Mutations in ADAMTSL4 cause a unique form of autosomal-recessive congenital ectopia lentis.

Several unique mutations of ADAMTSL4 leading to congenital ectopia lentis (CEL) have been previously reported by our team. The purpose of this study is to find out the possible mechanism of a recurrent novel intronic variant in ADAMTSL4 led to CEL. Twelve novel ADAMTSL4 mutations with a unique form congenital ectopic lentis were detected previously by panel-based NGS. Genetic analysis verified a novel heterozygous ADAMTSL4 variation c.2177+4A > G on Intron 11 in two unrelated patients with iris and lens abnormalities. MINI-Gene assay showed two splicing modes of mRNA that process two different bands A and B, and mutant-type shows replacement with the splicing mode of Exon 11 skipping. Construction of wild-type and mutant ADAMTSL4 vector showed the appearance of premature termination codons (PTC). In vitro expression detection showed significant down-regulated expression level of ADAMTSL4 mRNAs and proteins in cells transfected with mutant vectors compared with in wild-type group. On the contrary, translation inhibitor CHX and small interfering RNA of UPF1 (si-UPF1) significantly increased mRNA or protein expression of ADAMTSL4 in cells transfected with the mutant vectors. 12 novel mutations in ADAMTSL4 gene have been previously reported by our team in 6 CEL patients with a unique series of ocular abnormalities. The recurrent novel ADAMTSL4 mutation c.2177+4A > G triggering the splicing mode of Exon 11 skipping and NMD would cause the decrease of ADAMTSL4 proteins that participate in biosynthesis and assembly of microfibers, which might lead to CEL, and suggest that sequencing of certain intronic splicing varition might be a vital tool for genetic counseling and prenatal diagnoses.

Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029.

Objective: To provide the most up-to-date data on the burden of malignant mesothelioma (MM) and the projections through 2029 in China. Methods: Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease (GBD) 2019 database, including annual cases and deaths data and age-standardized rates of incidence, mortality, and disability-adjusted life-years (DALYs) associated with MM among different age groups. Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95% confidence interval (CI), while the projections through 2029 were calculated by the Bayesian age-period-cohort model. Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023. Results: We observed a significant elevation in incident new cases and deaths over the last 3 decades, increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases. We found a roughly 6% increase in the proportion of incident cases for those aged >70 years (30% in 2019 versus 24% in 1990), while for the proportion of deaths similar elevation for those aged >70 years was found. Additionally, men had significantly higher DALYs due to MM across age groups compared with women. Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons. By 2029, the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both. Conclusion: We found, for the first time using GBD data on the Chinese population, that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade, suggesting an urgent need for a complete ban on chrysotile asbestos in China.

Urea Synthesis via Coelectrolysis of CO2 and Nitrate over Heterostructured Cu-Bi Catalysts.

Electrocatalytic coupling of CO2 and NO3- to urea is a promising way to mitigate greenhouse gas emissions, reduce waste from industrial processes, and store renewable energy. However, the poor selectivity and activity limit its application due to the multistep process involving diverse reactants and reactions. Herein, we report the first work to design heterostructured Cu-Bi bimetallic catalysts for urea electrosynthesis. A high urea Faradaic efficiency (FE) of 23.5% with a production rate of 2180.3 µg h-1 mgcat-1 was achieved in H-cells, which surpassed most reported electrocatalysts in the literature. Moreover, the catalyst had a remarkable recycling stability. Experiments and density functional theory calculations demonstrated that introduction of moderate Bi induced the formation of the Bi-Cu/O-Bi/Cu2O heterostructure with abundant phase boundaries, which are beneficial for NO3-, CO2, and H2O activation and enhance C-N coupling and promote *HONCON intermediate formation. Moreover, favorable *HNCONH2 protonation and urea desorption processes were also validated, further explaining the reason for high activity and selectivity toward urea.

Genotype Associated With Visual Prognosis in Patients With Congenital Ectopia Lentis Following Lens Surgery: A Prospective Cohort Study.

PURPOSE: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL). DESIGN: Prospective clinical cohort study. METHODS: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing. Patients were grouped into children and adolescents/adults based on the age at surgery. The visual prognosis, including best-corrected visual acuity (BCVA) and amblyopia, was stratified into short-term and medium to long-term. RESULTS: This study included 329 probands with congenital EL, with a median age at lens surgery of 7.00 years (interquartile range [IQR] = 5.00, 12.50 years). Children with the non-FBN1 mutation exhibited inferior medium to long-term postoperative BCVA (0.26 [IQR: 0.14, 0.33] vs 0.15 [IQR: 0.10, 0.22], P = .034) and a higher prevalence of amblyopia (44.4% vs 16.8%, P = .012) compared to those with FBN1 mutation. Multivariable analysis showed that genotype (FBN1 vs non-FBN1 mutation) was significantly associated with medium to long-term postoperative BCVA (b = -0.128, 95% CI -0.214 to -0.042, P = .004) and amblyopia (OR = 0.20, 95% CI 0.05-0.78, P = .020) in children. Further classification of FBN1 genotype did not yield significant correlations with visual prognosis. However, no significant correlation was observed between genotype and short-term visual prognosis in the children. Children with less severe EL (OR = 0.13, 95% CI 0.02-0.85, P = .033) had lower risks of amblyopia in the short-term follow-up. For adolescent and adult patients with congenital EL, those with poor preoperative BCVA and long axial length should be informed of suboptimal visual prognosis. CONCLUSIONS: Genotype significantly influences the medium to long-term visual prognosis in children with congenital EL. Genotype, along with preoperative BCVA, may assist in establishing reasonable expectations for patients regarding their visual outcomes after the lens surgery.

Twenty-year oncology sperm banking experience at a Canadian academic fertility centre: a retrospective study examining the usage and reproductive outcomes from oncology patients.

BACKGROUND: Many cancer treatments pose a threat to fertility for patients. Semen cryopreservation before cancer treatment is an effective method to preserve fertility. There are sparse long-term data on the usage of samples from Canadian oncology sperm banks. METHODS: A retrospective chart review of all oncology sperm banking samples at a Canadian academic fertility centre from 2001 to 2020 was conducted. RESULTS: From 2001 to 2020, 4521 samples were banked by 2504 patients. The most frequent diagnoses among these patients were testicular cancer (29.5%) and lymphoma (26.9%). Of these patients, only 81 (3.2%) patients returned to use their samples with intrauterine insemination (IUI) or in vitro fertilisation (IVF) treatment and 62 (2.5%) patients transferred their samples to another clinic. The time between banking and return for usage of the sperm ranged from 1 to 131 months with a median of 18 months after banking. A total of 66 IVF cycles (104 embryo transfers) and 101 IUI cycles from 67 patients were reviewed. Of the 67 couples who used their samples, 53.7% achieved a clinical pregnancy. The clinical pregnancy rate was 6.6% per cycle for IUI and 30.8% per embryo transfer for IVF. Higher sperm concentration or total motile count was not associated with a higher chance of pregnancy. Patients who conceived had on average 1.9 ± 0.8 (p=0.02) more usable embryos per cycle than those who did not conceive. CONCLUSIONS: Sperm cryopreservation provides a valuable option for patients with cancer to achieve parenthood after potentially gonadotoxic cancer treatment. However, the overall usage of banked oncology sperm samples is very low.

Association analysis of miRNA-146a and miRNA-196a polymorphism with breast cancer risk in Khyber Pakhtunkhwa, Pakistan: a preliminary study.

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules, functioning either as oncogenes or tumor suppressor genes. SNPs in miRNAs might modify the expression of genes associated with miRNAs, enhancing susceptibility to breast cancer. Both miRNA-146a (rs2910164) and miRNA-196a (rs11614913) are identified and significantly associated with breast cancer risk in several ethnicities, but remains unexplored in Khyber Pakhtunkhwa population of Pakistan. METHODS: This study was aimed to check the relation of selected SNPs with breast cancer risk. The research cohort included 100 breast cancer patients and 100 healthy controls. All the participants were subjected for DNA extraction followed by T-ARMS PCR and gel electrophoresis. RESULTS: The results revealed a strong association between risk allele (G) of miRNA-146a and increased risk of breast cancer (OR = 2.04, P = 0.0006). Similarly, heterozygous and mutant genotypes also indicated high risk and significant association with breast cancer risk (CG; OR = 0.51, 9 P = 0.0001) (GG; OR = 3.76, P = 0.04). However, risk allele (T) of miRNA-196a (rs11614913) failed to exhibit significant association with breast cancer risk (OR = 0.92 P = 0.68). Similarly, the heterozygous and mutant genotype did not show significant association with breast cancer risk (CT; OR = 0.52, P = 0.125 (TT; OR = 0.88, P = 0.84). Furthermore, miRNA-146a (rs2910164) and miRNA-196a (rs11614913) polymorphisms exhibited non-significant associations with family history (P = 0.34, P = 0.77), PR status (P = 0.310, P = 0.397), ER status (P = 0.992, P = 0.981), nodal status (P = 0.86, P = 0.90), and menstrual status (P = 0.97, P = 0.09). Notably, miRNA-196a showed a significant association with the metastasis group (P = 0.010) and cancer stages (P = 0.047). CONCLUSIONS: In conclusion, this study highlights the association of miRNA-146a (rs2910164) polymorphism with breast cancer risk but suggested non-significant association of miRNA-196a (rs11614913) with breast cancer risk. However, these findings need to be confirmed through larger data set for more accurate result.

Genotype-phenotype Correlations of Ocular Posterior Segment Abnormalities in Marfan Syndrome.

Purpose: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 ( (FBN1). In addition to typical phenotypes such as ectopia lentis (EL) and aortic dilation, patients with MFS are prone to ocular posterior segment abnormalities, including retinal detachment (RD), maculopathy, and posterior staphyloma (PS). This study aims to investigate the correlations between FBN1 genotype and posterior segment abnormalities within a Chinese cohort of MFS. Design: Retrospective study. Participants: One hundred twenty-one eyes of 121 patients with confirmed FBN1 mutations between January 2015 and May 2023 were included. Methods: Comprehensive ophthalmic examination findings were reviewed, and the incidence of RD, atrophic, tractional, and neovascular maculopathy (ATN classification system), and PS was analyzed between different genotype groups. Only the more severely affected eye from each patient was included. Main Outcome Measures: Clinical features and risk factors. Results: Of 121 patients, 60 eyes (49.59%) exhibited posterior segment abnormalities, including RD (4, 3.31%), maculopathy (47, 38.84%), and PS (54, 44.63%). The mean age was 11.53 ± 11.66 years, with 79.34% of patients <20 years old. The location and region of mutations were found to be associated with the incidence of maculopathy (P = 0.013, P = 0.033) and PS (P = 0.043, P = 0.036). Mutations in the middle region had a lower incidence of maculopathy and PS (P = 0.028 and P = 0.006, respectively) than those in C-terminal region. Mutations in the transforming growth factor-ß (TGF-ß) regulating sequence exhibited a higher incidence of maculopathy and PS (P = 0.020, P = 0.040). Importantly, the location and region of mutations were also associated with the incidence of atrophic maculopathy (P = 0.013 and P = 0.033, respectively). Mutations in the middle region had a significantly lower probability of atrophic maculopathy (P = 0.006), while mutations in the TGF-ß regulating region had a higher incidence of atrophic maculopathy (P = 0.020). Conclusions: Maculopathy and PS were associated with the location and region of FBN1 mutations. Patients with mutations in the TGF-ß regulating region faced an increased risk of developing retinopathy. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Application of sutureless corneal incision for patients with congenital ectopia lentis - Is it feasible, effective and safe?

Purpose: To compare the clinical outcomes, feasibility, and safety between groups with sutured and sutureless wound closure in congenital ectopia lentis (CEL) patients. Methods: Patients with CEL who received phacoemulsification combined with intrascleral fixation of capsular hook (CH) and implantation of capsular tension ring (CTR) and in-the-bag intraocular lens (IOL) were included in this study. Results: A total of 68 eyes of 34 patients aged 18 years or younger were enrolled in this study. Incisions of 21 patients (34 eyes) did not require sutures while sutures were applied in 21 patients (34 eyes). Postoperative uncorrected distance visual acuity, best corrected distance visual acuity and intraocular pressure measurements were comparable on follow-up visits (P > 0.05). The magnitude of surgically induced astigmatism was significantly greater (P = 0.001) in the suture group (Median: 0.47; IQ: 1.63, 2.97) than in the sutureless group (Median: 0.88; IQ: 0.63, 1.35). No cases of endophthalmitis and retinal detachment were found postoperatively in either group, while suture-related complications were observed in the sutured group, including loose suture with discomfort in 5 (14.71%) eyes, loose suture with mucus infiltration in 3 (8.82%) eyes. In total, 22 sutures (64.71%) of 34 eyes required removal. Conclusions: Sutureless clear corneal incision in CEL patients can achieve satisfactory clinical results comparable to sutured wound closure in terms of the efficacy and safety. Advantages of this approach are the reduced risk of suture-related complications, no need for additional surgery under general anesthesia for suture removal, and less cost.

A microfluidic microalgae detection system for cellular physiological response based on an object detection algorithm.

The composition of species and the physiological status of microalgal cells serve as significant indicators for monitoring marine environments. Symbiotic with corals, Symbiodiniaceae are more sensitive to the environmental response. However, current methods for evaluating microalgae tend to be population-based indicators that cannot be focused on single-cell level, ignoring potentially heterogeneous cells as well as cell state transitions. In this study, we proposed a microalgal cell detection method based on computer vision and microfluidics, which combined microscopic image processing, microfluidic chip and convolutional neural network to achieve label-free, sheathless, automated and high-throughput microalgae identification and cell state assessment. By optimizing the data import, training process and model architecture, we solved the problem of identifying tiny objects at the micron scale, and the optimized model was able to perform the tasks of cell multi-classification and physiological state assessment with more than 95% mean average precision. We discovered a novel transition state and explored the thermal sensitivity of three clades of Symbiodiniaceae, and discovered the phenomenon of cellular heat shock at high temperatures. The evolution of the physiological state of Symbiodiniaceae cells is very important for directional cell evolution and early warning of coral ecosystem health.

Pathogenic variants in human DNA damage repair genes mostly arose in recent human history.

BACKGROUND: Genome stability is maintained by the DNA damage repair (DDR) system composed of multiple DNA repair pathways of hundreds of genes. Germline pathogenic variation (PV) in DDR genes damages function of the affected DDR genes, leading to genome instability and high risk of diseases, in particular, cancer. Knowing evolutionary origin of the PVs in human DDR genes is essential to understand the etiology of human diseases. However, answer to the issue remains largely elusive. In this study, we analyzed evolutionary origin for the PVs in human DDR genes. METHODS: We identified 169 DDR genes by referring to various databases and identified PVs in the DDR genes of modern humans from ClinVar database. We performed a phylogenetic analysis to analyze the conservation of human DDR PVs in 100 vertebrates through cross-species genomic data comparison using the phyloFit program of the PHAST package and visualized the results using the GraphPad Prism software and the ggplot module. We identified DDR PVs from over 5000 ancient humans developed a database to host the DDR PVs ( https://genemutation.fhs.um.edu.mo/dbDDR-AncientHumans ). Using the PV data, we performed a molecular archeological analysis to compare the DDR PVs between modern humans and ancient humans. We analyzed evolution selection of DDR genes across 20 vertebrates using the CodeML in PAML for phylogenetic analysis. RESULTS: Our phylogenic analysis ruled out cross-species conservation as the origin of human DDR PVs. Our archeological approach identified rich DDR PVs shared between modern and ancient humans, which were mostly dated within the last 5000 years. We also observed similar pattern of quantitative PV distribution between modern and ancient humans. We further detected a set of ATM, BRCA2 and CHEK2 PVs shared between human and Neanderthals. CONCLUSIONS: Our study reveals that human DDR PVs mostly arose in recent human history. We propose that human high cancer risk caused by DDR PVs can be a by-product of human evolution.

Influencing factors of effective lens position in patients with Marfan syndrome and ectopia lentis.

AIMS: The aim of this study was to analyse the effective lens position (ELP) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). METHODS: Patients with MFS undergoing lens removal and primary intraocular lens (IOL) implantation were enrolled in the study. The back-calculated ELP was obtained with the vergence formula and compared with the theoretical ELPs. The back-calculated ELP and ELP error were evaluated among demographic and biometric parameters, including axial length (AL), corneal curvature radius (CCR) and white-to-white (WTW). RESULTS: A total of 292 eyes from 200 patients were included. The back-calculated ELP was lower in patients undergoing scleral-fixated IOL than those receiving in-the-bag IOL implantation (4.54 (IQR 3.65-5.20) mm vs 4.98 (IQR 4.56-5.67) mm, p<0.001). The theoretical ELP of the SRK/T formula exhibited the highest accuracy, with no difference from the back-calculated ELP in patients undergoing in-the-bag IOL implantation (5.11 (IQR 4.83-5.65) mm vs 4.98 (IQR 4.56-5.67) mm, p=0.209). The ELP errors demonstrated significant correlations with refraction prediction error (PE): a 1 mm ELP error led to PE of 2.42D (AL<22 mm), 1.47D (22 mm≤AL<26 mm) and 0.54D (AL≥26 mm). Multivariate analysis revealed significant correlations of ELP with AL (b=0.43, p<0.001), CCR (b=-0.85, p<0.001) and WTW (b=0.41, p=0.004). CONCLUSION: This study provides novel insights into the origin of PE in patients with MFS and EL and potentially refines existing formulas.

Safety and efficacy of capsular tension ring and capsular hook implantation for managing ectopia lentis in Marfan syndrome: real-world study.

PURPOSE: To evaluate the safety and efficacy of capsular tension ring and capsular hook (CTR-CH) implantation in Marfan syndrome (MFS) patients with ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Retrospective propensity score-matched cohort study. METHODS: This study included patients with MFS who had in-the-bag intraocular lens (IOL) implantation assisted by CTR-CH or modified CTR (MCTR). The safety analysis focused on the resurgery rate. The efficacy analysis compared the corrected distance visual acuity (CDVA) and the incidence of laser capsulotomy after propensity score matching (PSM). RESULTS: This study encompassed 148 eyes that had the CTR-CH procedure and 162 eyes that received MCTR implantation. In the CTR-CH group, the median age at the time of surgery was 5 years, with a mean follow-up duration of 1.81 ± 0.4 years. 5 eyes (3.38%) required a second surgery because of retinal detachment (2, 1.35%), IOL decentration (2, 1.35%), and CH dislocation (1, 0.68%). The resurgery rate was comparable with that of the MCTR group ( P = .486). After PSM, a total of 108 eyes were recruited in each group. Postoperative CDVA was significantly improved in both groups (both P < .001), but comparable between the groups ( P = .057). The posterior capsular opacification took place earlier ( P = .046) while the anterior capsular opacification required laser capsulotomy at a later stage ( P = .037) compared with the MCTR group. CONCLUSIONS: The CTR-CH procedure was a feasible, safe, and efficient approach for managing EL in patients with MFS.

Mutations in TSPAN12 gene causing familial exudative vitreoretinopathy.

BACKGROUND: To report newly found TSPAN12 mutations with a unique form of familial exudative vitreoretinopathy (FEVR) and find out the possible mechanism of a repeated novel intronic variant in TSPAN12 led to FEVR. RESULTS: Nine TSPAN12 mutations with a unique form of FEVR were detected by panel-based NGS. MINI-Gene assay showed two splicing modes of mRNA that process two different bands A and B, and mutant-type shows replacement with the splicing mode of Exon11 hopping. Construction of wild-type and mutant TSPAN12 vector showed the appearance of premature termination codons (PTC). In vitro expression detection showed significant down-regulated expression level of TSPAN12 mRNAs and proteins in cells transfected with mutant vectors compared with in wild-type group. On the contrary, translation inhibitor CHX and small interfering RNA of UPF1 (si-UPF1) significantly increased mRNA or protein expression of TSPAN12 in cells transfected with the mutant vectors. CONCLUSIONS: Nine mutations in TSPAN12 gene are reported in 9 FEVR patients with a unique series of ocular abnormalities. The three novel TSPAN12 mutations trigger NMD would cause the decrease of TSPAN12 proteins that participate in biosynthesis and assembly of microfibers, which might lead to FEVR, and suggest that intronic sequence analysis might be a vital tool for genetic counseling and prenatal diagnoses.

Genetic Characteristics and Clinical Manifestations of Foveal Hypoplasia in Familial Exudative Vitreoretinopathy.

PURPOSE: This study aimed to ascertain the occurrence of foveal hypoplasia (FH) in individuals diagnosed with familial exudative vitreoretinopathy (FEVR). DESIGN: Retrospective cohort study. METHODS: In this study, FEVR families and sporadic cases were diagnosed at the Eye and ENT Hospital, Fudan University, between 2017 and 2023. All patients attended routine ophthalmologic examinations and genetic screenings. The classification of FH was determined using optical coherence tomography (OCT) scans. The FH condition was classified into 2 subgroups: group A (FH being limited to the inner layers) and group B (FH affecting the outer layers). A total of 102 eyes from 58 patients were suitable for analysis. RESULTS: Forty-nine mutations in LRP5, FZD4, NDP, TSPAN12, KIF11, CTNNB1, and ZNF408 were examined and detected, with 26 of them being novel. Forty-seven eyes (46.1%) revealed FH. The majority (53.2%) were due to the typical grade 1 FH. Patients with mutations in LRP5 and KIF11 were found to exhibit a higher prevalence of FH (P = .0088). Group B displayed the lowest visual acuity compared with group A (P = .048) and the group without FH (P < .001). The retinal arteriolar angle in group B was significantly smaller than in group A (P = .001) and those without FH (P < .001). CONCLUSIONS: This study offers a new diagnostic approach and expands the spectrum of FEVR mutations. LRP5 and KIF11 were found to be more susceptible to causing FH in patients with FEVR. FEVR eyes with FH exhibited both greater visual impairment and reduced retinal arteriolar angles. The assessment of foveal status in patients with FEVR should be valued.

Evolutionary origin of germline pathogenic variants in human DNA mismatch repair genes.

BACKGROUND: Mismatch repair (MMR) system is evolutionarily conserved for genome stability maintenance. Germline pathogenic variants (PVs) in MMR genes that lead to MMR functional deficiency are associated with high cancer risk. Knowing the evolutionary origin of germline PVs in human MMR genes will facilitate understanding the biological base of MMR deficiency in cancer. However, systematic knowledge is lacking to address the issue. In this study, we performed a comprehensive analysis to know the evolutionary origin of human MMR PVs. METHODS: We retrieved MMR gene variants from the ClinVar database. The genomes of 100 vertebrates were collected from the UCSC genome browser and ancient human sequencing data were obtained through comprehensive data mining. Cross-species conservation analysis was performed based on the phylogenetic relationship among 100 vertebrates. Rescaled ancient sequencing data were used to perform variant calling for archeological analysis. RESULTS: Using the phylogenetic approach, we traced the 3369 MMR PVs identified in modern humans in 99 non-human vertebrate genomes but found no evidence for cross-species conservation as the source for human MMR PVs. Using the archeological approach, we searched the human MMR PVs in over 5000 ancient human genomes dated from 45,045 to 100 years before present and identified a group of MMR PVs shared between modern and ancient humans mostly within 10,000 years with similar quantitative patterns. CONCLUSION: Our study reveals that MMR PVs in modern humans were arisen within the recent human evolutionary history.

Timely assessment of 5-year relative survival for patients with thyroid cancer from Taizhou, eastern China: a period analysis.

BACKGROUND: While timely assessment of long-term survival in thyroid cancer patients is critical for assessing early detection and screening programs for thyroid cancer, those data are sorely lacking in China. We aimed to timely and accurately assess the long-term survival of thyroid cancer patients in eastern China. METHODS: Patients diagnosed with thyroid cancer during 2004-2018 from four cancer registries in Taizhou, eastern China were included. The 5-year relative survival was estimated by period analysis and stratified by sex, age at diagnosis, and region. The 5-year RS of thyroid cancer patients during 2019-2023 was also predicted using the model-based period analysis. RESULTS: During 2014-2018, the overall 5-year relative survival of thyroid cancer patients was 87.7%, 91.2% for women and 79.4% for men. The 5-year RS decreased along with increasing age at diagnosis, decreasing from 94.9% for age <45 years to 81.3% for age >74 years, while 5-year RS was higher in urban areas than in rural areas (93.2% vs. 86.1%). The 5-year RS for thyroid cancer patients improved greatly between 2004-2008 to 2014-2018. The predicted overall 5-year RS could reach 91.4% over the upcoming 2019-2023 period. CONCLUSION: We provided, for the first time in China using period analysis, the most up-to-date 5-year RS for thyroid cancer patients from Taizhou, eastern China, which has important implications for timely evaluation on early detection and screening programs for patients with thyroid cancer in eastern China.

Durable Immunomodulatory Nanofiber Niche for the Functional Remodeling of Cardiovascular Tissue.

Functional remodeling and prolonged anti-inflammatory responses are both vital for repairing damage in the cardiovascular system. Although these aspects have each been studied extensively alone, attempts to fabricate scaffolds that combine these effects have seen limited success. In this study, we synthesized salvianic acid A (SA, danshensu) blocked biodegradable polyurethane (PCHU-D) and enclosed it within electrospun nanofibers to synthesize a durable immunomodulatory nanofiber niche (DINN), which provided sustained SA release during inflammation. Given its excellent processability, mechanical properties, and shape memory function, we developed two variants of the DINN as vascular scaffolds and heart patches. Both these variants exhibited outstanding therapeutic effects in in vivo experiments. The DINN was expertly designed such that it gradually decomposes along with SA release, substantially facilitating cellular infiltration and tissue remodeling. Therefore, the DINN effectively inhibited the migration and chemotaxis of inflammatory cells, while also increasing the expression of angiogenic genes. As a result, it promoted the recovery of myocardial function after myocardial infarction and induced rapid reendothelialization following arterial orthotopic transplantation repair. These excellent characteristics indicate that the DINN holds great potential as a multifunctional agent for repairing cardiovascular tissues.

Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome.

Purpose: The purpose of this study was to investigate the relationship between axial length (AL) growth and FBN1 genotype in patients with Marfan syndrome (MFS) after lens surgery and customize the selection of intraocular lens (IOL) power. Methods: Patients with MFS who had lens surgery and primary IOL implantation received panel-based next-generation sequencing (NGS). The rate of axial length growth (RALG) was calculated using pre- and postoperative AL measurements and corrected log10-transformed age. A multivariable regression model of RALG was developed after analyzing the effect of FBN1 genotypes and confounding factors. Results: A total of 139 probands of MFS with a median age at lens surgery of 6.25 years (interquartile range [IQR] = 4.67, 12.50 years) were followed up for a median duration of 2.08 years (IQR = 1.16, 3.00 years). The AL growth curve between the age of 3 and 15 years old was logarithmic. Dominant-negative (DN) variants affecting the disulfide-bridge forming cysteines and the conserved residues for calcium-binding had significantly higher RALG than DN variants affecting other structures (P = 0.001) but comparable to that of haplo-insufficiency variants (P = 1.000). Pre-operative AL (b = 0.563, P = 0.011) and genotype constant (b = 2.603, P = 0.011) were significantly associated with RALG in the final model. A Python-based calculator, Marfan IOL Calculator version 2.0, was programmed using the RALG to predict postoperative AL and customize IOL selection based on the ocular biometric parameters and FBN1 genotype. Conclusions: FBN1 genotype impacted the growth of AL in patients with MFS after IOL implantation. Knowing the FBN1 genotype could help cataract surgeons to customize IOL selection.

Use of period analysis to provide a timely assessment of 5-year relative survival for pancreatic cancer patients from Taizhou, eastern China.

Assessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014-2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients (< 55, 55-64, 65-74, and > 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004-2008, 2009-2013, and 2014-2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.