Objective To compare and analyze the changes in the use of lung cancer therapeutic drugs before and after the national initiation of health insurance negotiations, and to study the impact of a series of policies on the use of lung cancer drugs. Methods Descriptive statistical methods were used analyze the basic situation of lung cancer patients and the changes of corresponding therapeutic drugs in Peking University People's Hospital from 2014 to 2020, as well as to the hospital procurement data of lung cancer therapeutic drugs in the database of the Chinese Medicine Economic Information. Results From 2014 to 2020, the total cost per capita of lung cancer patients showed a trend of first increasing and then decreasing, increasing before the national drug negotiation and gradually decreasing after the negotiation. After 2017, the use of small ATC categories such as VEGF/VEGFR inhibitors and EGFR tyrosine kinase inhibitors increased significantly, along with a rise in the number of monoclonal antibody varieties. The DDDs of osimertinib, anlotinib, alectinib, crizotinib and other drugs in the medical insurance list increased significantly, and the average daily cost decreased significantly. Conclusion The number of hospitalization days for lung cancer patients had continued to shorten in recent years, and the structure of drug use had changed significantly. The adjustment of the medical insurance catalog had led to more innovative lung cancer drugs showing the trend of volume up and price down.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Under the background of new-era technological development and the implementation of national strategies, an increasing number of national major scientific and technological infrastructures led by universities have come into operation. How to take the advantages of national facilities to serve major scientific researches while fostering innovative graduates has become an important issue in recent studies. Taking Shanghai Jiao Tong University as an example and building upon the first National Facility for Translational Medicine (Shanghai), this paper focuses on the cultivation of graduates' innovative research and practical abilities, constructs a three-dimensional collaborative education system of "institutional empowerment-knowledge transfer-capability forging, " and explores the implementation pathway through which national major scientific and technological infrastructures empower innovative talent development. Practice has demonstrated that converting the research and technological advantages of national major scientific and technological infrastructures into high-quality educational resources yields remarkable outcomes in empowering innovative talent development, offering a replicable paradigm for universities to enhance the quality of innovative talent cultivation through national multidisciplinary cross-cutting science and technology platforms such as national major scientific and technological infrastructures.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Objective To investigate the gray matter volume(GMV)changes and molecular basis underlying antipsychotic-induced weight gain(AIWG).Methods One hundred twenty-nine first-episode schizophrenia patients from October 2019 to December 2021 were enrolled in this study.Patients with≥7%weight gain(weight gain,WG)and patients with<3%weight changes(weight stable,WS)were studied.All patients underwent T1-weighted MRI scanning at baseline and after 8 week treatment.Transcriptome-neuroimaging correlations were used to investigate brain gene profiles from the Allen Human Brain Atlas and GMV changes induced by AIWG.Results Thirty-three patients with WG and 27 with WS completed the GMV measures.Compared with baseline,the WG group showed reduced GMV in right hippocampus,left basal ganglia,and right inferior parietal lobule,etc.and increased GMV in bilateral thalamus(P<0.05).The WS group showed reduced GMV in bilateral orbital gyrus,bilateral inferior frontal gyrus and bilateral hippocampus(P<0.05).These GMV changes in WG group were spatially correlated with expression levels of 354 genes,which were exclusively enriched in Cushing syndrome,neuroinflammation and glutamatergic signaling,and Pnoc+.Conclusion The study has demonstrated increased GMV in thalamus in schizophrenia patients with AIWG which may be associated with Cushing syndrome and Pnoc+.These findings may provide important insights into the molecular mechanisms of AIWG.

Objective: To investigate the clinical and pathologic features, diagnosis and differential diagnosis of congenital hemangioma (CH). Methods: Forty cases of CH were diagnosed from January 2017 to December 2020 in Henan Provincial People's Hospital. The clinical and pathological and immunohistochemical data were analyzed, with review of literature. Results: There were 24 male and 16 female patients. The lesions were located in the head, neck (11 cases), limbs (14 cases), and trunk (15 cases). The clinical manifestations were congenital painless plaques or masses, the larger ones protruded on the skin surface, mostly dusky purple or bright red, with surrounding white halos. Under low magnification, the tumor was lobular and well demarcated, composed of neo-microvascular lumen of different sizes. The vascular endothelial cells were cuboidal or hobnail in appearance, forming stellar drainage vessels within the lobules. Extra-medullary hematopoiesis was seen in one case of rapidly involuting CH; there were different number of tortuous and dilated vascular lumen between the lobular structures, and some non-involuting CH cases were vascular malformations, which were devoid of lobulated structures. Immunohistochemistry showed that endothelial cells were strongly positive for CD31, CD34 and ERG, while D2-40 and GLUT-1 were negative. Conclusions: CH is a benign congenital vascular tumor with characteristic lobulated growth and abnormal blood vessels in the stroma. Pathological diagnosis often needs to be differentiated from infantile hemangioma, pyogenic granuloma, kaposiform hemangioendothelioma and vascular malformation.
Endothelial Cells/pathology* ; Female ; Hemangioendothelioma/pathology* ; Hemangioma/pathology* ; Humans ; Kasabach-Merritt Syndrome/pathology* ; Male ; Sarcoma, Kaposi/pathology* ; Skin Neoplasms/pathology*

Objective:To observe the curative effect and temperature safety management of ginger mud moxibustion of different thickness on ankylosing spondylitis patients with kidney yang deficiency type, and to explore the best curative effect combination and safety combination of ginger mud thickness in Du Meridian moxibustion.Methods:From March 2020 to March 2021, 90 patients with ankylosing spondylitis of kidney yang deficiency type who were treated with Du moxibustion in the Affiliated Hospital of Nanjing University of Chinese Medicine were selected. According to the thickness of ginger paste, they were randomly divided into 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group when the diameter and height of moxa wool were the same as 2 cm, 30 cases in each group. They were treated with Fu Yang Du moxibustion once a week for 60 minutes each time. Visual Analogue Scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), traditional Chinese medicine syndrome score were used to evaluate the curative effect of spinal function before and after the intervention for 6 weeks. The time when moxibustion temperature reached 43 ℃ and moxibustion temperature maintained at 43-45 ℃ were analyzed for safety evaluation.Results:After moxibustion, VAS scores of 2 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group were 2.89 ± 0.96, 2.01 ± 0.69, 2.93 ± 1.23, BASDAI scores were 3.51 ± 0.94, 2.69 ± 0.68, 3.13 ± 0.96 and BASFI scores were 1.71 ± 0.99, 0.99 ± 0.36, 1.61 ± 0.50, the traditional Chinese medicine syndrome scores were 15.97 ± 4.61, 12.08 ± 3.21, 13.79 ± 3.58. The scores of the three groups were statistically significant ( F values were 6.51-19.22, all P<0.05) . After the intervention, there were significant differences in the scores between 2 cm-thick ginger mud thickness group and 3 cm-thick ginger mud thickness group, 2 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group, 3 cm-thick ginger mud thickness group and 4 cm-thick ginger mud thickness group ( t values were -6.61-4.56, all P<0.05). Conclusions:Du moxibustion is an effective method to treat ankylosing spondylitis of kidney yang deficiency type. The best curative effect and safety combination is moxa velvet diameter height 2 cm, ginger mud thickness 3 cm.

Objective:To investigate the role of androgen receptor (AR) in CK5 +CK8 + cells isolated from prostate cancer LNCaP cells and its regulating mechanism. Methods:CK5 +CK8 + cells were isolated from LNCaP cells by using flow cytometry. Lentivirus vector carrying AR gene was transferred in CK5 +CK8 + cells. The experiments were divided into AR CK5 +CK8 + group transfering AR and V CK5 +CK8 + group transfering blank load. The expressions of AR, p-AKT and bcl-2 were tested by using Western blot assay under different concentrations of androgen (1 nmol/L and 10 nmol/L dihydrotestosterone). Methyl thiazolyl tetrazolium (MTT) assay, cell migration assay and soft agarose gel clone formation assay was used to detect the effect of AR on the biological property of CK5 +CK8 + cells. The effect of activated inhibitors such as LY 294002 (LY), γ-tocotrienol (γ-TT) and/or 5-fluorocytosine inducing AR expression (5-AZA) through AKT signal pathways on CK5 +CK8 + cells proliferation was detected by using MTT assay. Results:After AR gene was transferred into CK5 +CK8 + cells, the expression of AR was increased, while the expression of p-AKT and bcl-2 was decreased. After the treatment of 1 nmol /L dihydrotestosterone and 10 nmol/L dihydrotestosterone for 2, 4 and 6 d, the cell proliferation inhibited degree of AR CK5 +CK8 + cells was higher compared with that of V CK5 +CK8 + cells, and the difference was statistically significant (all P < 0.05). After the treatment of 1 nmol/L dihydrotestosterone and 10 nmol /L dihydrotestosterone for 3 d, the migration ability of AR CK5 +CK8 + cells was decreased compared with that of V CK5 +CK8 + cells (the number of cell migration: 54±9 vs. 113±21, 13±3 vs. 34±6), and the differences were statistically significant ( t=4.450, P<0.01; t=5.157, P<0.01).After the treatment of 1 nmol /L dihydrotestosterone and 10 nmol /L dihydrotestosterone for 3 weeks, the tumorigenic ability of AR CK5 +CK8 + cells was reduced compared with that of V CK5 +CK8 + cells (the number of clone: 39±7 vs. 105±16, 41±6 vs. 86±6), and the differences were statistically significant ( t=6.631, P<0.01; t=8.662, P<0.01). And 5 nmol /L LY + 10 nmol/L 5-AZA, 5 nmol /L LY + 5 nmol/L γ-TT, 10 nmol/L 5-AZA + 5 nmol/L γ-TT, 2.5 nmol/L LY + 5 nmol/L 5-AZA + 2.5 nmol/L γ-TT combined with 1 nmol/L dihydrotestosterone or 10 nmol/L dihydrotestosterone after the treatment of 2, 4, 6 d inhibited the proliferation of CK5 +CK8 + cells (all P < 0.05). Conclusion:AR plays an inhibitory role in CK5 +CK8 + cells isolated from prostate cancer cell line LNCaP and reduces the cell migration and tumorigenic ability through inhibiting activation of AKT-bcl-2 signal pathway.