Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

Mineralocorticoid receptor(MR) overactivation plays an important role in the development and progression of diabetic kidney disease(DKD) by mediating pro-inflammatory and pro-fibrotic processes, making it a key therapeutic target for DKD. Finerenone, a third-generation, highly selective, novel nonsteroidal mineralocorticoid receptor antagonist(MRA), mitigates MR overactivation through anti-inflammatory and anti-fibrotic effects and by improving the immune-inflammatory environment. This significantly reduces cardiovascular and renal composite endpoints in patients with type 2 diabetes mellitus(T2DM) and chronic kidney disease(CKD), and improve cardiorenal outcomes. Based on its novel molecular structure, Finerenone exhibits a lower incidence of adverse effects compared to the previous MRAs. This article elucidates the molecular structure and pathophysiological role of MR, and explores the molecular mechanisms through which finerenone provides cardiorenal benefits. It also discusses the advantages and safety of finerenone compared to first- and second-generation MRAs from a molecular structure perspective, providing evidence for its clinical application.

ObjectiveTo establish the quality standard of Liangditang benchmark samples. MethodUltra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF-MS） was used to qualitatively analyze the chemical composition of Liangditang on the basis of molecular and fragment ion peak information with cracking law. The mobile phase was methanol （A）-0.05% phosphate aqueous solution （B） for gradient elution （0-10 min， 5%-23.5%A； 10-20 min， 23.5%A； 20-58 min， 23.5%-63%A； 58-60 min， 63%-90%A）， the flow rate was 0.8 mL·min^-1， and the detection wavelength was 254 nm. Electrospray ionization was employed under positive ion mode， the detection range was m/z 100-1 700. Key quality attributes and sources were determined by comparing with single medicine and reference substances. Through mass transfer analysis of multiple batches from decoction pieces to benchmark samples， high performance liquid chromatography （HPLC） for determining the contents of index components and HPLC detection of characteristic maps were established. Through the determination of 15 batches of benchmark samples， the content range of the index components and the common peaks of the characteristic map were determined. Thin layer chromatography （TLC） was applied to the identification of 5 medicines in the formula. Moisture and dry extract yield of the benchmark samples were determined by drying method. ResultA total of 27 compounds were inferred from the benchmark samples of Liangditang， among which 9 compounds were confirmed by comparison with the control， including catalpol， harpagide， gallic acid， albiflorin， paeoniflorin， verbascoside， angoroside C， cinnamic acid and harpagoside. A method for determining the characteristic maps of the benchmark samples were established and 13 peaks were assigned， and the characteristic peaks were mainly derived from wine-processed products of Rehmanniae Radix， Scrophulariae Radix and wine-processed products of Paeoniae Radix Alba. The similarity between the characteristic map of 15 batches of benchmark samples and the control characteristic map was >0.9. Methods for the determination of paeoniflorin， harpagoside， L-hydroxyproline and glycine were established， and the contents of these four components in 15 batches of benchmark samples were within ±30% of the corresponding mean value， and the transfer rate of decoction pieces to the benchmark samples was stable and controllable. TLC was established to identify 5 prescription drugs （except Ejiao） with two kinds of test solutions， and the results showed that the method had good specificity. The average dry extract yield was 48.06%， and the average moisture was 5.58%， which were within the range of ±10% and ±30% of their mean values， respectively. ConclusionThe quality standard of Liangditang benchmark samples was as follows：the similarity between the benchmark samples and the control characteristic map is >0.9， the contents of paeoniflorin， harpagoside， L-hydroxyproline and glycine are 217-403， 24-46， 634-1 178， 1 253-2 328 mg per dose， the dry extract yield is 43.0%-53.0%， the moisture is 4.0%-7.0%， under the set detection conditions， the benchmark samples have corresponding characteristic spots by comparing with the control herbs of 5 medicines. This quality standard is stable and reliable， which fills the gap in the quality control of Liangditang， and can provide a reference for the establishment of the quality standard of Liangditang granules.

Objective:To analyze the clinical manifestations and laboratory features in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte (T-LGL) proliferation.Methods:The clinical data of 5 patients with myeloid neoplasms complicated with clonal T-LGL proliferation from November 2017 to November 2018 in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed retrospectively.Results:The median age was 60 years old. All patients had a history of abnormal peripheral blood cell counts for over 6 months. The absolute lymphocyte count in peripheral blood was less than 1.0×10 9/L. In addition to the typical T-LGL phenotype, the immunophenotype was heterogenous including CD4 +CD8 - in 2 patients, the other 3 CD4 -CD8 +. Four patients were αβ type T cells, the other one was γδ type. STAT3 mutation was detected in 1 patient by next-generation sequencing, the other 4 cases were negative. Conclusions:Clonal T-LGL proliferation with myeloid neoplasm develops in an indolent manner, mainly in elderly patients. Hemocytopenia is the most common manifestation. The diagnosis of T-LGL proliferation does not have specific criteria, that it should be differentiated from other T cell proliferative disorders, such as T-cell clones of undetermined significance. STAT3 or STAT5b mutation may help distinguish.

Objective To explore the effect of invasion and migration of hepatocellular carcinoma (HCC) endothelial cells (TECs) affected by overexpression of microRNA-3178 (miR-3178) through the transfection of miR-3178 mimic.Methods Real-time polymerase chain reaction (Real-time PCR) was used to identify differential expression of miR-3178 in normal hepatic sinusoidal endothelial cells (HSECs) and HCC TECs.Furthermore,HCC TECs were divided into 3 groups:control (CON) group,miRNA-3178 upregulation (Mimics,up-regulation of miR-3178 expression was achieved using miR-3178 mimics transfected into HCC TECs) group and negative control (NC,negative control sequence was transfected into HCC TECs) group.RT-PCR was used to detect expression of miR-3178 in HCC TECs before and after transfection.Transfection efficiency was observed by using an inverted fluorescence microscope.HCC TECs invasionand migration were measured by matrigel invasion and transwell migration assay.EGR3 protein expression of HCC TECs were identified by Western blotting analysis.EGR3 mRNA expression of HCC TECs were identified by RT-PCR analysis.Results The results of RT-PCR showed that miR-3178 was significantly down-regulated in HCC TECs compared to HSECs (P ＜0.05),and expression of miR-3178 was significantly increased after the transcienttransfection (P ＜ 0.05).The transfection efficiency in HCC TECs was morethan 90％.Number of migrated and invaded cells and in miR-3178 group was significantly less than those in other groups.Target gene prediction software showed EGR3 was a possible candidate target.Transfection of miR-3178 mimic significantly decreased the mRNA and protein expression levels of EGR3.Conclusion MiR-3178 was downregulated in HCC TECs and overexpression of miR-3178 can specifically inhibit migration and invasion of HCC TECsin vitro through inhibiting EGR3 expression,thus,miR-3178 might be a critical targeted therapy strategv for HCC.

Acupuncture has been applied in 183 countries and regions and gradually become a name card as TCM spreads across the world. The international influence of which plays a significant role in enhancing TCM development. The laws and regulations of TCM acupuncture along One-Belt-One-Road countries were compared and analyzed in this article. With comprehensive research and analysis, the international development strategy of acupuncture was rationally proposed. Combined with the historical background of China's national initiative One-Belt-One-Road, the acupuncture was taken as a breakthrough to lead the global spreading of TCM culture and Chinese herbs, so as to enhance China's soft strength, which could further create a fine cultural environment for the economic prosperity of One-Belt-One-Road countries. In addition, the strategy selection for China regarding TCM acupuncture development along One-Belt-One-Road countries was proposed, and the suggestive solution and implementation strategy for the essential missions and significant issues were provided.

BACKGROUND: Imatinib has a significant pro-apoptosis effect on chronic myelogenous leukemia (CML), but there are still some patients being resistant to it. Human umbilical cord mesenchymal stem cells (hUC-MSCs) affect the apoptosis of a variety of hematologic malignancies. However, the impacts of hUC-MSCs on the apoptosis of CML cells induced by imatinib remain unclear.OBJECTIVE: To investigate whether hUC-MSCs have an influence on the apoptosis of K562 cells induced by imatinib and to reveal the possible underlying mechanism.METHODS: K562 cells were cultured with hUC-MSCs or/and imatinib. Cellular apoptosis was measured with Annexin-V and PI staining by flow cytometry analysis. The protein expressions of Bax, Bcl-2, caspase-3, caspase-9 and cleaved-PARP in K562 cells were detected by western blot assay. Pan-caspase inhibitor Z-VAD-FMK was used to block apoptosis in each group, and during this process the effect of caspase apoptosis signaling pathway was detected.RESULTS AND CONCLUSION: The apoptosis of K562 cells was enhanced, when imatinib was combined with hUC-MSCs. Western blot analysis showed that the expression of pro-apoptotic protein Bax was enhenced and the expression of anti-apoptotic protein Bcl-2 was suppressed. Furthermore, the cleaved forms of caspase-9, caspase-3 and PARP in K562 cell were higher in the hUC-MSCs+imatinib group than in the imatinib group. The apoptosis of K562 cells induced by the hUC-MSCs combined with imatinib was significantly inhibited by Z-VAD-FMK. In conclusion, these findings indicate that hUC-MSCs can enhance imatinib-induced apoptosis of K562 cells by activating caspase apoptosis signaling pathway.

Objective To investigate the association between SLCO1B1/ApoE gene polymorphisms and lipid-lowering efficacy and safety of rosuvastatin.Methods DNA samples were extracted from blood using nano paramagnetic particle method.The SLCO1B1 521T＞C and ApoE gene polymorphisms were screened by PCR-pyrophosphate sequencing method.Totally 152 patients received rosuvastatin orally at a dose of 10 mg/d.The lipidlowering efficacy was evaluated through detecting serum low-density lipoprotein cholesterol (LDL-C) level before and 8 weeks after the treatment.The incidence of myopathic adverse effect was assessed by follow-up of the occurrence of myalgia.Results The gene distribution of SLCO1B1 521T＞C was 73.7％,23.7％ and 2.6％ respectively for TT,TC and CC in 152 patients,and the distribution of ApoE gene was 65.8％,13.2％ and 21.0％ respectively for ε3/ε3,ε3/ε2 and ε4/ε3.The genotype ε4/ε4,ε2/ε2 and ε4/ε2 were not detected.After orally receiving rosuvastatin 10 mg daily for 8 weeks,the decreased LDL-C levels showed significant differences (P＜0.05) among ApoE genotype ε3/ε2,ε3/ε3 and ε4/ε3 groups,and the frequencies of myalgia showed significant differences in the three genotype groups of SLCO1B1 521T＞C (P＜0.05).Conclusion The gene polymorphism of SLCO1B1/ApoE was correlated with efficacy and safety of rosuvastatin.The combined detection of SLCO1B1/ApoE genes can be utilized to predict efficacy and risk,and then realize individualized medication.

Xiyanping is used to treat infectious diseases with antibiotics in clinic. The aim of this study is to investigate the mechanism of Xiyanping through studying the effect of the combination of Xiyanping with Cefazolin on the chemotaxis and phagocytic function of peripheral blood neutrophils in mice. Ten healthy mice were in control group. Forty healthy mice in experimental group were infected with staphylococcus aureus, and were randomly divided further into four groups, i. e. model group, Xiyanping group, Cefazolin group and combination group (Xiyanping with Cefazolin). Mice in the control group and model group were given normal saline (NS) through abdomen while those in other groups were given Xiyanping, Cefazolin, and Xiyanping with Cefazolin, respectively. The chemotaxis of peripheral blood neutrophils was detected with the transwell method, and the phagocytic function of peripheral blood neutrophils was analyzed with flow cytometry (FCM). In the present study, there was no significance on the chemotactic index of peripheral blood neutrophils in all the groups (P > 0.05). The actual phagocytotic rate and index of peripheral blood neutrophils in the blank group, Xiyanping group, and the combination group were significantly higher than those of the model group and Cefazolin group (P < 0.05). However, those were not significant in the blank group, Xiyanping group, and the combination group (P > 0.05) or between the model group and Cefazolin group (P> 0.05). Our results suggested the combination of Xiyanping and Cefazolin could enhance the therapeutic effect by improving the phagocytic function of peripheral blood neutrophils.
Animals ; Anti-Bacterial Agents ; pharmacology ; Cefazolin ; pharmacology ; Chemotaxis ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Mice ; Neutrophils ; cytology ; drug effects ; Phagocytosis ; Staphylococcal Infections ; immunology ; Staphylococcus aureus

Objective To observe the ameloblast morphology and ultrastructure changes of dental fluorosis in rats.Methods Forty SD rats were divided into experimental group and control group (20 rats in each group) by body weight using random number table method.Rats in experimental group were given drinking water with 50 mg/L fluoride to establish dental fluorosis model,and rats in control group were given drinking water without fluoride.All rats were killed at the 56th day,then ameloblast morphology and ultrastructure were observed by means of HE staining and transmission electron microscopy (TEM) at secretory,transition,maturation and post-maturation stages.Results Rats in experimental group showed typical symptoms of dental fluorosis,and lower incisors presented brown and white stripes on enamel surface,chalk color patches and other typical dental fluorosis changes,rats in control group no abnormality.HE staining results showed that differences were not observed between the two groups at the secretory and transformation stages,and few distortions and interstitial space widened were found in the experimental group at maturation and post-maturation stages.TEM displayed ultrastructure changes of ameloblasts,and no differences were observed between the two groups at secretory and transformation stages.Apoptosis was observed in some ameloblasts at the maturation stage in the experimental group,such as rough endoplasmic reticulum expansion,swelling,some ribosome particles exfoliating from endoplasmic reticulum,mitochondrial swelling and disappearance of crista,some nuclear membrane broken down,chromatin condensation and karyolysis.At post-maturation stage,intercellular space of the experimental group was wider than that of the control group.Conclusions Morphological and ultrastructure damage of ameloblasts may have occurred at the maturation stage in the process of dental fluorosis.Ameloblasts may be more sensitive to fluoride in dental enamel formation at maturation stage.