Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

Clinically,polycystic liver disease(PLD)is a rare genetic disease.Most patients have no clinical symptoms,and a few patients with symptomatic PLD complicated by serious complications need to be treated.Liver transplantation is the only radical treatment for patients with symptomatic PLD.However,most patients are not able to receive liver transplantation due to a lack of donors,expensive surgical cost,and high risk.Because of its many advantages such as less trauma,fast recovery,repeatable,high safety and fewer complications,the minimally-invasive interventional techniques,represented by percutaneous cyst sclerotherapy and transcatheter arterial embolization,have been successfully employed for the treatment of symptomatic PLD in recent years,moreover,its clinical effect has been recognized by both doctors and patients.Therefore,as it can improve the local symptoms and the quality of life of patients,the therapy using minimally-invasive interventional technique will become the development direction for the treatment of symptomatic PLD.This article aims to make a comprehensive review concerning the principle,mechanism,guiding mode,clinical application,advantages and disadvantages,and related complications of percutaneous cyst sclerotherapy and transcatheter arterial embolization therapy in the treatment of symptomatic PLD.

Background Diurnal temperature range (DTR) is closely associated with cardiovascular health in the elderly, but there is a lack of research on the relationship between DTR and ischemic heart disease (IHD) in the elderly. Objective To investigate the effect of DTR on daily hospital admissions for IHD in people 65 years and older in Wuhan. Methods The study obtained data on elderly inpatients with IHD from all secondary and tertiary hospitals in Wuhan between January 1, 2017 and December 31, 2018, along with synchronous meteorological and air pollution data. Daily DTR was calculated as the difference between the maximum and minimum temperatures in a day. We employed distributed lag nonlinear models based on quasi-Poisson distribution to analyze the association between DTR and hospitalization risk in individuals aged 60 years and above. We assessed the extreme effects of DTR by selected DTR percentiles (the 1st percentile, P₁: 1.8 ℃; the 5th percentile, P₅: 2.9 ℃; the 95th percentile, P₉₅: 14.3 ℃; and the 99th percentile, P₉₉: 16.2 ℃) on hospitalization for IHD in the elderly population. Additionally, we conducted stratified analyses by gender, age (60-74 years and ≥75 years) and different subtypes (acute IHD and chronic IHD) to investigate the effects of DTR on hospitalizations for IHD across different genders, ages, and subtypes. Results This study included a total of 64212 first-time IHD hospitalizations among individuals aged 65 years and above in Wuhan from 2017 to 2018. The results showed a "J"-shaped exposure-response relationship between DTR and the cumulative risk of IHD hospitalization with a lag of 7 d; the optimal DTR was 5.0 ℃, and as DTR increased or the lag time lengthened, the risk of hospitalization for IHD in the elderly population increased. Extremely high DTR (P₉₉: 16.2 ℃) had a significant impact on the day of exposure (lag 0), with a cumulative RR of 1.58 (95%CI: 1.25, 1.99) at a lag of 7 d. The overall effects of DTR on IHD for different genders, ages, and subtypes of IHD exhibited similar patterns to the effects for overall population. High DTR had a significantly higher impact on hospitalization for chronic IHD (RR=1.46, 95%CI: 1.20, 1.79), compared to acute IHD (RR=1.29, 95%CI: 1.04, 1.61). At a cumulative lag of 7 d, elderly individuals aged 60-74 (RR=1.78, 95% CI: 1.30, 2.42) were more affected by high DTR in terms of IHD hospitalizations compared to those aged ≥75 (RR=1.35, 95% CI: 1.08, 1.70). Conclusion High DTR significantly increases the risk of hospitalization for IHD among elderly individuals. The effect of high DTR is particularly pronounced in patients with chronic IHD and elderly individuals aged 60–74 years.

Objective:To explore the differences in the spatial distributions of brain metastases (BMs) from adenocarcinoma and non-adenocarcinoma among non-small cell lung cancer (NSCLS), aiming to provide a reference for developing optimal treatment protocols.Methods:A retrospective analysis was performed on data from 283 patients with NSCLC who underwent radiotherapy at the Zhejiang Cancer Hospital from January 2020 to July 2023. These patients included 191 adenocarcinoma cases with an average age of 62.04 years and 92 non-adenocarcinoma cases with an average age of 63.85 years. CT images with detected BMs of these patients were synchronously deformed and registered into a standard brain template to determine the distribution of BMs in the template. The Dice coefficient was employed to analyze the similarity in the distribution of BMs from adenocarcinoma and non-adenocarcinoma, and two-sample t-test was performed respectively using SPM and Dpabi software to ensure the consistency of the result. For brain regions with the number of BMs greater than or equal to 4, the voxels with a size 2 mm × 2 mm × 2 mm were counted. Results:Non-adenocarcinoma tended to invade the posterior lobe of the cerebellum, precuneus, anterior lobe of the cerebellum, cuneus, middle occipital gyrus, and middle temporal gyrus, with corresponding voxel counts of 2 577, 2 291, 1 947, 1 550, 1 200, and 600, respectively. In contrast, adenocarcinoma was more commonly metastasized to the inferior parietal lobule, posterior lobe of the cerebellum, central frontal gyrus, precentral gyrus, middle temporal gyrus, and precuneus, with the corresponding voxel counts of 211, 201, 194, 186, 137, and 84, respectively.Conclusion:Brain metastases exhibit different distributions between adenocarcinoma and non-adenocarcinoma, and both subtypes prefer to invade specific brain regions.

Objective:To evaluate the accuracy of continuous photoplethysmography algorithms for atrial fibrillation diagnosis and atrial fibrillation burden evaluation via wearable devices.Methods:This study was a self-controlled prospective cohort study. A total of 254 consecutive inpatients were recruited from the Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University from September 2022 to November 2022. All participants were required to wear two devices at the same time: (1) an electrocardiogram (ECG) watch for acquisition of photoplethysmography (watch-recorded-photoplethysmography, W-PPG) and electrocardiogram (watch-recorded-electrocardiogram, W-ECG); (2) an ECG patch for acquisition of electrocardiogram (patch-recorded-electrocardiogram, P-ECG). The results were measured in 30 s data segments and individual participants, separately, which were calculated for sensitivity and specificity by comparing them with the results of expert-read ECG according to the receiver operating characteristic curve. Four groups were separated according to the proportion of the atrial fibrillation burden, and the difference of atrial fibrillation burden from algorithm and expert-read ECG was calculated.Results:All 254 subjects completed the study. The mean age of participants was (63.04±11.04) years old, 99 (38.98%) of them were female, and 97 (38.19%) patients had persistent atrial fibrillation. Expert-read ECG results were taken as standard criteria in all calculations. The P-ECG algorithm had a sensitivity of 94.86% (95% CI: 94.81%-94.91%) and a specificity of 99.30% (95% CI: 99.28%-99.31%) when measured in data segments. The W-PPG algorithm had a sensitivity of 96.07% (95% CI: 95.97%-96.18%) and a specificity of 98.62% (95% CI: 98.59%-98.65%). When measured in terms of individual participants, the P-ECG algorithm had a sensitivity of 92.55% (95% CI: 87.57%-95.71%) and a specificity of 96.39% (95% CI: 93.45%-98.09%), while the W-PPG algorithm had a sensitivity of 93.71% (95% CI: 88.75%-96.67%) and a specificity of 89.62% (95% CI: 85.61%-92.65%). When measured in terms of a single acquisition of W-ECG records, the W-ECG algorithm had a sensitivity of 92.04% (95% CI: 88.14%-94.78%) and a specificity of 96.19% (95% CI: 94.35%-97.47%). For atrial fibrillation burden assessment, the difference between the W-PPG analysis results and the expert-read ECG results was less than 2% in all burden distribution intervals. Conclusions:Continuous photoplethysmography algorithm applied to wearable devices to detect atrial fibrillation is a feasible strategy. Taking expert-read ECG results as standard, continuous monitoring of PPG by a smartwatch is highly accurate for atrial fibrillation diagnosis and can also be used to effectively complete atrial fibrillation burden assessment.

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.

Objective:To explore the clinical correlation and prognostic value of the Albumin-Bilirubin(ALBI)score in children with secondary hemophagocytic syndrome(sHLH).Methods:A retrospective analysis was conducted on the data of children's sHLH cases clearly diagnosed in the Affiliated Hospital of Zunyi Medical University from January 2012 to March 2023.Survival analysis was conducted according to the ALBI classification.Spearman correlation analysis was conducted between the ALBI score and clinical indicators.The Receiver Operating Characteristic(ROC)curve was used to evaluate the ALBI score,select the best cutoff value,and evaluate the accuracy of prognostic prediction value.Kaplan-Meier method was used to draw the survival curve.Log-rank method was used to compare the differences of survival curve between groups.Cox regression was used for prognostic analysis and restricted cubic spline curves used to calculate the relationship between ALBI scores and the risk of death in children with sHLH.Results:A total of 128 children with sHLH were included in this study,with a median age of 38(13.25,84)months.There were 70 males(54.69％)and 58 females(45.31％).The survival analysis results of ALBI grading showed that the survival rate of HLH patients with ALBI grade 3 was significantly lower than those with ALBI grades 1 and 2.Spearman correlation analysis results showed that ALBI score was positively correlated with splenomegaly,respiratory failure,disseminated intravascular coagulation(DIC),pulmonary hemorrhage,gastrointestinal hemorrhage,central nervous system involvement,ALT,AST,TG,LDH,PT,APTT,and SF(the correlation coefficients are:r=0.181,0.362,0.332,0.221,0.351,0.347,0.391,0.563,0.180,0.448,0.483,0.37,0.356),and was negatively correlated with HB,PLT,and FIB(the correlation coefficients are:r=-0.321,-0.316,-0.423),but was not significantly correlated with EBV infection,fungal infection,hepatomegaly,and ANC(P＞0.05).Using the ROC curve,the cutoff value of ALBI was-1.76.Single factor Cox regression analysis results showed that HB＜90 g/L,ALT ≥ 80 U/L,AST≥200 U/L,LDH ≥1 000 U/L,PT ≥20 s,APTT≥40 s,FIB＜1.5 g/L,ALBI ≥-1.76,combined pulmonary hemorrhage,DIC,central nervous system involvement,gastrointestinal bleeding,and not using blood purification may be the prognostic risk factors for children with sHLH(P＜0.05).Multivariate Cox regression results showed that FIB＜1.5 g/L(HR=2.119,95％CI:1.028-4.368),ALBI≥-1.76(HR=2.452,95％CI:1.233-4.875),and central nervous system involvement(HR=4.674,95％CI:2.486-8.789)were independent risk factors affecting prognosis,while blood purification(HR=0.306,95％CI:0.153-0.612)was an independent protective factor for prognosis.The application of restricted cubic splines shows that the risk of death increases with the increase of ALBI score.The area under the ROC curve(AUC)of the ALBI score for predicting the risk of 1-week,2-week,4-week,and overall mortality were 0.825,0.807,0.700,and 0.693,respectively,indicating good predictive performance for early mortality risk.According to subgroup analysis results of clinical manifestations,compared with the ALBI＜-1.76 group,ALBI≥-1.76 was associated with age ≤2 years,EBV infection,HLH-1994/2004 treatment,concomitant respiratory failure,and ANC≤1.0 × 109/L,HB＜90 g/L,PLT＜100 × 109/L,TG≥3.0 mmol/L,LDH ≥ 1 000 U/L,APTT≥40 s,and FIB＜1.5 g/L(P＜0.05).Conclusion:The ALBI score is related to the clinical characteristics and laboratory indicators of sHLH,and can be used as a beneficial indicator for assessing the prognostic risk of sHLH in children.It has good accuracy and clinical application value in predicting the prognosis of sHLH in children.

OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester-ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi-azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultra-high performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100 μmol·L-1).Kinetics analysis,involving half inhibitory concentra-tion(IC50),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con-stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC50 was 9.95 and 4.02 mol·L-1,respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55 μmol·L-1 for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*