Objective:To investigate COVID-19 vaccination status and relevant adverse reactions in patients with psoriasis treated with biological agents, and to explore the effect of COVID-19 vaccination on psoriatic lesions.Methods:Clinical data were collected from 572 psoriasis patients aged 18 - 60 years, who were registered in the management system of psoriasis patients treated with biological agents in the University of Hong Kong-Shenzhen Hospital from May 2019 to June 2021. The COVID-19 vaccination status was investigated by telephone interviews, and the vaccination-related information was obtained by fixed healthcare workers during a fixed time period according to a predesigned questionnaire. Measurement data were compared between two groups by using t test, and enumeration data were compared by using chi-square test or Fisher′s exact test. Results:The COVID-19 vaccination coverage rate was 43.13% (226 cases) among the 524 patients who completed the telephone interview, and was significantly lower in the biological agent treatment group (30.79%, 105/341) than in the traditional drug treatment group (66.12%, 121/183; χ2 = 60.60, P < 0.001) . The main reason for not being vaccinated was patients′ fear of vaccine safety (49.66%, 148/298) , followed by doctors′ not recommending (26.51%, 79/298) . In the biological agent treatment group after vaccination, the exacerbation of psoriatic lesions was more common in patients receiving prolonged-interval treatment (42.86%, 6/14) compared with those receiving regular treatment (4.40%, 4/91; Fisher′s exact test, P < 0.001) . Skin lesions were severely aggravated in two patients after COVID-19 vaccination, who ever experienced allergic reactions and whose skin lesions did not completely subside after the treatment with biological agents. Conclusions:The COVID-19 vaccination coverage rate was relatively low in the psoriasis patients treated with biological agents, and no serious adverse reaction was observed after vaccination. Prolonged-interval treatment due to COVID-19 vaccination ran the risk of exacerbation of skin lesions.

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

Objective: To evaluate the efficacy of cell free DNA (cf-DNA) screening in prenatal care by analyzing the follow-up information and pregnancy outcomes. Methods: All cf-DNA cases conducted in Women′s Hospital of Nanjing Medical University from August 2011 to December 2017 were enrolled. The general information of the pregnancies, cf-DNA results, confirmatory testing results, and the follow-up results were collected. The pregnancy outcomes were analyzed in cases with low risk cf-DNA results as well as with high risk results for common trisomies, which were trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). The sensitivity, specificity, positive predictive value and negative predictive value of cf-DNA screening were calculated. Results: (1) A total of 43 615 cf-DNA cases were involved, with 44 cases (0.10%, 44/43 615) test failure results, 314 cases (0.72%, 314/43 571) high risk results for common trisomies and 43 257 cases (99.27%, 43 257/43 571) low risk results. (2) Among 277 cases (88.21%, 277/314) high risk cases were successfully followed up, and 228 cases (82.31%, 228/277) underwent invasive confirmatory prenatal diagnosis. In the low risk results, 36 826 cases (85.13%, 36 826/43 257) were successfully followed up, and 572 (1.55%, 572/36 826) cases were found to have adverse pregnancy outcomes, among which 4 false negative cf-DNA results were confirmed. (3) In the 37 103 successfully followed up cf-DNA cases, the sensitivity for T21, T18, T13 were calculated as 97.96%, 96.67% and 100.00%, respectively; the specificity for T21, T18, T13 were calculated as 99.96%, 99.95% and 99.95%, respectively. The positive predictive value for T21, T18, T13 were calculated as 90.57%, 63.04% and 17.39%, respectively. The negative predictive value for T21, T18, T13 were calculated as 99.99%, 99.98% and 100.00%. Conclusions Cf-DNA is effective in detecting common trisomies, with a high sensitivity and specificity. However, the follow-up information revealed several potential limitations in current clinical practice, such as a number of cases with high risk results rejected invasive confirmatory testing, as well as the genetic diagnostic results for most low risk cases with an adverse pregnancy outcome aren′t obtained. Genetic counseling and the follow-up for all the cf-DNA cases should be emphasized in the future.

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors and . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.

Sodium hyaluronate is one of the natural components of articular cartilage and synovial fluid,which plays important roles in maintaining the structure and physiological functions of joints.Abnormal change of the content and physicochemical properties of sodium hyaluronate in the joints is one of the common pathological causes of osteoarthritis.Supplementation of exogenous sodium hyaluronate,which has similar physical and chemical properties as those in normal joints,has been considered as an effective strategy for clinical treatment of osteoarthritis.However,the benefits of intra-articular injection of sodium hyaluronate are still under debates.Moreover,different recommendations for clinical use were developed in several clinical guidelines.Several guidelines suggested that molecular weight of sodium hyaluronate was an important factor influencing the clinical benefits in osteoarthritis.Diverse products of sodium hyaluronate present different physicochemical and biological characteristics,which may lead to differences in clinical efficacy and safety.High-molecular-weight sodium hyaluronate,with highly modified and cross-linked sugar chains,potentially differ from those with low molecular weight in physicochemical properties,rheological characteristics,and physiological activities.In general,high-molecular-weight sodium hyaluronate have higher viscosity and elasticity.The exogenous hyaluronate,of which the molecular weight is similar to those in normal joints,probably have the similar rheological characteristics.A large number of clinical studies demonstrated that sodium hyaluronate products with high-molecular weight significantly relieved joint pain and improved joint functions in patients with osteoarthritis.In contrast,the clinical efficacy of the low-molecular-weight hyaluronate is still controversial,because several studies could not establish the superiority in osteoarthritis when comparing with the placebo.Studies on molecular mechanisms revealed that some physiological functions of sodium hyaluronate were molecular-weight dependent.High-molecular-weight sodium hyaluronate may have more pronounced impacts on the regulation of inflammation and maintaining the homeostasis of extracellular matrix.This review focused on the effects of sodium hyaluronate with different molecular weight in treating osteoarthritis.Evidence based on clinical studies related to the molecular-weight differences of sodium hyaluronate were presented.Furthermore,the optimal use of various products of sodium hyaluronate with different molecular weight was discussed.

Objective:To prepare biotin-poloxamer(BP) conjugate micelles for epirubicin through biotin conjugated on poloxam-er. Methods:Epirubicin(EPI) was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized by its particle size, zeta potential,surface morphology,as well as the efficiency of drug loading and drug encapsulation and drug release. Marrow leukemia HL-60 cells were used to evaluate the cell cytotoxicity of EPI-loaded BP micelles in vitro. The tumor model in nude mice was estab-lished through the subcutaneous injection of HL-60 cells, and then the inhibitory effect of EPI-loaded BP micelles on tumor volume growth was investigated.Results:It was found that the average particle size of EPI-loaded BP micelles was about 100 nm. In addition, the enhanced cellular uptake ability of EPI-loaded BP micelles was proved by fluorescence microscope observation. The efficiency order of the tumor volume growth inhibition was:EPI-loaded BP micelles > EPI-loaded MATP micelles> EPI-loaded poloxamer micelles>EPI. BP micelles showed significant antitumor activity and low toxicity when compared with the non-targeted micelles. Conclusion:With the advantages of EPR effect and tumor-targeting potential,BP conjugate micelles might be developed as a new system for chemo-therapeutics. However,the tumor targeting technique should be demonstrated further by the other cell experiments and large animal ex-periments.

Objective To obtain myoclonic epilepsy with ragged-red fibers (MERRF)-specific cardiomyocytes by the differentiation in vitro of inducing pluripotent stem cells (iPSC) derived from a MERRF patient and evaluate the application of the prepared cardiomyocytes in construction of MERRF syndrome model.Methods The patient-derived iPSCs and H9 embryonic stem (ES) cells,the control cell line,were unidirectionally differentiated into cardiomyocytes n in vitro.The obtained cardiomyocytes were identified and validated by detecting the presence of cardiomyocyte-specific markers using immunofluorescence staining and RT-PCR.The beating frequencies were recorded to compare the functional evaluation for the two groups of cardiomyocyte.Results Both the patient-derived iPSC and H9 ES cells were differentiated into cardiomyocytes successfully.The average beating frequencies of MERRF-induced cardiomyocytes (iCMs) were 13,24,15 and 18 times/min on the day 10,13,15 and 16 during the cell differentiation process.The average beating frequencies of H9-iCMs were 80,96,120 and 120 times/min,respectively.The beating ability of iPSC-differentiated cardiomyocytes was significantly lower than that of corresponding control (all P ＜ 0.05).Conclusion The patient-derived iPSCs may differentiated into cardiomyocytes.Based on the functional evaluation for these cardiomyocytes,the model for MERRF syndrome with mitochondrial mutations was generated and characterized in vitro.

Objective To perform prenatal diagnosis for a fetus with hydrocephalus and congenital heart disease by whole exome se-quencing ( WES) , and then provide genetic counseling for the next pregnancy. Methods DNAs from amniotic fluid cells of the fetus and peripheral blood of his/her parents were extracted, respectively, and then performed WES. After the process of library construc-tion, hybrid capture and sequencing, the obtained data were compared with the database from human genome and literatures and ana-lyzed by software. The pathogenic mutations were searched based on the American College of Medical Genetics and Genomics ( ACMG, 2015) guideline and verified by the Sanger sequencing. Results The WES results found that the compound heterozygous mutations ex-isted in POMT1 gene of the fetus, which were inherited from the splice site mutation c.605+1G>A( IVS7) of his/her mother and the frameshift mutation c.1367 c.1368 ( exon 15) insGA, p. L456Lfs?80 of his/her father, respectively. The Sanger sequencing results were consistent with that of WES. The fetus was affected by Walker-Warburg syndrome, and his/her parents decided to terminate the pregnancy finally. Conclusion The WES may diagnose Walker-Warburg syndrome rapidly and accurately, which may play an impor-tant role in clinical management and genetic counseling.

OBJECTIVETo develop and validate a method for mutation screening and prenatal diagnosis of TSC1/TSC2 mutations among patients with tuberous sclerosis complex (TSC) by Ion Torrent semiconductor sequencing.

METHODSPotential mutations of SC1/TSC2 gene was detected in 2 TSC families and 1 sporadic TSC patient using an Ion Torrent PGM sequencer. Candidate variants were validated by Sanger sequencing. The corresponding site of TSC2 in the fetus of family 2 was also detected with Sanger sequencing.

RESULTSIon Torrent semiconductor sequencing has identified a probably pathogenic TSC2 mutation (c.311-312insGCTG) in the patient from family 1, and a probably pathogenic TSC2 mutation (c.1790A>G) in the patient of family 2.

CONCLUSIONTargeted Ion Torrent PGM sequencing is an accurate and efficient method to detect TSC1/TSC2 mutations in TSC.

Adult ; Base Sequence ; DNA Mutational Analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Tuberous Sclerosis ; embryology ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult

Objective To develop and validate a method for detecting factor 8 gene (F8) mutations in hemophilia A patients by Ion Torrent semiconductor sequencing .Methods Intron 22 and intron 1 inversions of F8 gene were identified by long distance PCR (LD-PCR), other mutations in the F8 gene were identified by Ion Torrent sequencing.Candidate variants were validated by Sanger sequencing .Sanger sequencing was applied to screen HA carriers from 11 female family members in the 8 pedigrees.One pregnant woman was offered prenatal diagnosis via analyzing the fetal DNA obtained through amniocentesis . Results Four missense mutations ( c.1331A >C, 1648C >T, c.6506G >A, c.6544C >T), two frameshift mutations ( c.2393 _2394insT, c.6320delG), one splicing mutation ( IVS5 +5G >A), one nonsense mutation (c.43C >T) and one Inv22 mutation were identified in all nine probands respectively . Among 11 female family members, 10 females were identified to be HA carriers, and one didn′t carry the maternal pathogenic mutation.Prenatal diagnosis result showed that the fetus inherited the wild -type maternal allele and was predicted to be unaffected by HA .Conclusion The targeted Ion Torrent sequencing is a reliable and efficient method to detect F8 mutations in patients with Hemophilia A disease .