Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars.

BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

Integrative literature review on human papillomavirus vaccination recommendations in national immunization programs in select areas in the Asia-Pacific region.

There is limited literature on current human papillomavirus (HPV) vaccination in the Asia-Pacific region. This integrative literature review was conducted to describe HPV vaccination programs in Hong Kong, Indonesia, Japan, South Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Program descriptions, recommendations, f unding, and coverage data were extracted. Twenty-five citations were included. As of 2022, eight of the 10 areas of interest include HPV in their national immunization program (NIP) for school-aged girls; full implementation in Indonesia is expected in 2023 whereas Vietnam's NIP does not include HPV. Singapore also includes HPV vaccination for women (18-26 years). None of the HPV vaccination programs include males. In most areas (n = 7), programs include only one vaccine option. While female HPV NIPs are present in the Asia-Pacific region, opportunities remain to strengthen NIPs in broader populations (e.g., males, catch-up cohorts) to expand public health impact and provide gender equity in HPV vaccination.

Light Therapy in Chronic Migraine.

PURPOSE OF REVIEW: This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. RECENT FINDINGS: Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.

Tbxt alleviates senescence and apoptosis of nucleus pulposus cells through Atg7 mediated autophagy activation during intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a significant cause of low back pain, characterized by excessive senescence and apoptosis of nucleus pulposus cells (NPCs). However, the precise mechanisms behind this senescence and apoptosis remains unclear. This study aimed to investigate the role of Tbxt in IDD both in vitro and in vivo, using a hydrogen peroxide (H2O2)-induced NPCs senescence and apoptosis model, as well as a rat acupuncture IDD model. Firstly, the expression of p16 and cleaved-caspase 3 significantly increased in degenerated human NPCs, accompanied by a decrease in Tbxt expression. Knockdown of Tbxt exacerbated senescence and apoptosis in the H2O2-induced NPCs degeneration model. Conversely, upregulation of Tbxt alleviated these effects induced by H2O2. Mechanistically, bioinformatic analysis revealed that the direct downstream target genes of Tbxt were highly enriched in autophagy-related pathways and overexpression of Tbxt significantly activated autophagy in NPCs. Moreover, the administration of the autophagy inhibitor, 3-methyladenine, impeded the impact of Tbxt on the processes of senescence and apoptosis in NPCs. Further investigation revealed that Tbxt enhances autophagy by facilitating the transcription of ATG7 through its interaction with a specific motif within the promoter region. In conclusion, this study suggests that Tbxt mitigates H2O2-induced senescence and apoptosis of NPCs by activating ATG7-mediated autophagy.

PM2.5 regulates the progression of lung adenocarcinoma through the axis of HCG18, miR-195 and ATG14.

Relevant studies have indicated the association of HCG18 with tumour occurrence and progression. In this study, we observed that PM2.5 can enhance the growth of lung adenocarcinoma cells by modulating the expression of HCG18. Further investigations, including overexpression and knockout experiments, elucidated that HCG18 suppresses miR-195, which in turn upregulates the expression of ATG14, resulting in the upregulation of autophagy. Consequently, exposure to PM2.5 leads to elevated HCG18 expression in lung tissues, which in turn increases Atg14 expression and activates autophagy pathways through inhibition of miR-195, thereby contributing to oncogenesis.

Brachyury promotes extracellular matrix synthesis through transcriptional regulation of Smad3 in nucleus pulposus.

Metabolic dysfunction of the extracellular matrix (ECM) is one of the primary causes of intervertebral disc degeneration (IVDD). Previous studies have demonstrated that the transcription factor Brachyury (Bry) has the potential to promote the synthesis of collagen II and aggrecan, while the specific mechanism is still unknown. In this study, we used a lipopolysaccharide (LPS)-induced model of nucleus pulposus cell (NPC) degeneration and a rat acupuncture IVDD model to elucidate the precise mechanism through which Bry affects collagen II and aggrecan synthesis in vitro and in vivo. First, we confirmed Bry expression decreased in degenerated human nucleus pulposus (NP) cells (NPCs). Knockdown of Bry exacerbated the decrease in collagen II and aggrecan expression in the lipopolysaccharide (LPS)-induced NPCs degeneration in vitro model. Bioinformatic analysis indicated that Smad3 may participate in the regulatory pathway of ECM synthesis regulated by Bry. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter gene assays demonstrated that Bry enhances the transcription of Smad3 by interacting with a specific motif on the promoter region. In addition, Western blot and reverse transcription-qPCR assays demonstrated that Smad3 positively regulates the expression of aggrecan and collagen II in NPCs. The following rescue experiments revealed that Bry-mediated regulation of ECM synthesis is partially dependent on Smad3 phosphorylation. Finally, the findings from the in vivo rat acupuncture-induced IVDD model were consistent with those obtained from in vitro assays. In conclusion, this study reveals that Bry positively regulates the synthesis of collagen II and aggrecan in NP through transcriptional activation of Smad3.NEW & NOTEWORTHY Mechanically, in the nucleus, Bry enhances the transcription of Smad3, leading to increased expression of Smad3 protein levels; in the cytoplasm, elevated substrate levels further lead to an increase in the phosphorylation of Smad3, thereby regulating collagen II and aggrecan expression. Further in vivo experiments provide additional evidence that Bry can alleviate IVDD through this mechanism.

Prevalence of oral human papillomavirus infection among the general adult population in Hong Kong.

A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.

Self-Powered Colorful Dynamic Electrowetting Display Systems Based on Triboelectricity.

Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.

Using spatio-temporal graph neural networks to estimate fleet-wide photovoltaic performance degradation patterns.

Accurate estimation of photovoltaic (PV) system performance is crucial for determining its feasibility as a power generation technology and financial asset. PV-based energy solutions offer a viable alternative to traditional energy resources due to their superior Levelized Cost of Energy (LCOE). A significant challenge in assessing the LCOE of PV systems lies in understanding the Performance Loss Rate (PLR) for large fleets of PV systems. Estimating the PLR of PV systems becomes increasingly important in the rapidly growing PV industry. Precise PLR estimation benefits PV users by providing real-time monitoring of PV module performance, while explainable PLR estimation assists PV manufacturers in studying and enhancing the performance of their products. However, traditional PLR estimation methods based on statistical models have notable drawbacks. Firstly, they require user knowledge and decision-making. Secondly, they fail to leverage spatial coherence for fleet-level analysis. Additionally, these methods inherently assume the linearity of degradation, which is not representative of real world degradation. To overcome these challenges, we propose a novel graph deep learning-based decomposition method called the Spatio-Temporal Graph Neural Network for fleet-level PLR estimation (PV-stGNN-PLR). PV-stGNN-PLR decomposes the power timeseries data into aging and fluctuation components, utilizing the aging component to estimate PLR. PV-stGNN-PLR exploits spatial and temporal coherence to derive PLR estimation for all systems in a fleet and imposes flatness and smoothness regularization in loss function to ensure the successful disentanglement between aging and fluctuation. We have evaluated PV-stGNN-PLR on three simulated PV datasets consisting of 100 inverters from 5 sites. Experimental results show that PV-stGNN-PLR obtains a reduction of 33.9% and 35.1% on average in Mean Absolute Percent Error (MAPE) and Euclidean Distance (ED) in PLR degradation pattern estimation compared to the state-of-the-art PLR estimation methods.

Effects of Methionine Restriction from Different Sources on Sperm Quality in Aging Mice.

Decreased sperm quality causing poor pregnancy outcomes in aging males is a common problem. The aim of this study was to investigate the ameliorative effect of methionine restriction on sperm quality in aging mice, using methionine or 2-hydroxy-4-(methylthio)butanoate (HMTBA) as the methionine source, with a view to providing nutritional strategies to mitigate the decline in sperm quality in aging livestock. Fifty-one 6-week-old male mice were randomly divided into four groups: the non-aging group (NA, 0.86% methionine), the control diet group (CD, 0.86% methionine), the methionine-restricted group (MR, 0.17% methionine) and the HMTBA-restricted group (HR, 0.17% methionine). The mice in the CD, MR and HR groups were injected with a daily dose of 0.25 mL/20 g body weight of 10% D-galactose to establish an aging model. The test period was 42 days. The results showed that aging mice in the CD group had impaired testicular morphology and significantly decreased sperm quality compared to those in the NA group. Aging mice in the MR and HR groups showed attenuated impaired testicular morphology and improved sperm quality, especially sperm acrosomal integrity and membrane integrity, compared to mice in the CD group. In addition, mice in the MR and HR groups had reduced testicular inflammation and oxidative stress, increased spermidine levels, and reduced sperm RNA N6-methyladenosine (m6A) and DNA 5-methylcytosine (5mC) levels. Spermidine levels were positively correlated, whereas sperm RNA m6A and DNA 5mC levels were negatively correlated with sperm quality parameters. Our study suggests that methionine restriction alleviates the decline in sperm quality in aging mice, which may be related to changes in methionine metabolism and inhibition of sperm DNA and RNA methylation.

Cost of illness for colorectal cancer in Japan - a time trend and future projections (1996-2035) based on governmental statistics.

BACKGROUND: In Japan, the crude mortality rate of colorectal cancer is the second highest among men and highest among women by site. We aimed to calculate the social burden of colorectal cancer using the cost of illness (COI) method and identify the main factors that drove changes in the COI. METHODS: From 1996 to 2020, the COI was estimated by summing direct, morbidity, and mortality costs. In addition, the COI by 2035 was projected by fitting approximate curves obtained from historical data to health-related indicators by sex and age. Future projections of the number of patients by the stage of disease were also made to explore the factors that changed the COI. RESULTS: The number of deaths and incidence from colorectal cancer was expected to continue increasing due to population aging. However, the COI was projected to rise from 850.3 billion yen in 1996 to 1.451 trillion yen in 2020, and peaked at 1.478 trillion yen in 2023 before it declined. CONCLUSION: Although the increased number of deaths associated with population aging increased COI, it was expected that the COI would decrease around 2023 due to a decrease in the human capital value of the deceased. In addition, the mortality rate was expected to decrease in the future due to an increase in the percentage of early detection of colorectal cancer via widespread screening and advances in medical technology.

Factors influencing the bone mineral density in Duroc boars.

BACKGROUND: Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd). RESULTS: Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm. CONCLUSION: In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD.

Involvement of methodological experts and the quality of clinical practice guidelines: a critical appraisal of clinical practice guidelines and a questionnaire survey of the development groups in Japan.

OBJECTIVE: To evaluate whether the involvement of methodological experts improves the quality of clinical practice guidelines (CPGs) after adjusting for other factors. SETTING: The quality of Japanese CPGs published in 2011-2019 was assessed using the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. A questionnaire survey targeting CPG development groups was conducted through postal mail. PARTICIPANTS: 405 CPGs were retrieved from a Japanese CPG clearinghouse. Questionnaires were distributed to the 405 CPG development groups. Of the 178 respondents, 22 were excluded because of missing values. Finally, 156 participants representing their CPG development groups were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: CPG quality was assessed using the AGREE II tool. The characteristics of CPGs, including publication year, development organisation, versions, number of members in the development group and involvement of methodological experts, were corrected from the description in the CPGs and the questionnaire survey. We performed multiple logistic regressions using the quality of CPGs as the dependent variable and the involvement of experts as the independent variable, adjusting for other possible factors. RESULTS: A total of 156 CPGs were included. Expert involvement was significantly associated with the AGREE II instrument scores in domains 1 (ß=0.207), 2 (ß=0.370), 3 (ß=0.413), 4 (ß=0.289), 5 (ß=0.375), 6 (ß=0.240) and overall (ß=0.344). CONCLUSION: This study revealed that the involvement of methodological experts in the CPG development process improves the quality of CPGs. The results suggest the importance of establishing a training and certification programme for experts and constructing expert referral systems that meet CPG developers' needs to improve the quality of CPGs.

The Effects of Claw Health and Bone Mineral Density on Lameness in Duroc Boars.

To investigate the effects of claw lesion types and bone mineral density on lameness in boars, the data of claw lesion score, gait score, and bone mineral density, measured by a Miniomin ultrasound bone densitometer, were collected from a total of 739 Duroc boars. Firstly, we discovered that the prevalence of claw lesions was as high as 95.26% in boars. The percentage of lameness of boars with SWE was higher than those with other claw lesions. Meanwhile, the results showed that the probability of lameness was higher in boars with lower bone mineral density (p < 0.05). Logistic regression models, including variables of boar age, body weight, serum mineral level, and housing type, were used to identify the influencing factors of bone mineral density in this study. The results found that bone mineral density increases with age before reaching a maximum value at 43 months of age, and begins to decrease after 43 months of age. Elevated serum Ca levels were significantly associated with an increase in bone mineral density (p < 0.05). Aside from the above findings, we also made an interesting discovery that boars in the individual pen model significantly increased bone mineral density compared to those in the individual stall model. In conclusion, claw lesions and bone mineral density were significantly associated with lameness. Age, serum Ca, and housing type are the potential influencing factors for bone mineral density in boars.

Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus.

Nucleus pulposus (NP) degeneration is characterized by the decreased cellularity of nucleus pulposus cells (NPCs) and diminished content of hydrophilic extracellular matrix (ECM). Overexpression of brachyury has been reported to reverse the degenerated NPCs into healthy phenotypes. However, the direct correlation between brachyury and ECM has not been fully elucidated. This study revealed that brachyury expression decreased in human degenerated NP tissues and Lipopolysaccharide (LPS)-induced degenerated rat NPCs model. In vitro and in vivo experiments further showed that brachyury deficiency suppressed the synthesis of aggrecan and collagen II in NP. Mechanistically, ChIP-qPCR assays demonstrated that brachyury bound to the promoter region of aggrecan in NPCs. Furthermore, luciferase reporter assays revealed that brachyury transcriptionally activated aggrecan expression through binding with a novel specific motif. In rat in vivo model, brachyury overexpression partially reversed the degenerative phenotype. In conclusion, brachyury positively regulated ECM synthesis via directly promoting aggrecan transcription in NPCs. Accordingly, it may be helpful to be developed into a promising therapeutic target for NP degeneration.

Time-resolved ICP-MS analysis of mineral element contents and distribution patterns in spermatogenic cells of different types.

Mineral elements play an important role in the spermatogenesis, maturation, and fertilization of sperm. It is of great scientific significance to study the role of mineral elements in spermatogenesis by accurately measuring the content of elements in different spermatogenic cells and analyzing the distribution pattern of elements in spermatogenesis. Here, time-resolved inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze the content and distribution patterns of mineral elements in spermatogenic cells of different types at the single cell level. Firstly, spermatogonia, spermatocytes, round spermatids and elongating spermatids were successfully isolated from testis of mice of different weeks of age by differential adherent method and discontinuous bovine serum albumin (BSA) density gradient method. Then, signal profiles and elemental distributions of 24Mg, 31P, 52Cr, 55Mn, 56Fe and 66Zn in spermatogenic cells were obtained with dwell time at 0.1 ms. Based on the results of acid digestion, we derived a formula to calculate element content in single cell from peak area for each element, and the feasibility and universality of the formula in the quantitative detection of single cell elements were verified by sperm samples to a certain extent. The detection results of element content in single cell showed that the content of 31P in elongating spermatids was significantly higher than that in spermatogonia, spermatocytes and round spermatids (P < 0.01), and the distribution range was wider. However, the 52Cr and 56Fe content of elongating spermatids was lower than that of spermatogonia, spermatocytes and round spermatids (P < 0.05). When spermatogonia developed into round spermatids, the contents of 55Mn and 66Zn in single cell increased significantly (P < 0.05), then decreased to the lowest in elongating spermatids. In addition, the significant decrease of 52Cr, 55Mn, 56Fe and 66Zn content in elongating spermatids also be visually observed from the center of the fitting curve of the element signal intensity distribution moving to the left. This study provides an elemental view of the changes in elemental content at various stages of spermatogenesis at the single-cell level. Time-resolved ICP-MS is used to detect mineral elements content and distribution patterns in spermatogenic cells of testis, which is helpful to better explore the stages and modes of action of various elements in spermatogenesis, and provide direct evidence for revealing the effects of element content changes on spermatogenesis and semen quality regulation.

Development and usability of a hospital standardized ADL ratio (HSAR) for elderly patients with cerebral infarction: a retrospective observational study using administrative claim data from 2012 to 2019 in Japan.

BACKGROUND: Maintenance of activities of daily living (ADL) during acute hospitalization is an important treatment goal, especially for elderly inpatients with diseases that often leave disabilities, such as cerebral infarction. However, studies assessing risk-adjusted ADL changes are limited. In this study, we developed and calculated a hospital standardized ADL ratio (HSAR) using Japanese administrative claims data to measure the quality of hospitalization care for patients with cerebral infarction. METHODS: This study was designed as a retrospective observational study using the Japanese administrative claim data from 2012 to 2019. The data of all hospital admissions with a primary diagnosis of cerebral infarction (ICD-10, I63) were used. The HSAR was defined as the ratio of the observed number of ADL maintenance patients to the expected number of ADL maintenance patients multiplied by 100, and ratio of ADL maintenance patients was risk-adjusted using multivariable logistic regression analyses. The c-statistic was used to evaluate the predictive accuracy of the logistic models. Changes in HSARs in each consecutive period were assessed using Spearman's correlation coefficient. RESULTS: A total of 36,401 patients from 22 hospitals were included in this study. All variables used in the analyses were associated with ADL maintenance, and evaluations using the HSAR model showed predictive ability with c-statistics (area under the curve, 0.89; 95% confidence interval, 0.88-0.89). CONCLUSIONS: The findings indicated a need to support hospitals with a low HSAR because hospitals with high/low HSAR were likely to produce the same results in the subsequent periods. HSAR can be used as a new quality indicator of in-hospital care and may contribute to the assessment and improvement of the quality of care.

Case report: Novel homozygous HPGD variant leads to primary hypertrophic osteoarthropathy with intussusception and acro-osteolysis in a Chinese family.

Objective: To perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis. Case presentation: At the age of 7 years, a boy born to a consanguineous couple was diagnosed with PHO attributed to delayed closure of the cranial suture, eczema, clubbing of fingers, and swelling of the knee and ankle. Clinical characteristics and follow-up data for 3 years were collected and analyzed. Trio whole-exome sequencing (WES) and copy number variant sequencing were used to screen for causative genetic variants. Candidate variants of the patient and his parents were confirmed by Sanger sequencing. When he was 7 years old, trio WES found that he had biallelic novel variants c.498 + 1G > A, inherited from his parents, in the HPGD gene. The patient was markedly malnourished. Ultrasonography and computed tomography showed intussusception with a gradual expansion of the duodenum, localized intestinal wall thickening, and acro-osteolysis. Cross-sectional blood tests showed that the patient had continuously decreased levels of serum 25-hydroxy vitamin D and serum ferritin at the age of 7and 10 years. Conclusion: PHO due to HPGD defects is rare in pediatric patients, and finding homozygous novel c.498 + 1G > A has expanded the spectrum of causative variants of HPGD and provided a clue for genotype-phenotype correlation analysis. Similar to mouse model results, human HPGD deficiency may also cause abnormal digestive tract development, and related secondary vitamin D deficiency and acro-osteolysis should be considered in HPGD-related PHO.

Cognitive Function and Depressive Symptoms among Chinese Adults Aged 40 Years and Above: The Mediating Roles of IADL Disability and Life Satisfaction.

The purpose of this study was to investigate the relationship between cognitive function and depressive symptoms among Chinese adults aged 40 years and above, as well as the series of multiple mediating effects of Instrument Activities of Daily Living disability and life satisfaction on this relationship. The data was obtained from the China Health and Retirement Longitudinal Study (CHARLS, 2013-2018), including 6466 adults aged 40 years and above. The mean age of the adults was 57.7 ± 8.5. The SPSS PROCESS macro program was conducted to examine the mediating effects. The results indicated that there was a significant association between cognitive function and depressive symptoms five years later (B = -0.1500, 95%CI: -0.1839, -0.1161), which could also be demonstrated through three mediation pathways: (1) the mediating pathway through IADL disability (B = -0.0247, 95%CI: -0.0332, -0.0171); (2) the mediating pathway through life satisfaction (B = 0.0046, 95%CI: 0.0000, 0.0094); and (3) the chain mediation pathway through IADL disability and life satisfaction (B = -0.0012, 95%CI: -0.0020, -0.0003). Both IADL disability and life satisfaction have been proven to be crucial mediators for the relationship between cognitive function and depressive symptoms five years later. It is necessary to improve individuals' cognitive function and reduce the negative impact of disability on them, which is important to enhance their life satisfaction and prevent depressive symptoms.