Usung gatufloxacun ( GTFX) as template molecule, magnetuc surface molecularly umprunted polymers ( M-MIPs) were prepared on the surface of modufued magnetuc suluca ( Fe3 O4@SuO2 ) wuth surface molecular umpruntung technuque. The polymers were characteruzed by transmussuon electron mucroscopy ( TEM ) and vubratung sample magnetometer ( VSM ) . The statuc adsorptuon experuments and Scatchard analysus suggested that there were two types of bundung sutes un the M-MIPs. The maxumum adsorptuon capacutues of M-MIPs and magnetuc non-umprunted polymers ( M-NIPs) for GTFX were 35. 1 mg/g and 23. 1 mg/g, respectuvely. The selectuvuty coeffucuents of GTFX M-MIPs to cuprofloxacun (CPFX), norfloxacun (NFLX), melamune (MEL) and tetracyclune (TC) were 2. 43, 5. 18, 6. 61 and 12. 99, and the relatuve selectuvuty coeffucuents of M-MIPs to M-NIPs for these four drugs were 2. 09, 1. 95, 3. 15 and 2. 43, respectuvely, unducatung the good specufuc recognutuon capabuluty for GTFX. Combuned wuth hugh performance luquud chromatographuc analysus, the M-MIPs were applued to extract and enruch GTFX un mulk sample wuth the recoverues more than 91 . 5%.

The bladder cancer is a common malignant tumor in urinary system.The standard treatment for muscle invasive bladder cancer is radical cystectomy.Considering the damage to patients and the drastic effect on their life caused by the radical cystectomy,many domestic and overseas scholars suggest a comprehensive treatment based on a bladder-keeping surgery with adjuvant therapy including radiotherapy,chemotherapy and frequent follow-up,which showslow operation-related risk and complication rate compared with the radical cystectomy.As a result,patients are able to preserve the function of bladder.

Objective:To explore if there is premature senescence of chondrocytes in patients with Kashin-Beck disease (KBD) and osteoarthritis.Methods:Five knee cartilage samples of KBD, osteoarthritis and control groups were collected, respectively, from the Second Affiliated Hospital of Xi'an Jiaotong University. DNA was then extracted from cartilage samples and DNA methylation was analyzed by Illumina Infinium HumanMethylation450 BeadChip. At the same time, based on genome-wide methylation data, the online DNA methylation aging clock calculator (https://dnamage.genetics.ucla.edu/home) was used to calculate the DNA methylation age (DNAm age) of samples, and the results were compared with their actual ages.Results:In the comparison between KBD group and control group, 1 212 differentially methylated CpG sites were found, including 497 hypermethylated CpG sites and 715 hypomethylated CpG sites, corresponding to 264 hypermethylated genes and 368 hypomethylated genes, respectively. In the comparison between osteoarthritis group and control group, 656 differentially methylated CpG sites were found, including 343 hypermethylated CpG sites and 313 hypomethylated CpG sites, corresponding to 177 hypermethylated genes and 174 hypomethylated genes, respectively. In the above comparison, 367 overlapped CpG sites (corresponding to 182 genes) were found, which were differentially methylated in both KBD and control groups and osteoarthritis and control groups. The results of DNA methylation aging clock showed that the average age acceleration differences between DNAm age and actual age of KBD, osteoarthritis and control groups were 2.549, 0.017, and - 5.364 years, respectively, the DNAm ages of KBD and osteoarthritis groups were greater than the actual ages.Conclusion:The chondrocytes show premature senescence in both KBD and osteoarthritis.

OBJECTIVE: To detect the disease-causing mutation in a family with hereditary spherocytosis type Ⅰ. METHODS: Genomic DNA was extracted from peripheral blood samples of the proband and his relatives. Next-generation sequencing was used to detect the mutations of relevant genes. Suspected pathogenic mutation was verified by Sanger sequencing. RESULTS: The proband was found to harbor a novel frameshifting mutation in the coding region of ANK1 gene, which has resulted in abnormal structure or function of the protein. The mutation was confirmed by Sanger sequencing, with both his father and brother found to have carried the same mutation. CONCLUSION The c.247delG mutation of proband hereditary spherocytosis typeⅠin this family due to mutation of the ANK1 gene．.
Ankyrins ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation ; Open Reading Frames ; Spherocytosis, Hereditary ; genetics

OBJECTIVETo detect potential mutation in a family affected with congenital dyserythropoietic anemia type II (CDA II).

METHODSTargeted sequence capture and next-generation sequencing (NGS) were used to analyze the exons and exon-intron boundaries of the SEC23B gene in a clinically suspected CDA II patient. Genotypes of the relatives were validated by Sanger sequencing. Potential impact of amino acid substitution on the structure and function of SEC23B protein was predicted with MutationTaster and PolyPhen-2. The protein structure was predicted with SWISS-MODEL software.

RESULTSThe proband was found to harbor double heterozygous mutations of the SEC23B gene, c.1727T>C (p.F576S) and c.1831C>T (p.R611W), which resulted in amino acid substitutions p.F576S and p.R611W. Both mutations were confirmed by Sanger sequencing. The sister of the proband was found to have carried c.1727T>C (p.F576S), while her father and son have carried c.1831C>T (p.R611W) mutation. In addition, the proband was detected to have carried c.211C>T (p.R71X) of the HFE gene, which resulted in substitution of arginine by a stop codon. The impact of above mutations on the structure or function of protein was predicted to be harmful. Splenectomy and iron chelation therapy have achieved effective improvement of anemia and iron overload. Computer simulation suggested that the mutations have altered the 3D structure of the SEC23B protein.

CONCLUSIONThe novel compound mutations of c.1727T>C and c.1831C>T of the SEC23B gene probably underlie the CDA II in the family, and there is a strong correlation between the genotype and phenotype.

Adult ; Anemia, Dyserythropoietic, Congenital ; genetics ; Computer Simulation ; Family ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Phenotype ; Vesicular Transport Proteins ; genetics

Based on the concept of “imbalance of qi movement with the latent cancer toxin”， it is believed that the development process of tumor pre-metastatic niche （PMN） could be summarized as tumor derived secretory factors， exosomes and other “cancer toxin”， which latent in the body， were diffusion-prone by means of meridians and membrane-sources. Besides， the latent toxin induced the imbalance of qi movement， especially the distant weakest qi， and the local sweat pore and collateral vessels were blocked， which resulted in phlegm and blood stasis， and the cross-aggregation of poison. We also proposed therapeutic principles of PMN as first regulating qi and then clearing and expelling toxin， and tried to discuss the theoretical model of traditional Chinese medicine for PMN based on the theory of qi regulation and detoxification， aimed at providing ideas for the future theory construction of traditional Chinese medicine prevention and treatment for malignant tumor metastasis.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Objective:To investigate the impact of body mass index (BMI) on delayed extubation of patients with acute Stanford type A aortic dissection (ATAAD).Methods:A total of 400 ATAAD patients who were admitted to our hospital from October 2021 to October 2023 and underwent surgical treatment were selected as the research objects. According to BMI, they were divided into obese group (BMI≥28 kg/m 2, 119 cases) and non-obese group (BMI<28 kg/m 2, 281 cases). The differences of preoperative clinical characteristics, intraoperative and postoperative data between the two groups were compared. Starting from transferring to the ICU and ending with the first successful extubation, The risk factors of postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients were analyzed, and the predictive efficacy of related factors for postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients was evaluated. Results:Compared with the non-obese group, the proportion of hypertension, diabetes, admission heart rate, admission systolic blood pressure, admission diastolic blood pressure and preoperative white blood cell count in the obese group were significantly increased, and the differences were statistically significant ( P<0.05). The cardiopulmonary bypass time, aortic cross-clamp time, operation time, red blood cell transfusion volume, invasive mechanical ventilation time, secondary operation rate and total hospitalization cost in the obese group were significantly higher than those in the non-obese group, and the differences were statistically significant ( P<0.05). Univariate logistic regression analysis showed that BMI, cardiopulmonary bypass time, ascending aortic cross-clamp time, operation time, age, hypertension, and red blood cell transfusion were related factors for postoperative invasive mechanical ventilation time ≥48 h in ATAAD patients ( P<0.05). Logistic multivariate regression analysis showed that increased BMI ( OR=1.213, P<0.05) and increased age ( OR=1.020, P<0.05) were independent risk predictors of postoperative invasive mechanical ventilation time≥48 h in ATAAD patients. Receiver operating characteristic curve ( ROC) analysis showed that the area under the ROC curve ( AUC) of BMI for predicting the duration of postoperative invasive mechanical ventilation in ATAAD patients≥48 h was 0.682 ( P<0.05), and the best predictive cut-off value was 25.64 kg/m 2. Conclusion:BMI≥28kg/m 2 increases the difficulty of surgery and the duration of invasive mechanical ventilation in ATAAD patients. BMI has a high predictive value for the duration of invasive mechanical ventilation in ATAAD patients after surgery ≥48 h, and effective intervention measures can be formulated to improve the treatment effect of patients.

Objective: To detect the disease-causing mutation in a family with hereditary spherocytosis type Ⅰ. Methods: Genomic DNA was extracted from peripheral blood samples of the proband and his relatives. Next-generation sequencing was used to detect the mutations of relevant genes. Suspected pathogenic mutation was verified by Sanger sequencing. Results: The proband was found to harbor a novel frameshifting mutation in the coding region of ANK1 gene, which has resulted in abnormal structure or function of the protein. The mutation was confirmed by Sanger sequencing, with both his father and brother found to have carried the same mutation. Conclusion The c. 247delG mutation of proband hereditary spherocytosis typeⅠin this family due to mutation of the ANK1gene.