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.

In recent years, with the continuous studies on tumor metabonomics, more and more results have shown that changes of metabolism play important roles in the occurrence and development of malignant tumor. Carcinogenic factors can destroy the metabolic balance of human body, induce metabolic reprogramming, and then mediate a variety of biological behaviors to partici-pate in the proliferation and invasion of cancer cells. Lipids provide the body with the necessary energy and essential fatty acids, and a variety of lipid molecules and metabolites are involved in cell signal transduction. Lipid metabolism is an important link in the metabolic system of the body, and the relationship between the occurrence and development of pancreatic cancer and lipid metabo-lism is not clear. The purpose of this paper is to reveal the changes of lipid metabolism in pancreatic cancer, summarize some preclinical studies and clinical trials, and deeply explain the research status of abnormal lipid metabolism associated with pancreatic cancer, so as to provide new ideas for the study of pancreatic cancer pathogenesis and accurate treatment.

Objective:To preliminarily observe the clinical efficacy of microwave hyperthermia combined with intensity-modulated radiotherapy (IMRT) and chemotherapy for patients with locally advanced gastric cancer.Methods:Forty patients who could not been operated or refused operation were enrolled in this clinical trial, who were confirmed as locally advanced proximal or distal gastric cancer by gastroscopy pathology and imaging. Radiotherapy was delivered by IMRT technology for 5 times per week with a total dose of 46 to 56 Gy (median dose of 50 Gy) in 25 to 28 fractions. Synchronous hyperthermia was given at 42 to 44℃ twice a week, 45 min/time. S-1 or capecitabine-based synchronous chemotherapy was performed, d1-14/3 weeks. The symptom remission rate, adverse reactions, objective remission rate (complete and partial remission) and survival were observed.Results:A total of 40 patients, aged between 56 and 83 years (median age of 71 years), were enrolled in this study. The male-to-female ratio was 7: 1. Among them, 38 cases (95%) showed symptom remission. The most common adverse reactions were grade 1-2 gastrointestinal reactions and leukopenia. The objective remission rate was 87.5%, the 2-year progression-free survival and overall survival rates were 68.6% and 70.5%, respectively.Conclusion:Preliminary findings demonstrate that microwave hyperthermia combined with chemoradiotherapy achieve satisfactory outcomes and yield tolerable toxicity in patients with locally advanced gastric cancer.

Esophageal cancer is the most common malignant tumors in the digestive system. The treatments include surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy. In order to prolong the survival time and reduce the recurrence rate, most of the patients with locally advanced esophageal cancer were treated with combined radiotherapy and chemotherapy. There are many ways of concurrent chemoradiotherapy, together with the application of molecular targeting and immune drugs in esophageal cancer, there are different modes of combined therapy, which are of great significance to improve clinical efficacy and treatment compliance. This article reviews the progress of concurrent chemoradiotherapy for esophageal cancer in recent years.

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 study the effect of CDCA5 silencing on the growth of human breast cancer cell line MDA-MB-435s in vitro and its mechanism.Methods The expression of CDCA5 in breast cancer tissue,the adjacent normal tissue and human breast cancer cell lines MCF-7,MDA-MB-231 and MDA-MB-435s was tested by Western blot.The target sequences of CDCA5 small interfering RNA (siRNA),control siRNA (siRNA-NC) and blank groups were designed.PCR was used to observe the gene silencing effect on CDCA5.The cell viability was measured by MTT assay in siRNA,siRNA-NC and Blank groups.Cell cycle was determined by flow cytometry.Plkl,SA2 and pSA2 protein expression was tested by Western blot.Rssults The expression of CDCA5 was higher in breast cancer tissue than in the adjacent normal tissue.The expression of CDCA5 was higher in human breast cancer cell line MDA-MB-435s than in MCF-7 or MDA-MB-231 cell line.The expression level of CDCA5 was downregulated significantly in siRNA group than other groups.The cell viability was decreased and the cell percentage of G2/M phase was elevated in siRNA group compared with those in siRNA-NC and Blank groups.Inhibition of the CDCA5 gene can suppress the expression of Plk1 and pSA2.Conclusion Silencing CDCA5 expression can effectively inhibit the proliferation of breast cancer cells,whose mechanism may lie in arresting cell cycle in G2/M phase by suppressing CDCA5/Plkl/SA2 signaling pathway.

BACKGROUND:Recently, the effects of human umbilical cord mesenchymal stem cel s (hUCMSCs) and placenta-derived mesenchymal stem cel s (PDMSCs) on treatment of acute graft versus host disease (aGVHD) have been confirmed in some in vitro studies or animal models. But there are stil no reports comparing the therapeutic effects of these two cel types. OBJECTIVE:To compare the immunosuppressive function of hUCMSCs and PDMSCs in vitro or in a mouse aGVHD model. METHODS:(1) In vitro experiment. Human peripheral blood mononuclear cel s (PBMCs) were isolated and divided into four groups:PBMCs cultured alone, PBMCs stimulated with phytohaemagglutinin (PHA), PHA stimulated-PBMCs cocultured with hUCMSCs, PHA stimulated-PBMCs cocultured with PDMSCs. After 5 days, PBMCs proliferation and interferon-γlevel in cel supernatant were measured. (2) In vivo experiment. Fifty-seven BABL/C(H-2d) mice exposed to 8.5 Gy irradiation were randomly divided into five groups:only saline injection group, syngeneic bone marrow transplantation group, al ogeneic bone marrow transplantation group, aGVHD group, hUCMSCs treatment group, PDMSCs treatment group. The clinical aGVHD score, histopathology of skin, liver, and smal intestine, and survival time were analyzed at days 11, 14, 21 after transplantation. RESULTS AND CONCLUSION:(1) In vitro test:compared with the hUCMSCs, PDMSCs had stronger anti-inflammatory function. (2) In vivo test:The clinical scores on acute graft versus host disease were significantly lower in the hUCMSCs and PDMSCs treatment groups than that in the aGVHD group (P<0.05). The survival rates of mice were significantly increased in the hUCMSCs and PDMSCs treatment groups compared to the aGVHD group (P<0.05). Evident skin lesions were not found in al groups. Although smal intestine mucosal lesions were found in al groups, the damage level seemed similar. Notably, significant difference was found in the liver that multifocal necrosis and a large number of inflammatory cel s were seen in the aGVHD group, but less necrosis and inflammatory cel s in the hUCMSC and PDMSC treatment groups. In conclusion, hUCMSC and PDMSC are comparably effective in the treatment of aGVHD in mice.

OBJECTIVETo compare the efficacy difference between fire acupuncture with centro-square needles (FACSN) and filiform needling (FN) for knee osteoarthritis (KOA).

METHODSSeventy-two patients were randomly assigned into an FACSN group and an FN group, 36 cases in each one.points, Xuehai (SP 10), Liangqiu (ST 34), Neixiyan (EX-LE 4), Dubi (ST 35), Zusanli (ST 36), Yanglingquan (GB 34) and Yinlingquan (SP 9) were selected in the two groups. The FACSN group was treated with FACSN, and three acupoints were selected for each treatment; the FN group was treated with FN, and all the acupoints were selected for each treatment. The cupping treatment was given after acupuncture in the two groups. The treatment was given once every other day, without treatment on Sundays. The treatment was given three times a week, 6 times as one course; totally 2 courses were provided. The visual analogue scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were observed in the two groups before treatment, two weeks, four weeks into treatment and at one-month follow-up visit. In addition, the comprehensive efficacy was compared between the two groups.

RESULTSCompared before treatment, the score of VAS and the total score of WOMAC were improved in the two groups at each time point after treatment (all<0.01); the scores of VAS at each time point after treatment in FACSN group were lower than those in the FN group (all<0.05); four weeks into treatment and at one-month follow-up visit, the total score of WOMAC in the FACSN group was lower than that in the FN group (both<0.05). Two weeks into treatment, the total effective rate was 88.9% (32/36) in the FACSN group, which was higher than 61.1% (22/36) in the FN group (<0.01); four weeks into treatment and at one-month follow-up visit, the cured and remarkable effective rates were 66.7% (24/36) and 83.3% (30/36) in the FACSN group, which were higher than 41.7% (15/36) and 44.4% (16/36) in the FN group (<0.05,<0.01), respectively.

CONCLUSIONSFire acupuncture with centro-square needles has relatively high cured and remarkable effective rate for KOA, with rapid onset; as for pain relief, the efficacy is superior to filiform needling.

OBJECTIVETo explore the therapeutic effect of enhancer of Zeste homolog 2 (EZH2) inhibitor GSK343 on periodontitis by regulating microphage differentiation.

METHODSMacrophage RAW264.7 cells were divided into the blank (A group), control (B group), lipopolysaccharide (LPS) stimulation (C group), and LPS+GSK343 (D group) groups. Phenotype transformations was determined through Western blot analysis and enzyme-linked immunosorbent assay by detecting the differentiation of phenotypic biological markers, including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and Arginase-1 (Arg-1). Metergasis was identified by performing a phagocytosis test on Escherichia coli (E. coli).

RESULTSMacrophage RAW264.7 cells produced classical phenotypic biomarkers (M1) TNF-α and iNOS under LPS stimulation. The expression levels of IL-10 and Arg-1 increased after adding GSK343 into the culture medium. GSK343 also induced the conversion of M1 macrophages into M2 macrophages. Macrophage RAW264.7 cells exerted a phagocytic effect on E. coli, and this effect was enhanced after adding LPS into the culture medium. GSK343 regulated the macrophage RAW264.7 phagocytosis of E. coli.

CONCLUSIONSGSK343 possibly participates in the regulation of macrophage differentiation and, consequently, in the latent treatment of periodontitis.

Arginase ; Cell Differentiation ; Enhancer of Zeste Homolog 2 Protein ; Enzyme Inhibitors ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; Indazoles ; pharmacology ; Interleukin-10 ; Lipopolysaccharides ; Macrophages ; Nitric Oxide Synthase Type II ; Periodontitis ; Phagocytosis ; Pyridones ; pharmacology ; Tumor Necrosis Factor-alpha