[The Optimal Storage Condition and Storage Time of Umbilical Cord Blood from Collection to Preparation].

OBJECTIVE: To explore the optimal storage condition and time of umbilical cord blood from collection to preparation. METHODS: Collect cord blood samples from 30 healthy newborns, with each new born's umbilical cord blood was divided into two parts on average. One part was stored in cold storage (4 ℃) and the other was stored at room temperature (20-24 ℃). Samples were taken at 24, 36, 48, 60 and 72 h, respectively, total nucleated cells (TNC) count and TNC viability was analyzed. Flow cytometry was used to detect the ratio of viable CD34+ cells to viable CD45+ cells and viability of CD34+ cells, and colony-forming unit-granulocyte-macrophage (CFU-GM) count was performed by hematopoietic progenitor cell colony culture. The change trend of each index over time was observed, and the differences in each index was compared between cold storage and room temperature storage under the same storage time. RESULTS: The TNC count (r 4 ℃=-0.9588， r 20-24 ℃=-0.9790), TNC viability (r 4 ℃=-0.9941， r 20-24 ℃=-0.9970), CD34+ cells viability (r 4 ℃=-0.9932， r 20-24 ℃=-0.9828) of cord blood stored in cold storage (4 ℃) and room temperature storage (20-24 ℃) showed a consistent downward trend with the prolongation of storage time. The percentage of viable CD34+ cells (r 4 ℃=0.9169， r 20-24 ℃=0.7470) and CFU-GM count (r 4 ℃=-0.2537， r 20-24 ℃=-0.8098) did not show consistent trends. When the storage time was the same, the TNC count, TNC viability, CD34+ cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature. Under the same storage time (24, 36, 48, 60 or 72 h), TNC viability in room temperature storage was significantly lower than that in cold storage (P <0.001), but TNC count, percentage of viable CD34+ cells and CFU-GM count were not significantly different between room temperature storage and cold storage. When stored at room temperature for 24 h and 36 h, the viability of CD34+ cells was significantly lower than that in cold storage (P <0.001, P <0.01), when the storage time for 48, 60 and 72 h, there was no significant difference in the CD34+ cells viability between room temperature storage and cold storage. CONCLUSION: It is recommended that cord blood be stored in cold storage (4 ℃) from collection to preparation, and processed as soon as possible.

Establishment and validation of a prediction model for nonrecovery of left ventricular ejection fraction in acute myocardial infarction patients combined with decreased left ventricular ejection fraction.

BACKGROUND: This study aimed to investigate the risk factors for nonrecovery of left ventricular ejection fraction (LVEF) during follow-up in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) combined with reduced LVEF, and establish and verify a risk prediction model based on these factors. METHODS: In this study, patients with AMI who underwent PCI in a high-volume PCI center between December 2018 and December 2021 were consecutively enrolled, screened, and randomly assigned to the model establishment and validation cohorts. A predictive model method based on least absolute shrinkage and selection operator regression was used for establishment and validation. RESULTS: Cardiac troponin I, myoglobin, left ventricular end-diastolic dimension, multivessel disease, and no-reflow were identified as potential predictors of LVEF recovery failure. The areas under the curve were 0.703 and 0.665 in the model establishment and validation cohorts, respectively, proving that the prediction model had some predictive ability. The calibration curves of the two cohorts showed good agreement with those of the nomogram model. In addition, the decision curve analysis showed that the model had a net clinical benefit. CONCLUSION: This prediction model can assess the risk of nonrecovery of LVEF in patients with AMI undergoing PCI combined with LVEF reduction during follow-up, and conveniently screen high-risk patients with nonrecoverable LVEF early.

Spatial analysis of the osteoarthritis microenvironment: techniques, insights, and applications.

Osteoarthritis (OA) is a debilitating degenerative disease affecting multiple joint tissues, including cartilage, bone, synovium, and adipose tissues. OA presents diverse clinical phenotypes and distinct molecular endotypes, including inflammatory, metabolic, mechanical, genetic, and synovial variants. Consequently, innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches. Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints, causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues. This issue has led to standardization difficulties and hindered the success of clinical trials. Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues, encompassing DNA, RNA, metabolites, and proteins, as well as their chemical properties, elemental composition, and mechanical attributes, can contribute to a more comprehensive understanding of the disease subtypes. Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment, providing a more holistic view of cellular function. Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various -omics lenses, such as genomics, transcriptomics, proteomics, and metabolomics, with spatial data. This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates. Furthermore, advanced imaging techniques, including high-resolution microscopy, hyperspectral imaging, and mass spectrometry imaging, enable the visualization and analysis of the spatial distribution of biomolecules, cells, and tissues. Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes. This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis. It explores their applications, challenges, and potential opportunities in the field of OA. Additionally, this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.

Boosted Oxygen Kinetics of Hierarchically Mesoporous Mo2C/C for High-current-density Zn-air Battery.

The high-current-density Zn-air battery shows big prospects in next-generation energy technologies, while sluggish O2 reaction and diffusion kinetics barricade the applications. Herein, the sequential assembly is innovatively demonstrated for hierarchically mesoporous molybdenum carbides/carbon microspheres with a tunable thickness of mesoporous carbon layers (Meso-Mo2C/C-x, where x represents the thickness). The optimum Meso-Mo2C/C-14 composites (≈2 µm in diameter) are composed of mesoporous nanosheets (≈38 nm in thickness), which possess bilateral mesoporous carbon layers (≈14 nm in thickness), inner Mo2C/C layers (≈8 nm in thickness) with orthorhombic Mo2C nanoparticles (≈2 nm in diameter), a high surface area of ≈426 m2 g-1, and open mesopores (≈6.9 nm in size). Experiments and calculations corroborate the hierarchically mesoporous Mo2C/C can enhance hydrophilicity for supplying sufficient O2, accelerate oxygen reduction kinetics by highly-active Mo2C and N-doped carbon sites, and facilitate O2 diffusion kinetics over hierarchically mesopores. Therefore, Meso-Mo2C/C-14 outputs a high half-wave potential (0.88 V vs RHE) with a low Tafel slope (51 mV dec-1) for oxygen reduction. More significantly, the Zn-air battery delivers an ultrahigh power density (272 mW cm-2), and an unprecedented 100 h stability at a high-current-density condition (100 mA cm-2), which is one of the best performances.

Mesoporous TiO2 Single-Crystal Particles from Controlled Crystallization-Driven Mono-Micelle Assembly as an Efficient Photocatalyst.

Mesoporous materials with crystalline frameworks have been widely explored in many fields due to their unique structure and crystalline feature, but accurate manipulations over crystalline scaffolds, mainly composed of uncontrolled polymorphs, are still lacking. Herein, we explored a controlled crystallization-driven monomicelle assembly approach to construct a type of uniform mesoporous TiO2 particles with atomically aligned single-crystal frameworks. The resultant mesoporous TiO2 single-crystal particles possess an angular shape ∼80 nm in diameter, good mesoporosity (a high surface area of 112 m2 g-1 and a mean pore size at 8.3 nm), and highly oriented anatase frameworks. By adjusting the evaporation rate during assembly, such a facile solution-processed strategy further enables the regulation of the particle size and mesopore size without the destruction of the oriented crystallites. Such a combination of ordered mesoporosity and crystalline orientation provides both effective mass and charge transportation, leading to a significant increase in the hydrogen generation rate. A maximum hydrogen evolution rate of 12.5 mmol g-1 h-1 can be realized, along with great stability under solar light. Our study is envisaged to extend the possibility of mesoporous single crystal growth to a range of functional ceramics and semiconductors toward advanced applications.

Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics / 药学学报

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications.

Organs-on-a-chip, or OoCs, are microfluidic tissue culture devices with micro-scaled architectures that repeatedly achieve biomimicry of biological phenomena. They are well positioned to become the primary pre-clinical testing modality as they possess high translational value. Current methods of fabrication have facilitated the development of many custom OoCs that have generated promising results. However, the reliance on microfabrication and soft lithographic fabrication techniques has limited their prototyping turnover rate and scalability. Additive manufacturing, known commonly as 3D printing, shows promise to expedite this prototyping process, while also making fabrication easier and more reproducible. We briefly introduce common 3D printing modalities before identifying two sub-types of vat photopolymerization - stereolithography (SLA) and digital light processing (DLP) - as the most advantageous fabrication methods for the future of OoC development. We then outline the motivations for shifting to 3D printing, the requirements for 3D printed OoCs to be competitive with the current state of the art, and several considerations for achieving successful 3D printed OoC devices touching on design and fabrication techniques, including a survey of commercial and custom 3D printers and resins. In all, we aim to form a guide for the end-user to facilitate the in-house generation of 3D printed OoCs, along with the future translation of these important devices.

Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case-control study.

OBJECTIVES: To assess the predictive value of endoscopic grading of gastric atrophy using Kimura-Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC. METHODS: A single-center, case-control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura-Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups. RESULTS: Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura-Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106-9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874-171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura-Takemoto classification within 6-12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650-13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable. CONCLUSIONS: Endoscopic Kimura-Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.

Coaggregation of polyglutamine (polyQ) proteins is mediated by polyQ-tract interactions and impairs cellular proteostasis.

Nine polyglutamine (polyQ) proteins have already been identified that are considered to be associated with the pathologies of neurodegenerative disorders called polyQ diseases, but whether these polyQ proteins mutually interact and synergize in proteinopathies remains to be elucidated. In this study, 4 polyQ-containing proteins, androgen receptor (AR), ataxin-7 (Atx7), huntingtin (Htt) and ataxin-3 (Atx3), are used as model molecules to investigate their heterologous coaggregation and consequent impact on cellular proteostasis. Our data indicate that the N-terminal fragment of polyQ-expanded (PQE) Atx7 or Htt can coaggregate with and sequester AR and Atx3 into insoluble aggregates or inclusions through their respective polyQ tracts. In vitro coprecipitation and NMR titration experiments suggest that this specific coaggregation depends on polyQ lengths and is probably mediated by polyQ-tract interactions. Luciferase reporter assay shows that these coaggregation and sequestration effects can deplete the cellular availability of AR and consequently impair its transactivation function. This study provides valid evidence supporting the viewpoint that coaggregation of polyQ proteins is mediated by polyQ-tract interactions and benefits our understanding of the molecular mechanism underlying the accumulation of different polyQ proteins in inclusions and their copathological causes of polyQ diseases.

Stepwise Monomicelle Assembly for Highly Ordered Mesoporous TiO2 Membranes with Precisely Tailored Mesophase and Porosity.

Mesoporous materials with crystalline frameworks have been acknowledged as very attractive materials in various applications. Nevertheless, due to the cracking issue during crystallization and incompatible hydrolysis and assembly, the precise control for crystalline mesoscale membranes is quite infertile. Herein, we presented an ingenious stepwise monomicelle assembly route for the syntheses of highly ordered mesoporous crystalline TiO2 membranes with delicately controlled mesophase, mesoporosity, and thickness. Such a process involves the preparation of monomicelle hydrogels and follows self-assembly by stepwise solvent evaporation, which enables the sensitive hydrolysis of TiO2 oligomers and dilatory micelle assembly to be united. In consequence, the fabricated mesoporous TiO2 membranes exhibit a broad flexibility, including tunable ordered mesophases (worm-like, hexagonal p6mm to body-centered cubic Im3̅m), controlled mesopore sizes (3.0-8.0 nm), and anatase grain sizes (2.3-8.4 nm). Besides, such mesostructured crystalline TiO2 membranes can be extended to diverse substrates (Ti, Ag, Si, FTO) with tailored thickness. The great mesoporosity of the in situ fabricated mesoscopic membranes also affords excellent pseudocapacitive behavior for sodium ion storage. This study underscores a novel pathway for balancing the interaction of precursors and micelles, which could have implications for synthesizing crystalline mesostructures in higher controllability.

Updates on global epidemiology, risk and prognostic factors of gastric cancer.

Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.

Surface Stretching Enables Highly Disordered Graphitic Domains for Ultrahigh Rate Sodium Storage.

Hard carbons (HCs) with high sloping capacity are considered as the leading candidate anode for sodium-ion batteries (SIBs); nevertheless, achieving basically complete slope-dominated behavior with high rate capability is still a big challenge. Herein, the synthesis of mesoporous carbon nanospheres with highly disordered graphitic domains and MoC nanodots modification via a surface stretching strategy is reported. The MoOx surface coordination layer inhibits the graphitization process at high temperature, thus creating short and wide graphite domains. Meanwhile, the in situ formed MoC nanodots can greatly promote the conductivity of highly disordered carbon. Consequently, MoC@MCNs exhibit an outstanding rate capacity (125 mAh g-1 at 50 A g-1 ). The "adsorption-filling" mechanism combined with excellent kinetics is also studied based on the short-range graphitic domains to reveal the enhanced slope-dominated capacity. The insight in this work encourages the design of HC anodes with dominated slope capacity toward high-performance SIBs.

Controlling Microenvironments with Organs-on-Chips for Osteoarthritis Modelling.

Osteoarthritis (OA) remains a prevalent disease affecting more than 20% of the global population, resulting in morbidity and lower quality of life for patients. The study of OA pathophysiology remains predominantly in animal models due to the complexities of mimicking the physiological environment surrounding the joint tissue. Recent development in microfluidic organ-on-chip (OoC) systems have demonstrated various techniques to mimic and modulate tissue physiological environments. Adaptations of these techniques have demonstrated success in capturing a joint tissue's tissue physiology for studying the mechanism of OA. Adapting these techniques and strategies can help create human-specific in vitro models that recapitulate the cellular processes involved in OA. This review aims to comprehensively summarise various demonstrations of microfluidic platforms in mimicking joint microenvironments for future platform design iterations.

Effects of planting density on photosynthetic characteristics of flag leaf and senescence of leaf and root under wide-width sowing condition.

To determine the optimal planting density under wide-width sowing condition, we investigated the effects of different planting densities on photosynthetic characteristics of flag leaves, senescence characteristics of flag lea-ves and roots, grain yield, and water use efficiency under four planting density levels, 90×104 plants·hm-2 (D1), 180×104 plants·hm-2 (D2), 270×104 plants·hm-2 (D3) and 360×104 plants·hm-2 (D4), in field condition set in Yanzhou, Shandong during the growing season of 2018-2019 and 2019-2020. The results showed that compared with D1 and D4 treatments, D2 treatment significantly improved photosynthetic characteristics of wheat flag leaves during grain filling, increased the activity of superoxide dismutase (SOD) and soluble protein content, reduced the malondialdehyde (MDA) content, and delayed the senescence of flag leaves and roots. Compared with other treatments, D2 treatment significantly increased root length, root surface area and root volume in 0-40 cm soil layer. Compared with D1, D3 and D4 treatments, the grain yield of D2 treatment was increased by 11.8%, 2.5%, 6.4% in 2018-2019 and 22.7%, 5.7%, 17.1% in 2019-2020, respectively. In addition, water use efficiency was increased by 9.2%, 8.8%, 14.2% in 2018-2019 and 21.1%, 6.2%, 21.5% in 2019-2020, respectively. The planting density at 180×104 plants·hm-2 improved photosynthetic characteristics of flag leaves and root morphology during filling stage, delayed plant senescence, increased grain number per spike and grain weight. Consequently, the highest grain yield and water use efficiency were obtained under D2 treatment, which was the optimal treatment under the experimental wide-width sowing condition.

Preparation, physicochemical characterization and cytocompatibility study of self-assembled silk fibroin nanoparticles / 药学学报

This study aimed to prepare silk fibroin nanoparticles (SF-NPs) and assess the physicochemical properties and biocompatibility of the formulation. An optimized and simplified solvent displacement method was employed to obtain SF-NPs. Single-factor prescription screening, such as silk fibroin (SF) solution concentration, the ratio of SF solution to organic solvent, ultrasonication power and time, and different types of organic phases, was used to optimize the formulation. The characterization of the optimal formulation included particle size, polydispersity index (PDI), zeta potential, morphology, and stability. The in vitro cell compatibility of the nanoparticles was evaluated using CCK-8 and Calcein-AM/PI cell viability staining. The results showed that when SF concentration was 20 mg·mL-1, volume ratio of aqueous phase to acetone was 1∶6, ultrasonic power was 80 W and ultrasonic time was 3 min, the best SF-NPs was obtained. The nanoparticles prepared in this study exhibit a near-spherical shape, with a uniform size distribution, having an average size of 144.8 nm, a PDI of 0.174, and a zeta potential of -27.35 mV. Results from in vitro cell experiments demonstrate excellent cell compatibility of SF-NPs, showing the ability to promote cell proliferation. The SF-NPs which were successfully prepared in this study exhibit uniform particle size and excellent biocompatibility.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway / 中国骨伤

OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

The antitumor effect of cisplatin chemotherapy promoted by Taohong Siwu Decoction on mice with lung adenocarcinoma / 中国药理学通报

Aim To study the antitumor effect of cispl-atin ( DDP) chemotherapy promoted by Taohong Siwu Decoction (TSD) on mice with lung adenocarcinoma mice. Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma trans¬plantation mouse model. Normal control, Model, TSD, DDP, TSD + DDP groups were set up. The change of transplanted tumor volume after administration was observed, the weight of transplanted tumor was weighed, the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry, TUNEL was detected by fluorescence staining, Bcl-2, Bax, cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting, and the content of D-dirtier in plasma was measured by ELISA. Results DDP plus TSD significantly inhibited the growth of transplanted tumor. Ki67 expression in tumor tissue was lower than that in DDP group (28. 3% ±3. 1% vs 40. 3% ±2.1% ). The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor. The positive rate of TUNEL was significantly higher than that of DDP group (41. 0% ±3.0% vs 30.7% ± 4.5%). Bax, cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group, while the expression of Bcl-2 was significantly lower than that of DDP group. Moreover, we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins ( P < 0.05 ) . The plasma D-dimer content in TSD + DDP group was significantly lower than that in DDP group (188. 50 ± 28. 46 vs 269.80 ± 35.92) μg • L