Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

Objective To investigate the association between physical activity levels and blood lipids among college freshmen, and to provide scientific evidence for the health management of college freshmen. Methods An electronic questionnaire survey on physical activity was conducted on freshmen of a university, and fasting blood biochemical indicators were detected. The International Physical Activity Questionnaire (IPAQ) short form was used to evaluate the physical activity levels of the participants. Dyslipidemia was defined as an abnormality in any one of the following serum lipid parameters: total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or non-high-density lipoprotein cholesterol. Binary logistic regression and stratified analyses were employed to explore the relationship between physical activity and blood lipids. Results A total of 3 401 participants were included, with an average age of 18.45 ± 0.92 years, and 60.5% were female. The prevalence of dyslipidemia was 17.7%, with a higher rate among males (22.1%) than females (14.8%). After adjusting for confounding factors related to blood lipids, high-intensity physical activity was negatively associated with the risk of elevated LDL-C among males (OR = 0.36, 95% CI: 0.13–0.99, P = 0.049). Conclusion Among freshmen at a medical college in Hubei Province, high-intensity physical activity is negatively associated with the risk of elevated LDL-C in males, but this association needs to be further confirmed by larger prospective cohort studies.

OBJECTIVE To compare the long-term cost-effectiveness of gonadotrophin-releasing hormone analogue （GnRHa） combined with recombinant human growth hormone （rhGH） （combination therapy regimen） versus GnRHa monotherapy （monotherapy regimen） in the treatment of central precocious puberty （CPP）. METHODS From the societal perspective and based on a real-world study conducted at West China Second Hospital of Sichuan University， the cost-effectiveness analysis was performed to compare the long-term cost-effectiveness of two pharmacotherapy regimens for CPP girls， with final height as outcome indexes， using per capita disposable income of rural residents and urban residents （20 133-49 283 yuan） in 2022 as the social willing-to-pay （WTP） threshold. The robustness of the basic analysis result was verified by using one-way sensitivity analysis and probability sensitivity analysis， and the cost-effectiveness of different combinations of long-acting preparations was compared using scenario analysis. RESULTS The basic analysis result showed that the combination therapy regimen required an additional cost of 25 193.49 yuan for every one-centimeter improvement in the final height of girls with CPP compared with the monotherapy regimen， which was not cost-effective for residents in rural areas， but it was cost-effective for residents in urban areas. One-way sensitivity analysis showed that the uncertain factors with potential impacts on the results were， in order， the price of rhGH， the final height of pediatric patients in the combination therapy regimen group， the course of rhGH in the combination therapy regimen group， and the final height of pediatric patients in the monotherapy regimen group. Probabilistic sensitivity analysis indicated that the probability of the combination therapy regimen being cost-effective was higher than that of the monotherapy regimen when WTP was more than 26 010 yuan/cm. When GnRHa long-acting preparation was used for intramuscular injection every 3 months， the combination therapy regimen was not cost-effective for rural residents， but was cost-effective for urban residents； when rhGH long-acting preparation was injected subcutaneously once a week， the combination therapy regimen was not cost-effective for residents in both rural areas and urban areas. CONCLUSIONS The combination of GnRHa and rhGH is only recommended for CPP children with better affordability to improve final height. The benefits， risks， and affordability of treatment should be comprehensively considered before the decisions on pharmacotherapy， to avoid abuse of rhGH due to the blind pursuit of height growth.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Background The neck, shoulders, and lower back are the primary affected areas of work-related musculoskeletal disorders. In manual tasks, combinations of hand functional height (defined as working height below the waist), awkward postures, and cognitive load are common risk factors. However, there is limited literature documenting how these factors specifically alter biomechanical load on the neck, shoulders, and lower back when working at hand functional height. Objective To explore quantitative differences in biomechanical load on the neck, shoulders, and lower back of workers performing manual tasks at hand functional height under different postures and cognitive load combinations. Methods A 3x2 within-subject design was implemented, with three postures (squat, kneeling, and stoop) and two levels of cognitive load (with cognitive load induced by a 2back task and without cognitive load). Ten male university students were recruited to perform a predetermined assembly task (a sequence of loosening and tightening screws) at hand functional height. Surface electromyography (sEMG) and 3D motion capture system were employed to assess the participants’ trunk biomechanical load in executing the tasks. Additionally, subjective perception, including fatigue, muscle pain, and cognitive load, were evaluated using scales. Results Significant variations in biomechanical load were observed across the three postures (P<0.05). The stoop posture exhibited the lowest muscle activation in most target muscles, except for the sternocleidomastoid, and showed the fastest decline in instantaneous median frequency (IMF) of the erector spinae, with a rate of (-0.050±0.008) Hz per unit time (0.128 s), and the greatest trunk flexion angle (35.14°±4.40°). Performing the task by squatting resulted in the highest muscle activation, especially in the upper trapezius, where maximum voluntary contraction percentage reached 20.07%±1.26%. In addition, the squatting posture also resulted in larger joint angles in the sagittal plane for the neck (−7.03°±2.70°), shoulders (60.20°±7.89°), and lower back (34.42°±4.20°). The kneeling posture showed intermediate muscle activation, the slowest IMF decline for the erector spinae in the lower back (−0.005±0.008) Hz per unit time (0.128s), and the joint angles were closest to neutral. The task performance results were also superior in the kneeling posture. Regarding cognitive load, no significant differences were found for most biomechanical indicators, except for subjective cognitive load scores, neck flexion, and shoulder external rotation angles. Conclusion In assembly tasks performed at hand functional height, kneeling results in moderate biomechanical load on the neck, shoulders, and lower back while also improves task performance compared to squatting and forward bending. Additionally, no significant effects of cognitive load under the 2back condition on biomechanical load are observed.

The shaoyang meridian is an important pivot between the internal organs and meridians system， with the functions of regulating qi and blood， balancing yin and yang， and coordinating the ascending and descending movement of qi. Dysfunction of the shaoyang pivot can lead to spleen and kidney deficiency， impaired liver and gallbladder qi regulation， and stagnation of qi and blood. It is believed that the onset and progression of Crohn's disease are closely related to shaoyang pivot dysfunction， with the core pathogenesis characterized by shaoyang disharmony， spleen deficiency， dampness retention， and blood stasis. Based on this understanding， the treatment principle centers on harmonizing the shaoyang pivot， supplemented by methods such as warming and nourishing the spleen and stomach， tonifying shaoyang， and soothing the liver and benefiting the gallbladder. Acupuncture is employed to target key acupoints along the shaoyang meridian to restore its regulatory functions， improve spleen and stomach transformation and transportation， facilitate liver and gallbladder qi flow， and promote the circulation of qi and blood. This provides a practical therapeutic approach for acupuncture-based treatment of Crohn's disease.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint