OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective:To explore the effects of lutein on the adhesion,invasiveness and metastasis of human prostate cancer PC-3M cells and its action mechanism.Methods:We divided human prostate cancer PC-3M cells into a control,a low-dose lutein,a medium-dose lutein and a high-dose lutein group,and treated them with 0,10,20 and 40 μmol/L lutein,respectively.Then we ex-amined the adhesion of the cells to matrix by cell adhesion assay and the changes in cell pseudopodia by Phalloidin staining,detected the expressions of paxillin,matrix metalloproteinase 2(MMP-2),MMP-9,recombinant tissue inhibitors of metalloproteinase 1(TIMP-1),E-cadherin,N-cadherin and vimentin by Western blot,determined the invasiveness and migration of the cells by scratch and Tran-swell assays,and observed their dynamic movement by high-intension imaging.Results:Compared with the control,the lutein inter-vention groups showed significant reduction in the number of the cells adhered to matrix,the number of cell pseudopodia,the expres-sions of paxillin,MMP-2,MMP-9,N-cadherin and vimentin,the rates of migration,invasion and metastasis,and the distances of dis-placement and movement of the cells.However,the expressions of TIMP-1 and epithelial-mesenchymal transition-related E-cadherin were upregulated significantly.Conclusion:Lutein can inhibit cell adhesion,reduce the expressions of MMPs,and suppress cell in-vasion and migration by inhibiting the proeess of epithelial-mesenchymal transition.

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
Commerce ; Medicine, Chinese Traditional ; Tablets ; Water ; Drug Compounding

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

OBJECTIVE: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities. METHODS: Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. RESULTS: PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC ₅₀: 9.03 ± 4.83 μmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 μmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 μmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 μmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 μmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 μmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity. CONCLUSION Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
Humans ; Pregnancy ; Female ; Rats ; Animals ; Placenta ; Progesterone/pharmacology* ; Aromatase/pharmacology* ; Cell Line, Tumor ; Fluorocarbons ; Alkanesulfonic Acids ; Structure-Activity Relationship ; Hydroxysteroid Dehydrogenases/pharmacology*

Objective:To study the policy framework and core content of assistive technology (AT) services, compare the current status of AT in countries with different levels of development, and discuss the future development of international policies and services of AT. Methods:Based on the policy and theoretical framework of AT of the United Nations (UN) and World Health Organization (WHO), the policy framework and main contents of international AT services were analyzed; the policies, assistive products and service development of AT services in countries with different levels of development worldwide were compared; and the policy and innovative technology development hotspots of international AT were explored. Results:AT service is an important component of rehabilitation services, and the development of AT services is a key step toward achieving the UN Sustainable Development Goal 3, "Ensure healthy lifestyles and promote the well-being of people of all ages". UN and WHO advocated AT services policy. The framework is based on the UN Convention on the Rights of Persons with Disabilities (CRPD) on articles related to AT, and WHO documents of AT and rehabilitation, such as World Report on Disability, the Global Plan of Action on Disability, Rehabilitation in the Health System, and Rehabilitation in the Health System: A Guide to Action, as well as WHA 71.8 on Assistive Technology, Improving Access to Assistive Technology. The core elements of the international AT policy aim to build integrated, people-centered health services, emphasize the integration of AT into the health system and rehabilitation services, establish and develop AT services in six building blocks of WHO health system, thereby improving access to quality AT to achieve universal health coverage. Further in the fields of technology and service innovation, it proposed to establish a 5P model. High-income countries and low- and middle-income countries are facing many difficulties and large differences in AT service policies, assistive product provision, and service coverage. In the future, adoption of the 5P model proposed by WHO for policy and service delivery and technological changes, and the innovation of assistive product development and AT service models will be the hot spots of AT development. Conclusion:The policy on AT at international level is centered on the concept of UN CRPD and is based on prospect of policy documents issued by the UN and WHO on AT services, with the core objective of developing AT services to provide timely, appropriate, and affordable to persons with disabilities, aging, and people needed to improve their health, quality of life and well-being. It proposes to integrate AT into universal health coverage and to deliver AT service through primary health care in order to achieve the UN SDG 3 goal with full coverage of AT. It proposes to integrate AT into rehabilitation services, i.e. leadership and governance, financing, AT professionals, AT delivery, medicine and technology, and health information system monitoring AT services. There are differneces in AT products and AT delivery due to the globel differneces in economic and social development levels and challenges in access to AT services. It is necessary to develop relevant policies, planning and innovations in assistive products and AT services. AT development in the future will focus on the 5P model of AT to implement reforms in the field of product and service delivery as well as technological innovation in order to improve the coverage, availability, accessibility and affordability, integrate AT into the health system within the framework of universal health coverage, achieve full coverage of universal AT services, and enhance the quality of AT and improve consumers' well-being.

Objective:To study the prevalence of people with disability, and the demand, service policies and service system for assistive technology (AT) services in Australia. Methods:Referring to policy recommendation and indicators in World Health Organizaion's Rehabilitation in Health Systems, Australia's assistive technology service policy framework, services development and trend of development were analyzed by the means of content analysis and development research. Results:There are about 4.4 million people with disability in Australia, of which 1.4 million (32%) with severe or profound disabilities. Federal, state and territorial governments have respectively issued legislation, policy and related service project, including the National Disability Strategy, National Disability Agreement, the National Disability Insurance Scheme, National Standards for Disability Services and others assistance programs to support disability services. There are about two million Australians with disabilities received AT services support from the mentioned programme and scheme. Australia provides more than ten thousands kinds of AT appliances per year, covering all kinds of products in WHO's Priority Assistive Products List. Conclusion:Australia has developed a federal National Disability Strategy, AT service policies and standards, and established federal and state AT insurance and financial support programs for people with disabilities based on the unmet needs of AT services, and federal and state networks for AT services have been established, and service coordination mechanisms at federal and state levels have been established through the National Disability Agreement, covering all types of people with demand of AT in Australia. It meets the requirements of the policy recommendations and assessment indicators in the WHO's Rehabilitation in Health Systems policy guidelines involving AT services. The future development areas in AT will focus on the fields of policy development, ICF implementation, service delivery system, upgrading of service quality and standard, and new technology application.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.