Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Odontoma is a hamartoma or developmental malformation of dental tissues and often causes delayed or im-pacted permanent teeth.This paper reports a case of surgical removal of an odontoma that is closely attached to the labial bone plait and examines the extraction of accompanying high-impacted maxillary canine beside the nose and maxillary sinus.Digital technology was used in reconstructing a part of a patient's maxilla,odontoma,related teeth,and other adja-cent anatomical structures,accurately determine the lesion boundary,and design an optimal surgical plan.The minimally invasive extraction of lesions and embedded teeth with a double-fenestration technique through the upper and lower paths not only preserved the continuity of the labial alveolar bone plate in the operative area and prevented postoperative bone collapse but also reduced the risk of maxillary sinus mucosal injury and perforation,improved surgical efficiency,and reduced the surgical trauma.These features were in line with the concept of minimally invasive alveolar surgery.

Objective: To investigate the correlation of functional connectivity (FC) and the integrity of connective fibres between hippocampus and thalamus in Alzheimer′s disease(AD) and amnestic mild cognitive impairment (aMCI). Methods: Both resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data of 40 AD patients, 37 aMCI patients and 41 normal control subjects matching with age and educational level were collected. These subjects were all recruited from outpatient Department of Neurology in the Second Medical Center of Chinese PLA General Hospital, as well as poster, from May 2016 to January 2018. The FC strength between bilateral hippocampus and thalamus, as well as the parameters representing integrity of connective fibres, including fractional anisotropy (FA) and mean diffusivity(MD),were analyzed. Also, the correlations between FC strength and FA or MD strength were analyzed in the study. Results: Compared to that of normal control subjects, the FC strength between billateral hippocampus and thalamus in patients with AD, aMCI were not significantly different(P>0.05). The integrity of bilateral connective fibres between hippocampus and thalamus were damaged in AD patients when compared to normal control subjects(P<0.01). A positive correlation of connective fibres integrity with FC strength between hippocampus and thalamus was found in the left side(r=0.25,P<0.05) but rather in the right side. Conclusion In AD and aMCI patients, structural connectivity between left hippocampus and thalamus affects the functional connectivity between them.

Objective To explore the risk factors for lower extremity amputation in patients with diabetic foot.Methods The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed.The patients were divided into the non-amputation and amputation groups.Within the amputation group , subjects were further divided into the minor and major amputation subgroups.Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation.Results Among 1 771 patients with diabetic foot , 323 of them ( 18.24%) were in the amputation group ( major amputation: 41; minor amputation:282 ) and 1 448 ( 81.76%) in the non-amputation group.Compared with non-amputation patients, those in the amputation group had a longer hospital stay and higher estimated glomerular filtration rate(eGFR)levels.Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-reaction protein (CRP), ESR, ferritin, fibrinogen and WBC levels of the amputation group were higher , while hemoglobin albumin, transferrin, TC, TG, HDL-C and LDL-C were lower than those of the non-amputation group (all P<0.05 ).The proportion of hypertension ( 52.48% vs 59.98%) , peripheral vascular disease ( PAD ) (68.11% vs 25.04%), and coronary heart disease (21.33% vs 28.71%) were different between the amputation and non-amputation groups (all P<0.05).Multivariable logistic regression analyses showed that Wagner′s grade , PAD and CRP were the independent risk factors associated with lower extremity amputation in hospitalized patients with diabetic foot.Conclusion Wagner′s grade, ischemia of lower limbs and infection are closely associated with amputation of diabetic foot patients.

Objective To investigate the value of platelet, serum sodium and serum creatinine levels in the prognosis of patients with liver failure. Methods The clinical data of 155 patients with liver failure were retrospectively analyzed, and the patients were divided into improvement survival group (87 cases) and deterioration died group (68 cases) according to the prognosis. The hospitalization time of every patient was divided into 4 roughly equal time period, and observed at 5 points of time:T1-T5. The levels and abnormal rates of platelet, serum sodium and serum creatinine were compared. Results The T3 - T5 serum creatinine levels in deterioration died group were significantly higher than those in improvement survival group: (102.14 ± 75.67) μmol/L vs. (78.21 ± 26.68) μmol/L, (116.45 ± 110.64)μmol/L vs. (78.77 ± 29.25) μmol/L, (161.43 ± 153.23) μmol/L vs. (76.40 ± 27.26) μmol/L, and the T1 - T5 serum sodium and platelet levels were significantly lower than those in improvement survival group:(135.05 ± 6.24) mmol/L vs. (137.52 ± 5.26) mmol/L, (137.01 ± 4.99) mmol/L vs. (139.00 ± 3.89) mmol/L, (134.80 ± 16.74) mmol/L vs. (139.15 ± 3.77) mmol/L, (134.40 ± 11.69) mmol/L vs. (138.30 ± 8.75) mmol/L, (133.30 ± 8.93) mmol/L vs. (139.01 ± 9.10) mmol/L, and (122.46 ± 72.59) × 109/L vs. (149.70 ± 71.70) ×109/L, (110.18 ± 65.10) × 109/L vs. (152.09 ± 82.79) ×109/L, (107.32 ± 70.49) ×109/L vs. (169.32 ± 100.65) ×109/L, (97.06 ± 58.15) ×109/L vs. (183.57 ± 112.68) ×109/L, (94.66 ± 57.00) × 109/L vs. (191.36 ± 118.64) ×109/L, and there were statistical differences (P<0.05). The abnormal rates of T3-T5 serum creatinine, T2 - T5 serum sodium and T1 - T5 platelet in deterioration died group were significantly higher than those in improvement survival group, the serum creatinine: 22.06%(15/68) vs. 6.90% (6/87), 27.49% (19/68) vs. 8.05% (7/87) and 42.65% (29/68) vs. 10.34% (9/87), the serum sodium: 32.35% (22/68) vs. 13.79% (12/87), 39.71% (27/68) vs. 14.94% (13/87), 48.53% (33/68) vs. 12.64%(11/87) and 60.29%(41/68) vs. 11.49%(10/87), the platelet:45.59%(31/68) vs. 21.84%(19/87), 55.88% (38/68) vs. 24.14% (21/87), 54.41% (37/68) vs. 25.29% (22/87), 55.88% (38/68) vs. 21.84%(19/87) and 61.76% (42/68) vs. 20.69% (18/87), and there were statistical differences (P<0.05). Abnormal rate of platelet was highest in each time point. Conclusions In the course of pathological changes in deterioration and dead patients, the platelet is the first and most easily affected compare with serum sodium and serum creatinine; the platelet may be a sensitive marker for predicting clinical outcome in patients with liver failure.

BACKGROUNDBased on the excellent medical care and management system for Chinese veterans, as well as the detailed medical documentation available, we aim to construct a Chinese Veteran Clinical Research (CVCR) platform on non-communicable diseases (NCDs) and carry out studies of the primary disabling NCDs.

METHODSThe Geriatric Neurology Department of Chinese People's Liberation Army General Hospital and veterans' hospitals serve as the leading and participating units in the platform construction. The fundamental constituents of the platform are veteran communities. Stratified typical cluster sampling is adopted to recruit veteran communities. A cross-sectional study of mental, neurological, and substance use (MNS) disorders are performed in two stages using screening scale such as the Mini-Mental State Examination and Montreal cognitive assessment, followed by systematic neuropsychological assessments to make clinical diagnoses, evaluated disease awareness and care situation.

RESULTSA total of 9 676 among 277 veteran communities from 18 cities are recruited into this platform, yielding a response rate of 83.86%. 8 812 subjects complete the MNS subproject screening and total response rate is 91.70%. The average participant age is (82.01±4.61) years, 69.47% of veterans are 80 years or older. Most participants are male (94.01%), 83.36% of subjects have at least a junior high school degree. The overall health status of veterans is good and stable. The most common NCD are cardiovascular disorders (86.44%), urinary and genital diseases (73.14%), eye and ear problems (66.25%), endocrine (56.56%) and neuro-psychiatric disturbances (50.78%).

CONCLUSIONWe first construct a veterans' comprehensive clinical research platform for the study of NCDs that is primarily composed of highly educated Chinese males of advanced age and utilize this platform to complete a cross-sectional national investigation of MNS disorders among veterans. The good and stable health condition of the veterans could facilitate the long-term follow-up studies of NCDs and provide prospective data to the prevention and management of NCDs.

Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cross-Sectional Studies ; Disease ; Female ; Health Status ; Humans ; Male ; Veterans ; statistics & numerical data

Objective To study the functional connectivity (FC) pattern of thalamus in patients with Alzheimer' s disease (AD).Methods In the present study,resting state functional magnetic resonance imaging (MRI) data were obtained from 30 patients with AD and 26 subjects with normal cognition (NC).The altered functional connectivity pattern in AD was evaluated by comparing to NC.Then a correlation analysis was performed between the strength of FC of the identified regions and various clinical variables for evaluating the relationships between the strength of FC and the cognitive abilities (MMSE,immediate recall and delayed recall of Auditory Verbal Learning Test) of the AD patients.Results The MMSE(19.7 ± 4.1),immediate recall (2.8 ± 1.7) and delayed recall (0.7 ± 1.3) of Auditory Verbal Learning Test in AD patients were lower than NC group (28.8 ± 1.0,5.9 ± 1.2,5.7 ± 2.2 ; t =11.09,8.09,10.51,all P ＜0.05).Compared to NC,AD patients showed decreased FC between the left thalamus and several regions of brain including right posterior/middle cingulate cortex (PCC/MCC.R),left medial prefrontal cortex (MPFC.L) and right superior frontal gyms/medial prefrontal cortex (SFG/MPFC.R).For the right thalamus,decreased FC was found in SFG/MPFC.R,PCC/MCC.R and right hippocampus.We also found increased FC between the bilateral thalamus and many regions of brain including inferior temporal gyrus,medial temporal gyrus,SFG,postcentral gyrus,paracentral lobule,inferior frontal gyms and insula.Significant correlations between the fitted FC strength and clinical variables were also detected.Conclusions FC pattern of thalamus in AD group is impaired.Increased FC in AD may indicate the presence of a compensatory mechanism.The alteration is related with cognitive function in AD.

Objective To investigate the effects of spontaneous agonal respiration on coronary perfusion pressure (CPP) during untreated cardiac arrest (ventricular fibrillation) in swine model.Methods Ten male healthy domestic swines (25.0 ± 1.5) kg were anaesthetised,intubated and mechanically ventilated.The catheterizations were separately inserted into the right atrium and thoracic aorta to monitor aortic pressure (AOP) and right atrial pressure (RAP).A pacing electrode was inserted into the right ventricle to induce ventricular fibrillation (VF).VF was induced by intra-ventricular stimulation withalternating electric current and untreated for 8 minutes.AOP and RAP were recorded until respiratory activity ceased.The CPP before and after agonal respiration was calculated and analyzed by paired-sample T test.Results All animals presented with agonal respiration from 1 to 6 minutes after VF during the first attempt.The CPP was (7.18 ±4.22) mmHg at 1 sec before agonal respiration,(11.78 ±5.16) mmHg at 0 sec after agonal respiration,(8.75 t:4.38) mmHg at 5 sec after agonal respiration and (8.23 ± 4.55)mmHg at 6 sec after agonal respiration.The CPP at 0 sec after agonal respiration was higher than that before agonal respiration (t =-3.140,P =0.012).The CPP at 5 sec after agonal respiration was higher than that at 1 sec before agonal respiration (t =-2.828,P =0.020).There was no difference in CPP between at 6 sec after agonal respiration and at 1 sec before agonal respiration (t =-1.778,P =0.109).Conclusions Agonal respiration accompanies ventricular fibrillation.After agonal respiration,the coronary perfusion pressure is increased for 5 seconds being in favor of cardiaopulmonary resuscitation.

ObjectiveTo investigate the characteristics of spontaneous activities throughout the whole brain with Alzheimer's disease (AD) by resting state functional magnetic resonance imaging ( fMRI ).Methods The subjects included 23 AD patients and 21 normal controls (NC),who underwent a neuropsychological test battery including MMSE and Auditory Verbal Learning Test (AVLT) and restingstate fMRI using GE Signa 3.0 T MR scanner.The neuropsychological scores were compared between two groups.Regional homogeneity (ReHo) method was used to explore the different regional spontaneous activities throughout the brain between normal controls and patients with AD.Results In AD group,clinical variables (MMSE scores:20 ±4,AVLT-Immediate Recall:2.6 ± 1.6,AVLT-Delay Recall:0.4 ±0.7,AVLT-Recognition:5.8 ± 3.7 ) were lower than NC group( 29 ± 1,5.9 ± 1.2,5.5 ± 2.0,9.2 ± 1.1,T =10.58,7.21,10.99,3.96,all P ＜ 0.01 ).With the threshold of P ＜ 0.01 for each voxel and a cluster size of at least 100 voxels,decreased ReHo indexes were found in default mode network (DMN) including the medial prefrontal cortex,posterior cingulate gyrus/precuneus,right superior temporal gyrus and bilateral superior parietal lobule/inferior parietal lobule in AD,while increased ReHo indexes were found in left putamen and thalamus compared with controls.ConclusionThe DMN are damaged in AD and spontaneous activities of putamen and thalamus are reinforced as compensation response of subcortical structures.