Objective To evaluate the advantages of powder-liquid double-chamber bag products compared with traditional powder injection. Methods The systematic review method was used to collect the literature on powder-liquid double-chamber bag, extract common evaluation indicators, evaluate the use value of powder-liquid double-chamber bag products, and conduct a comprehensive comparison with traditional powder injection products. Results A total of 23 articles were included in the literature. The effectiveness indicators used for evaluation were the stability of the liquid medicine, the accuracy of the preparation concentration, and the residual amount of the liquid medicine; the safety indicators were the incidence of insoluble particles and the incidence of punctures and scratches. The economic indicators were preparation cost, occupied volume of preparation supplies, waste weight, hospitalization cost and incidence of blood infection. The applicability indicators were preparation time, average occupation of medical staff, packaging weight and storage and transportation volume, environmental adaptability, and ease of waste disposal. Accessibility indicators are the number of manufacturers, raw material supply capacity, and patient affordability. Through the evaluation of literature evidence, it was found that the stability and concentration accuracy of the powder-liquid double-chamber bag were higher than those of the traditional powder injection, and the domestic supply had been achieved. The double-chamber bag method can reduce the infusion reaction and shorten the preparation time of the liquid medicine. Conclusion Compared with traditional powder injectabler products, powder-liquid double-chamber bags have advantages in the dimensions of effectiveness, safety, economy, suitability and innovation, and the accessibility dimension meets the requirements.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the effects of transcranial magnetic stimulation(TMS)combined with human umbilical cord mesen-chymal stem cells(hUC-MSCs)on ferroptosis following spinal cord injury(SCI)in rats.Methods Allen percussion was used to estab-lish the SCI model.A total of 60 SD rats were randomly divided into sham,SCI,TMS,hUC-MSC,and TMS+hUC-MSC groups,with 12 rats in each group.Motor function was evaluated using the Basso-Beattie-Bresnahan(BBB)score.Spinal cord tissues were sampled and stained with hematoxylin and eosin(HE)as well as Nissl to observe tissue damage as well as the changes in neurons and Nissl bodies,respectively.The colorimetric method was used to detect the contents of ferrous ions(Fe2+)and reduced glutathione(GSH).Transmission electron microscopy was applied to observe the ultrastructure of the mitochondria.Western blotting was performed to detect the expres-sion levels of SLC7A11,GPX4,and ACSL4.Results The SCI group had lower BBB scores,higher Fe2+and ACSL4 protein expression levels,and lower GSH,SLC7A11,and GPX4 protein expression levels than the sham group(P<0.05).The mitochondrial cristae reduced with membrane shrinkage,neuronal damage was severe,and Nissl bodies were absent in the SCI group.The TMS,hUC-MSC,and TMS+hUC-MSC groups had higher BBB scores,lower Fe2+and ACSL4 protein expression levels,and higher GSH,SLC7A11,and GPX4 protein expression levels than the SCI group(P<0.05).The mitochondrial cristae increased with an intact membrane structure,the pathological damage was attenuated,neuronal morphology was restored,and Nissl bodies were clearly visible in TMS,hUC-MSC,and TMS+hUC-MSC groups.Conclusion TMS combined with hUC-MSC inhibits ferroptosis through activating the SLC7A11/GSH/GPX4 pathway,alleviates secondary injury after SCI,and promotes functional recovery and neural remodeling in rats.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.

Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

Implementation Science is an interdisciplinary field dedicated to systematically studying how to effectively translate evidence-based research findings into practical application and implementation. In the health-related context, it focuses on enhancing the efficiency and quality of healthcare services, thereby facilitating the transition from scientific evidence to real-world practice. This article elaborates on Theories, Models, and Frameworks (TMF) within health-related Implementation Science, clarifying their basic concepts and classifications, and discussing their roles in guiding implementation processes. Furthermore, it reviews and prospects current research from three aspects: the constituent elements of TMF, their practical applications, and future directions. Five representative frameworks are emphasized, including the Consolidated Framework for Implementation Research (CFIR), the Practical Robust Implementation and Sustainability Model (PRISM), the Exploration, Preparation, Implementation, Sustainment (EPIS)framework, the Behavior Change Wheel (BCW), and the Normalization Process Theory (NPT). Additionally, resources such as the Dissemination & Implementation Models Webtool and the T-CaST tool are introduced to assist researchers in selecting appropriate TMFs based on project-specific needs.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the relationship between the mechanism of mild hypothermia-induced reduction of neuronal apoptosis during cerebral ischemia-reperfusion (I/R) and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in rats.Methods:Forty SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 5 groups ( n=8 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (IR group), hypothermia + cerebral I/R group (HIR group), hypothermia + cerebral ischemia-reperfusion + solvent group (HIR-DMSO group) and hypothermia + ischemia-reperfusion + CaMKK2 inhibitor STO-609 group (HIR-STO609 group). A global cerebral I/R injury model was established using the four-vessel occlusion method. In HIR group, HIR-DMSO group, and HIR-STO609 group, an ice blanket was used to reduce the body temperature immediately after cerebral ischemia, bringing the core body temperature down to 32.5-33.5 ℃, and rewarming was carried out 4 h later. One hour before developing the model, STO-609 solution 4 μl was injected into the lateral ventricle in HIR-STO609 group, and the equal volume of dimethyl sulfoxide solution was given instead in HIR-DMSO group. At the end of reperfusion, the modified neurological severity score (mNSS) was performed. Then the rats were sacrificed under deep anesthesia, and the hippocampal tissues were taken to observe the pathological results of the hippocampal tissues (using HE staining and Nissl staining) and to determine the apoptosis rate of neurons (by TUNEL method) and expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X (Bax), CaMKK2, phosphorylated AMPK (p-AMPK) and AMPK (by Western blot). Results:Compared with Sham group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, and the ratio of p-AMPK/AMPK was decreased in IR group ( P<0.05). Compared with IR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly decreased, the expression of Bax was down-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was up-regulated, and the ratio of p-AMPK/AMPK was increased in HIR group ( P<0.05). Compared with HIR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, the ratio of p-AMPK/AMPK was decreased ( P<0.05), and no significant change was found in the aforementioned parameters in HIR-DMSO group ( P>0.05). Conclusions:Mild hypothermia can inhibit neuronal apoptosis by up-regulating the CaMKK2/AMPK signaling pathway, thus reducing cerebral I/R injury in rats.