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Background Internet addiction (IA) among adolescents has become a global health problem, and public awareness of it is increasing. Many IA risk factors relate to parents and the family environment. This study examined the relationship between IA and parenting approaches and family functionality. Methods A cross-sectional study was conducted with 2021 secondary students to identify the prevalence of IA and to explore the association between adolescent IA and familial variables, including parents’ marital status, family income, family conflict, family functionality, and parenting approaches. Results The results revealed that 25.3 % of the adolescent respondents exhibited IA, and logistic regression positively predicted the IA of adolescents from divorced families, low-income families, families in which family conflict existed, and severely dysfunctional families. Interestingly, adolescents with restricted Internet use were almost 1.9 times more likely to have IA than those whose use was not restricted. Conclusions Internet addiction is common among Chinese adolescents in Hong Kong, and family-based prevention strategies should be aligned with the risk factors of IA.

Remote,rural ethnic-minority communities face greater disaster-related public health risks due to their lack of resources and limited access to health care.The Ethnic Minority Health Project(EMHP) was initiated in 2009 to work with remote,disaster-prone ethnic-minority villages that live in extreme poverty.One of the project’s aims is to develop and evaluate bottom-up health risk reduction efforts in emergency and disaster risk management(HealthEDRM).This article shares project updates and describes field intervention results from the Yi ethnic community of Hongyan village in China’s Sichuan Province,an area that experiences recurrent floods.It was found that 64% of the village respondents had never considered any form of disaster preparation,even with the recurrent flood risks.Health intervention participants showed sustained knowledge retention and were nine times more likely to know the correct composition of oral rehydration solution(ORS) after the intervention.Participants also retained the improved knowledge on ORS and disaster preparedness kit ownership12 months after the intervention.

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac 1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion （tMCAO） was performed on Epacl-deficient （Epacl-/- ） mice, Epac2-deficient （Epac2-/-） mice, and their wild type counter-parts （Epacl＋/＋ and Epac2＋/＋）. Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neu-ronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 （AQP4）, glial fibrillary acidic protein （GFAP）, peroxiredoxin 6 （Prx6） were observed in ipsilateral retinae. Epac2 / ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2＋/＋. However, Epacl-/- ipsilateral retinae displayed similar pathology as those in Epacl＋/＋ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.

BackgroundTreatment cessation in chronic HBV infection may be durable in certain patient subgroups before hepatitis B surface antigen (HBsAg) seroclearance. The role of serum HBV RNA in determining treatment cessation suitability has not been well-investigated.MethodsNucleos(t)ide analogue (NUC) treatment was discontinued in non-cirrhotic patients with chronic HBV with serum HBsAg <200 IU/mL and fulfilling internationally recommended criteria for treatment cessation. Patients were monitored till 48 weeks with baseline and serial measurements of serum HBsAg, HBV RNA and hepatitis B core-related antigen. NUCs were resumed when HBV DNA reaches >2000 IU/mL regardless of alanine aminotransferase (ALT) levels.Results114 entecavir-treated patients (median age 58.4 years, median serum HBsAg 54.4 IU/mL) with median treatment duration of 6.7 years were recruited. The 48-week cumulative rate of HBV DNA >2000 IU/mL was 58.1%. End-of-treatment serum HBV RNA and off-treatment serial HBV RNA were both independently associated with HBV DNA >2000 IU/mL (HR 2.959, 95% CI 1.776 to 4.926, p<0.001; HR 2.278, 95% CI 1.151 to 4.525, p=0.018, respectively). Patients with HBV RNA ≥44.6 U/mL had a cumulative 48-week rate of 93.2%, while combining HBV RNA undetectability and HBsAg <10 IU/mL had a cumulative 48-week rate of 9.1%. 24 patients (38.7%) developed off-treatment ALT elevation, highest peak ALT was 1515 U/L. 8 patients (median serum HBsAg 2.6 IU/mL) developed HBsAg seroclearance.ConclusionSerum HBV RNA measurement is essential for deciding on entecavir cessation in patients with chronic HBV, especially with low HBsAg levels. Patients can be stratified on their risk of off-treatment relapse based on both viral determinants.Trial registration number NCT02738554

Bariatric surgery is effective for obesity management but associated with kidney stone formation. Give the different post-operative physiology between restrictive type and malabsorptive type bariatric surgery, this study aims to compare difference in post-operative lithogenic risk profiles between these surgical types by assessing the postoperative 24-hour urine chemistry profiles. We conducted a prospective cross-sectional study of consecutive adults undergoing bariatric surgery at a tertiary center in Hong Kong between April 2017 and October 2019. A total number of 35 patients underwent malabsorptive and 55 underwent restrictive procedures. Baseline demographics, comorbidities, and postoperative 24-hour urine chemistry were assessed within 12 months after surgery. Abnormal urinary parameters were identified, with between-group comparisons performed using Mann–Whitney U and Chi-squared tests. Propensity scores were estimated using selected covariates, and stabilized inverse probability of treatment weighting (IPTW) was applied. IPTW-weighted logistic regression was used to compare the odds of abnormal urinary parameters between surgical groups. At 12 months, the malabsorptive group demonstrated significantly higher urinary oxalate and lower urinary creatinine, potassium, calcium, magnesium, citrate, urate, pH, and calcium phosphate activity compared with the restrictive group. The prevalence of hyperoxaluria (51.4% vs. 25.5%, p  = 0.012), hypocitraturia (71.4% vs. 36.4%, p  = 0.001), and acidic urine (54.3% vs. 20.0%, p  = 0.001) was higher in the malabsorptive group. Conversely, hyperuricosuria was more common in restrictive patients (29.1% vs. 11.4%, p  = 0.049). No significant differences were observed for urine volume, sodium, phosphate, or calcium oxalate activity. IPTW-weighted logistic regression demonstrated that malabsorptive procedures were associated with significantly higher odds of hyperoxaluria (OR 2.95, 95% CI 1.03–8.44), hypocitraturia (OR 4.13, 95% CI 1.40–12.21), hypomagnesuria (OR 3.26, 95% CI 1.11–9.57), and acidic urine pH (OR 3.76, 95% CI 1.33–10.64). Malabsorptive bariatric surgery is associated with more lithogenic urinary profiles than restrictive surgery, particularly hyperoxaluria, hypocitraturia, hypomagnesuria, and acidic urine, underscoring increased risk of postoperative nephrolithiasis. Close monitoring of urinary parameters and multidisciplinary management are recommended to mitigate stone risk.

INTRODUCTION:Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions.METHODS:This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older. Participants were randomly assigned in a 1:1:1 ratio to undergo Endocuff with AI, AI alone, or standard high-definition (HD) colonoscopy. The primary outcome was adenoma detection rate (ADR) between the Endocuff-AI and AI groups while secondary outcomes included detection rates of polyp (PDR), sessile serrated lesion (sessile detection rate [SDR]), and advanced adenoma (advanced adenoma detection rate) between the 2 groups.RESULTS:A total of 682 patients were included (mean age 65.4 years, 52.3% male), with 53.7% undergoing diagnostic colonoscopy. The ADR for the Endocuff-AI, AI, and HD groups was 58.7%, 53.8%, and 46.3%, respectively, while the corresponding PDR was 77.0%, 74.0%, and 61.2%. A significant increase in ADR, PDR, and SDR was observed between the Endocuff-AI and AI groups (ADR difference: 4.9%, 95% CI: 1.4%-8.2%, P = 0.03; PDR difference: 3.0%, 95% CI: 0.4%-5.8%, P = 0.04; SDR difference: 6.4%, 95% CI: 3.4%-9.7%, P < 0.01). Both Endocuff-AI and AI groups had a higher ADR, PDR, SDR, and advanced adenoma detection rate than the HD group (all P < 0.01).DISCUSSION:Endocuff in combination with AI further improves various colonic lesion detection rates when compared with AI alone.

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort ( p  = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival ( p  = 0.002). Multivariate analysis identified histological type ( p  = 0.026), metastasis ( p  = 0.031) and KMT2C mutational status ( p  = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.

Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea‐binding aptamers using tissue‐SELEX on pig cornea. The top two abundant aptamers, Cornea‐S1 and Cornea‐S2, could bind to pig cornea, and their Kd values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer‐functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The Kd of Cornea‐S1‐ or Cornea‐S2‐functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea‐S1 or Cornea‐S2 enhanced liposome uptake within 15 min and extended retention to 24 h. Aptamer CsA liposomes achieved similar anti‐inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea‐S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break‐up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea‐SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases. Using pig cornea as a target, aptamers were selected using the tissue‐SELEX method. By attaching the aptamers to liposomes loaded with cyclosporin A, improved treatment of dry eye disease was achieved in vitro and in vivo.

Glioblastoma frequently exhibits therapy-associated subtype transitions to mesenchymal phenotypes with adverse prognosis. Here, we perform multi-omic profiling of 60 glioblastoma primary tumours and use orthogonal analysis of chromatin and RNA-derived gene regulatory networks to identify 38 subtype master regulators, whose cell population-specific activities we further map in published single-cell RNA sequencing data. These analyses identify the oligodendrocyte precursor marker and chromatin modifier SOX10 as a master regulator in RTK I-subtype tumours. In vitro functional studies demonstrate that SOX10 loss causes a subtype switch analogous to the proneural–mesenchymal transition observed in patients at the transcriptomic, epigenetic and phenotypic levels. SOX10 repression in an in vivo syngeneic graft glioblastoma mouse model results in increased tumour invasion, immune cell infiltration and significantly reduced survival, reminiscent of progressive human glioblastoma. These results identify SOX10 as a bona fide master regulator of the RTK I subtype, with both tumour cell-intrinsic and microenvironmental effects. Glioblastoma is divided into four subtypes based on molecular profiling at the methylome and transcriptome level. Here the authors perform an integrative analysis of these subtypes resulting in the identification of SOX10 whose loss induces a mesenchymal phenotype and promotes tumour progression.

Among the various targeting ligands for drug delivery, aptamers have attracted much interest in recent years because of their smaller size compared to antibodies, ease of modification, and better batch-to-batch consistency. In addition, aptamers can be selected to target both known and even unknown cell surface biomarkers. For drug loading, liposomes are the most successful vehicle and many FDA-approved formulations are based on liposomes. In this paper, aptamer-functionalized liposomes for targeted drug delivery are reviewed. We begin with the description of related aptamers selection, followed by methods to conjugate aptamers to liposomes and the fate of such conjugates in vivo. Then a few examples of applications are reviewed. In addition to intravenous injection for systemic delivery and hoping to achieve accumulation at target sites, for certain applications, it is also possible to have aptamer/liposome conjugates applied directly at the target tissue such as intratumor injection and dropping on the surface of the eye by adhering to the cornea. While previous reviews have focused on cancer therapy, the current review mainly covers other applications in the last four years. Finally, this article discusses potential issues of aptamer targeting and some future research opportunities.