Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective: To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies. Methods: From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined. Results: Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect. Conclusion Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.

Objective To investigate muscle mass reduction and the effect of exercise training intervention in non-obese patients with type 2 diabetes (T2DM). Methods A total of 324 non-obese patients with T2DM admitted to the First Affiliated Hospital of Xinjiang Medical University were enrolled from February 2023 to February 2025. Dual-energy X-ray absorptiometry was adopted to detect and analyze the data of appendicular skeletal muscle index (ASMI). Non-obese T2DM patients were classified into an observation group (n=162, receive sports training intervention) and a control group (n=162, receiving routine exercise intervention) by adopting random number grouping criteria. Both groups were intervened for 3 months. The muscle mass indicators [ASMI, body mass index (BMI), and body fat rate], exercise ability [6-minute walking distance (6MWD), grip strength, and one-leg standing time], metabolic indicators [fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and homeostasis model assessment insulin resistance index (HOMA-IR)], and quality of life [Diabetes Quality of Life Scale (DQOL)] were compared between the two groups to evaluate the effectiveness of sports training intervention. Results A total of 324 non-obese T2DM patients were enrolled, including 123 cases with reduced muscle mass (37.96%). There were no significant differences in the baseline data and the proportion of patients with muscle mass reduction between the two groups before intervention (P>0.05). After intervention, the ASMI, 6MWD, grip strength, and one-leg standing time in the observation group were higher or longer than those of the control group (P<0.05), while the body fat rate, FPG, HbA1c, HOMA-IR and DQOL scores were lower than those of the control group (P<0.05). Conclusion The incidence of muscle mass reduction is relatively high among non-obese T2DM patients, and exercise training intervention has significant effects on improving muscle mass, metabolic status, exercise capacity and quality of life in non-obese T2DM patients.

Hereditary hemochromatosis （HH） is a hereditary disease characterized by iron overload resulting from mutations in genes involved in iron metabolism. Type ⅣA HH， also known as classical ferroportin disease， is caused by loss-of-function mutations in the SLC40A1 gene and has the clinical manifestations of a significant increase in serum ferritin， normal or low transferrin saturation， and marked iron deposition in the spleen. This article reports a case of type ⅣA HH with a significant asymptomatic increase in serum ferritin. Magnetic resonance imaging showed that the severity of iron overload in the spleen was significantly higher than that in the liver； liver biopsy showed mild fatty liver disease and iron deposition in Kupffer cells； gene variation analysis identified a heterozygous mutation in SLC40A1 c.485_487del （p.Val162del）. Screening of family members showed that the proband’s mother carried the same variation and had the manifestation of iron overload in the liver and spleen， which further confirmed the pathogenicity of this variation. This case highlights that type ⅣA HH often has an insidious onset and is frequently misdiagnosed. For patients with an unexplained persistent increase in serum ferritin， active genetic testing for HH should be considered， even in the presence of concurrent liver diseases， in order to realize early diagnosis and intervention.

Objective:To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021, and to explore the effects of age, period, and cohort on pancreatic cancer incidence and mortality.Methods:Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates, and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed.Results:In 2021, the incidence of pancreatic cancer in China was 8.34/100 000, and the mortality rate was 8.41/100 000, representing increases of 150.45% and 145.19%, respectively, compared to 1992 (3.33/100 000 and 3.43/100 000) . By sex, the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000) . From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends, with average annual increases of 0.80% and 0.62%, respectively, both of which were statistically significant (both P<0.001) . Age effect results indicated a general increasing trend in pancreatic cancer incidence, with a steady rise in the 15-49 age group, a sharp increase after the age of 50, and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group, with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk ( RR) for pancreatic cancer incidence, with the highest risk in 2017-2021 ( RR=1.09, 95% CI: 1.05-1.13, P=0.012) , compared to the reference period 2002-2006 ( RR=1) . The RR for pancreatic cancer mortality showed a fluctuating trend, with the highest risk in 2012-2016 ( RR=1.60, 95% CI: 1.07-2.38, P=0.021) , compared to the reference period 2002-2006 ( RR=1) . The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort ( RR=1) , the incidence ( RR=1.18, 95% CI: 0.99-1.40, P=0.032) and mortality ( RR=1.63, 95% CI: 0.12-11.53, P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend, while those attributable to smoking showed a decreasing trend. Conclusions:From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise, with males having higher incidence and mortality rates than females. Age, period, and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.

Objective To investigate the relationship between stationing years of personnel on an island and their traditional Chinese medicine(TCM)constitution,thus providing a reference for adjusting the health status of stationed personnel,preventing and treating diseases.Methods Based on The Scale of Constitution in Chinese Medicine Questionnaire,TCM constitution of 734 personnel stationed on an island was investigated.Pearson χ2 method was used for data analysis.Results Of the 734 personnel stationed on an island 345(47.0%)were of the balanced constitution type and 389(53.0%)were of the biased constitution types.Among the people with biased constitution types,composite constitution accounted for 80.5%(313 people)and the simple accounted for the rest(19.5%,76 people).The top three types of the biased were dampness heat(15.2%),qi deficiency(14.0%),and yin deficiency(10.7%).The distribution of TCM constitution types was significantly different in terms of stationing years on the island(P<0.05).There was a significant difference in the balanced type and yin deficiency type between people with stationing time≤2 years and>8 years(P<0.05).There was a significant difference in qi deficiency type and qi depression type between people with stationing time≤2 years and>5 years(P<0.05).Compared to people with stationing time≤2 years,significant difference was found in yang deficiency type in people with stationing time ranging from 2 to 5 years and those with>8 years(P<0.05).There were significant differences in the phlegm dampness type,blood stasis type,and specific diathesis type between people with stationing time≤2 years and people with stationing time ranging from>2～5 years and>8 years(P<0.05).There were significant differences in the dampness heat type between people with stationing time≤2 years and people with stationing time ranging from>5～8 years and>8 years,between pepole with stationing time ranging from>2～5 years and people with stationing time>8 years(P<0.05).Conclusion The dampness heat type,qi deficiency type and yin deficiency type are common biased TCM constitution in personnel stationed on islands.The longer the time spent on islands,the greater the possibility of forming biased constitution.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

[Objective] To resolve the ambiguities of HLA genotyping generated by next generation sequencing (NGS) using nanopore sequencing technology. [Methods] A total of 38 samples with ambiguous HLA genotyping by NGS in our laboratory were collected, and HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 loci in these samples were amplified using primers in the same commercial NGS HLA genotyping kit, then subjected to third-generation library construction, and sequenced on the nanopore sequencer. The sequencing data were converted into Fastq files and analyzed by software, and the genotypes of 11 HLA loci were obtained. The ambiguities were counted directly. [Results] The high-resolution genotyping at the second domain of 11 HLA loci of 38 samples using the third generation sequencing (TGS) were consistent with the results of the NGS method at a rate of 100%. The genotypes for the HLA-A, -B, -C, -DRB3, -DRB4, -DQA1 and -DPA1 loci by TGS were all only one result, and the discrimination rate for ambiguities of the HLA-A, -B, -C, and -DQA1 loci (all caused by the difficulty in phasing due to the short NGS read length) was 100%. Among the HLA-DRB1, -DRB5, -DQB1 and -DPB1 loci, the discrimination rate of TGS for the ambiguities caused by non-amplification of exon 1 was 0% and by the short NGS read length was 100%. [Conclusion] Nanopore technology was used to identify the ambiguities of 11 HLA loci in this study, and the ambiguities caused by the short read length disadvantage of the NGS method could be solved effectively and the accuracy of HLA genotyping would be improved.

Objective: To analyze the relationship between parental psychological control and Internet Gaming Disorder (IGD) among junior high school students, so as to provide evidence for preventing IGD development in adolescents. Methods: From August 2019 to February 2020, a survey was conducted among 1 169 junior high school students from three middle schools in Xian using stratified cluster sampling. The Parental Psychological Control Scale and IGD Scale were administered to assess parental psychological control and IGD prevalence. Univariate and binary Logistic regression analyses were used to explore IGD risk factors and their correlation with parental psychological control. Results: The detection rate of IGD in middle school students was 19.9%(184/1 169). Multivariate Logistic regression revealed that compared to those with lower parental psychological control scores(≤21 points), students with higher parental psychological control scores (>21 points) had a higher risk of IGD (OR=1.82, 95%CI=1.21-2.74), a 1.58fold higher risk of selfperceived gaming addiction (95%CI=1.07-2.30), as well as reduced likelihood of seeking external help to reduce gaming time (OR=0.66, 95%CI=0.47-0.94) (P<0.05). Conclusions Parental psychological control may elevate the risks of IGD and selfperceived addiction while diminishing proactive helpseeking behaviors to reduce gaming time. Parents should enhance communication with adolescents and provide positive guidance to mitigate potential gamingrelated harms.