BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny

OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin， granulocyte colony-stimulating factor and cytarabine （CAG） regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS CNKI， Wanfang data， VIP， Sino Med， PubMed， Embase， the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th， 2023. Randomized controlled trials （RCTs） about thalidomide combined with CAG regimen （trial group） versus CAG regimen （control group） in the treatment of elderly AML patients were collected， and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally， 7 RCTs were included， with a total of 601 patients， including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z＝4.75， P＜0.000 01， OR＝2.80， 95%CI （1.83，4.28）]， complete remission rate [Z＝2.82， P＝0.005， OR＝1.61， 95%CI （1.16， 2.25）]， and improving platelet count [Z＝2.70， P＝0.007， MD＝64.02， 95%CI （17.53， 110.51）]， vascular endothelial growth factor [Z＝13.63，P＜0.000 01， MD＝－65.17， 95%CI（－74.54， －55.80）]， vascular endothelial growth factor receptor [Z＝12.03， P＜ 0.000 01， MD＝－499.01， 95%CI （－580.31， －417.71）] and basic fibroblast growth factor [Z＝4.17， P＜0.000 1，MD＝－0.23， 95%CI（－0.35， －0.12）]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z＝0.99， P＝0.32， OR＝0.52， 95%CI（0.14，1.89）]， nausea and vomiting [Z＝ 1.06， P＝0.29， OR＝0.66， 95%CI （0.30，1.43）]， constipation or diarrhea [Z＝0.92， P＝0.36， OR＝0.65， 95%CI（0.26， 1.63）]， drowsiness [Z＝1.38， P＝0.17， OR＝0.57， 95%CI（0.26， 1.27）] or myelosuppression [Z＝0.88，P＝0.38，OR＝0.68，95%CI（0.28， 1.62）]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Medicine is the subject of studying human and its inherent humanistic attribute endows medicine with the temperature it deserves. However, with the continuous improvement of medical testing technology and treatment technology, medical workers pay more attention to diseases and ignore humanistic care, which has become an important factor in the aggravation of patients’ burden and the tension relationship between doctors and patients. There are many virtues in Chinese traditional culture. Sun Simiao’s medical ethics thought of "great doctor with professionalism and sincerity" embodies the core value of the humanistic spirit of Chinese traditional medicine. In his medical ethics thought, the moral and ethics of "great doctor with professionalism and sincerity", the medical practice attitude of "being cautious and diligent", the values of "benevolence for the world" and the professional conduct of "honesty and truth" still have strong practical significance at present. It is the good material to cultivate the humanistic spirit of medical students. This is of great value to integrate Sun Simiao’s medical ethics thought into cultivate medical students with both "professionalism" and "sincerity", practice the original intention of medical and health undertakings, and carry forward cultural self-confidence.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Objective:To investigate the correlation between the levels of CC chemokine ligand 2 (CCL2) and periostin (POSTN) in serum and alveolar lavage fluid of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) complicated with respiratory virus infection and lung function.Methods:From March 2020 to March 2023, 96 patients with acute exacerbation of COPD admitted to our hospital were collected. Among them, 34 patients with concurrent respiratory virus infection were included in the infected group, and 62 patients without respiratory virus infection were included in the uninfected group. Enzyme linked immunosorbent assay (ELISA) was applied to detect the expression levels of CCL2 and POSTN in serum and alveolar lavage fluid. Pearson method was applied to analyze the correlation between CCL2 and POSTN levels in serum and alveolar lavage fluid of infected patients and lung function indicators.Results:The levels of CCL 2 ( t=12.633, 9.253 2, 2) and POSTN ( t=12.370, 7.383) were significantly increased in the infected group compared with the uninfected group ( P<0.05). Compared with the uninfected group, the 6-minute walking test (6 MWT), peak expiratory flow rate (peak expiratory flow, PEF), forced expiratory volume at the first second (forced expiratory volume in one second, FEV 1), and the forced lung capacity (forced vital capacity, FVC), FEV 1/FVC, and maximum middle breath mean flow rate (maximal mid-expiratory flow curve, MMEF) were significantly lower ( t=14.141, 24.165, 22.421, 21.223, 5.278, 29.456, P<0.05). Correlation analysis showed that the levels of CCL2 and POSTN in the serum and alveolar lavage fluid of the infected group were negatively correlated with the levels of 6MWT, PEF, FEV1, FVC, FEV1/FVC, and MMEF ( P<0.05). Conclusions:CCL2 and POSTN levels were highly expressed in serum and alveolar lavage fluid of patients with respiratory virus infection during acute exacerbation of COPD, which were closely related to lung function.