This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

AIM:To observe the effect of the plus power ring zone(PPRZ)area and distribution on myopia progression.METHODS:This retrospective study enrolled 137 pre-teens aged 8-12 at Taiyuan Aier Eye Hospital between 2019 and 2021. They were fitted with Ortho-K lenses for the first time due to refractive error, with a one-year follow-up period. To indicate the peripheral plus ring zone overlapping with the pupil zone(PPROPZ)accompanying PPRZ, participants were divided based on the PPROPZ to PPRZ ratio. The experimental group had 103 eyes with a PPROPZ to PPRZ ratio of ≥0.2, and the control group had 103 eyes with a ratio of <0.2. Participants had a spherical diopter in the range of -6.00 D to -0.75 D, against-the-rule astigmatism less than 1.00 D, with-the-rule astigmatism less than 1.50 D, and corneal curvatures of 39.00 D to 46.00 D. They had a stable best corrected visual acuity of 0.10 LogMAR(20/25)or better when wearing orthokeratology(Ortho-K)lenses. PPRZ and PPROPZ were measured using ImageJ; corneal topography assessed corneal-related parameters, and an optical biometer measured the axial length of the eyes pre and post-one years of lens wear.RESULTS: Changes in axial length elongation were found to decrease when either the PPRZ(P<0.01)or PPROPZ(P<0.001)was increased significantly. The axial length growth was faster in the control group(0.37±0.2 mm)than in the experimental group(0.21±0.11 mm). Furthermore, we found that a larger horizontal visible iris diameter(HVID)corresponded to slower axial growth of the eye. In contrast, axial length growth showed no correlation with surface regularity index(SRI), surface asymmetry index(SAI), flat keratometry value(Kf), steep keratometry value(Ks).CONCLUSION:For orthokeratology, wearers with larger PPROPZ to PPRZ ratio usually experiences a reduction in axial length growth. The PPRZ and PPROPZ are negatively correlated with the axial length. Our findings provide a recommendation and methods for studying the myopia control mechanism through Ortho-K lenses.

Gastric cancer (GC) is a globally prevalent malignancy with a particularly heavy burden in China. Helicobacter pylori ( H. pylori ) is a Group I carcinogen for GC, with a higher seroprevalence rate indicating a higher GC incidence. However, only approximately 3% of the individuals with H. pylori infection eventually develop GC, and about 2.6% still progress to GC even 10-20 years after the eradication of H. pylori . Thus, the pathogenic mechanism of H. pylori for GC must be elucidated, and high-risk individuals precisely identified. Furthermore, GC can occur even in individuals who have never been infected with H. pylori . As H. pylori infection rates decline, the proportion of H. pylori -negative GC cases is increasing annually, gaining significant research attention. In this review, potential pathogenic mechanisms of H. pylori infection are explored from the aspects of H. pylori virulence factors and host factors (genetic susceptibility and immune microenvironment). Possible risk factors for H. pylori -negative GC include infections by other microorganisms (e.g., bacteria, fungi, and viruses), autoimmune gastritis, bile reflux, genetic mutations, and environmental factors. We aim to review the potential mechanisms for GC with varying H. pylori infection statuses, identify the high-risk individuals, and pose questions that need to be addressed. In the future, as the prevalence of H. pylori infection gradually decreases, GC prevention and management must evolve to address host-specific factors and the growing challenge of H. pylori -negative GC by integrating multidisciplinary perspectives.
Stomach Neoplasms/genetics* ; Humans ; Helicobacter Infections/complications* ; Helicobacter pylori/pathogenicity* ; Risk Factors

OBJECTIVE: To explore the changes of CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) and programmed death-ligand 1 (PD-L1) expression in gastric mucosal epithelial cells after Helicobacter pylori infection and the regulation of CMTM6 on PD-L1, and to analyze the mRNA expression differences before and after CMTM6 gene knock-out in helicobacter pylori infected gastric epithelial cells by microarray analysis. METHODS: The standard Helicobacter pylori strain ATCC 26695 was co-cultured with human gastric epithelial cell GES-1 for 6, 24 and 48 hours, and the mRNA and protein levels of CMTM6 and PD-L1 were detected by real-time quantitative PCR and Western blot. Using CRISPR/Cas9 to construct CMTM6 gene knockout plasmid and knockout CMTM6 gene of GES-1 cells. Helicobacter pylori was co-cultured with CMTM6 gene knockout and wild type GES-1 cells for 48 hours to detect PD-L1 transcription and protein level changes, and CMTM6 gene knockout GES-1 cells were treated with the proteasome inhibitor MG-132 to detect the changes in PD-L1 protein levels. Agilent Human ceRNA Microarray 2019 was used to detect the differentially expressed genes in CMTM6 gene knockout and wild-type GES-1 cells co-cultured with Hp for 48 hours, and the signal pathway of differentially expressed genes enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: The mRNA and protein levels of CMTM6 and PD-L1 in GES-1 cells were significantly up-regulated after Helicobacter pylori infection, and CMTM6 mRNA was most significantly up-regulated 48 hours after infection. After CMTM6 gene knockout, the CD274 gene transcription level of Helicobacter pylori infected GES-1 cells did not change significantly, but PD-L1 protein level was significantly down-regulated, and the PD-L1 level increased after the application of proteasome inhibitor MG-132. After CMTM6 gene knockout, 67 genes had more than two times of differential expression. The transcription levels of TMEM68, FERMT3, GPR142, ATP6V1FNB, NOV, UBE2S and other genes were significantly down-regulated. The transcription levels of PCDHGA6, CAMKMT, PDIA2, NTRK3, SPOCK1 and other genes were significantly up-regulated. After CMTM6 gene knockout, ubiquitin-conjugating enzyme E2S (UBE2S) gene expression was significantly down-regulated, which might affect protein ubiquitination degradation. After CMTM6 gene knockout, adrenoceptor alpha 1B (ADRA1B), cholinergic receptor muscarinic 1 (M1), CHRM1, platelet activating factor receptor (PTAFR) gene expression was significantly up-regulated. CONCLUSION Helicobacter pylori infection up-regulates the expression level of CMTM6 in gastric mucosa cells, and CMTM6 can stabilize PD-L1 and maintain the protein level of PD-L1. CMTM6 gene knockout may affect biological behaviors such as protein ubiquitination and cell surface receptor expression.
Humans ; MARVEL Domain-Containing Proteins/metabolism* ; Helicobacter pylori/physiology* ; B7-H1 Antigen/genetics* ; Helicobacter Infections/metabolism* ; Epithelial Cells/metabolism* ; Gastric Mucosa/metabolism* ; Chemokines/metabolism* ; Cell Line ; Gene Knockout Techniques ; Myelin Proteins

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective To investigate the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1β(PGC-1β),hypoxia-inducible factor-1α(HIF-1α),and resistin(RETN)in gouty arthri-tis(GA),and analyze their correlation with the degree of joint damage.Methods A total of 134 patients with GA in the hospital from January 2022 to October 2023 were selected as GA group,and 134 healthy people who underwent the physical examination in the same period were selected as control group.The serum expression levels of PGC-1β,HIF-1α and Retn were compared between the two groups.The expression levels of PGC-1β,HIF-1α and Retn in serum and synovial fluid of patients with different clinical characteristics in GA group were compared,the degree of joint destruction was graded according to the subjective pain grading method(VAS)and the patients were divided into a severe GA subgroup of 78 cases and a mild GA subgroup of 56 ca-ses.The expression levels of PGC-1β,HIF-1α,RETN,bone destruction factors[β-cross linked degradation products(β-CTX),tartrate resistant acid phosphatase-5b(TRACP5b),receptor activator of nuclear factor kappa B ligand(RANKL)]and inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)]were compared among different degrees of joint destruction,and the correlation between serum and syno-vial fluid PGC-1β,HIF-1α,RETN and the degree of joint destruction,bone destruction factors,and inflamma-tory factors was analyzed.Results The expression level of PGC-1β in serum of GA group was lower than that of the control group,while the expression levels of HIF-1α and RETN in serum were higher than those of the control group(P＜0.05).There were statistically significant differences in serum and synovial fluid PGC-1β,HIF-1α,and RETN levels among GA patients with different clinical stages,affected joints,disease duration,and annual seizure frequency(P＜0.05).The expression levels of PGC-1β in the serum and synovial fluid of the severe GA subgroup were lower than those of the mild GA subgroup(P＜0.05),while the expression lev-els of HIF-1α and RETN were higher than those of the mild GA subgroup(P＜0.05).The expression levels ofβ-CTX and TRACP5b in the severe GA subgroup were higher than those in the mild GA subgroup(P＜0.05),while the expression level of RANKL was lower than that in the mild GA subgroup(P＜0.05).PGC-1βin serum and synovial fluid was negatively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and positively correlated with RANKL.HIF-1α and RETN were positively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and negatively correlated with RANKL.Conclusion PGC-1β,HIF-1α,and RETN are abnormally expressed in patients with GA,and are closely associ-ated with the degree of joint destruction,bone destruction factors,and inflammatory factors.They are expec-ted to become reliable indicators for evaluating the occurrence and progression of GA.

Objective To explore the symptom clusters in renal transplant recipients and con-struct a concurrent symptom network to identify core symptoms.Methods A total of 343 patients with followed up after renal transplantation were selected as the study subjects.A general information questionnaire and the Chinese version of the Modified Transplant Symptom Occurrence and Symptom Distress Scale were employed to analyze the occurrence of symptoms in patients.In this study,only symptoms with an incidence rate greater than 20％and Spearman correlation coefficient greater than 0.40 between symptom severity and total score were retained.Exploratory factor analysis was used to extract symptom clusters with a factor loading of ≥0.45 as the criterion.The R language was utilized to construct symptom network,based on which core symptoms and bridge symptoms were identified.Results A total of 5 symptom clusters were extracted in this study:the neuro-gastrointestinal symp-tom cluster,the mood-related symptom cluster,the hormone-related symptom cluster,the energy de-ficiency symptom cluster and the vision-related symptom cluster.The core symptoms were anxiety(rs=1.75),mood swings(rs=1.50)and muscle weakness(rs=1.27).The top three symptoms in terms of bridge strength were muscle weakness(rb=0.87),lack of vitality(rb=0.66)and fa-tigue(rb=0.65).Conclusion Multiple symptoms are presented in patients after renal transplanta-tion.Based on the results of symptom network analysis,clinicians can strengthen the assessment of core symptoms and bridge symptoms to develop precise intervention strategies and improve the effectiveness of symptom management.

Various types of industrial parks in Shanghai play an important role in promoting industrial upgrading and technological progress， yet they are also fraught with occupational health hazards. To effectively promote workplace health and enable various industrial parks to play a positive role， the Shanghai Municipal Government has proposed accelerating the construction of healthy industrial parks. To meet the requirements for the scientific and standardized construction of healthy parks， the Shanghai Municipal Center for Disease Control and Prevention has compiled the Guidelines for Healthy Industrial Park Construction（Guidelines）. Adhering to the overall principles of scientific， feasibility， advancement， and standardization， the Guidelines address three construction levels： industrial parks， employers， and employees. They set clear requirements for organizational management， healthy environments， health services， health activities， and occupational health in the workplaces， respectively. The Shanghai healthy industrial park evaluation form was provided as an informative appendix for the Guidelines. The Guidelines offer a scientific basis for standardizing and guiding the construction of healthy industrial parks， providing new solutions and technical support for urban occupational health management.