Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Successful Treatment of Cutaneous Protothecosis Due to Prototheca wickerhamii with Terbinafine.

Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.

Multifunctional DNA Nanoflower Applied for High Specific Photodynamic Cancer Therapy in vivo.

Photodynamic therapy (PDT) is a newly emerged strategy for disease treatment. One challenge of the application of PDT drugs is the side-effect caused by the non-specificity of the photosensitive molecules. Most of the photosensitizers may invade not only the pathogenic cells but also the normal cells. In recent, people tried to use special cargoes to deliver the drugs into target cells. DNA nanoflowers (NFs) are a kind of newly-emerged nanomaterial which constructed through DNA rolling cycle amplification (RCA) reaction. It is reported that the DNA NFs were suitable materials which have been widely applied as nanocargos for drug delivery in cancer chemotherapeutic treatment. In this paper, we have introduced a new multifunctional DNA NF which could be prepared through an one-pot RCA reaction. This proposed DNA NF contained a versatile AS1411 G-quadruplex moiety, which plays key roles not only for specific recognition of cancer cells but also for near-infrared ray based photodynamic therapy when conjugating with a special porphyrin molecule. We demonstrated that the DNA NF showed good selectivity toward cancer cells, leading to highly efficient photo-induced cytotoxicity. Moreover, the in vivo experiment results suggested this DNA NF is a promising nanomaterial for clinical PDT.

Intention to have a third child among millennial parents with two children in eastern China: A cross-sectional survey.

AIM: This Study Aimed to Assess the Intention to Have a Third Child among Millennial Parents (25-40 years old) with Two Children in a City in Eastern China and to Explore the Influencing Factors Related to Fertility Intention. DESIGN: A cross-sectional design study. METHODS: A convenience sampling method was used to enrol participants of childbearing age who visited two tertiary hospitals in Hang zhou, a city in eastern China, from June 2021 to March 2022. We conducted a face-to-face questionnaire survey with 520 participants and calculated the prevalence of intention-related factors. Multivariate logistic regression was used to analyse the independent influencing factors of fertility intention. RESULTS: In total, 105 (20.2%) participants had the intention to have a third child. The results showed that 'employment status', 'age', 'reasons for wanting a third child', the considered 'biggest barrier to having a third child', 'views on the three-child policy', 'desired free services', 'supporting work policies' and 'assistance policies' were significant independent influencing factors of intention to have a third child (p-value < 0.05). The intention of the participants 'over 30 years old' was 2.466 times that of those '30 years old and under', and 'older age/personal health status' was considered the 'biggest barrier to having a third child'. Regarding policy and social reasons, the participants who need 'medical assistance' policy negatively affect the intention to have a third child (OR = 0.453, 95% CI = 0.247-0.830). IMPLICATIONS FOR HEALTHCARE/NURSING: Nursing plays an important role in health promotion. Nurses can help couples make wise decisions about fertility by providing professional consultation, education, evaluation and support. They can also provide corresponding nursing and guidance to improve couples' health quality and overall reproductive success. CONCLUSIONS: The general level of intention to have a third child of Millennial parents with two children is still low. The participants who are 'housewives/househusbands', 'over 30 years old', and satisfied with the state of 'medical assistance' have higher fertility intentions. PATIENT OR PUBLIC CONTRIBUTION: It is particularly meaningful for the policymakers to improve the social support system and raise universal awareness to encourage childbirth.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

A prospective and consecutive study assessing short-term clinical and radiographic outcomes of Chinese domestically manufactured 3D printing trabecular titanium acetabular cup for primary total hip arthroplasty: evaluation of 236 cases.

Purpose: We prospectively evaluate the short-term clinical and radiographic outcomes of the only Chinese domestically produced trabecular titanium acetabular cup(3D ACT™ cup) in primary total hip arthroplasty (THA), aiming to provide evidence-based support for its clinical application. Methods: A total of 236 patients, who underwent primary THA using 3D ACT™ cup in the Department of Joint Surgery at our hospital between January 2017 and June 2019, were included in this study. General patient data, imaging information, functional scores, and complications were collected to evaluate the early clinical efficacy. Results: All patients were followed up for 33-52 months, with an average of (42.2 ± 9.2) months. At the last follow-up, the preoperative HHS score increased significantly from 43.7 ± 6.8 to 85.6 ± 9.3 points (P < 0.01). Similarly, the preoperative WOMAC scores showed significant improvement from 59.2 ± 5.8 to 13.1 ± 3.5 points (P < 0.01). 92.3% of the patients expressed satisfaction or high satisfaction with the clinical outcome. Furthermore, 87.7% of the acetabular cups were positioned within the Lewinnek safe zone, achieving successful reconstruction of the acetabular rotation center. The cup survival rate at the last follow-up was 100%. Conclusions: The utilization of the only Chinese domestically manufactured 3D printing trabecular titanium acetabular cup in primary THA demonstrated favorable short-term clinical and radiographic outcomes. The acetabular cup exhibits excellent initial stability, high survival rate, and favorable osseointegration, leading to a significant enhancement in pain relief and functional improvement. In the future, larger sample sizes and multicenter prospective randomized controlled trials will be required to validate the long-term safety and effectiveness of this 3D ACT™ cup.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Tracking the carbon flows in municipal waste management in China.

Municipal solid waste (MSW), a carbon-intensive waste stream, may create both instant and indirect impacts onto environmental and climate management. Despite multiple studies made for greenhouse gases (GHGs) emissions of municipal waste, this research aims to achieve a comprehensive assessment for the carbon cycle by exploring evolution of waste composition and temporal-spatial disparities in waste management. Carbon flows embodied in MSW have been estimated across 31 provinces in Mainland China in the period 2000-2018. This improved estimation could be 15-40% smaller than the conventional estimation employing a constant waste composition. Aggregately some 578 ± 117 megatonnes carbon (MtC) were contained in MSW, including 239 ± 60 Mt of fossil carbon and 339 ± 58 Mt of degradable organic carbon. After treatment, 299 ± 66 MtC were possibly deposited in landfills and dumps. 279 ± 51 MtC were released to the atmosphere, creating net GHGs emissions equivalent to1870 ± 334 megatonnes of CO2 (MtCO2e). MSW generation in China nearly doubled during the period, net GHGs emissions increased by 1.8×, whereas fossil carbon grew by a factor of 3.5, mainly propelled by an increasing content of waste plastic in MSW. More rapid growth was witnessed in provinces in southern China than in northern. Distinct spatial-temporal evolution of waste and carbon metabolism was driven by increment, composition, and management effects. In the long run, the increment and composition effects may drop off. Enhanced practices of waste management integrating the circular economy are needed to fully recycle carbon flows, minimize emissions, and manage carbon deposits in aging landfills and dumps.

Candida auris-associated hospitalizations and outbreaks, China, 2018-2023.

The emerging human fungal pathogen Candida auris has become a serious threat to public health. This pathogen has spread to 10 provinces in China as of December 2023. Here we describe 312 C. auris-associated hospitalizations and 4 outbreaks in healthcare settings in China from 2018 to 2023. Three genetic clades of C. auris have been identified during this period. Molecular epidemiological analyses indicate that C. auris has been introduced and local transmission has occurred in multiple instances in China. Most C. auris isolated from China (98.7%) exhibited resistance to fluconazole, while only a small subset of strains were resistant to amphotericin B (4.2%) and caspofungin (2.2%).

Pregnancy management of IVF-ET pregnancies in a patient with classical 21-hydroxylase deficiency: A case report and review of the literature.

OBJECTIVE: To report a rare case of a woman with classical 21-hydroxylase deficiency who twice had singleton pregnancies with live births after in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Case report and literature review. PATIENT: A 35-year-old woman with classical 21-hydroxylase deficiency underwent external genital plastic surgery during adolescence and achieved second pregnancy after IVF-ET with long-term glucocorticoid replacement therapy. METHODS: During regular antenatal testing, we focus on monitoring patients' weight gain, blood pressure, increasing trend of uterine height and abdominal circumference, and fetal growth trend. Individualized glucocorticoid therapy during pregnancy, glucocorticoid stress dose at delivery, management of systemic metabolism to prevent maternal and infant complications, and newborn screening are realized. RESULT: In the second pregnancy, the glucocorticoid dosage was not increased. 17-hydroxyprogesterone and testosterone tended to increase in late pregnancy, but they were lower than in the first pregnancy. Blood pressure and blood glucose were normal, but lipids were abnormally elevated, D-dimer also showed a sharp rise under labor stress. A mature male infant was delivered by cesarean at 33+4 weeks of gestation due to placental abruption. CONCLUSION: Repeated pregnancies in patients with classical 21-hydroxylase deficiency are rare, especially with Assisted Reproductive Technology. We present a case including a comparison of her two pregnancy monitoring indicators, glucocorticoid medication and delivery to achieve a successful delivery. We review the available literature to analyze pregnancies with classical 21-hydroxylase deficiency.

Continuous glucose monitoring-derived glycemic metrics and adverse pregnancy outcomes among women with gestational diabetes: a prospective cohort study.

Background: Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM. Methods: We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes. Findings: Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8 mmol/L) to distinguish individuals with and without any adverse pregnancy outcome. Interpretation: The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine.

Combined effect of cortical superficial siderosis and cerebral microbleed on short-term and long-term outcomes after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes after ICH. METHODS: Based on a single-centre stroke registry database, patients with spontaneous ICH who had CT scan within 48 hours after ictus and MRI subsequently were identified. Eligible patients were divided into four groups (cSS-CMB-, cSS-CMB+, cSS+CMB-, cSS+CMB+) according to cSS and CMB on susceptibility-weighted image of MRI. Primary outcomes were haematoma volume on admission and unfavourable outcome defined as modified Rankin Scale scores ≥3 at 3 months. Secondary outcomes were all-cause death, recurrence of stroke and ICH during follow-up (median follow-up 2.0 years, IQR 1.0-3.0 years). RESULTS: A total of 673 patients were identified from 1044 patients with spontaneous ICH. 131 (19.5%) had cSS and 468 (69.5%) had CMB. Patients with cSS+CMB+ had the highest rate of poor outcome at 3 months, as well as all-cause death, recurrent stroke and ICH during follow-up. In cSS- patients, CMB was associated with smaller haematoma (ß -0.13; 95% CI -0.22 to -0.03; p=0.009), but it still increased risks of recurrent ICH (OR 4.6; 95% CI 1.3 to 15.6; p=0.015) and stroke (OR 2.0; 95% CI 1.0 to 4.0; p=0.049). These effects of CMB became unremarkable in the context of cSS+. CONCLUSIONS: Patients with different combinations of cSS and CMB have distinct patterns of short-term and long-term outcomes. Although CMB is related to restrained haematoma, it does not improve long-term outcomes. TRIAL REGISTRATION NUMBER: NCT04803292.

Multifunctional Photothermal Hydrogel in the Second Near-Infrared Window for Localized Tumor Therapy.

A copper selenide-embedded gellan gum hydrogel (Cu2-xSe@GG) is designed as an "all-in-one" antitumor agent. The obtained nanocomposite hydrogel exhibits strong near-infrared light absorption and high photothermal conversion efficiency in both the NIR-I and NIR-II biowindows. The photothermal conversion efficiency achieves 58.8% under the irradiation of 0.75 W/cm2 with a 1064 nm laser. Furthermore, the nanocomposite hydrogel has catalase- and peroxidase-mimicking activities, which could alter the tumor microenvironment by reducing hypoxia and/or increasing the production of reactive oxygen species. Moreover, the multifunctional Cu2-xSe@GG nanocomposite hydrogel can also be used as an immune agonist resiquimod (R848) carrier to promote immune regulation and enhance the therapeutic effect. The single-syringe R848/Cu2-xSe@GG treatment achieves synergetic photothermal immunotherapy, showing 97.4% of tumor regression rate from an initial large tumor of 300 mm3.

Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours (HOPE): protocol for a randomised, controlled, multicentre study.

BACKGROUND: While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke (AIS) within 4.5 hours of symptom onset, there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic window. AIM: To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5-24 hours after stroke onset (for stroke with unknown onset time, the midpoint of the time last known to be well and symptom recognition time; for wake-up stroke, the midpoint of the time last known to be well or sleep onset and wake up time) will benefit from intravenous thrombolysis. DESIGN: HOPE is a prospective, multicentre, randomised, open-label blinded endpoint trial with the stage of phase III. The treatment allocation employs 1:1 randomisation. The treatment arm under investigation is alteplase with standard therapy, the control arm is standard therapy. Eligibility imaging criteria include ischaemic core volume ≤70 mL, penumbra ≥10 mL and mismatch ≥20%. STUDY OUTCOMES: The primary outcome is non-disabled functional outcome (assessed as modified Rankin Scale score of 0-1 at 90 days). DISCUSSION: HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5-24 hours, which has the potential to extend time window and expand eligible population for thrombolysis therapy.

Thermo-Responsive Hydrogels Coupled with Photothermal Agents for Biomedical Applications.

Intelligent hydrogels are materials with abilities to change their chemical nature or physical structure in response to external stimuli showing promising potential in multitudinous applications. Especially, photo-thermo coupled responsive hydrogels that are prepared by encapsulating photothermal agents into thermo-responsive hydrogel matrix exhibit more attractive advantages in biomedical applications owing to their spatiotemporal control and precise therapy. This work summarizes the latest progress of the photo-thermo coupled responsive hydrogel in biomedical applications. Three major elements of the photo-thermo coupled responsive hydrogel, i.e., thermo-responsive hydrogel matrix, photothermal agents, and construction methods are introduced. Furthermore, the recent developments of these hydrogels for biomedical applications are described with some selected examples. Finally, the challenges and future perspectives for photo-thermo coupled responsive hydrogels are outlined.

Combination therapy with itraconazole and terbinafine for phaeohyphomycosis caused by Exophiala spinifera: A case report and literature review.

Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.