Impact of an Epstein-Barr Virus Serology-Based Screening Program on Nasopharyngeal Carcinoma Mortality: A Cluster-Randomized Controlled Trial.

PURPOSE: Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population. METHODS: Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538). RESULTS: A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856). CONCLUSION: In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.

Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular reactive oxygen species (ROS) in Prolactin-secreting Pituitary Adenoma.

AIMS: Dopamine agonists (DA) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. RESULTS: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to BRC both in vitro and in vivo. Mechanistically, we demonstrated that intracellular ROS function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NRF2 expression, which regulates intracellular ROS levels, thereby enhancing cell viability, and conferring DA resistance to PA cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL-adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas.

Role of the screening with coronary computed tomography angiography on lipid management and risk factors control in an asymptomatic Chinese population: a community-based, parallel-group, open-label, randomized clinical trial (RESPECT2).

BACKGROUND: Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. METHODS: Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12 months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12 months, mean changes in lipid levels from baseline to 12 months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. DISCUSSION: The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Theoretical study of piezoelectric and light absorption properties, and carrier mobilities of Janus TiPX (X = F, Cl, and Br) monolayers.

Janus TiPX (X = F, Cl, and Br) monolayers were systematically investigated through first-principles calculations. The Janus TiPX monolayers exhibit mechanical and dynamic stability. Two monolayers are indirect bandgap semiconductors, except the TiPBr monolayer, which has the features of a quasi-direct bandgap semiconductor. Biaxial strain can modify the band gap of single layers. The Janus TiPX monolayers have remarkable flexibility and piezoelectric properties. In particular, the TiPF monolayer shows high horizontal (44.18 pm V-1) and vertical piezoelectric coefficients (-3.59 pm V-1). These values exceed those of conventional bulk materials, like GaN (3.1 pm V-1) and α-quartz (2.3 pm V-1). All of the monolayers have absorption coefficients of 105 cm-1 for visible and ultraviolet (UV) light, which are one order of magnitude greater than that of MoSSe. Furthermore, TiPX monolayers have high carrier mobility. Janus TiPX monolayers represent a class of two-dimensional (2D) materials with exceptional properties and multifunctionality, holding significant promise for various applications in piezoelectric sensors, solar cells, and nano-electronic devices.

CDT1, transcriptionally regulated by E2F2, promotes lung adenocarcinoma progression.

CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.

Enhanced-permeability delivery system for hydroxyl radical-responsive NIR-II fluorescence-monitored thrombolytic therapy.

Pathological thrombus can cause serious acute diseases that present a significant threat to human health, such as myocardial infarction and stroke. Challenges remain in achieving effective thrombolysis and real-time monitoring of therapeutic effects while minimizing side effects. Herein,a multifunctional nanoplatform (TG-OPDEA@UK/MnO2-H1080) with enhanced thrombus-permeability was developed to monitor the therapeutic effect of antioxidant-thrombolysis by hydroxyl radical-responsive NIR-II fluorescence imaging. The polyzwitterion poly (oxidized N,N-Diethylaminoethyl methacrylate-co-n-butyl methacrylate) (OPDEA) was prepared as the matrix of nanoparticles to simultaneously loading urokinase (UK) and MnO2 QDs, as well as NIR-II fluorescent molecule, H-1080. Subsequently, the fibrin targeted peptide CREKA was modified on the surface of the nanoparticles. OPDEA exhibits efficient loading capacity while endowing nanoparticles with the ability to effectively increased penetration depth of UK by 94.1 % into the thrombus, for extensive thrombolysis and fluorescence monitoring. The loaded UK exhibited good thrombolytic effect and greatly reduced the risk of bleeding by 82.6 %. TG-OPDEA@UK/MnO2-H1080 showed good thrombolytic efficacy and specific thrombus monitoring in the mouse carotid artery thrombosis model induced by ferric chloride (FeCl3). This work prepares a nanoplatform for thrombolytic therapy and real-time efficacy assessment based on an independent externally forced thrombus penetration delivery strategy.

Cystoderma yongpingense sp. nov. (Squamanitaceae, Agaricales) a new species from southwestern China.

The present study introduces a novel fungus, Cystoderma yongpingense, which was identified in the southwestern region of China. The new species is characterized by a pileus that ranges in color from light orange-red to orange-red; the pileus has a wrinkled surface and is accompanied by a persistent annulus that is membranous and floccose-scaly. Above the annulus, the color transitions from white to yellowish brown. This proposal is substantiated through analyses encompassing both morphological characteristics and phylogenetic relationships. The phylogenetic position of the newly discovered species has been further corroborated through comprehensive maximum likelihood and Bayesian sequence analyses of the ITS + nrLSU DNA regions. Additionally, the technical description of C. yongpingense is enhanced by detailed illustrations and comparative studies with species that are closely related.

Utilizing A hydrophobic primary container surface to reduce the formation of subvisible particles in monoclonal antibody solution caused by fluid shear.

The exposure of protein molecules to interfaces may cause protein aggregation and particle formation in protein formulations, especially hydrophobic interfaces, which may promote protein aggregation in solution. In this study, we found that modification of the surface properties by application of a hydrophobic Octadecyltrichlorosilane (OTS) could reduce the generation of protein aggregates and particles in protein solution induced by fluid shear. A stable protein adsorption layer was formed at the hydrophobic interface through the strong hydrophobic interaction between the protein and hydrophobic surface, which could prevent the aggregated protein from falling off into the bulk solution to form subvisible particles and insoluble protein aggregates. In addition, human complement enzyme linked immunosorbent assay results showed that the particles that were generated in the OTS-coated container did not activate human complement which indicated the OTS-coated container could be used as primary containers for certain types of monoclonal antibody formulation.

Dengue epidemic in China before 1978.

Dengue, an acute febrile disease transmitted by Aedes mosquitoes, is caused by the dengue virus (DENV), presenting a formidable challenge to global public health. By examining clues from ancient Chinese books and conducting a comprehensive review, this study elucidates the characteristics of potential dengue epidemics in China prior to 1978. This evidence indicates that China may not have experience dengue epidemics before 1840. During 1840-1949, however, it experienced a noticeable dengue occurrence and prevalence in the 1870s, 1920s, and 1940s. Then from 1949 to 1978, only sporadic reports were accounted. The disparity in the frequency of dengue occurrences across three time periods suggests that the persistent characteristic of dengue epidemics in China primarily arises from imported cases resulting from international exchanges, subsequently leading to local outbreaks influenced by global epidemic trend. This research offers a novel perspective on retrospectively examining the historical trajectory of dengue epidemics and provides valuable insights into exploration of DENV epidemic patterns.

Optimal dosing regimen of caspofungin in adolescents with allogeneic haematopoietic stem cell transplantation.

OBJECTIVES: The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures. METHODS: Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM. RESULTS: A total of 86 samples of 30 adolescents (12-17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population. CONCLUSIONS: Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.

Real-world effectiveness and safety of advanced therapies for the treatment of moderate-to-severe ulcerative colitis: Evidence from a systematic literature review.

BACKGROUND: Effectiveness and safety of advanced therapies for ulcerative colitis (UC) warrant assessment in the real world. OBJECTIVE: To perform a systematic review and summarize real-world evidence of advanced therapies approved for moderate-to-severe UC. METHODS: A systematic literature review was conducted using real-world studies of biologics or small molecules in UC using Embase, MEDLINE, and MEDLINE-In Process databases. Only products approved in any jurisdiction during the search were included. English-language full-papers (January 2005 to February 2022) and congress abstracts (January 2019 to February 2022) were included. Studies with less than 30 patients or only biologic-naive patients were excluded. RESULTS: A total of 139 studies were included out of 3,930 identified articles (75%, published between 2019 and 2022; 64%, retrospective observational; 53%, from 5 countries [Italy, United States, Spain, United Kingdom, and Belgium]). Most studies were single agent (highest: vedolizumab = 50, tofacitinib = 24, and adalimumab = 18), and rates of clinical remission (CR) and adverse events varied widely. From the published comparative effectiveness studies (16), the rates of CR were numerically higher with vedolizumab vs anti-tumor necrosis factor (TNF)-α agents. Compared with vedolizumab, the effectiveness of tofacitinib was numerically greater in CR (occasionally significant). Rates of steroid-free CR were comparable between ustekinumab and tofacitinib. Infliximab was the most effective anti-TNFα agent, as reported by 2 studies. Remarkably, adverse events were similar across therapies in comparative studies. CONCLUSIONS: Vedolizumab and tofacitinib were the most assessed therapies. In comparative studies, remission rates were numerically higher with tofacitinib vs vedolizumab and for vedolizumab vs anti-TNFα. Tofacitinib was comparable with ustekinumab for steroid-free CR. Safety was comparable across therapies. Future studies should explore the literature gaps identified, including limited comparative studies with small sample sizes, variations in study designs and patient characteristics, varied definitions of CR, and limited use of patient-reported outcome measures in real-world settings.

The effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration.

The saline wastewater produced in industrial activities and seawater use would flow into wastewater treatment plants and affect the characteristic of extracellular polymeric substance (EPS) of activated sludge, which could potentially impact the removal of antibiotics via adsorption. Nonetheless, the effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration and the underlying mechanism remain largely unknown. In this study, the effect of salinity on the adsorption removal of a typical antibiotic, i.e., trimethoprim (TMP) at trace concentration (25.0 µg/L) was evaluated. The results showed the content of EPS was decreased significantly from 56.36 to 21.70 mg/g VSS when the salinity was increased from 0 to 10 g/L. Protein fractions occupied the predominant component of EPS, whose concentration was decreased from 38.17 to 12.83 mg/g VSS. The equilibrium adsorption capacity of activated sludge for TMP was decreased by 49.70% (from 4.97 to 2.50 µg/g VSS). The fluorescence quenching results indicated the fluorescence intensity of tryptophan-like substances was decreased by 30% and the adsorption sites of EPS were decreased from 0.51 to 0.21 when the salinity was increased. The infrared spectrum and XPS results showed that the nitrogen-containing groups from protein were decreased significantly. The circular dichroic analysis showed α helix structure of protein in EPS was decreased with the increase of salinity, which was responsible for the decrease of adsorption capacity for TMP.

Optimal therapeutic strategies for hepatic metachronous oligometastatic nasopharyngeal carcinoma: Insights from a retrospective study.

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC.

Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis.

OBJECTIVES: To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI. METHODS: The rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction (HAMI) group were established. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites. RESULTS: A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95. CONCLUSIONS: N8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.

A Robust Network Sodium Carboxymethyl Cellulose-Epichlorohydrin Binder for Silicon Anodes in Lithium-Ion Batteries.

Silicon (Si), as an ideal anode component for lithium-ion batteries, is susceptible to substantial volume changes, leading to pulverization and excessive electrolyte consumption, ultimately resulting in a rapid decline in the cycle stability. Herein, a new sodium carboxymethyl cellulose-epichlorohydrin (CMC-ECH) binder featuring a three-dimensional (3D) network cross-linked structure is synthesized by a simple ring-opening reaction, which can effectively bond the Si anode through abundant covalent and hydrogen bonds to mitigate its pulverization. Benefitting from the merits of the CMC-ECH binder, the electrochemical performance is significantly enhanced compared to the CMC binder. The CMC-ECH binder is applied to Si anodes, a specific capacity of 1054.2 mAh g-1 can be maintained at 0.2 C following 200 cycles under an elevated Si mass loading of around 1.0 mg cm-2, and the corresponding capacity retention is 65.6%. In the case of the LiFePO4//Si@CMC-ECH full battery, the cycle stability exhibits a substantial enhancement compared with the LiFePO4//Si@CMC full battery. Furthermore, the CMC-ECH binder demonstrates compatibility with micron-Si anode materials. Based on the above, we have successfully developed a facilely prepared water-based CMC-ECH binder that is suitable for Si and micron-Si anodes in lithium-ion batteries.

Suppression of HSV-1 infection and viral reactivation by CRISPR-Cas9 gene editing in 2D and 3D culture models.

Although our understanding of herpes simplex virus type 1 (HSV-1) biology has been considerably enhanced, developing therapeutic strategies to eliminate HSV-1 in latently infected individuals remains a public health concern. Current antiviral drugs used for the treatment of HSV-1 complications are not specific and do not address latent infection. We recently developed a CRISPR-Cas9-based gene editing platform to specifically target the HSV-1 genome. In this study, we further used 2D Vero cell culture and 3D human induced pluripotent stem cell-derived cerebral organoid (CO) models to assess the effectiveness of our editing constructs targeting viral ICP0 or ICP27 genes. We found that targeting the ICP0 or ICP27 genes with AAV2-CRISPR-Cas9 vectors in Vero cells drastically suppressed HSV-1 replication. In addition, we productively infected COs with HSV-1, characterized the viral replication kinetics, and established a viral latency model. Finally, we discovered that ICP0- or ICP27-targeting AAV2-CRISPR-Cas9 vector significantly reduced viral rebound in the COs that were latently infected with HSV-1. In summary, our results suggest that CRISPR-Cas9 gene editing of HSV-1 is an efficient therapeutic approach to eliminate the latent viral reservoir and treat HSV-1-associated complications.

Cost-Effectiveness of Varicella Vaccination for 1-4-Year-Olds in Shanghai, China.

INTRODUCTION: Varicella has not yet been included in the National Immunization Program (NIP) in China, and varicella vaccination strategies vary by region. To determine the optimal varicella vaccination strategy in Shanghai, China, the cost-effectiveness and 5-year costs of 5 immunization scenarios were analyzed. METHODS: A static decision tree-Markov model was developed in 2022 to assess the cost-effectiveness and 5-year costs of voluntary and routine varicella vaccination programs in the 2019 birth cohort in Shanghai from a societal perspective. Parameters were collected in 2022 from the varicella surveillance system, a questionnaire survey of 414 guardians of patients with childhood varicella, and semi-structured interviews with 20 experts on varicella outbreaks from different institutions in Shanghai. The outcomes included varicella cases avoided, quality-adjusted life year (QALY) loss, and incremental costs per QALY (ICER). The 5-year costs were compared with local medical expenditures. RESULTS: Among the 5 scenarios, one dose of routine varicella vaccination was the most cost-saving (USD 70.2) and cost-effective (Dominant) with a 5-year immunization expenditure of USD 9.9 million. Two doses of routine varicella vaccination had the highest QALY (29.9), and its ICER (USD 791.9/QALY) was below the willingness-to-pay threshold (USD 5,203-23,767/QALY). The 5-year immunization expenditure was USD 19.8 million. The effectiveness and price of vaccines, vaccination coverage, and per capita income are the 4 main factors that affect ICERs. CONCLUSIONS: In Shanghai, the 2 doses of routine varicella vaccination strategy for 1- and 4-year-olds with a 95% coverage rate was found to be the optimal varicella immunization strategy.

Gene therapy and gene editing strategies in inherited blood disorders.

Gene therapy has shown significant potential in treating various diseases, particularly inherited blood disorders such as hemophilia, sickle cell disease, and thalassemia. Advances in understanding the regulatory network of disease-associated genes have led to the identification of additional therapeutic targets for treatment, especially for ß-hemoglobinopathies. Erythroid regulatory factor BCL11A offers the most promising therapeutic target for ß-hemoglobinopathies and reduction of its expression using the commercialized gene therapy product Casgevy was approved for use in the UK and USA in 2023. Notably, the emergence of innovative gene editing technologies has further broadened the gene therapy landscape, presenting new possibilities for treatment. Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future.

Parental willingness to pay and preference for human papillomavirus vaccine for girls aged 9-14 in subsidy scenarios in Shanghai, China.

Multiple studies have documented low human papillomavirus (HPV) vaccine uptake among Chinese girls. It remains crucial to determine the parental willingness to pay (WTP) HPV vaccine for girls. We conducted a cross-sectional study recruiting 3904 parents with girls aged 9-14 in Shanghai, China, employing an online questionnaire with a convenience sampling strategy. Parental WTP, both range of payment and estimated point value, were determined for themselves (or wives) and daughters. HPV vaccine uptake was 22.44% in mothers and 3.21% in daughters. Respondents favored WTP ≤ 1000 CNY/138 USD for themselves (or wives), whereas showed increasing WTP along with valency of HPV vaccine for daughters (2-valent: 68.62% ≤1000 CNY/138 USD; 4-valent: 56.27% 1001-2000 CNY/138-277 USD; 9-valent: 65.37% ≥2001 CNY/277 USD). Overall, respondents showed higher WTP for daughters (median 2000 CNY/277 USD; IQR 1000-3600 CNY/138-498 USD) than for themselves (2000 CNY/277 USD; 1000-3500 CNY/138-483 USD) or wives (2000 CNY/277 USD; 800-3000 CNY/110-414 USD) (each p < .05). Furthermore, parental WTP was higher for international vaccine and 9-valent vaccine (each p < 0.05). Between two assumed government subsidy scenarios, parental preference for 9-valent vaccine remained consistently high for daughters (approximately 24% in each scenario), whereas preference for themselves (or wives) was sensitive to payment change between the subsidy scenarios. Using a discrete choice experiment, we found domestic vaccine was commonly preferred; however, certain sociodemographic groups preferred multivalent HPV vaccines. In conclusion, the valency of HPV vaccine may influence parental decision-making for daughters, in addition to vaccine price. Our findings would facilitate tailoring the HPV immunization program in China.

Designing Nanocomposite-Based Electrochemical Biosensors for Diabetes Mellitus Detection: A Review.

This review will unveil the development of a new generation of electrochemical sensors utilizing a transition-metal-oxide-based nanocomposite with varying morphology. There has been considerable discussion on the role of transition metal oxide-based nanocomposite, including iron, nickel, copper, cobalt, zinc, platinum, manganese, conducting polymers, and their composites, in electrochemical and biosensing applications. Utilizing these materials to detect glucose and hydrogen peroxide selectively and sensitively with the correct chemical functionalization is possible. These transition metals and their oxide nanoparticles offer a potential method for electrode modification in sensors. Nanotechnology has made it feasible to develop nanostructured materials for glucose and H2O2 biosensor applications. Highly sensitive and selective biosensors with a low detection limit can detect biomolecules at nanomolar to picomolar (10-9 to 10-12 molar) concentrations to assess physiological and metabolic parameters. By mixing carbon-based materials (graphene oxide) with inorganic nanoparticles, nanocomposite biosensor devices with increased sensitivity can be made using semiconducting nanoparticles, quantum dots, organic polymers, and biomolecules.