Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Objective: To investigate the mechanism of action of curcumol on mitochondrial autophagy in hepatic stellate cells and its molecular mechanism against liver fibrosis. Methods : Hepatic stellate cells were divided into blank group, model group(lipopolysaccharide 5 mg/L), and low, medium and high curcumol group(12.5, 25 and 50 mg/L); Thiazolyland(MTT) was used to detect the effects of curcumol on the viability of hepatic stellate cells; flow cytometry was used to detect the effects of curcumol on apoptosis of hepatic stellate cells; 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylimidacarbocyanine iodide(JC-1) was used to detect the mitochondrial membrane potential; effects of curcumol on mitochondrial morphology and autophagosome were detected by transmission electron microscopy; effect of curcumol on mitochondrial localisation were detected by fluorescent probe; Immunoblotting assay was performed to detect the effects of curcumin on PTEN-induced putative kinase 1(PINK1), Parkinson's disease protein(Parkin), microtubule-associated protein light chain 3(LC3), autophagy-associated protein(Beclin1), mitochondrial inner membrane translocase 23(Timm23), mitochondrial outer membrane translocase 20(Tomm20), Bcl-2 associated X protein(Bax), B lymphocytoma-2(Bcl2), cleaved-cysteine protease 3(Caspase3), α-smooth muscle actin(ɑ-SMA), collagen type Ⅰ(Collagen Ⅰ), and collagen type Ⅲ(Collagen Ⅲ) protein expression. Results : Compared with the blank control group, cell proliferation rate, Caspase3, Bcl2, LC3Ⅱ, Beclin1, PINK1, Parkin, ɑ-SMA, CollagenⅠ, CollagenⅢ proteins significantly increased in the model group(P<0.01), co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01), while Timm23 and Tomm20 proteins, mitochondrial membrane potential decreased significantly(P<0.01), apoptosis rate decreased, and Bax protein expression decreased. Compared with the model group, after curcumol intervention, cell proliferation rate, Bcl2, Timm23, Tomm20, α-SMA, CollagenⅠ and CollagenⅢ protein expression significantly decreased in the curcumol low-, medium-and high-concentration groups(P<0.01), and the mitochondrial membrane potential significantly decreased(P<0.01), whereas apoptosis rate, Caspase3, Bax, LC3Ⅱ, Beclin1, PINK1 and Parkin proteins significantly increased(P<0.05), the co-localisation of mitochondria and lysosomes increased, and the number of mitochondrial autophagosome significantly increased(P<0.01). Conclusion Curcumol exerts ameliorative effects on hepatic fibrosis by modulating mitochondrial hyperautophagy mediated by the PINK1/Parkin signaling pathway, and promoting hepatic stellate cell apoptosis.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective To investigate the mechanism underlying the neuroprotective effect of linarin(LIN)against microglia activation-mediated inflammation and neuronal apoptosis following spinal cord injury(SCI).Methods Fifty C57BL/6J mice(8-10 weeks old)were randomized to receive sham operation,SCI and linarin treatment at 12.5,25,and 50 mg/kg following SCI(n=10).Locomotor function recovery of the SCI mice was assessed using the Basso Mouse Scale,inclined plane test,and footprint analysis,and spinal cord tissue damage and myelination were evaluated using HE and LFB staining.Nissl staining,immunofluorescence assay and Western blotting were used to observe surviving anterior horn motor neurons in injured spinal cord tissue.In cultured BV2 cells,the effects of linarin against lipopolysaccharide(LPS)-induced microglia activation,inflammatory factor release and signaling pathway changes were assessed with immunofluorescence staining,Western blotting,RT-qPCR,and ELISA.In a BV2 and HT22 cell co-culture system,Western blotting was performed to examine the effect of linarin against HT22 cell apoptosis mediated by LPS-induced microglia activation.Results Linarin treatment significantly improved locomotor function(P<0.05),reduced spinal cord damage area,increased spinal cord myelination,and increased the number of motor neurons in the anterior horn of the SCI mice(P<0.05).In both SCI mice and cultured BV2 cells,linarin effectively inhibited glial cell activation and suppressed the release of iNOS,COX-2,TNF-α,IL-6,and IL-1β,resulting also in reduced neuronal apoptosis in SCI mice(P<0.05).Western blotting suggested that linarin-induced microglial activation inhibition was mediated by inhibition of the TLR4/NF-κB signaling pathway.In the cell co-culture experiments,linarin treatment significantly decreased inflammation-mediated apoptosis of HT22 cells(P<0.05).Conclusion The neuroprotective effect of linarin is medicated by inhibition of microglia activation via suppressing the TLR4/NF-κB signaling pathway,which mitigates neural inflammation and reduce neuronal apoptosis to enhance motor function of the SCI mice.

Health insurance fund regulation (HIFR) is a vital issue in the modernization of healthcare security governance, with its importance as a primary task of the healthcare security department continually reinforced in policy practice. This study focused on the 22 specialized policies issued by the National Healthcare Security Administration from its establishment in 2018 to March 2024, deeply analyzed their issue characteristics, and summarized the evolutionary trends of policy changes, as well as the knowledge production patterns that existed in the series of policy formulation, implementation, and feedback processes. Our analysis revealed that the diverse issue characteristics had led to heterogeneous directions in HIFR policies. The policy development process presented distinct composite evolutionary trends, mainly manifested in four aspects: the integration of regulatory system and content, the convergence of professional and societal forces, the parallelism of special governance and regular supervision, and the complementarity of conventional and emerging methods. Additionally, the study demonstrated that the knowledge production embedded in policy evolution encompassed four different dimensions: problem rectification, norm setting, pilot experience, and technical absorption. Together with issue characteristics and policy evolution, they formed an integrated, dynamic, and open system of knowledge production, continuously promoting the renewal and iteration of regulation policies.

Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.

The Healthy China construction initiative highlights the concept of patient-centered value-based health care,and the value appeal of doctors'medical service is also increasing.This study attempts to introduce the concept of public service motivation in general public organizations into professional public healthcare organizations——public hospitals,and proposes the concept of"value-based medical service motivation"as an expression of public service motivation for doctors in public hospitals.Through qualitative analysis and quantitative measurement,this paper constructs the concept of"public hospital doctors'value-based medical service motivation",finds its conceptual structure,namely responsibility commitment,professional adherence,reputation maintenance,and norm compliance,and finally forms a value-based medical service motivation scale.This paper confirms that doctors in public hospitals in China have multi-dimensional value-based medical service motivation,present different motivational expressions or behavioral tendencies,and constantly deal with and balance the public value tensions in the practice of realizing the patient-centered value-based medical goal.This scale provides an effective tool for measuring doctors'value-based service motivation,and provides theoretical and practical support for further investigating the influencing factors of doctors'motivation for value-based medical services,improving the medical service capacity of public hospitals,adjusting medical behavior,and advancing doctor-patient trust.

Objective:To construct and purify four respiratory syncytial virus (RSV) PreF proteins through gene sequence design and optimization and evaluate their immunogenicity.Methods:Coronin-1A and T4 trimer protein gene sequences were optimized with Human and CHO codons, and then added to RSV F protein sequence. The above plasmids were transfected into Expi293F cells for protein expression. After purification by nickel column, four trimer proteins were prepared. SDS-PAGE and Western blot were performed for protein identification. BALB/c mice were immunized at week 0 and week 3, and blood samples were collected to measure the activities of binding and neutralizing antibodies in serum.Results:SDS-PAGE and Western blot showed that the four proteins had stable trimer structure. Antigen-antibody affinity test showed that the four trimer proteins had strong affinity with RSV-specific monoclonal antibodies 8897, D25, Motavizumab, AM14 and Palivizumab. The titers of antibodies induced by the two T4 trimers were higher after the initial immunization, while there was a substantial increase in the titers of antibodies induced by Human codon-optimized trimer protein after the second immunization.Conclusions:PreF trimer protein can be prepared by adding any of the two different heterotrimer motifs, and induce effective binding and neutralizing antibodies in mice.