Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

Objective To investigate the effects of light-at-night exposure on anxiety and depression behaviors in mice and to explore the underlying neural mechanisms.Methods Six-week-old male C57BL/6J mice were randomly assigned to a control(Ctrl)group and a light-at-night exposure(LAN)group.Mice in the LAN group were exposed to 460 nm blue light for 1 h daily during the zeitgeber time(ZT)13-14 while the Ctrl group mice were maintained under a 12-h light/12-h dark cycle.Behavioral tests were conducted at different time points following LAN exposure to evaluate anxiety and depression behaviors in the mice.Immunofluorescence staining was used to observe the effect of LAN on c-fos expressions in the medial prefrontal cortex(mPFC),basal ateral amygdala(BLA),paraventricular nucleus(PVN)and paraventricular thalamus(PVT).ELISA was performed to measure changes in serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)levels.Golgi staining was applied to measurethe dendritic spine density and morphology from mPFC and CA1.Western blotting analysis was conducted to detect expression levels of brain-derived neurotrophic factors(BDNFs),phosphorylated tropomyosin receptor kinase B(p-TrkB)/TrkB,postsynaptic density protein 95(PSD95)and synaptophysin(SYP)in the mPFC.Results Mice exhibited anxiety-like behaviors after 14 days of LAN exposure,with depression-like behaviors emerging after 28 days.LAN exposure of 28 days led to a significant increase in the number of c-fos-positive neurons in the mPFC,BLA,PVN and PVT(P＜0.05),resulted in elevated serum corticosterone levels(P＜0.01)and reduced protein expression levels of BDNF and SYP(P＜0.05).Furthermore,there was a marked decrease in synapse numbers and synaptic density in the mPFC(P＜0.01).Conclusion Prolonged exposure to blue light at night enhances neuronal activity in the mPFC and BLA and suppresses the BDNF/TrkB signaling pathway by activating the hypothalamic-pituitary-adrenal axis(HPA),thus leading to synaptic structural and functional damage and inducing anxiety and depression behaviors in mice.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

The cross regional loose medical alliance is an important carrier in the current integrated development process of medical services in the Yangtze River Delta region. Smith policy implementation process model was used to analyze the development difficulties of cross regional loose medical alliances from idealized policies, policy implementation institutions, policy target groups, and policy implementation environment. Such medical alliances were formed under the background of integrated development in the Yangtze River Delta, with Shanghai′s tertiary public hospitals as leading units and medical institutions in Jiangsu, Zhejiang, and Anhui provinces as member units. Analysis showed that the policies for such medical alliances development had not yet clearly defined the organizational management mode, operational mechanism, and implementation path, and the corporate governance structure of medical alliance was immature; The policy implementation agencies were relatively lagging behind in the support of special funds and the formulation of related supporting policies; Participation of policy target groups was insufficient and their incentive mechanisms was imperfect; There were problems in the policy implementation environment, namely inconsistent medical and health service regulations and systems in different regions, different health financing capabilities of local governments, insufficient coordination of medical institution management concepts, and a lack of unified standards in information systems. Based on the above difficulties, this study proposed to strengthen the development planning and layout of cross regional loose medical alliances, and improve the corporate governance structure; To strengthen the government′s main responsibility and improving policy implementation capabilities; To improve the internal cooperation and operation mechanism of cross regional loose medical alliances, and enhance the sense of identity of the target group; To optimize the policy implementation environment and implement various support measures, so as to provide references for further promoting the coordinated development of high-quality medical resources in the Yangtze River Delta region.

Objective:To explore the effectiveness of deep learning image reconstruction (DLIR) algorithm compared to adaptive statistical iterative reconstruction (ASIR-V) algorithm in improving the quality of low-dose brain CT images.Methods:Retrospective inclusion of patients who underwent brain CT examination in the People's Liberation Army General Hospital from November 2021 to August 2022. Four different algorithms were used to reconstruct low-dose CT scans of all patients to obtain 30% intensity ASIR-V (ASIR-V-30%) images, low intensity DLIR (DLIR-L) images, medium intensity DLIR (DLIR-M) images, and high intensity DLIR (DLIR-H) images. The regions of interest were selected from four sets of images, including superficial white matter, superficial gray matter, deep white matter, and deep gray matter, and their CT values and standard deviations were measured for calculating signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).Subjective evaluation of image quality was conducted by three neuroimaging physicians based on the Likert 5-component scale. The objective and subjective scores of the 4 groups of images were analyzed using ANOVA or Kruskal Wallis. If there are overall differences, pairwise comparisons were conducted within the group.Results:A total of 109 patients were enrolled, including 104 males and 5 females, aged 65-110 years (89.16 ± 9.53) years. The radiation exposure of brain CT low-dose scanning was (0.93 ± 0.01)mSv, significantly lower than that of conventional scanning (2.92 ± 0.01) mSv ( t = 56.15, P < 0.05). The differences in objective image quality analysis of ASIR-V-30%, DLIR-L, DLIR-M, and DLIR-H images of low-dose CT in SNR deep gray matter, SNR deep white matter, SNR superficial gray matter, SNR superficial white matter, CNR deep gray white matter, and CNR superficial gray white matter were statistically significant( F =98.23, 72.95, 68.43, 58.24, 241.13, 289.91, P < 0.05). Among them, DLIR-H images had the lowest noise in deep gray matter, deep white matter, superficial gray matter, and superficial white matter, and had statistically significant differences compared to other image groups ( t = 167.43, 275.46, 182.32, 361.54, P < 0.05). The subjective score of DLIR-H image quality was superior to ASIR-V-30%, DLIR-L, and DLIR-M, with the statistically significant difference ( t = 7.25, 8.32, 9.63, P < 0.05). Conclusions:Compared with ASIR-V, DLIR algorithm can effectively reduce image noise and artifacts in low-dose brain CT, and improve SNR and CNR. The subjective and objective image quality evaluation of DLIR-H is the best.

Ninety percent of clinical drug development fails despite implementation of many successful strategies, which raised the question whether certain aspects in target validation and drug optimization are overlooked? Current drug optimization overly emphasizes potency/specificity using structure‒activity-relationship (SAR) but overlooks tissue exposure/selectivity in disease/normal tissues using structure‒tissue exposure/selectivity-relationship (STR), which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity. We propose structure‒tissue exposure/selectivity-activity relationship (STAR) to improve drug optimization, which classifies drug candidates based on drug's potency/selectivity, tissue exposure/selectivity, and required dose for balancing clinical efficacy/toxicity. Class I drugs have high specificity/potency and high tissue exposure/selectivity, which needs low dose to achieve superior clinical efficacy/safety with high success rate. Class II drugs have high specificity/potency and low tissue exposure/selectivity, which requires high dose to achieve clinical efficacy with high toxicity and needs to be cautiously evaluated. Class III drugs have relatively low (adequate) specificity/potency but high tissue exposure/selectivity, which requires low dose to achieve clinical efficacy with manageable toxicity but are often overlooked. Class IV drugs have low specificity/potency and low tissue exposure/selectivity, which achieves inadequate efficacy/safety, and should be terminated early. STAR may improve drug optimization and clinical studies for the success of clinical drug development.

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

Nanomedicine usually refers to nanoparticles that deliver the functional drugs and siRNAs to treat cancer. Recent research has suggested that cancer cells can also make nanoparticles that also deliver functional molecules in promoting cancer metastasis, which is the leading cause of various cancer mortalities. This nanoparticle is called tumor-derived vesicles, or better-known as tumor-derived exosomes (TEXs). TEXs are nanoscale membrane vesicles (30-140 nm) that are released continuously by various types of cancer cells and contain tumor-derived functional biomolecules, including lipids, proteins, and genetic molecules. These endogenous TEXs can interact with host immune cells and epithelial cells locally and systemically. More importantly, they can reprogram the recipient cells in favor of promoting metastasis through facilitating tumor cell local invasion, intravasation, immune evasion, extravasation, and survival and growth in distant organs. Growing evidence suggests that TEXs play a key role in cancer metastasis. Here, we will review the most recent findings of how cancer cells harness TEXs to promote cancer metastasis through modulating vascular permeability, suppressing systemic immune surveillance, and creating metastatic niches. We will also summarize recent research in targeting TEXs to treat cancer metastasis.

Objective: To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor Ⅴ (FⅤ) deficiency. Methods: All of the exons, flanking sequences, and 5′ and 3′ untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. Results: The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FⅤ activity (FⅤ∶C) and FⅤ antigen (FⅤ∶Ag) were reduced by 13% and 17%, respectively. The FⅤ∶C and FⅤ∶Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c. 2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c. 1538G>A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p. Ser923LeufsX8 variant, while his mother and son carried the heterozygous p. Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p. Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p. Ser923LeufsX8 variant, and the result has predicted a corresponding disease. Conclusion A heterozygous deletional mutation c. 2851delT in exon 13 of the F5 gene and a heterozygous c. 1538G>A polymorphism harbored by the proband may be associated with the decreased FⅤ level in this pedigree.

Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy.