A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

Neurodegenerative diseases (NDDs) are a group of heterogeneous neurological disorders that can cause progressive loss of neurons in the central nervous system or peripheral nervous system, resulting in a decline in motor function. Motion capture, as a high-precision and high-resolution technology for capturing human motion data, drives NDDs motor assessment to effectively extract kinematic features and thus assess the patient's motor ability or disease severity. This paper focuses on the recent research progress in motor assessment of NDDs driven by motion capture data. Based on a brief introduction of NDDs motor assessment datasets, we categorized the assessment methods into three types according to the way of feature extraction and processing: NDDs motor assessment methods based on statistical analysis, machine learning and deep learning. Then, we comparatively analyzed the technical points and characteristics of the three types of methods from the aspects of data composition, data preprocessing, assessment methods, assessment purposes and effects. Finally, we discussed and prospected the development trends of NDDs motor assessment.
Humans ; Neurodegenerative Diseases/diagnosis* ; Machine Learning ; Biomechanical Phenomena ; Deep Learning ; Motion ; Motion Capture

OBJECTIVES: The prevalence of overweight and obesity among children and adolescents continues to rise, becoming one of the most serious global public health issues of the 21st century. Given the differing growth and development environments between urban and rural children, associated risk factors also vary. This study aims to explore the distribution characteristics and influencing factors of overweight and obesity among urban and rural primary and secondary school students in Hunan Province, providing scientific evidence for targeted interventions. METHODS: A stratified, randomized cluster sampling method was used to select participants. A total of 197 084 students from primary and secondary schools across 14 prefectures in Hunan Province underwent physical examinations and questionnaire surveys. Population and spatial distribution characteristics of overweight and obesity were analyzed. Spatial distribution maps and spatial autocorrelation analyses were conducted using ArcGIS. Multivariate Logistic regression was used to identify influencing factors for overweight and obesity. RESULTS: The overall overweight and obesity rates among students in Hunan Province were 14.7% and 10.9%, respectively. Both rates were higher in urban areas than in rural counties (16.0% vs 13.9% for overweight; 12.1% vs 10.2% for obesity). Among both urban and rural students, boys had higher rates of overweight and obesity than girls. Higher-grade students had a higher overweight rate but a lower obesity rate than lower-grade students. In urban areas, the overweight and obesity rates of Han Chinese primary and secondary school students are lower than those of ethnic minority students (both P<0.05). In rural areas, the obesity rate of Han primary and secondary school students is lower than that of ethnic students (P<0.05). Across cities and prefectures, urban overweight and obesity rates ranged from 14.7% to 18.7% and 8.4% to 20.6% respectively, while rural rates ranged from 10.9% to 17.2% and 6.6% to 13.7% respectively. Spatial autocorrelation analysis revealed high-value clusters of overweight/obesity in urban areas of Changde and Zhangjiajie, and in rural areas of Loudi, Huaihua, and Shaoyang. Multivariate Logistic regression showed that gender, school stage, ethnicity, frequency of fresh vegetable intake, and sleep duration were associated with overweight and/or obesity in both urban and rural students. In urban students, frequency of fried food and fresh fruit intake, breakfast habits, physical activity on weekdays and holidays, and screen time on computers were also significant. In rural students, TV viewing time and sedentary duration were additional relevant factors. CONCLUSIONS The situation of overweight and obesity among primary and secondary school students in Hunan Province remains concerning. Greater attention should be paid to regions with high-value clusters of overweight/obesity, and targeted interventions should be developed based on urban-rural differences in influencing factors.
Humans ; China/epidemiology* ; Adolescent ; Male ; Female ; Rural Population/statistics & numerical data* ; Child ; Overweight/epidemiology* ; Students/statistics & numerical data* ; Urban Population/statistics & numerical data* ; Risk Factors ; Prevalence ; Obesity/epidemiology* ; Surveys and Questionnaires ; Pediatric Obesity/epidemiology* ; Schools

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

Objective To investigate the correlation between changes in physiological indicators and altitude,age,and sex among ethnic Tibetan college students living in Xizang on long-term basis upon their first ever visit to a low-altitude region,thereby providing health guidance for long-term residents of high-altitude regions when they visit low-altitude environments for the first time.Methods A cluster random sampling method was used to select 170 healthy first-year college students of Tibetan ethnicity(85 males and 85 females),from Xizang Minzu University.The participants did not have any respiratory,circulatory,or nervous system diseases,nor any family history of such conditions.Based on their responses to questionnaires and the monitoring data of their physiological indicators,an analysis was conducted to assess the incidence and duration of deacclimatization symptoms among these Tibetan college students during the first month after their arrival at a low-altitude region.In addition,the R programming language and the SPSS software were used to analyze the correlation between changes in blood pressure,heart rate,and body weight and the participants'age,sex,and the altitude of their long-term residence in Xizang before and after their arrival at a low-altitude region.Results Statistical analysis revealed that Tibetan college students experienced deacclimatization symptoms within the first week of their first ever visit to a low-altitude region,primarily characterized by dizziness,fatigue,and drowsiness.The incidence was 41.9％among female students and 22.5％among male students.Furthermore,after arriving at low-altitude region,the participants experience an initial decrease followed by a recovery in both blood pressure and heart rate.They gained an average of 1.5 kg in body mass compared with their initial measurements upon arrival in a low-altitude region.Significant differences in blood pressure,heart rate,and body mass were observed among Tibetan students of different sexes and altitudes of their long-term residence in Xizang after their arrival in a low-altitude region.Conclusion After arriving at a low-altitude region,Tibetan college students exhibit marked changes in physiological indicators,showing strong correlations between systolic blood pressure,body mass,etc.,and sex,altitude,and other parameters.

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective As a signaling molecule,NO regulates key physiological processes and is closely related to periodontitis.To investigate the effect of flavonoid NO donor composite nanoparticles(G10@HAP/MSN@ZnO@COS)on osteogenic differentiation of periodontal ligament stem cells(PDLSCs)by regulating macrophage polarization.Methods The novel NO donor drug G10 was loaded on hydroxyapatite/mesoporous silicanant particles(HAP/MSN),filled with zinc oxide(ZnO),and then coated with chitosan(COS)to prepare composite nanoparticles(G10@HAP/MSN@ZnO@COS).The best concentration of G10@HAP/MSN@ZnO@COS was screened to promote cell proliferation by CCK-8 cell experiment.After the mouse mononuclear macrophages were stimulated by lipopo-lysaccharide,the mice were divided into four groups:Control group,G10 group,HAP/MSN@ZnO@COS group and G10@HAP/MSN@ZnO@COS group.Each group was cultured with fresh medium,5 μg/mL G10,5 μg/mL HAP/MSN@ZnO@COS and 5 μg/mL G10@HAP/MSN@ZnO@COS for 72 h respectively.ELISA and RT-qPCR were used to detect the expression of cytokines(TNF-α,IL-6,IL-1β,iNOS,IL-10)and mRNA expression in each group,and the phenotypic changes of M1/M2 were evaluated.The supernatant of each culture medium was used as conditioned medium to culture PDLSCs,and the osteogenic ability and cell miner-alization were evaluated by alkaline phosphatase activity test and alizarin red staining.Results CCK-8 experiment showed that G10@HAP/MSN@ZnO@COS of 5 μg/mL could significantly promote the proliferation of PDLSCs.The results of ELISA showed that compared with Control group,the expression of M1 type marker IL-1β,IL-6,TNF-α and iNOS in G10@HAP/MSN@ZnO@COS group was significantly decreased(P＜0.000 1),while the expression of M2 type marker IL-10 was significantly increased(P＜0.000 1).The results of RT-qPCR were consistent with those of ELISA,which showed that the expression of M1-related genes in G10@HAP/MSN@ZnO@COS group decreased significantly(P＜0.01).The results of alizarin red staining and alkaline phosphatase activity test showed that the number of mineralized nodules and alkaline phosphatase activity in G10@HAP/MSN@ZnO@COS-CM group were significantly higher than those in other groups(P＜0.000 1).Conclusion Composite nanoparticles(G10@HAP/MSN@ZnO@COS)can effectively inhibit the polarization of macrophages to M1 phenotype and promote it to M2 phenotypic polarization.The anti-inflammatory microenvironment regulated by G10@HAP/MSN@ZnO@COS can en-hance the osteogenic differentiation of PDLSCs.