Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15(CASC15),a long-stranded non-coding RNA(lncRNA),in hepatocellular carcinoma(HCC).Methods Bioinformat-ics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Tr-answell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1(LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression.Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells(P<0.05).The results of cell function experiments on proliferation,inva-sion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibi-tory effect,consistent with the results of apoptosis experiments(P<0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby pro-moting HCC cell proliferation,invasion and migration,and inhibiting apoptosis.Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Objective To investigate the effect of automatic nucleic acid purifiers QIAsymphony SP and QIAcube in the DNA extraction of samples of trace amount or mixed with inhibitors. Methods Different kinds of purification methods using QIAsymphony SP and QIAcube were applied to extract swabs which contained 30, 100, 150 and 300 cells and other samples which contained six types of inhibitors-heme, humic acid, lard, soil, rust and grease. PCR amplification and STR typing were performed on the extracted DNA templates to compare extracting efficiency and inhibitor removal ability of four different purification methods. Results Different purification methods showed similar extraction effects, 70.83%-100.00% of loci could be detected by amplification of DNA extracted from samples with 30, 100 and 300 cells, and the six types of inhibitors could be removed well. Conclusion The two automatic nucleic acid purifiers have a good inhibitor removal effect. For swabs with only 30 cells, after DNA extraction and amplification, the locus detection rate of samples can still be high, which can meet the requirements of local DNA laboratory work, and realize the standardization construction of the laboratory.
DNA ; DNA Fingerprinting ; Nucleic Acids/genetics* ; Polymerase Chain Reaction

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

Objective To evaluate the feasibility, safety and efficacy of the treatment of chronic symptomatic internal carotid artery long?segmental occlusion. Methods Fifty?one cases of chronic symptomatic internal carotid artery long?segmental occlusion (arterial occlusion more than 2 anatomical segments) who were treated with hybrid surgery (plaque located at the carotid sinus) or endovascular revascularization (plaque located at the distal end of the internal carotid artery occlusion) from May 2015 to May 2018 were reviewed. Recanalization, perioperative complications, stroke events, and reocclusion events during the follow?up period were recorded. Results The occlusion was recanalized successfully in 45 of 51 patients (88.2%, 45/51), 6 patients failed because the guidewire could not cross the distal arterial occlusion. And the technical success rate was 96.0% (24/25) in hybrid surgery and 80.8% (21/26) in endovascular revascularization. Perioperative complications occurred in 2 patients who underwent combined endovascular treatment. One patient had a small branch embolism due to intraoperative thrombus shift, and 1 patient had large area cerebral infarction. The complications occurred in 2 patients who underwent thybrid surgery, including 1 case of internal carotid cavernous fistula and 1 case of acute reocclusion of internal carotid artery. Forty?four patients with successful operation received clinical follow?up, with the median follow?up time of 24 months (7-43 months). No recurrent stroke and death occurred during the follow?up period. Clinical symptoms were improved in 34 cases. Totally 44 patients received imaging follow?up, and during the median imaging follow?up time of 8 month (4-28 months), 6 cases had reocclusion, and 2 cases had restenosis. Conclusion The treatment of chronic symptomatic internal carotid artery long?segmental occlusion is technically feasible and safety with good short?term efficacy. However, its exact efficacy remains to be confirmed by long?term follow?up studies with large samples.

Objective: To evaluate the feasibility, safety and efficacy of the treatment of chronic symptomatic internal carotid artery long-segmental occlusion. Methods: Fifty-one cases of chronic symptomatic internal carotid artery long-segmental occlusion (arterial occlusion more than 2 anatomical segments) who were treated with hybrid surgery (plaque located at the carotid sinus) or endovascular revascularization (plaque located at the distal end of the internal carotid artery occlusion) from May 2015 to May 2018 were reviewed. Recanalization, perioperative complications, stroke events, and reocclusion events during the follow-up period were recorded. Results: The occlusion was recanalized successfully in 45 of 51 patients (88.2%, 45/51), 6 patients failed because the guidewire could not cross the distal arterial occlusion. And the technical success rate was 96.0% (24/25) in hybrid surgery and 80.8% (21/26) in endovascular revascularization. Perioperative complications occurred in 2 patients who underwent combined endovascular treatment. One patient had a small branch embolism due to intraoperative thrombus shift, and 1 patient had large area cerebral infarction. The complications occurred in 2 patients who underwent thybrid surgery, including 1 case of internal carotid cavernous fistula and 1 case of acute reocclusion of internal carotid artery. Forty-four patients with successful operation received clinical follow-up, with the median follow-up time of 24 months (7-43 months). No recurrent stroke and death occurred during the follow-up period. Clinical symptoms were improved in 34 cases. Totally 44 patients received imaging follow-up, and during the median imaging follow-up time of 8 month (4-28 months), 6 cases had reocclusion, and 2 cases had restenosis. Conclusion The treatment of chronic symptomatic internal carotid artery long-segmental occlusion is technically feasible and safety with good short-term efficacy. However, its exact efficacy remains to be confirmed by long-term follow-up studies with large samples.

Objective: To screen for hotspot gene mutations associated with genetic deafness in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis in high-risk families. Methods: Between November 2012 and October 2017, 26 117 pregnant women were screened by molecular hybridization microarray for 9 hot-spot mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191 del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G, IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype analysis was carried out in husbands of women carrying mutations, and prenatal diagnosis was carried out in the fetuses with high risk of deafness. Results: Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations, 7 with hearing impairment were affected by homozygous or compound heterozygous mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4 heterozygous mutations, and 21 carried heterozygous mutations in two genes simultaneously. In 394 families, the husbands accepted gene sequence testing, and 27 in which were determined as carriers of mutations in identical genes as their wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were diagnosed as hereditary deafness. In 9 families who did not receive prenatal diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery. Conclusion In order to prevent birth defects with congenital hearing problems, it is effective to provide screening for hotspot mutations in pregnant women and to perform prenatal diagnosis on high risk pregnancies.

Objective To evaluate the feasibility of transvenous embolization treatment for cerebral arteriovenous malformations(bAVM). Methods From November 2016 to April 2017, the information of 6 patients with brain arteriovenous malformation in our center accepting the intravenous radical embolization were collected, who were ruptured bAVM, bAVM with a single drainage vein, not suitable for surgery confirmed by neurosurgeon consultation or explicitly refused craniotomy. The modified Rankin Scale score of five patients were smaller than three before treatment.The location of draining vein flowing venous sinus was shown by rotational DSA and 3D reconstructed images.A liquid embolic agent was injected via Sonic catheter to completely embolism the brain arteriovenous malformation under controlling blood pressure and blocking the blood provisionally.The perioperative complications and modified Rankin Scale score were observed and recorded 30 days after treatment. Results The transvenous embolization treatment was successfully performed in six patients with 7 embolization procedures.There were no definite operation-related complications. the mRS of all cases were ≤1 within 30 days after operation. Conclusion The embolization technique via the internal jugular vein is feasible for bAVM patients with a single drainage vein,while the long-term outcome need more evaluations.

Objective To explore the feasibility,safety and effect of endovascular revascularization for chronic long segment internal carotid artery occlusion. Methods The cases of chronic long segment internal carotid artery occlusion who were treated by endovascular revascularization in our center from May 2015 to April 2017 were reviewed. Eleven cases met the inclusion criteria:the duration of the occlusion was more than three weeks and the segment of the occlusion was beyond the petrosal segment of internal carotid arteries from the initial segment. All of the cases had the related symptoms and had declining cerebral perfusion. The analysis index included:baseline information,radiological information,perioperative results, clinical follow-up and imaging follow-up. The imaging follow-up index were the re-stenosis or re-occlusion of the revascularized artery. Results The occlusion was recanalized successfully in 9 of 11 patients,the two procedures were abandoned after repeated attempts and the guide wire could not reach the true lumen when navigating in the cavernous segment. Six cases of the nine successfully recanalized cases accepted perfusion-weighted imaging scan. Cerebral perfusion of all the cases were improved. Thrombus shifting was observed in one case and occluded a subbranch,mechanical thrombectomy was performed successfully,the case was recovered well without sequela. No symptomatic stroke or death was happened in the perioperative period. All of the nine cases who successfully recanalized acquired clinical follow-up,median follow-up time was ten months(4—28 months). No ischemic stroke and death happened after the procedures. Seven of nine cases improved in the clinical symptoms. Five cases accepted the imaging follow-up. The meantime was six months. No re-occlusion was happened. Conclusions Endovascular revascularization for chronic long segment internal carotid artery occlusion is feasible,safe,and short-term effective. More clinical research is needed to verify the long-term effect.