Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Objective:To explore the short-term efficacy and safety of intra-arterial thrombolysis (IAT) in the treatment of retinal artery occlusion (RAO) with the assistance of the rescue green channel in the eye stroke center.Methods:A prospective, interventional, single-center study. Thirty-eight eyes from 38 RAO patients who received IAT treatment in Guangdong Provincial People’s Hospital were enrolled. All the patients were rescued via the green channel in our eye stroke center. Data from comprehensive ocular examinations including best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) were collected. BCVA was measured with Snellen chart and converted to the logarithmic minimum angle of resolution (logMAR) unit for statistical analysis. RTVue XR OCTA was used to measure vascular densities (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC), and central retinal thickness (CRT). All RAO eyes attempted IAT treatment and 34 eyes were successful. Four eyes failed to complete IAT because of the occlusion of internal or common carotid arteries on the same side with the RAO eyes. Ocular examinations in post-operative 1-3 days were performed with the same devices and methods as those before surgery. Parameters measured before and after surgery include BCVA, VD of SCP, DCP, RPC, and CRT. Data of the green channel collected include the time intervals from onset of RAO to first presentation in local hospitals, and from onset of RAO to our eye stroke center. Comparisons of VD and CRT between the RAO eyes and contralateral healthy eyes were performed with independent samples Mann-Whitney U test; comparisons of VD and CRT in RAO eyes before and after IAT surgery were performed with paired samples Wilcoxon Rank Sum test. Results:Among the 34 RAO patients who had successful IAT surgery, 18 (52.9%, 18/34) were males and 16 (47.1%, 16/34) were females; the mean age was (51.0±12.9) years old. There were 30 and 4 eyes diagnosed as central RAO and branch RAO respectively. The logMAR BCVA before and after IAT surgery was 2.52±0.61 and 2.18±0.85 respectively, and the difference was statistically significant ( Z=-3.453, P=0.002). Before surgery, VD of SCP, DCP and RPC were significantly decreased and CRT was significantly increased in the affected eye compared with the contralateral healthy eyes, with the statistical significance ( P<0.001). Compared with those before surgery, the VD of SCP and DCP were significantly improved after surgery ( Z=-2.523, -2.427; P=0.010, 0.014), while there was no difference in VD of RPC and CRT ( Z=-1.448, -1.454; P=0.150, 0.159). The time interval between onset of RAO and first visit to the hospital was (6.56±6.73) hours; the time interval between onset of RAO and the arrival at our hospital was (24.11±19.90) hours. No cerebral stroke was observed in the early postoperative period and no cerebrocardiovascular events were observed later. he time interval between onset of RAO and the arrival at our hospital was (24.11±19.90) hours. No cerebral stroke was observed in the early postoperative period and no cerebrocardiovascular events were observed later. Conclusions:The short-term efficacy and safety of IAT in the treatment of RAO were satisfactory. The rescue time window might be prolonged.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To summarize the experience and effect of mitral valvuloplasty in the treatment of mitral valve disease in infants.Methods:The clinical data of 140 infants with mitral valve disease from June 2010 to June 2020 were retrospectively analyzed. There were 62 males and 78 females, with body weight of(6.4±1.4)kg and age of(196.6±80.1)days. Among them, 131 cases were moderately or above mitral insufficiency, and 9 cases were mitral stenosis. The perioperative and follow-up clinical data were recorded, and the therapeutic effect and prognostic factors of mitral valve plastic surgery were analyzed.Results:All 140 children were received surgery of mitral valve repair under cardiopulmonary bypass. Cardiopulmonary bypass time was(79.1±41.9)min, aortic cross clamp time was(46.8±20.0)min, 7(5%)early death. Mechanical ventilation time was(74.2±149.8)h. After surgery, mild mitral regurgitation was found in 48 cases, mild-moderate regurgitation in 53 cases, moderate regurgitation in 32 cases, moderate-severe regurgitation in 6 cases, severe regurgitation in 1 case, with no mitral stenosis. During the follow-up period of 6-126 months, 3 cases died in the long term, and 11 cases were reoperated. Freedom from >moderate mitral regurgitation at 5 years after surgery was 81.2%. Longer cardiopulmonary bypass time and postoperative mitral regurgitation were risk factors for death and moderate or above regurgitation at the follow-up.Conclusion:Mitral valvuloplasty can effectively treat the mitral regurgitation and stenosis in infants. The prognosis of children with short cardiopulmonary bypass time and good valve plastic effect is better. For infants with Carpentier type I, good shaping effect can be achieved by mitral annuloplasty alone, while for type Ⅱ and type Ⅲ, treatment should be tailored to deal with the problems at all levels of the valve, and additional annuloplasty should be performed.

Objective:To summarize single-center experience and short-term outcomes of surgical treatment of pediatric cardiac fibromas.Methods:There was a retrospective study of 10 patients who underwent surgical treatment of cardiac fibromas between January 2018 and October 2021. Fibromas were located in the left ventricle in 7 cases, and in the right ventricle in 3 cases. Mean tumor diameter was(5.6±2.0) cm.Results:Median age at surgery was 3.1 years old(5 months-9 years old). Nine patients received complete resection, and the other one received partial resection. One patient with giant left ventricular fibroma required extracorporeal membrane oxygenation support for ventricular fibrillation after weaning from cardiopulmonary bypass, and was successfully weaned on the third postoperative day. There was no early mortality. Median follow-up time was 6 months(1 month-3 years). No tumor recurrence nor ventricular arrhythmia was documented during the follow-up period.Conclusion:Pediatric cardiac fibromas can be usually treated by complete resection, with relief of cardiac dysfunction and ventricular arrythmia after surgery, and with satisfactory results.

Objective:To analyze the intellectual property risk of international cooperative scientific research involving human genetic resources, explore possible risk control measures regarding to intellectual property.Methods:By means of literature review, this paper analyzes the special attributes and strategic position of human genetic resources, reviews the policies and systems involving human genetic resources in international cooperative scientific research, identifies the intellectual property risk points, and puts forward suggestions on risk management and control from the perspective of intellectual property protection.Results:The management of human genetic resources in China is evolving quickly. However, there is still a lack of practical guidelines on intellectual property protection and development, more substantial engagement and contribution of Chinese investigators in the international collaborative research should be promoted, and the perception and awareness of the significance of human genetic resources should be enhanced.Conclusions:In the international cooperative scientific research involving human genetic resources, we should clarify the operating rules at the level of intellectual property protection, improve the substantive participation of Chinese investigators, enhance the strategic awareness and risk awareness of human genetic resources, and provide support at the level of executive management institutions.

Objective To explore the clinical significance of serum Golgi protein 73 (GP73) in liver cirrhosis and its association with radiological parameters. Methods We included 177 patients with liver cirrhosis and 61 patients with chronic hepatitis admitted to The First Hospital of Jilin University from January 2016 to December 2018, with 70 healthy subjects who underwent physical examination during the same period as the control. We compared GP73, alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), and main portal vein diameter between the patients with liver cirrhosis, patients with chronic hepatitis, and healthy subjects. The GP73 level was further compared between liver cirrhosis subgroups by various classification methods. The correlation between GP73 and ALT, AST, ALB, TBIL, PT, and main portal vein diameter was analyzed. Results The GP73 level was significantly higher in the liver cirrhosis group than in the chronic hepatitis group and the healthy control group (P < 0.001). Patients with decompensated cirrhosis had a significantly higher serum GP73 level than those with compensated cirrhosis (P < 0.001). The serum GP73 levels in the Child-Pugh B and C cirrhosis subgroups were significantly higher than that in the Child-Pugh A cirrhosis subgroup (P < 0.05). In the liver cirrhosis group, the GP73 level was positively correlated with AST, ALT, TBIL, PT, and main portal vein diameter, while negatively correlated with ALB. Conclusion Serum GP73 is significantly increased in patients with liver cirrhosis, which is closely related to liver injury indicators. Serum GP73 shows important clinical value for the early diagnosis and prognosis assessment of liver cirrhosis.

OBJECTIVE: To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis. OBJECTIVE: Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI. OBJECTIVE AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.
Acute Kidney Injury/epidemiology* ; Aged ; COVID-19 ; China/epidemiology* ; Humans ; Male ; Retrospective Studies ; SARS-CoV-2