Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

ObjectiveTo explore the effects of hypoxia on the migration ability of human oligodendrocyte precursor cells （hOPCs） and its regulatory mechanisms. MethodsBased on the variations in oxygen concentration within the culture system， three experimental groups were set up： the 21%O₂ group （normoxic control group）， the 5%O₂ group， and the 2%O₂ group. The migration ability of hOPCs under normoxia （21%O₂）， 5%O₂， and 2%O₂ conditions was detected through the Transwell migration assay. RT-qPCR， transcriptome sequencing， and flow cytometry were used to detect the expression changes of genes and proteins such as hypoxia-inducible factor 1 alpha （HIF-1α） and chemokine （C-X-C Motif） receptor 4 （CXCR4）. Bioinformatics analysis was combined to analyze the KEGG pathways related to migration， so as to explore the effects of different oxygen concentrations on the migration ability of hOPCs and their possible mechanisms. ResultsHypoxia treatments at concentrations of 5%O₂ and 2%O₂ could both promote the in vitro migration of hOPCs， and the promoting effect of migration was more significant at the 2%O₂ concentration （P<0.001）. After hypoxia treatment， the mRNA expression levels of HIF-1α， CXCR4， etc. in hOPCs significantly increased （P<0.001）. Compared with the 5%O₂ concentration， the expression of CXCR4 in cells was higher at the 2%O₂ concentration （P<0.000 1）. Flow cytometry analysis detection showed that the expression of CXCR4 increased significantly after hypoxia treatment （P<0.01）， and with the decrease of oxygen concentration， its expression level further increased （P<0.000 1）. Ordinary transcriptome sequencing analysis indicated that hypoxia treatment could activate the PI3K-Akt signaling pathway and the Axon guidance pathway. ConclusionHypoxia treatment can enhance the in vitro migration ability of hOPCs， and this effect is negatively correlated with the oxygen concentration. Its mechanism may be related to the up-regulation of the expression of genes such as HIF-1α and CXCR4， and the activation of the migration related signaling pathway including PI3K-Akt signaling pathway and axon guidance pathway.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

OBJECTIVE: In order to enhance the efficacy of anti-breast cancer, paclitaxel nanoparticles (PTX NPs) and polypyrrole nanoparticles (PPy NPs) were combined with photothermal therapy and chemotherapy. At the same time, the two dosage forms of PTX NPs and PTX NPs gel were compared. METHODS: PTX NPs were prepared by self-assembly method, and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium (MTT) and other methods, and the efficacy and side effects in vivo were further investigated. RESULTS: The average hydrated diameter, PDI and electric potential of PTX NPs were (210.20 ± 1.57) nm, (0.081 ± 0.003) mV and (15.80 ± 0.35) mV, respectively. MTT results showed that the IC₅₀ value of PTX NPs on 4 T1 cells was 0.490 μg/mL, while that of PTX injection was 1.737 μg/mL. The cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX injection. The tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%, respectively. Together with local photothermal stimulation, the tumor inhibition rate of the PTX NPs reached 91.05%, surpassing that of the gel under the same conditions (48.98%), moreover, the organ index and H&E staining results of PTX NPs showed a decrease in toxicity. CONCLUSION This combination therapy can significantly enhance the effect of anti-breast cancer, and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Abstract: To study the protective effect of asiaticoside(AS) on Isoproterenol Hydrochloride(ISO)-induced myocardial injury in mice. Methods: Sixty male C57BL/6 mice were randomly divided into blank control(CON) group, model group [ISO,ISO 10/(kg·d)], Low dose group [ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)], Medium dose group [ISO+AS-M, ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)], High dose group [ISO+AS-H, ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)]. Heart mass ratio was counted; changes were observed in electrocardiogram; Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and cardiac troponin T(cTn-T) in serum; Masson staining was used to observe the fibrosis of mouse myocardial tissue; Western blot was used to detect the ratio of Bax and Bcl-2 protein expression levels(Bax/Bcl-2) and the expression levels of Caspase-3 and NLRP3 proteins in myocardial tissue; real-time quantitative polymerase chain reaction(qPCR) was used to detect the mRNA expression levels ofANP,BNP,β-MHC,TNF-α, IL-6, Type Ⅰ collagen(COLⅠ), and Type Ⅲ collagen(COLⅢ). Results: Compared with the CON group, the ISO group had an elevated heart-to-mass ratio(P<0.01), a lower heart rate(P<0.05), a prolonged QT interval(P<0.05), elevated expression of myocardial injury markers cTn-T,ANP,BNP, andβ-MHC(P<0.01); increased expression of IL-1β in the serum(P<0.01), increased expression ofTNF-αin the cardiac tissue and increasedIL-6expression(P<0.001), and NLRP3 protein expression was elevated(P<0.05); myocardium showed a large number of collagen fibers bluish staining(P<0.001),COLⅠ,COLⅢmRNA expression levels increased(P<0.001), and Bax/Bcl-2 ratio(P<0.001) and Caspase-3 expression were significantly elevated(P<0.05). Compared with ISO group, heart-to-mass ratio of mice in ISO+AS-L and ISO+AS-M groups decreased(P<0.05), heart rate increased, QT interval was shortened, cTn-T, ANP, BNP and β-MHC decreased(P<0.001), myocardial collagen fiber blue-staining decreased(P<0.01). The mRNA expression levels ofCOLⅠandCOLⅢdecreased(P<0.05). The expression levels of IL-1β and TNF-α decreased(P<0.01). NLRP3, Caspase-3 protein expression and Bax/Bcl-2 ratio decreased(P<0.05). The expression level ofIL-6in ISO+AS-M group decreased(P<0.01). The expression levels ofANP,BNP, andTNF-αmRNA expression were reduced in the ISO+AS-H group(P<0.001); the degree of myocardial fibrosis was improved(P<0.05), and the expression levels ofCOLⅠandCOLⅢmRNA were reduced(P<0.05). Conclusion AS has a protective effect against ISO-induced myocardial injury in mice by ameliorating cardiac fibrosis, inhibiting cardiomyocyte apoptosis and attenuating myocardial tissue inflammatory response.

OBJECTIVE:Exercise intervention is considered the cornerstone of rehabilitation after anterior cruciate ligament reconstruction.However,no clear conclusion has been reached regarding which exercise therapy is more effective in improving knee muscle strength and function in patients after anterior cruciate ligament reconstruction.To this end,this study used a network meta-analysis method to compare the efficacy of exercise therapy after anterior cruciate ligament reconstruction,providing evidence-based medical basis for selecting the best exercise therapy. METHODS:A computer search was conducted in PubMed,Web of Science,Embase,The Cochrane Library,and EBSCO to collect randomized controlled trials addressing exercise therapy following anterior cruciate ligament reconstruction.The search time limit was from the establishment of the database to 2023-11-20.Outcome indicators included three continuous variables:quadriceps muscle strength,hamstring muscle strength,and knee joint function score.EndNote X9.1 was used for literature screening.The Cochrane risk of bias assessment tool was used to evaluate the quality of the included literature.The GRADE score was used to rate the strength of evidence for the results of the article.Network meta-analysis was performed using Stata 16.0. RESULTS:A total of 36 randomized controlled trials were included,involving 1 179 patients undergoing anterior cruciate ligament reconstruction.The overall quality of the included literature was moderate.Nine types of exercise therapies were involved:isokinetic training,cross training,eccentric training,aquatic rehabilitation,blood flow restriction training,motor control training,plyometric training,whole-body vibration training,and multimodal training;the control measure was conventional rehabilitation training.The results of the network meta-analysis showed that compared with conventional rehabilitation training,eccentric training[standardized mean difference(SMD)=2.08,95%confidence interval(CI):0.56 to 3.60,P=0.007)had the best improvement effect on quadriceps muscle strength in patients undergoing anterior cruciate ligament reconstruction,followed by multimodal training(SMD=1.69,95%CI:0.11 to 3.27,P=0.249)and whole body vibration training(SMD=0.81,95%CI:0.11 to 1.51,P=0.042).In terms of improving patients'hamstring muscle strength,multimodal training(SMD=2.08,95%CI:0.30 to 3.86,P=0.022)had the best effect,followed by plyometric training(SMD=1.51,95%CI:0.18 to 2.84,P=0.026)and isokinetic training(SMD=1.37,95%CI:0.06 to 2.67,P=0.039).Multimodal training(SMD=4.60,95%CI:2.40 to 6.80,P<0.001)was the most effective in improving knee joint function scores,followed by eccentric training(SMD=1.75,95%CI:0.24 to 3.25,P=0.023)and aquatic rehabilitation(SMD=1.65,95%CI:0.07 to 3.24,P=0.041). CONCLUSION:Evidence of low to moderate strength suggests that multimodal training may be the most effective exercise therapy in improving knee muscle strength and function in patients after anterior cruciate ligament reconstruction,followed by eccentric training,plyometric training,isokinetic training,whole body vibration training,and aquatic rehabilitation.More high-quality clinical randomized controlled trials are still needed in the future to verify the reliability of the conclusions.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.