BACKGROUND: Immune-related adverse events (irAEs) are commonly occurred in patients treated with immune checkpoint inhibitors. However, evidence of irAEs derived from the Chinese population is relatively lacking. The aim of this study was to investigate the incidence and outcomes of irAEs in Chinese patients with lung cancer after receiving immune checkpoint inhibitors (ICIs). METHODS: Clinical and follow-up data from lung cancer patients who received at least one time of ICIs from January 2018 to September 2021 at Huadong Hospital, Fudan University were included. Statistical descriptions and Kaplan-Meier method were used to analyze the overall incidence of irAEs, as well as the incidence and outcomes of each type of irAEs. RESULTS: 135 patients were included in the study. 106 patients (78.5%) presented at least one type of irAEs, and the median time to first irAEs onset was 28 d. Most irAEs occurred at early time after treatment, and most irAEs were mild-moderate and reversible. 57 patients (42.2%) died at the study cutoff. The mortality rate of severe irAEs was 12.6% (n=17), and among them 7 patients (41.2%) died of pneumonitis. The median progression-free survival (PFS) and overall survival (OS) time of the total population was 505 d (95%CI: 352-658) and 625 d (95%CI: 491-759), respectively. Patients who presented any irAEs achieved a longer PFS than those who did not (median PFS: 533 d vs 179 d, P=0.037, HR=0.57), while patients who presented skin toxicities achieved a longer OS than patients who did not (median OS: 797 d vs 469 d, P=0.006, HR=0.70). CONCLUSIONS In real-world settings, irAEs in lung cancer patients were commonly observed, with pneumonitis as the most common fatal irAEs. In addition, patients who presented any irAEs may tend to achieve a longer PFS.
Humans ; Lung Neoplasms ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Incidence ; Antineoplastic Agents, Immunological/therapeutic use* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Retrospective Studies

Objective:To investigate the value of combined detection of biomarkers in early diagnosis and prognosis of patients with septic myocardial injury.Methods:The clinical data of 103 patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology from October 2018 to January 2021 were enrolled. According to the cardiac troponin I (cTnI) at admission of ICU, they were divided into septic myocardial injury group (cTnI ≥ 0.15 μg/L) and non-septic myocardial injury group (cTnI < 0.15 μg/L). The serum levels of heart-type fatty acid-binding protein (H-FABP), procalcitonin (PCT), C-reactive protein (CRP), MB isoenzyme of creatine kinase (CK-MB), cTnI and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 6 hours after ICU admission and the worst value of acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours after ICU admission in 103 patients was recorded as well as the 28-day prognosis of patient with septic myocardial injury. Spearman correlation analysis was used to analyze the correlation of each index; receiver operating characteristic curve (ROC curve) was drawn, and the area under ROC curve (AUC) was calculated to analyze the early diagnosis and prognostic value of each index and APACHEⅡ score alone or combined detection in patients with septic myocardial injury.Results:① Among 103 patients with sepsis, 58 patients were complicated with myocardial injury and 45 patients were not complicated with myocardial injury. The serum levels of PCT, CRP, NT-proBNP, CK-MB, cTnI, H-FABP and APACHEⅡ score in patients with septic myocardial injury were significantly higher than those in patients without septic myocardial injury [PCT (μg/L): 3.46±1.35 vs. 1.89±0.43, CRP (mg/L): 81.1±26.8 vs. 65.3±19.1, NT-proBNP (U/L): 8 261.4±2 346.9 vs. 6 120.2±1 809.6, CK-MB (U/L): 15.89±6.25 vs. 12.14±4.24, cTnI (μg/L): 1.50 (0.91, 2.21) vs. 0.18 (0.16, 0.19), H-FABP (μg/L): 26.45±8.24 vs. 12.82±5.73, APACHEⅡ score: 24.0 (18.0, 29.0) vs. 16.0 (14.0, 18.0), all P < 0.01]. Spearman correlation analysis showed that PCT, CRP and APACHEⅡ scores were positively correlated with NT-proBNP, CK-MB, cTnI and H-FABP. ROC curve analysis showed that H-FABP in the diagnosis of septic myocardial injury (AUC = 0.916) was superior to NT-proBNP (AUC = 0.756) and CK-MB (AUC = 0.675); the AUC of NT-proBNP and CK-MB combined with H-FABP was 0.921, the sensitivity was 82.1%, and the specificity was 88.2%.② Twenty-three patients survived in 28 days, and 35 died. The levels of serum PCT, CRP, NT-proBNP, CK-MB, cTnI, H-FABP and APACHEⅡ score in death group were significantly higher than those in survival group [PCT (μg/L): 3.86±1.27 vs. 2.84±1.24, CRP (mg/L): 92.3 (65.0, 101.7) vs. 74.3 (65.7, 79.8), NT-proBNP (ng/L): 9 106.4±2 013.9 vs. 6 975.5±2 266.7, CK-MB (U/L): 17.90±6.49 vs. 12.82±4.46, cTnI (μg/L): 2.11±0.86 vs. 1.12±0.44, H-FABP (μg/L): 30.08±7.90 vs. 20.93±5.14, APACHEⅡ score: 25.0 (20.0, 30.0) vs. 19.0 (17.0, 24.0), all P < 0.01]. ROC curve analysis showed that H-FABP in evaluating 28-day death of patients with septic myocardial injury (AUC = 0.839) was superior to PCT (AUC = 0.707), CRP (AUC = 0.716), NT-proBNP (AUC = 0.761), CK-MB (AUC = 0.733), cTnI (AUC = 0.824) and APACHEⅡ score (AUC = 0.724); the AUC of NT-proBNP and cTnI combined with H-FABP was 0.888, the sensitivity was 91.4%, and the specificity was 82.6%. Conclusions:H-FABP plays an important role in the early diagnosis and prognosis of septic myocardial injury. Early combined detection of NT-proBNP, CK-MB and H-FABP can significantly improve the diagnostic ability of septic myocardial injury, and NT-proBNP and cTnI combined with H-FABP can significantly improve the ability to predict the adverse prognosis of sepsis myocardial injury.

Objective:To study the survival outcomes in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) treated with sorafenib combined with transcatheter arterial chemoembolization (TACE) versus sorafenib alone.Methods:The data of 92 patients with BCLC stage C HCC at Tianjin Medical University Cancer Institute& Hospital from January 2008 to December 2015 were retrospectively studied. There were 82 males and 10 females. The average age was 56.3 years. Classified according to whether there were vascular invasion and/or distant metastasis, patients were divided into the vascular invasion group ( n=24), the metastasis group ( n=48), and the vascular invasion combined with metastasis group ( n=20). All patients were treated with sorafenib, but some patients received combined treatment with TACE. The survival data of these patients on follow-up was collected. The Kaplan-Meier method was used for survival analysis, and the survival rates were compared by the log-rank test. Univariate and multivariate Cox analyses were used to determine the prognostic factors of patients’ survival. Results:There were no significant differences in the baseline clinical data among the three groups (all P>0.05). Multivariate Cox regression analysis showed that pre-treatment alpha fetal protein >20 μg/L ( HR=1.90, 95% CI: 1.13-3.12), alkaline phosphatase >125 U/L ( HR=1.60, 95% CI: 1.03-2.49) and sorafenib alone ( HR=2.11, 95% CI: 1.23-3.54) were independent risk factors of survival for these patients. There were no significant differences in the cumulative survival rates among the three groups ( P>0.05). In the vascular invasion group, the cumulative survival rates of patients treated with combined sorafenib and TACE ( n=4) were significantly higher than those treated with sorafenib alone ( n=20) ( P<0.05). Conclusion:Compared with sorafenib alone, sorafenib combined with TACE resulted in better prognosis for patients with BCLC stage C HCC. Subgroup analysis showed that patients with vascular invasion had significantly better survival treated with combined sorafenib and TACE than sorafenib alone.

Objective To analyze the main practices of capitation payment system reform in the case areas and put forward enlightenments and suggestions in this regard. Methods The implementation practices of the case areas were summarized, and descriptive statistical analysis was carried out on the implementation effects. Results By analyzing the effectiveness of the case areas′reform, it was found that the case areas are curbing the excessive growth of medical expenses (for example, outpatient fees per visit of Dingyuan county-level hospitals decreased from 245.11 yuan in 2015 to 218.40 yuan in 2017), increasing the actual compensation ratio of residents ( for example, the actual compensation ratio of Funan increased from 59.80% in 2015 to 63.28% in 2017), forming a medical treatment pattern within the county (for example, out-of-county compensation ratio in Dingyuan decreased from 37.38% in 2015 to 31.13% in 2017), achieving double-way referrals (for example, the number of referrals to superior hospitals of Jimo increased from 98 in 2015 to 328 in 2017), improving the subsidence of quality services, and controlling the risks of medical insurance funds. Conclusions At present, the reform of the case areas has been implemented steadily and achieved results. It is recommended to further improve such aspects as reform coordination, insurance standard setting, incentive mechanism establishment, and leadership to ensure the reform progress.

Pilot areas have achieved initial success in capitation reform. On the other hand, challenges remain unsolved in terms of practical pathways, change of national medical insurance management system, related measures, incentives and allocative mechanism for implement of the reform. With the concerning on progress, practice, effects and challenges of typical areas, this article established an institutional framework. On such basis, we propose to design and refine a scheme in terms of 5 aspects, namely strengthening the basic medical care packages′financing, setting contents and standard of the basic medical care packages rationally, establishing effective evaluation system and formulating supporting measures.

Objective To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). Methods A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. Results A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg·kg-1·h-1in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) μg·kg-1·h-1in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. Conclusions Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

Objective To investigate the level of nurses′preparedness and influencing factors of nurses with low seniority in Anhui province. Methods Totally 295 nurses with low seniority were recruited by convenience sampling method. They were investigated by a self-designed demographic data questionnaire and the Disaster Preparedness Evaluation Tool. Results The score of the disaster nursing ability of the nursing managers was 163.85 ± 32.41, the mean score was 3.64 ± 0.72. Regression analysis showed that the gender, the experience of disaster rescue,disaster training were the influencing factors of disaster preparedness. Conclusions The capacity of disaster preparedness for nurses is not ideal. There is still room for improvement among nurses in Anhui province to enhance disaster preparedness, and improved disaster nursing training system is needed to achieve this.

Objective To explore the clinical efficacy of knee osteoarthritis treated by abdominal acupuncture combined with sodium hyaluronate injected in intraarticular.Methods 120 patients with knee osteoarthritis were randomly divided into observation group and control group,60 patients in each group.The observation group was treated by abdominal acupuncture combined with sodium hyaluronate injected in intraarticular.The control group was treated with intraarticular injection of sodium hyaluronate alone.Results After a follow up of 6 months, the total effective rate of the treatment group was 95.00%,which was higher than 78.33% of the control group, the difference was statistically significant (x2=7.21,P<0.01).Conclusion Abdominal acupuncture combined with intraarticular injection of sodium hyaluronate is a good way to treat middle and old age patients with knee osteoarthritis.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Animals ; Bacillus ; Bacteria ; Chemokine CCL2 ; Flow Cytometry ; Injections, Intraperitoneal ; Interferon-gamma ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Lymph Nodes ; Mice* ; Mycobacterium bovis ; Mycobacterium* ; Pathology ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Background and objectivehTe prognosis for patients with lung cancer and brain metastases remains poor, with approximately 6 months of survival, despite active measures atfer treatment. In this study, we determined and ana-lyzed clinical parameters that affect the survival of patients with lung cancer and brain metastases to provide clinical guidance. MethodsLung cancer cases with brain metastases were retrospectively collected during 2002 and 2008 from Shanghai Chest Hospital, Shanghai Jiao Tong University.Kaplan-Meier method andCox regression were performed for univariate and multi-variate analyses, respectively, to explore independent predictors inlfuencing the survival of patients with lung cancer and brain metastases.Results Age, Eastern Cooperative Oncology Group performance status (ECOG PS), metastasis interval, number of metastasis, treatment method, treatment period, symptoms of brain metastases, extracranial metastasis, and brain metastasis order were factors that affect the survival of patients with brain metastases as conifrmed through theKaplan-Meiermethod. Treatment periods and extracranial metastasis were independent survival predictors in patients with lung cancer and brain me-tastasis as indicated byCox proportional hazard model.ConclusionTreatment periods and extracranial metastasis were inde-pendent predictors of survival of patients with lung cancer and brain metastasis. Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis.