Objective:To investigate the value of neutrophil lymphocyte ratio (NLR) and systemic immune inflammatory index (SII) for the diagnosis of coronary artery lesions in patients with acute phase of Kawasaki disease (KD).Methods:It was a cross-sectional study. Children with acute Kawasaki disease admitted to Linyi Central Hospital from January 2018 to December 2021 were enrolled and divided into the Kawasaki disease complicated with coronary artery disease group (KD-CAL group) and the Kawasaki disease without coronary artery disease group (KD-NCAL group). The demographic data, blood routine and C-reactive protein (CRP) test results before intravenous injection of γ globulin were collected, and NLR and SII were calculated. Multivariate logistic regression model was used to analyze the risk factors of coronary artery disease in children with Kawasaki disease. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of NLR and SII for coronary artery lesions in children with Kawasaki disease.Results:A total of 109 children with acute phase of KD aged 1 month to 9 years were enrolled, including 66 boys (60.6%). There were no significant differences in age and gender composition between the KD-CAL group ( n=17) and the KD-NCAL group ( n=92) (all P>0.05). Compared with the KD-NCAL group, the NLR, SII and CRP levels in the KD-CAL group were higher (all P<0.05). Multivariate logistic regression analysis showed that NLR and SII were independent risk factors of coronary artery disease in children with Kawasaki disease (NLR, OR=1.265, 95% CI:1.066-1.502, P=0.007; SII, OR=1.001, 95% CI:1.000-1.002, P=0.015). ROC curve results showed that thearea under the curve ( AUC) of NLR in diagnosis of coronary artery lesions was 0.812 (95% CI:0.703-0.921, P<0.05), taking 5.4 as cutoff value, the sensitivity was 73.9% and specificity was 76.5%; the AUC of SII in diagnosis of coronary artery lesions was 0.830 (95% CI:0.741-0.919, P<0.05), taking 1 623 as the cut-off value, the sensitivity was 66.3% and specificity was 88.2%; the AUC of the combination of NLR and SII was 0.875(95% CI:0.790-0.959, P<0.05), the sensitivity and specificity were 85.9% and 76.5%, respectively. Conclusion:NLR and SII have certain diagnostic value for coronary artery disease in children with acute Kawasaki disease, and the combination of NLR and SII has better value than single index.

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction pro-cesses,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tu-mors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

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*

Objective:Central nervous system leukemia(CNSL)is one of the main causes of recurrence and death in patients with acute leukemia.This study aims to dynamically monitor minimal residual disease(MRD)in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry(FCM),and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. Methods:A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed,and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients,and its role in assessing the prognostic value of patients was discussed. Results:Among the 199 acute leukemia cases,a total of 31 cases(15.58%)were positive MRD in the cerebrospinal fluid,of which 18 cases(58%)were detected earlier than the corresponding bone marrow specimens.Among the 19 patients with acute T lymphoblastic leukemia,134 patients with acute B lymphoblastic leukemia,and 46 patients with acute myeloid leukemia counted,there were 4,18,and 9 patients with positive MRD in the cerebrospinal fluid.The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156,demonstrating a low concordance between them. Conclusion:Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia,and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow,which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.

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

To explore the different chloroplast genome characteristics of Sinopodophyllum hexandrum, five chloroplast genome sequences of S. hexandrum were compared. Its genome map, repeat sequence, codon preference, inverted repeat (IR)/single-copy (SC) boundary, alignment of chloroplast genome sequences and phylogenetic were analyzed using bioinformatics tools. The results showed that: the total length of five chloroplast genomes of S. hexandrum, with a typical tetrad structure, were 157 203-157 940 bp, and a total of 133-137 genes were annotated, reflecting the diversity of chloroplast genomes of S. hexandrum. Different chloroplast genomes of S. hexandrum has different simple sequence repeat (SSR), where simple repeat of single nucleotide of A/T were the majority among the SSR detected. The interspersed repetitive sequences included direct, palindromic and inverted repeats. The value of effective number of codon (ENc) which was analyzed by using codon bias was 51.14~51.17, the proportion of GC and GC3s was less than 50%, the codon usage pattern tended towards frequently use of A/U-ending bases. Genome sequences and the IR/SC boundaries of five chloroplast genomes of S. hexandrum were relatively conservative. Phylogenetic analysis showed that S. hexandrum and Podophyllum pettatum had the closest genetic relationship. In summary, the chloroplast genome characteristics and evolutionary relationship of different chloroplast genomes of S. hexandrum were obtained, which may facilitate the utilization, protection, variety identification and genetic evolution of S. hexandrum resources.
Phylogeny ; Genome, Chloroplast ; Chloroplasts/genetics* ; Genomics ; Evolution, Molecular

Objective:To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.Methods:The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio ( PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed. Results:A total of 132 764 AE reports with denosumab as the primary suspected drug were collected, involving 5 571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114 617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32 863/114 617), death (14.2%, 16 230/114 617), osteonecrosis of the jaw (6.0%, 6 861/114 617), arthralgia (4.7%, 5 420/114 617), and limb pain (4.1%, 4 727/114 617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone ( PRR=402.7), malignant giant-cell tumour of bone ( PRR=325.2), C-telopeptide increase ( PRR=169.4), exostosis of jaw ( PRR=163.2), and ionised calcium abnormal ( PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41 757/114 617), musculoskeletal and connective tissue disorders (32.7%, 37 455/114 617), general disorders and administration site conditions (18.2%, 20 814/114 617), surgical and medical procedures (4.1%, 4 744/114 617), and investigations (2.9%, 3 290/114 617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity. Conclusions:Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.

Objective:To explore the risk of cholangitis induced by different immune checkpoint inhibitors (ICIs).Methods:Through the OpenVigil data platform, adverse event (AE) reports related to nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, ipilimumab, and tremelimumab from the first quarter of 2011 to the third quarter of 2021 in the US FDA Adverse Event Reporting System (FAERS) database were collected. Risk signal mining for cholangitis was performed using reported odds ratio ( ROR) method. The detection threshold of the risk signal was set as that the number of AE reports was greater than or equal to 3 and the lower limit of the 95% confidence interval ( CI) of the ROR was greater than 1. The higher the ROR and its 95 %CI lower limit, the stronger the signal intensity. The intensity of the risk signal of cholangitis due to different ICIs was compared and the main characteristics (sex, age, type of primary tumor, time of occurrence of AE, and outcome) of patients with ICIs-related cholangitis were analyzed descriptively. Results:A total of 52 440 AE reports related to the above 8 ICIs were collected, of which 410 cases were about cholangitis. The drugs that were detected with positive risk signals were nivolumab, pembrolizumab, atezolizumab, durvalumab monotherapy, and ipilimumab combined with nivolumab. Their number of AE reports were 213, 107, 48, 5, and 29 (402 patients in total), and the corresponding ROR (lower limit of 95 %CI) were 37.88 (32.89), 26.07 (21.46), 32.12 (24.10), 13.63 (5.65), and 14.46 (10.02), respectively. The risk signal intensity was nivolumab, atezolizumab, pembrolizumab, ipilimumab combined with nivolumab, and durvalumab in order. Seeing from the available data among the reports, males were more than females (233∶110=2.1∶1), 55.2% (222/402) of patients were 65 years old and over, and 48.0% (193/402) of patients were non-small cell lung cancer. ICIs-related cholangitis could result in hospitalization or prolongation of hospitalization in 42.3% (170/402), requiring emergency treatment in 40.0% (161/402), life-threatening in 2.0% (8/402), and death in 15.7% (63/402) of patients. Conclusions:The risk of cholangitis induced by ICIs is different and the risk signal of nivolumab is the strongest. Cholangitis is a serious AE of ICI, which should attract clinical attention.

Objective:To explore the risk of cholangitis induced by different immune checkpoint inhibitors (ICIs).Methods:Through the OpenVigil data platform, adverse event (AE) reports related to nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, ipilimumab, and tremelimumab from the first quarter of 2011 to the third quarter of 2021 in the US FDA Adverse Event Reporting System (FAERS) database were collected. Risk signal mining for cholangitis was performed using reported odds ratio ( ROR) method. The detection threshold of the risk signal was set as that the number of AE reports was greater than or equal to 3 and the lower limit of the 95% confidence interval ( CI) of the ROR was greater than 1. The higher the ROR and its 95 %CI lower limit, the stronger the signal intensity. The intensity of the risk signal of cholangitis due to different ICIs was compared and the main characteristics (sex, age, type of primary tumor, time of occurrence of AE, and outcome) of patients with ICIs-related cholangitis were analyzed descriptively. Results:A total of 52 440 AE reports related to the above 8 ICIs were collected, of which 410 cases were about cholangitis. The drugs that were detected with positive risk signals were nivolumab, pembrolizumab, atezolizumab, durvalumab monotherapy, and ipilimumab combined with nivolumab. Their number of AE reports were 213, 107, 48, 5, and 29 (402 patients in total), and the corresponding ROR (lower limit of 95 %CI) were 37.88 (32.89), 26.07 (21.46), 32.12 (24.10), 13.63 (5.65), and 14.46 (10.02), respectively. The risk signal intensity was nivolumab, atezolizumab, pembrolizumab, ipilimumab combined with nivolumab, and durvalumab in order. Seeing from the available data among the reports, males were more than females (233∶110=2.1∶1), 55.2% (222/402) of patients were 65 years old and over, and 48.0% (193/402) of patients were non-small cell lung cancer. ICIs-related cholangitis could result in hospitalization or prolongation of hospitalization in 42.3% (170/402), requiring emergency treatment in 40.0% (161/402), life-threatening in 2.0% (8/402), and death in 15.7% (63/402) of patients. Conclusions:The risk of cholangitis induced by ICIs is different and the risk signal of nivolumab is the strongest. Cholangitis is a serious AE of ICI, which should attract clinical attention.