Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Real-world Effectiveness of mRNA COVID-19 Vaccines Among US Nursing Home Residents Aged ≥65 Years in the Pre-Delta and High Delta Periods.

Background: Long-term care residents were among the most vulnerable during the COVID-19 pandemic. We estimated vaccine effectiveness of mRNA COVID-19 vaccines in Medicare nursing home residents aged ≥65 years during pre-Delta and high Delta periods. Methods: We conducted a retrospective cohort study from 13 December 2020 to 20 November 2021 using Medicare claims data. Exposures included 2 and 3 doses of Pfizer-BioNTech and Moderna COVID-19 vaccines. We used inverse probability weighting and Cox proportional hazards models to estimate absolute and relative vaccine effectiveness. Results: Two-dose vaccine effectiveness against COVID-19-related death was 69.8% (95% CI, 65.9%‒73.3%) during the pre-Delta period and 55.7% (49.5%‒61.1%) during the high Delta period, without adjusting for time since vaccination. We observed substantial waning of effectiveness from 65.1% (54.2%‒73.5%) within 6 months from second-dose vaccination to 45.2% (30.6%‒56.7%) ≥6 months after second-dose vaccination in the high Delta period. Three doses provided 88.7% (73.5%‒95.2%) vaccine effectiveness against death, and the incremental benefit of 3 vs 2 doses was 74.6% (40.4%‒89.2%) during high Delta. Among beneficiaries with a prior COVID-19 infection, 3-dose vaccine effectiveness for preventing death was 78.6% (50.0%‒90.8%), and the additional protection of 3 vs 2 doses was 70.0% (30.1%‒87.1%) during high Delta. Vaccine effectiveness estimates against less severe outcomes (eg, infection) were lower. Conclusions: This nationwide real-world study demonstrated that mRNA COVID-19 vaccines provided substantial protection against COVID-19-related death. Two-dose protection waned after 6 months. Third doses during the high Delta period provided significant additional protection for individuals with or without a prior COVID-19 infection.

Transcriptome analysis reveals the molecular mechanisms of rubber biosynthesis and laticifer differentiation during rubber seed germination.

The molecular mechanisms underlying the initiation of natural rubber synthesis and laticifer differentiation have not been fully elucidated. In this study, we conducted a time-series transcriptome analysis of five rubber tree tissues at four stages of seed germination. A total of 161,199 DEGs were identified between the two groups, including most 16,673 DEGs (A3 vs B3 and A3 vs C3) and lest 1,210 DEGs (C2 vs D2). We found that the maturation of the seed is accompanied by the formation of laticifer cells in cotyledon. Meanwhile, the analysis of hormones related genes expression may provide effective clues for us to promote the differentiation of laticifer cells in seeds by hormones in the future. In this study, hormone-related gene enrichment analyses revealed that IAA, GA, and CTK were activated in laticifer containing tissues. Similarly, GO and GEGG analysis showed that hormone pathways, especially the auxin pathway, are enriched. Gene expression clustering was analyzed using the short time-series expression miner (STEM), and the analysis revealed four distinct trends in the gene expression profiles. Moreover, we enriched transcription factor (TF) enrichment in cotyledon and embryonic axis tissues, and the MYB type exhibited the most significant difference. Furthermore, our findings revealed that genes related to rubber synthesis exhibited tissue-specific expression patterns during seed germination. Notably, key genes associated with rubber biosynthesis, specifically small rubber particle protein (SRPP) and cis-prenyltransferase (CPT), exhibited significant changes in expression in cotyledon and embryonic axis tissues, suggesting synchronous rubber synthesis with seed germination. Our staining results reveled that laticifer cells were exits in the cotyledon before seed imbibition stage. In conclusion, these results lay the foundation for exploring the molecular mechanisms underlying laticifer differentiation and rubber synthesis during seed germination, deepening our understanding of the initiation stages of rubber biosynthesis and laticifer differentiation.

Global burden of MDR-TB and XDR-TB attributable to high fasting plasma glucose from 1990 to 2019: a retrospective analysis based on the global burden of disease study 2019.

PURPOSE: High fasting plasma glucose (HFPG) has been identified as a risk factor for drug-resistant tuberculosis incidence and mortality. However, the epidemic characteristics of HFPG-attributable multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) remain unclear. We aimed to analyze the global spatial patterns and temporal trends of HFPG-attributable MDR-TB and XDR-TB from 1990 to 2019. METHODS: Utilizing data from the Global Burden of Disease 2019 project, annual deaths and disability-adjusted life years (DALYs) of HFPG-attributable MDR-TB and XDR-TB were conducted from 1990 to 2019. Joinpoint regression was employed to quantify trends over time. RESULTS: From 1990 to 2019, the deaths and DALYs due to HFPG-attributable MDR-TB and XDR-TB globally showed an overall increasing trend, with a significant increase until 2003 to 2004, followed by a gradual decline or stability thereafter. The low sociodemographic index (SDI) region experienced the most significant increase over the past 30 years. Regionally, Sub-Saharan Africa, Central Asia and Oceania remained the highest burden. Furthermore, there was a sex and age disparity in the burden of HFPG-attributable MDR-TB and XDR-TB, with young males in the 25-34 age group experiencing higher mortality, DALYs burden and a faster increasing trend than females. Interestingly, an increasing trend followed by a stable or decreasing pattern was observed in the ASMR and ASDR of HFPG-attributable MDR-TB and XDR-TB with SDI increasing. CONCLUSION: The burden of HFPG-attributable MDR-TB and XDR-TB rose worldwide from 1990 to 2019. These findings emphasize the importance of routine bi-directional screening and integrated management for drug-resistant TB and diabetes.

Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

BACKGROUND: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.) are needed to contextualize reports following COVID-19 vaccination. METHODS: We estimated annual and monthly IRs of overall TTS, common site TTS, and unusual site TTS for adults aged 18-64 years in Carelon Research and MarketScan commercial claims (2017-Oct 2020), CVS Health and Optum commercial claims (2019-Oct 2020), and adults aged ≥ 65 years using CMS Medicare claims (2019-Oct 2020); IRs were stratified by age, sex, and race/ethnicity (CMS Medicare). RESULTS: Across data sources, annual IRs for overall TTS were similar between Jan-Dec 2019 and Jan-Oct 2020. Rates were higher in Medicare (IRs: 370.72 and 365.63 per 100,000 person-years for 2019 and 2020, respectively) than commercial data sources (MarketScan IRs: 24.21 and 24.06 per 100,000 person-years; Optum IRs: 32.60 and 31.29 per 100,000 person-years; Carelon Research IRs: 24.46 and 26.16 per 100,000 person-years; CVS Health IRs: 30.31 and 30.25 per 100,000 person-years). Across years and databases, common site TTS IRs increased with age and were higher among males. Among adults aged ≥ 65 years, the common site TTS IR was highest among non-Hispanic black adults. Annual unusual site TTS IRs ranged between 2.02 and 3.04 (commercial) and 12.49 (Medicare) per 100,000 person-years for Jan-Dec 2019; IRs ranged between 1.53 and 2.67 (commercial) and 11.57 (Medicare) per 100,000 person-years for Jan-Oct 2020. Unusual site TTS IRs were higher in males and increased with age in commercial data sources; among adults aged ≥ 65 years, IRs decreased with age and were highest among non-Hispanic American Indian/Alaska native adults. CONCLUSION: TTS IRs were generally similar across years, higher for males, and increased with age. These rates may contribute to surveillance of post-vaccination TTS.

Characteristics and surgery outcomes of macular hole diagnosed after rhegmatogenous retinal detachment repair.

PURPOSE: To report the characteristics and the visual and anatomical outcomes of secondary macular holes (SMHs) diagnosed after rhegmatogenous retinal detachment (RRD) repair and their associated factors. METHODS: Retrospective, interventional case series. All consecutive patients who were diagnosed with SMH after RRD repair at Beijing Tongren eye center from January 2016 to April 2021 were included. Patients who had their primary RRD repair in other hospitals and were referred to our center after diagnosis of SMH were also included. The minimum follow-up time after RRD repair was 6 months. RESULTS: 37 SMHs were diagnosed within a series of 5696 RRDs. Including 24 eyes referred from other hospitals after the diagnosis of SMH, 61 eyes were included. The type of primary RRD repair surgery included 22/61 (36%) eyes with scleral buckling procedure (SBP) and 39/61 (64%) eyes with pars plana vitrectomy (PPV). 21/61 (34%) eyes had recurrent RD. The median time to SMH diagnosis was 150 days (range, 7 ~ 4380 days). Macular hole (MH) closure was achieved in 77% eyes. Visual acuity (VA) improvement of at least 2 lines of Snellen's visual acuity was observed in 51% eyes. Final MH closure status was associated with preoperative MH diameter (for every 50 µm increment) (P = 0.046, OR = 0.875, 95%CI: 0.767 ~ 0.998). VA improvement was associated with final MH closure status (P = 0.009, OR = 8.742, 95%CI: 1.711 ~ 44.672). Final VA (logMAR) was associated with recurrent RD (P < 0.001, B = 0.663, 95%CI: 0.390 ~ 0.935), preoperative MH diameter (P = 0.001, B = 0.038, 95%CI: 0.017 ~ 0.058), VA at the time of SMH diagnosis (P < 0.001, B = 0.783, 95%CI: 0.557 ~ 1.009) and final MH closure status (P = 0.024, B = -0.345, 95%CI: -0.644 ~ -0.046). For patients without recurrent RD, VA improvement and final VA was associated with final MH closure status (P = 0.016 and P < 0.001, respectively), while for patients with recurrent RD, VA improvement or final VA did not associate with final MH closure status (P > 0.05). CONCLUSION: For SMH diagnosed after RRD repair, final MH closure status was associated with preoperative MH diameter. Recurrent RD, larger preoperative MH diameter, worse VA at the time of SMH diagnosis and failed MH closure are predictive factors for worse final VA. Visual outcome is associated with final MH closure status in patients without recurrent RD, but not as so in patients with recurrent RD.

NAMPT mediates PDGF-induced pulmonary arterial smooth muscle cell proliferation by TLR4/NF-κB/PLK4 signaling pathway.

Nicotinamide phosphoribosyltransferase (NAMPT), a pleiotropic protein, promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which is associated with the genesis and progression of pulmonary arterial hypertension (PAH). NAMPT is highly increased in PAH patient's plasma and highly relevant to PAH severity. The mRNA and protein levels of NAMPT are elevated in PAH animal models. However, the underlying molecular mechanisms how NAMPT mediated platelet-derived growth factor (PDGF)-induced PASMCs proliferation are still unclear. The present study aimed to address these issues. Primary cultured PASMCs were attained from male Sprague-Dawley (SD) rats. Western blotting, RT-PCR, ELISA, cell transfection, Cell Counting Kit-8 (CCK-8) and EdU incorporation assays were used in the experiments. We showed that PDGF upregulated NAMPT expression through the activation of signal transducers and activators of transcription 5 (STAT5), and elevated extracellular NAMPT further promoted the activation of NF-κB through Toll-like receptor 4 (TLR4), which ultimately upregulated polo-like kinase 4 (PLK4) expression leading to PASMCs proliferation. Knockdown of STAT5, NAMPT or PLK4, and inhibition of TLR4 or NF-κB suppressed PDGF-induced PASMCs proliferation. Our study suggests that NAMPT plays an essential role in PDGF-induced PASMCs proliferation via TLR4/NF-κB/PLK4 pathway, suggesting that targeting NAMPT might be valuable in ameliorating pulmonary arterial hypertension.

HMGB1-induced activation of ER stress contributes to pulmonary artery hypertension in vitro and in vivo.

BACKGROUND: HMGB1 and ER stress have been considered to participate in the progression of pulmonary artery hypertension (PAH). However, the molecular mechanism underlying HMGB1 and ER stress in PAH remains unclear. This study aims to explore whether HMGB1 induces pulmonary artery smooth muscle cells (PASMCs) functions and pulmonary artery remodeling through ER stress activation. METHODS: Primary cultured PASMCs and monocrotaline (MCT)-induced PAH rats were applied in this study. Cell proliferation and migration were determined by CCK-8, EdU and transwell assay. Western blotting was conducted to detect the protein levels of protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor-4 (ATF4), seven in absentia homolog 2 (SIAH2) and homeodomain interacting protein kinase 2 (HIPK2). Hemodynamic measurements, immunohistochemistry staining, hematoxylin and eosin staining were used to evaluate the development of PAH. The ultrastructure of ER was observed by transmission electron microscopy. RESULTS: In primary cultured PASMCs, HMGB1 reduced HIPK2 expression through upregulation of ER stress-related proteins (PERK and ATF4) and subsequently increased SIAH2 expression, which ultimately led to PASMC proliferation and migration. In MCT-induced PAH rats, interfering with HMGB1 by glycyrrhizin, suppression of ER stress by 4-phenylbutyric acid or targeting SIAH2 by vitamin K3 attenuated the development of PAH. Additionally, tetramethylpyrazine (TMP), as a component of traditional Chinese herbal medicine, reversed hemodynamic deterioration and vascular remodeling by targeting PERK/ATF4/SIAH2/HIPK2 axis. CONCLUSIONS: The present study provides a novel insight to understand the pathogenesis of PAH and suggests that targeting HMGB1/PERK/ATF4/SIAH2/HIPK2 cascade might have potential therapeutic value for the prevention and treatment of PAH.

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BACKGROUND: Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations. METHODS: We conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell's Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). RESULTS: The primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies' results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP. CONCLUSION: We did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.

Low miR-182-5p Expressing Extracellular Vesicles Derived From Human Bone Marrow Stromal Cells of Subjects With Steroid-Induced Osteonecrosis of the Femoral Head Aggravate Disease Progression.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory, progressive disease. However, the underlying mechanisms that aggravate femoral head necrosis remain unclear. Extracellular vesicles (EVs) act as molecular carriers in intercellular communication. We hypothesize that EVs derived from human (h) bone marrow stromal cells (BMSC) resident in SONFH lesion areas promote the pathogenesis of SONFH. In the present study, we determined the modulatory effects of SONFH-hBMSCs-derived EVs on the pathogenesis of SONFH in vitro and in vivo. We found that the expression of hsa-miR-182-5p was downregulated in SONFH-hBMSCs and EVs isolated from those hBMSCs. After tail vein injection, EVs isolated from hBMSCs transfected with hsa-miR-182-5p inhibitor aggravated femoral head necrosis in the SONFH mouse model. We conclude that miR-182-5p regulates bone turnover in the SONFH mouse model via targeting MYD88 and subsequent upregulation of RUNX2 expression. We further assume that EVs derived from hBMSCs resident in SONFH lesion areas aggravate femoral head necrosis by downregulating miR-182-5p secreted from hBMSC located outside these lesions. We suggest that miR-182-5p could provide a novel target for future therapeutic approaches to treat or prevent SONFH. © 2023 American Society for Bone and Mineral Research (ASBMR).

Agar-based hydrogel polymer electrolyte for high-performance zinc-ion batteries at all climatic temperatures.

Aqueous zinc-ion batteries (ZIBs) have received numerous attention because of their inherent safety and low cost. However, ZIBs are highly sensitive to temperature; the realization of full-temperature ZIBs is of great importance. In this study, an agar-based composite hydrogel polymer electrolyte (AG-HGPE) with the blend of agar and polyacrylamide (PAM) was prepared. It has a non-porous homogeneous structure, and shows various merits, e.g., strong liquid absorption rate, good mechanical properties, and large Zn2+ transference number. The corresponding Zn-symmetric cells possess reversible zinc stripping/plating phenomenon up to 500 h at a current density of 1 mA cm-2 and an areal capacity of 1 mAh cm-2. The Zn/AG-HGPE/V2O5 cells exhibit good rate performance and stable cyclic behaviors at -25°C, 25°C and 50°C, as well as excellent adaptability to the changes of ambient temperature. The research paves a new route for developing green energy storage devices running in wide temperature range.

Using organo-mineral complex material to prevent the migration of soil Cd and As into crops: An agricultural practice and chemical mechanism study.

The migration and transformations of Cd and As in soil are different, so it is difficult to simultaneously control them. In this study, an organo-mineral complex (OMC) material was prepared using modified palygorskite and chicken manure, the Cd and As adsorption capacities and mechanism of the OMC were explored, and the response of the crop to the OMC was clarified. The results show that the maximum Cd and As adsorption capacities of the OMC under pH values of 6-8 are 12.19 mg·g-1 and 5.07 mg·g-1, respectively. In the OMC system, the modified palygorskite contributed more to the adsorption of the heavy metals than the organic matter. Cd2+ may form CdCO3 and CdFe2O4, and AsO2- may form FeAsO4, As2O3, and As2O5 on the surfaces of the modified palygorskite. Organic functional groups such as hydroxyl, imino, and benzaldehyde groups can participate in the adsorption of Cd and As. The Fe species and carbon vacancy in the OMC system promote the conversion of As3+ into As5+. A laboratory experiment was conducted to compare five commercial remediation agents with OMC. Planting Brassica campestris in the OMC remediated soil with excessive contamination increased the crop biomass and decreased the Cd and As accumulation sufficiently to meet the current national food safety standards. This study emphasizes the effectiveness of OMC in preventing the migration of Cd and As into crops while promoting crop growth, which can provide a feasible soil management strategy for CdAs co-contaminated farmland soil.

A comparative study of transscleral sutured intraocular lens fixation and sutureless flanged intraocular lens fixation.

BACKGROUND: To compare the intraocular lens (IOL) tilt and decentration and visual outcomes of transscleral sutured IOL fixation and sutureless flanged IOL fixation. To investigate the influence of IOL tilt and decentration on internal higher-order aberrations (HOAs) in these two techniques. METHODS: Patients who received transscleral sutured or sutureless flanged IOL fixation procedures were included in this prospective, non-randomized, comparative study. Corrected distance visual acuity (CDVA) was measured at baseline and at every postoperative visit for 12 months. IOL tilt and decentration were measured using a second-generation anterior segment optical coherence tomography (Casia2) and internal HOAs were measured using iTrace Visual Function Analyzer at 3 months postoperatively. RESULTS: The study included 27 eyes from the transscleral sutured IOL fixation group and 26 eyes from the sutureless flanged IOL fixation group. There was no significant difference in CDVA between the two groups at all time points. The two groups did not differ in refractive difference from the predicted value, corneal endothelial cell loss, IOL tilt, IOL decentration, internal astigmatism or internal HOAs. Vertical IOL decentration significantly correlated with total internal optical aberration (r = 0.288, P = 0.036), total internal HOA (r = 0.440, P = 0.001), internal coma (r = 0.348, P = 0.001), vertical internal coma (r = 0.388, P = 0.004), average height of modulation transfer function (r = - 0.364, P = 0.007) and Strehl ratio (r = - 0.297, P = 0.031). Horizontal IOL decentration significantly correlated with horizontal internal coma (r = 0.312, P = 0.023). CONCLUSIONS: Transscleral sutured IOL fixation and sutureless flanged IOL fixation had similar IOL positions and visual outcomes. IOL decentrations correlated with internal HOAs and thus should be avoided.

MTCLF: A multitask curriculum learning framework for unbiased glaucoma screenings.

BACKGROUND AND OBJECTIVE: Glaucoma is a disease that causes irreversible damage to the optic nerve. Research on accurate automatic screening algorithms is essential for the prevention and treatment of glaucoma. However, due to the imbalance of existing datasets and the existence of some hard samples that accompany other diverse and complex fundus diseases, the performance of current glaucoma screening algorithms is limited. In addition, the lack of interpretability also makes it difficult for the current algorithms to meet the requirements of clinical applications. METHOD: In this paper, we propose a new multitask curriculum learning framework (MTCLF) for unbiased glaucoma screenings and visualizations of model decision-making areas. MTCLF is a teacher-student framework. The teacher network is used to generate the label evidence map. The student network can diagnose glaucoma and predict the evidence map at the same time with the well-designed dual-branch CNN structure and collaborative learning module. We design two curriculum coefficients θ and σ to guide the training process of the student network in the sample space so that the student network can adaptively balance the sample contribution, reduce the prediction bias and mine hard samples. RESULTS: The experimental results show that the accuracy, sensitivity, specificity, AUC and F2-score of MTCLF based on the LAG dataset for glaucoma diagnoses are 0.967, 0.961, 0.970, 0.996, and 0.958, respectively. These results are superior to those of the state-of-the-art methods. CONCLUSION: MTCLF not only achieves the best performance for unbiased glaucoma diagnoses but also generates a reliable evidence map to help clinicians explore fine lesion areas.

Next-generation sequencing panel analysis in 24 Chinese patients with congenital ectopia lentis.

BACKGROUND: Congenital ectopia lentis (CEL) is a rare but serious disease. We use next-generation sequencing to detect genes associated with lens abnormalities in 24 patients with bilateral CEL and search for pathogenic genes and mutation sites. MATERIALS AND METHODS: A total of 24 patients diagnosed with CEL from January 2019 to November 2019 were enrolled in this study, and their clinical data were collected and genome-wide deoxyribonucleic acid was extracted from peripheral venous blood. Targeted gene capture technology was used to obtain 188 exons of lens abnormality-related genes, which were sequenced using a high-throughput method. The mutation sites were determined through data analysis and verified by the Sanger method. According to the data from previous studies, the association between the genotype and clinical phenotype was analysed. RESULT: Of the 24 patients, 23 had mutations in the fibrillin-1 (FBN1) gene, and 20 were diagnosed with Marfan syndrome. The 23 cases of FBN1 mutations were all heterozygous mutations, including 17 missense mutations, 3 splicing variants, 2 exon deletion mutations, 1 codon mutation, and 9 new mutations. A total of 17 mutations were located in the calcium-binding epidermal growth factor domain, including 16 mutations that contained missense mutations of cysteine. In addition, a heterozygous mutation of the gap junction protein alpha 8 (GJA8) gene was detected in one patient. CONCLUSION: In this study, we identified 23 FBN1 gene mutations and 1 GJA8 gene mutation in 24 patients with CEL. Of these, 9 new FBN1 mutations and 14 known mutations were found. The results expanded the mutation spectrum of the FBN1 gene, suggesting that FBN1 mutation may be the main cause of CEL in Chinese patients.

Feasibility of Apatinib in Radioiodine-Refractory Differentiated Thyroid Carcinoma.

Objectives: Our aim was to describe our experience in using apatinib as treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC). Methods: Forty-seven patients undergoing apatinib treatment for RAIR-DTC were prospectively enrolled in this study. The study endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and rate of adverse events. Results: No patients achieved complete response, while 36 (76.6%) and 8 (17.0%) patients achieved partial response and stable disease, respectively. The ORR and DCR were 76.6% and 93.6%, respectively. The median PFS and OS were 18 and 59 months, respectively. A total of 91 adverse events occurred, of which 21 were graded as grade 3 or higher. There were no drug-related deaths. Conclusions: Apatinib has distinct anti-RAIR-DTC efficacy in terms of ORR, PFS, and OS and has a favorable safety profile. It is a feasible treatment option for RAIR-DTC.

Clinical Features and Mortality of Endogenous Panophthalmitis in China: A Six-Year Study.

PURPOSE: To report the clinical features, treatment strategy, and mortality of patients with endogenous panophthalmitis (EP). METHODS: Fifteen patients (16 eyes) diagnosed with EP from December 2012 to December 2018 were investigated with a standard protocol at a tertiary medical center of the largest eye center in Northern China. Mortality was followed up. RESULTS: All participants were Han Chinese. The mean age was 58.3, 62.5% were male, and 93.3% were unilaterally involved. The average number of predisposing factors was 3.0. The top two predisposing factors were diabetes mellitus (DM, 93.3%) and pyogenic liver abscess (PLA, 66.7%). All patients initially presented at an ophthalmic emergency due to severe ocular symptoms. All patients were co-managed by relevant specialists and were admitted to medical or surgical wards instead of the eye center unless the systemic condition was well controlled. Only four eyes were eligible for vitrectomy. The mean follow-up duration was 12.5 months. The mortality rate was 0%. The predominant causative organism was Klebsiella pneumoniae (80.0%), and there were no positive fungal cases. CONCLUSIONS: EP is a rare, life-threatening disease. DM and PLA could predispose its development. The predominant causative organism was Klebsiella pneumoniae. The interdisciplinary cooperation system of the management of EP may reduce the mortality rate.Abbreviations :EP: endogenous panophthalmitis; EE: endogenous endophthalmitis; DM: diabetes mellitus; PLA: pyogenic liver abscess; ACI: acute cerebral infarction; UTI: urinary tract infection; ICU: intensive care unit; VA: visual acuity; LP: light perception; HM: hand motion; NLP: no light perception; K. pneumoniae: Klebsiella pneumoniae; CT: computed tomography; MRI: magnetic resonance imaging; CRP: C-reactive protein; PCT: procalcitonin; FBG: fasting blood glucose; WBC: white blood cell; NEUT: neutrophil proportion; BDG: 1,3-ß-D-glucan; GM: galactomannan; IVI: intravitreal injection; PPV: pars plana vitrectomy; ILAS: invasive liver abscess syndrome; cps: capsular polysaccharide; CSF: cerebrospinal fluid; SD: standard deviation.

Quantitative CT parameters correlate with lung function in chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Objective: This study aimed to analyze the correlation between quantitative computed tomography (CT) parameters and airflow obstruction in patients with COPD. Methods: PubMed, Embase, Cochrane and Web of Knowledge were searched by two investigators from inception to July 2022, using a combination of pertinent items to discover articles that investigated the relationship between CT measurements and lung function parameters in patients with COPD. Five reviewers independently extracted data, and evaluated it for quality and bias. The correlation coefficient was calculated, and heterogeneity was explored. The following CT measurements were extracted: percentage of lung attenuation area <-950 Hounsfield Units (HU), mean lung density, percentage of airway wall area, air trapping index, and airway wall thickness. Two airflow obstruction parameters were extracted: forced expiratory volume in the first second as a percentage of prediction (FEV1%pred) and FEV1 divided by forced expiratory volume lung capacity. Results: A total of 141 studies (25,214 participants) were identified, which 64 (6,341 participants) were suitable for our meta-analysis. Results from our analysis demonstrated that there was a significant correlation between quantitative CT parameters and lung function. The absolute pooled correlation coefficients ranged from 0.26 (95% CI, 0.18 to 0.33) to 0.70 (95% CI, 0.65 to 0.75) for inspiratory CT and 0.56 (95% CI, 0.51 to 0.60) to 0.74 (95% CI, 0.68 to 0.80) for expiratory CT. Conclusions: Results from this analysis demonstrated that quantitative CT parameters are significantly correlated with lung function in patients with COPD. With recent advances in chest CT, we can evaluate morphological features in the lungs that cannot be obtained by other clinical indices, such as pulmonary function tests. Therefore, CT can provide a quantitative method to advance the development and testing of new interventions and therapies for patients with COPD.