic nerve activity.Pulse transit time(PTT)decline index represents vascular sympathetic stability.Results SD1(β =-0.512,P＜0.05)and PTT decline index(β =-0.271,P＜0.05)were negatively correlated with spindle index respectively,while SD2 was positively correlated with spindle index(β =0.474,P＜0.05).The sleep change index,NREMⅠ phase proportion and cortical EEG microarousal index were negatively correlated with spindle index(r =-0.316,r =-0.359,r =-0.326;all P＜0.05).Age was negatively correlated with spindle index(β =-0.422,P＜0.05).δ power of deep sleep was negatively correlated with Spindle wave amplitude(β = 0.65,P＜0.001).No correlation was found between sex and sleep spindles.Conclusions The production of sleep spindles depends on good sleep and stable autonomic nerves.It is related to cognition and reflects the strength of synaptic connections,which provides evidence for clinical intervention and regulation of sleep spindles,and also provides a new physiological indicator for evaluating cognitive and brain function.

Objective Air pollution is a leading public health issue.This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai. Methods The study monitored 27 asthma outpatients for a year,collecting data on weather,patient self-management[daily asthma diary,peak expiratory flow(PEF)monitoring,medication usage],spirometry and serum markers.To explore the potential mechanisms of any effects,asthmatic mice induced by ovalbumin(OVA)were exposed to PM2.5. Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma.Acute exposure showed a correlation between PEF and levels of ozone(O3)and nitrogen dioxide(NO2).Chronic exposure indicated that interleukin-5(IL-5)and interleukin-13(IL-13)levels correlated with PM2.5 and PM10 concentrations.In asthmatic mouse models,exposure to PM2.5 increased cytokine levels and worsened lung function.Additionally,PM2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways. Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation.Specifically,PM2.5 significantly contributes to these adverse effects.Further research is needed to elucidate the mechanisms by which PM2.5 impacts asthma.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (M-EMR) for G1 rectal neuroendocrine tumors (RNETs) .Methods:Data of 121 patients with pathologically confirmed G1 RNETs treated with ESD ( n=105) or M-EMR ( n=16) in Nanjing Drum Tower Hospital from January 2017 to September 2020 were retrospectively analyzed. The complete resection rate, complication incidence, hospital stay, treatment cost and other indicators of the two groups were compared by using inverse probability of treatment weighting (IPTW). Results:There were significant differences in tumor number ( χ2=8.76, P=0.003), tumor invasion depth ( χ2=6.96, P=0.008), utilization of metal clips [82.9% (87/105) VS 93.8% (15/16), χ2=8.78, P=0.003], number of metal clips ( χ2=8.41, P=0.016), hemostasis using hot clamp [78.1% (82/105) VS 18.7% (3/16), χ2=20.64, P<0.001], traction procedure [2.9% (3/105) VS 18.7% (3/16), χ2=4.45, P=0.035] and treatment cost (17 568.6 ± 8 911.0 yuan VS 8 120.8±1 528.2 yuan, t=3.65, P<0.001) between the ESD group and the M-EMR group. After verifying the stability of the results using IPTW sensitivity analysis, there was still significant difference in the treatment cost ( t=2.07, P<0.001). Conclusion:Both ESD and M-EMR demonstrate comparable efficacy in treating G1 RNETs; however, M-EMR exhibites lower treatment costs.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To analyze the epidemiological characteristics and clinical features of pertussis cases reported in Shandong Province of China.Methods:Data on pertussis cases in Shandong Province from 2007 to 2022 were collected from China Information System for Disease Control and Prevention. At the same time, some case information was collected from the database of notifiable pertussis in Shandong Province from 2007 to 2022. The distribution characteristics and clinical features of pertussis were analyzed. A spatial distribution map of pertussis cases in Shandong Province was drawn.Results:A total of 26 122 pertussis cases were reported in Shandong Province during 2007-2022, with an annual incidence rate ranging from 0.11 to 5.77 cases per 100 000 people. Cases occurred throughout the whole year, with a seasonal peak occurring in spring and summer, especially in July and August. In recent years, reported cases were mainly distributed in the central and western regions of Shandong Province, with fewer cases in the eastern region. The hot spots of the disease shifted from Heze and Dezhou City in 2007-2013 to Jinan and Tai′an city in 2014-2022. The age range of onset was from 1 day to 93 years old. The proportion of cases with age≤1 year was the largest (41.81%, 10 922/26 122), and the proportion of cases aged 0-6 months decreased from 32.21% (67/208)-55.67% (157/282) within the period of 2007 to 2013 to 16.78% (883/5 263)-41.97% (444/1 058) within the period of 2014 to 2022, with a statistically significant trend ( χ2 trend=670.01, P<0.001). There were 13 682 male cases and 12 440 female cases, with a male-female ratio of 1.10∶1. The male-female ratio was 1.45∶1 (806∶556) from 2007 to 2013 and 1.08∶1 (12 876∶11 884) from 2014 to 2022. The proportion of women increased from 42.31% (88/208) in 2007 to 47.84% (2 518/5 263) in 2022, and with a significant trend ( χ2 trend=22.25, P<0.001). In pertussis cases, the proportions of scattered children, kindergarten children and students were 71.38% (18 645/26 122), 15.13% (3 951/26 122), and 11.60% (3 031/26 122), respectively. The top five clinical symptoms of pertussis cases were paroxysmal spasmodic cough (86.33%, 21 411 cases), flushing (39.61%, 9 824 cases), restless sleep (34.51%, 8 558 cases), fever (30.80%, 7 638 cases), and crowing (27.53%, 6 829 cases). Among 24 802 cases, there were 15 542 cases (62.66%) with a history of immunization against pertussis vaccine. Conclusion:From 2007 to 2022, the incidence rate of pertussis cases in Shandong Province shows an upward trend, with the majority being young children, and the clinical symptoms are relatively typical.

Objective To observe the value of intravascular ultrasound(IVUS)for assisting endovascular therapy for renal artery stenosis(RAS).Methods Thirty patients with RAS who underwent endovascular therapy were retrospectively analyzed.Parameters of renal artery and plaques in RAS segment measured with CT angiography(CTA)and IVUS before treatment were compared.Bland-Altman diagram was performed to evaluate the consistency of lumen cross-sectional stenosis rate and plaque eccentricity index between CTA and IVUS.The stent parameters measured with IVUS were recorded immediately after implantation of balloon-expandable covered stents.Results Before treatment,the minimum lumen diameter,lumen cross-sectional stenosis rate and stenotic segment length of IVUS were all larger,while maximum lumen diameter and lumen eccentricity index of IVUS were both smaller than those of CTA(all P＜0.05).No significant difference of plaque eccentricity index,plaque type nor stenosis distal remodeling was found between CTA and IVUS(all P＞0.05).The average difference between IVUS and CTA for evaluating lumen cross-sectional stenosis rate and plaque eccentricity index was-0.020(-0.096,0.050)and-0.020(-0.130,0.091),respectively.The consistency of IVUS and CTA for evaluating plaque eccentricity index was better than that of lumen cross-sectional stenosis rate.The stent symmetry,stent eccentricity index,stent expansion coefficient and stenosis coverage rate immediately after implantation measured with IVUS was(82.69±14.61)%,(1.54±9.16)%,(99.81±10.70)%and 100%,respectively.Among 30 cases,2 cases(2/30,6.67%)underwent postdilation since poor stent apposition.Conclusion IVUS could assist evaluating lumen and plaque parameters of stenotic renal arteries,guiding stent release and real-timely monitoring the effect of endovascular therapy.