It is believed that diabetes complicated with coronary heart disease is closely related to the functional interplay of the heart， spleen， and kidneys. This paper proposed the concept of the heart-spleen-kidney as a unified system for understanding and treating the disease. At the early stage， spleen and kidney deficiency leads to the internal accumulation of phlegm， dampness， and turbid lipids， causing impaired blood circulation and vascular obstruction， so treatment should focus on tonify the kidneys and strengthening the spleen， activating blood circulation and resolving stasis， using the self-prescribed Tangxin Maiwen Formula （糖心脉温方）. As the disease progresses， further decline of spleen and kidney function results in inadequate nourishment of the heart， leading to blood stasis and the accumulation of phlegm， dampness， and turbid lipids， which may transform into pathogenic heat and toxins， causing heart damage， then treatment should emphasize on boosting qi and nourishing yin， clearing heat， activating blood and resolving toxins， using the self-prescribed Tangxin Maiqing Formula （糖心脉清方）. In advanced stages， three zang organs， the heart， spleen， and kidneys， become severely impaired， leading to mental activity fail to be nourished and abnormal cognitive functions， so treatment should focus on harmonizing the three zang organs simultaneously， using the self-prescribed Yunpi Tiaoxin Decoction （运脾调心汤）. This approach aims to provide a clinical framework for the diagnosis and treatment of diabetes with coronary heart disease.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials （RCT） of traditional Chinese medicine （TCM） for treating chronic atrophic gastritis （CAG）， so as to provide references for constructing the core outcome set （COS） of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated， and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included， with a sample size of 44-398 cases. 164 outcome indicators were reported， with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes， followed by physical and chemical examination （69.41%）， TCM syndrome （12.69%）， symptoms and signs （11.15%）， safety indicators （5.37%）， quality of life （0.65%）， long-term prognosis （0.65%）， and economic evaluation （0.08%）. According to the statistical analysis， there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG， including various indicators， non-standard name reports， unclear primary and secondary indicators， random combination of subjective and objective indicators， neglected patient report outcome indicators， missing long-term prognosis and economic indicators， insufficient reporting of safety indicators， and inconsistent measurement tools and measurement time points. ConclusionIn the past five years， there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.

Objective To analyze the problems of review of anti-tumor drug prescriptions and medical orders assisted by an information system to improve the review rules,and to provide a reference for improving review quality of anti-tumor drug prescription.Methods The problem with the pre-review of anti-tumor drug prescriptions and medical orders assisted by the information system in Sichuan Cancer Hospital during 2020-2022 were collected.The data came from the MEDICOM PASS system in Sichuan Cancer hospital.Clinical pharmacists made comments on relevant problems and analyzed the results.Results A total of 9 325 antitumor drug pre-approval problems,including 6 279 outpatient prescriptions(67.3%)and 3 046 inpatient orders(32.7%),among which 6 153(66.0%)were unsuitable indications,1 933(20.7%)were drug contraindications,449(4.8%)were problematic routes of administration,345(3.7%)were unsuitable drug compatibility,177(1.9%)were inappropriate drug frequency,133(1.4%)were problematic drug populations,74(0.8%)were unsuitable single doses,39(0.4%)were unacceptable drug interactions,22(0.2%)were unsuitable drug total.The results of clinical pharmacists'comments were 4 459 reasonable cases,with a false positive rate of 47.8%.The false positive problems included 2 264(50.8%)cases of unsuitable indications,1 933(43.3%)cases of drug contraindications,231(5.2%)cases of problematic routes of administration,and 31(0.7%)cases of unsuitable populations.Conclusion The review of anti-tumor drug prescriptions assisted by an information system can effectively intercept irrational drug use and improve the review quality of prescriptions and medical orders.However,the evidence-based medicine date of antitumor drugs is updated quickly.Pharmacists should constantly improve the prescription review rules based on the latest evidence-based medicine data.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.

Mycotoxins are secondary metabolites produced by pathogenic fungi.They often contaminate various crops,and are detrimental to human and animal health.Mycotoxins have a variety of toxic effects,such as neurotoxicity,hepatotoxicity,immunotox-icity,teratogenicity,and carcinogenicity.However,the mechanism of immunotoxicity is still unclear.Dendritic cells(DCs),as the most potent antigen presenting cells,play a vital role in initiating innate and adaptive immune responses.Previous studies have found that mycotoxins can affect the endocytosis of DCs,the ability to stimulate T cell activation,the secretion of cytokines and chemokines.Thus,this review is aim to summarize the effects of mycotoxins on DCs-mediated immune responses,which may provide reference for researches to clarify the immunotoxicity mechanism of mycotoxins.

Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.