ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

Objective: To understand the growth and development levels of four physical measurements in children aged 3-6 years in China, so as to provide a reference for child nutrition improvement and health promotion. Methods: A stratified random sampling method was used to collect physical measurement data from 120 kindergartens 25 842 children aged 3-6 years across 24 provinces and cities in seven natural geographical regions of North China, Northeast China, East China, Central China, South China, Southwest China and Northwest China from 2020 to 2023. The development levels of head circumference, chest circumference, waist circumference, and hip circumference were evaluated using a grading method. The analysis of gender and age differences was conducted using Mann-Whitney U- test and Kruskal-Wallis test, and the comparison of abnormal detection rates for different genders was conducted using Chi square test. Results: The distribution range of children aged 3-6 was 51.74(50.08, 53.33) cm in terms of head circumference, 55.73(52.09, 59.04) cm in terms of chest circumference, 53.04(48.92, 56.40) cm in terms of waist circumference, and 59.36(56.30, 62.32) cm in terms of hip circumference. The detection rate of abnormal head circumference in boys and girls aged 3-6 years old was relatively high (19.71%-42.02%), and the detection rate of abnormal physical circumference development levels in boys was higher than that in girls of all ages ( χ 2=5.63-83.35, P <0.05). The detection rate of abnormal hip circumference (4.89%-6.53%) and chest circumference (4.51%-6.38%) in boys and girls aged 3-6 was relatively low, and there was no statistically significant difference in the abnormal rate between different ages and genders ( χ 2=0.00-1.61, 0.00-3.71, P >0.05). The detection rate of abnormal waist circumference in boys and girls aged 3-6 was relatively high (13.70%-42.45%), and the detection rate of abnormal waist circumference in girls was higher than that in boys aged 4-6 groups ( χ 2=10.49-58.18, P < 0.05). Conclusions The overall physical development of children aged 3-6 years in China is improving, but the abnormal detection rates for head circumference and waist circumference are relatively high. Child healthcare should focus on preventing and treating abdominal obesity, with differentiated health intervention strategies based on different age groups and genders.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

BACKGROUND

Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia.

This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team.

The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described.

Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder.

Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.

BACKGROUND AND OBJECTIVES

With the global population aging, there is an emerging need for access to quality longterm care (LTC) services. Many countries have developed LTC systems while others are at the infancy stage. This paper aimed to provide an overview of the country’s readiness for LTC based on the perspectives of relevant stakeholders. Specifically, it described the roles, initiatives, and challenges of relevant organizations and community leaders for LTC provision. It also described the older persons (OPs) and carers’ perspectives towards LTC including their awareness, capacity, and preferences.

The study utilized a descriptive design using qualitative methods of data collection namely key informant interviews (KIIs) and focus group discussions (FGDs). Participating institutions and their designated representatives were purposively sampled as key informants. OPs and carers from select barangays in NCR and Region IVA participated in the FGDs. Guided by the interpretivism approach, thematic analysis was performed. A trained research assistant coded the FGD and KII transcripts through the Nvivo PRO plus software and verified by the first author. Themes were reviewed and validated by the multidisciplinary team.

A total of 15 KIIs and two FGDs were conducted. The participating institutions and organizations were found to have varied roles and initiatives relevant to LTC; from strategic planning, development of policies and standards of care, training and capacity-building, and up to the actual implementation of LTC services. Identified challenges include implementation issues, financial issues, lack of political and stakeholder support, OPs and familial issues, and lack of knowledge on LTC.

Participants shared their description on what LTC is, an LTC facility, and the conditions of those in LTC facility. OPs expressed their willingness to utilize LTC services and identified several factors related to their preferred LTC arrangements. Carers identified various topics related to taking care of OPs that they would like to learn.

The roles, initiatives, and awareness of relevant stakeholders, older persons, and carers towards LTC were found to greatly vary. Policy makers, health workforce, families, communities, and the older persons themselves should have a better understanding of longterm care before they can provide or utilize the system. With the current landscape of LTC provision, the country still has a long way to go in achieving the integrated continuum of LTC appropriate to promote healthy aging. Promoting awareness, integrating LTC in the current programs and services for older persons in the country, capacitating the formal and non-formal caregivers, and strengthening collaborations are recommended.

Further research on quantitative measures of readiness for long-term care with focus on the health system and in-depth studies on the varieties or models of long-term care are recommended.

BACKGROUND

Intimate partner violence (IPV) is a global public health issue with profound physical, psychological, and social consequences. Despite legislative measures in the Philippines, there is limited research on the profile of IPV survivors consulting specialized healthcare units.

This study aimed to describe the profile of female survivors of IPV consulting at the Philippine General Hospital Women’s Desk (PGH-WD), focusing on sociodemographic, psychological, relationship, community, and partner factors as contributors to their risk of experiencing IPV.

A cross-sectional study was conducted to analyze data from IPV survivors who consulted the PGH-WD between January 2022 and December 2023. Data collection involved a chart review of eligible cases, guided by predefined inclusion and exclusion criteria. Inclusion criteria required that participants be female survivors of IPV aged 19 years and above, with consultations specifically related to IPV. Exclusion criteria included male survivors, non-Filipino nationals, individuals not residing in the Philippines, and charts missing key components. Descriptive statistics were used to analyze sociodemographic, psychological, relationship, community, and partner-related factors. Survivors were categorized into low-, moderate-, or high-risk groups based on the number of identified risk factors.

A total of 518 charts were reviewed, of which 106 met the inclusion criteria and were analyzed. Survivors’ ages ranged from 19 to 74 years, with 46 (43.4%) aged 19–34. Most survivors belonged to lower socioeconomic strata, with 61 (57.5%) categorized as poor. Psychological distress was common, with 24 (22.6%) reporting depression and 22 (20.8%) having attempted suicide. Relationship factors included dissatisfaction in 91 cases (85.9%) and prior abuse by partners in 88 (83.0%). Community factors showed that 104 survivors (98.1%) were aware of the Anti-Violence Against Women and Children (Anti-VAWC) law, and 101 (95.5%) reported having social support networks. Partner-related factors were less frequently reported, with 3 survivors (2.8%) indicating perpetrator substance use and 2 (1.9%) reporting histories of childhood abuse. Risk profiling categorized survivors into low-risk (39/106, 36.8%), moderate-risk (39/106, 36.8%), and high-risk (28/106, 26.4%) groups based on the number of identified risk factors.

This study provided a detailed profile of female IPV survivors consulting at the PGH-WD. Survivors were predominantly younger women from lower socioeconomic backgrounds, with high rates of psychological distress, relationship dissatisfaction, and histories of prior partner abuse. Community factors, including strong social support networks and awareness of the Anti-VAWC law, were identified as potential protective mechanisms post-IPV.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*