OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

Objective The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were collected for the analysis of its mechanical characteristics,thus to establish a standardized operating procedure to guide clinical teaching of this technique.Methods Ten healthy male trainees(aged 20-30 years)from the Tuina Department of Guangdong Provincial of Chinese Medicine were selected as the subjects.A multi-point thin-film pressure testing system was used to collect mechanical parameters during the operation of Lin's squeezing-pressing adjustment manipulation.The mechanical characteristics were analyzed,and then a mathematical model of time-mechanics curve was constructed.Results(1)The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were as follows:preload force averaged(279.45±19.36)N with a duration of(0.98±0.03)s,the valley value of preload force averaged(137.45±3.59)N,the maximum impact force was(495.56±7.33)N,the impact duration averaged(0.15±0.01)s,the impact velocity averaged(3 183.96±94.76)N/s,and the impulse was(57.16±1.82)N/s.(2)The fitting function of impact force showed large absolute values for both ascending and descending slopes,and the ascending slope was significantly greater than the descending slope,indicating that the Lin's manipulation stressed on rapid outburst of the strength and withdrawal of the strength.(3)One-way ANOVA revealed no statistically significant differences in the preload force and its duration and valley value,the maximum impact force,and impact time among different operators(P＞0.05).Conclusion The analysis of kinetic parameters demonstrates that skilled operators maintain relatively stable mechanical parameters when performing Lin's squeezing-pressing adjustment manipulation.This study provides a preliminary digital analysis of the mechanical characteristics of Lin's bone-setting manipulation in addressing"bone misalignment and tendon displacement",which supplies objective evaluation criteria for the technique.

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

Objective To investigate the anti-fatigue effect of PTR-SeNPs in vivo by measuring the muscle relative length of hindlimb,load-bearing swimming time as well as serum and liver indexes of mice.Methods 48 male C57/BL6 mice were randomly assigned into 4 groups with 12 mice in each group,including vehicle control group(control group),swimming training exercise group(EC group)with vehicle treatment,swimming training exercise with low dose of PTR-SeNPs group(LPTR-SeNPs)and high dose of PTR-SeNPs group(HPTR-SeNPs).The mice were intragastrically administrated with normal saline in both control group and EC group,as well as 2.5 and 10 μmol/(kg·bw)PTR-SeNPs in LHPTR-SeNPs group,respectively,once per day for consecutively 21 days.After swimming training exercise,the muscle structures in the hind limb of mice were examined by magnetic resonance imaging.Furthermore,the burdened swimming time was measured,the serum content of blood lactic acid(BLA),urea nitrogen(BUN),alanine aminotransferase(ALT),glutamic oxalate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as the hepatic level of glycogen(HG),malondialdehyde(MDA)and activity of catalase(CAT)and superoxide dismutase(SOD)were determined.Results Compared with the control group,the serum contents of BLA,BUN,ALT,AST and LDH in EC group(P<0.05 or P<0.01)and hepatic CAT in HPTR-SeNPs group(P<0.01)were significantly increased.The muscle relative length of hind limbs and the burdened swimming time were extended by HPTR-SeNPs markedly(P<0.05).There was no significant difference in MDA level in LHPTR-SeNPs group.Compared with EC group,the burdened swimming time of mice was significantly prolonged(P<0.01),the contents of BLA and BUN were obviously decreased in the HPTR-SeNPs group(P<0.05 or P<0.01),the level of HG was significantly increased in the LHPTR-SeNPs groups(P<0.05 or P<0.01),the serum content of ALT,AST and LDH were markedly decreased in the HPTR-SeNPs group(P<0.05 or P<0.01).Hepatic SOD activity was remarkably increased in LPTR-SeNPs group(P<0.05),the level of CAT was evidently increased(P<0.01)and AST was decreased(P<0.05)in the HPTR-SeNPs group.Conclusion PTR-SeNPs could improve the liver physiological function,increase glycogen storage,reduce the accumulation of metabolites and enhance the body's antioxidant capacity to ameliorate fatigue significantly,which could present the potential to be developed into health care products or drugs.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective:To investigate the functional connectivity of default mode network (DMN) and limbic system, the expression level of inflammatory cytokine and their correlation in bipolar disorder type Ⅱ(BDⅡ) patients with depressive episodes.Methods:Thirty-three BD Ⅱ patients with depressive episodes and forty-six healthy controls were recruited to complete the resting-state functional magnetic resonance imaging (rs-fMRI). After image preprocessing, the DMN and limbic system were extracted from the image data by independent component analysis (ICA), so as to compare the differences of functional connectivity of resting brain network between the patients and the controls.Serum levels of inflammatory cytokines interleukin-6 (IL-6), interleukin-8(IL-8), interleukin-10(IL-10), tumor necrosis factor-α (TNF-α), and C-C motif chemokine ligand 4 (CCL4) in patients and healthy controls were detected.The correlation between functional connectivity of different brain regions and inflammatory cytokines was analyzed.SPSS 17.0 software was used for data statistical analysis.The two samples were compared using t-test or Mann-Whitney U-test, and Spearman was used for correlation testing. Results:In BDⅡ patients, the functional connectivity of the right medial prefrontal cortex(cluster-size=7 voxel, cluster-level PGRF<0.05, MNI: x=6, y=54, z=9, t=-3.765) and the left superior frontal gyrus(cluster-size=10 voxel, cluster-level PGRF<0.05, MNI: x=-21, y=54, z=15, t=-4.139) in DMN decreased, while the left cerebellum Ⅳ and Ⅴ lobules of limbic system (cluster-size=21 voxel, cluster-level PGRF<0.05, MNI: x=-15, y=-24, z=-30, t=4.468) and cerebellar tonsil of left cerebellum posterior lobe(cluster-size=8 voxel, cluster-level PGRF<0.05, MNI: x=-15, y=-51, z=-45, t=4.138) in the limbic system increased.Compared with the healthy controls, the serum levels of IL-10(7.39 (6.33, 9.32) pg/mL vs 6.54 (5.84, 7.39) pg/mL, Z=-2.937, P=0.003)and CCL4 (39.31 (25.77, 68.70) pg/mL vs 31.30 (20.32, 40.89) pg/mL, Z=-2.209, P=0.027) were higher in BDⅡ patients.The functional connectivity of the left cerebellum Ⅳ and Ⅴ lobules was positively correlated with the serum levels of IL-10 ( r=0.432, P=0.031) and that of the cerebellar tonsil of left cerebellum posterior lobe was positively correlated with the serum levels of IL-10 ( r=0.429, P=0.032) and CCL4 ( r=0.402, P=0.046). Conclusion:The functional connectivity of DMN and limbic system in BDⅡ patients with depressive episode is abnormal in resting-state fMRI.The expression level of inflammatory cytokines in patients' serum increases, and has correlation with the functional connection of limbic system.

Objective:To evaluate left atrial(LA) function and its value in predicting left ventricular(LV) remodeling in patients with coronary heart disease (CHD) by four dimensional automatic left atrial quantitation (4D Auto LAQ).Methods:A total of 176 patients with CHD were prospectively enrolled in Fuwai Central China Cardiovascular Hospital from October 2021 to September 2022. They were divided into two groups according to left ventricular mass index: LV remodeling group (female>95 g/m 2, male>115 g/m 2, n=88) and Non-LV remodeling group (female≤95 g/m 2, male≤115 g/m 2, n=88). The 3D dynamic image of LA was analyzed by 4D Auto LAQ on machine to obtain the LA parameters, including the minimum, maximum, pre-systolic and emptying volumes of LA (LAVmin, LAVmax, LAVpreA, LAEV), LA ejection fraction (LAEF), LA reservoir longitudinal and circumferential strains (LASr, LASr-c), LA conduit longitudinal and circumferential strains (LAScd, LAScd-c) and LA contraction longitudinal and circumferential strains (LASct, LASct-c). Logistic regression models were used to analyze the value of LA parameters in predicting LV remodeling in patients with CHD. ROC curve was used to evaluate LA parameters and left atrial volume index (LAVI) to predict the diagnostic efficiency of LV remodeling. Results:Compared with the Non-LV remodeling group, LAVmin, LAVmax, LAVpreA were significantly increased and LAEF, LASr, LAScd, LASct, LASr-c, LAScd-c, LASct-c were significantly decreased in the LV remodeling group ( P<0.05). Logistic regression model showed that LASct-c was an independent risk factor for LV remodeling in patients with CHD after adjustment( OR=2.018, 95% CI=1.214-3.355). ROC curve analysis showed that the area under the curve of LASct-c for predicting LV remodeling in CHD patients was 0.844, the sensitivity was 0.784, and the specificity was 0.761. Conclusions:4D Auto LAQ can effectively evaluate LA function in patients with CHD.LASct-c can be used as a reference index to predict LV remodeling in patients with CHD, which provides a new evaluation method in prognosis evaluation of CHD patients.

Objective:To analyze the left atrial (LA) function and predict the value of diastolic dysfunction (LVDD) in patients with heart failure (HF) by four-dimensional automatic left atrial quantitation (4D Auto LAQ) technology.Methods:A total of 90 patients with HF(LVDD group) and 30 healthy volunteers (control group)were enrolled from January 2021 to July 2021 in Fuwai Central China Cardiovascular Hospital. The patients with HF were divided into 3 groups according to the degree of LVDD: grade Ⅰ( n=30), grade Ⅱ( n=30), grade Ⅲ( n=30). Four-dimensional dynamic images of LA were collected by 4D Auto LAQ technology for on-machine analysis. LA volume and strain parameters were obtained, including LA maximum volume index (LAVImax), LA reservoir longitudinal and circumferential strains (LASr, LASr-c), LA conduit longitudinal and circumferential strains (LAScd, LAScd-c) and LA contraction longitudinal and circumferential strains (LASct, LASct-c). Pearson linear correlation was used to analyze the correlation between LA strain parameters and diastolic function parameters (LAVImax, E/A, E/e′) in HF patients. ROC curves were plotted to analyze the diagnostic performance of LA strain parameters and LAVImax for grade Ⅲ LVDD, the area under the curve (AUC) was calculated and pairwise comparisons were made. Results:①Compared with the control group, LAVmin, LAVpreA, LAScd, LASct, LAScd-c, and LASct-c were increased, and LASr, and LASr-c were decreased in the grade Ⅰ, Ⅱ, and Ⅲ LVDD groups (all P<0.05). LAVmin, LAVpreA, LAVmax, LAVImax, LAScd, LASct, LAScd-c and LASct-c were increased, and LASr and LASr-c were decreased in grade Ⅲ LVDD group compared with grade Ⅰ and Ⅱ LVDD groups (all P<0.05). ②Pearson correlation analysis showed that LASr, LASct, LASr-c and LASct-c were strongly correlated with diastolic function parameters (LAVImax, E/A, E/e′) (all P<0.01). ③ROC curve analysis showed that LASr-c had significantly better performance (AUC 0.868, sensitivity 96.7%, specificity 66.7%) than other parameters in the diagnosis of grade Ⅲ LVDD. Conclusions:4D Auto LAQ can effectively evaluate the LA volume and function in patients with HF. LASr-c is optimal in predicting grade Ⅲ LVDD, 4D Auto LAQ provides a new reference for evaluating diastolic function in patients with HF.

Objective:To explore whether the introduction of the O-PIRTAS (objective, preparation, instructive vedio, review, test, activity, summary) teaching model can help in curriculum learning and improve students' medical humanities literacy.Methods:Taking 118 sophomores of clinical medicine and nursing majors from Xiamen Medical College as control group, and 122 students as experimental group and as control group, the research lasting 8 weeks was carried out around five modules. The control group adopted the traditional teaching mode, while the experimental group used the O-PIRTAS model. After teaching, by comparing the exam results and issuing questionnaires, the teaching effects of the two methods on students' caring ability, empathy, emotional intelligence and supportive communication ability were compared. SPSS 22.0 was used for t test and chi-square test. Results:The average score of the experimental group [(83.61±2.13) points] was higher than that of the control group [(78.03±2.02) points], with significant differences ( t=3.60, P<0.001). As for the statistical analysis of the questionnaire, the students in experimental group scored higher in empathy, emotional intelligence and supportive communication skills than those in control group ( t=-3.20, P=0.002; t=-3.93, P<0.001; t=-4.00, P<0.001). Conclusion:Applying O-PIRTAS flipped classroom teaching model to medical humanities English courses helps to improve students' curriculum learning and medical humanities literacy, improve the effectiveness of the classroom and better play the educational role of the curriculum.