Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,catechin,epicatechin,rhein 8-O-β-D-glucoside,chlorogenic acid,chrysophanol 8-O-β-D-glucoside,emodin-8-O-β-D-glucoside,emodin-3-methyl ether-8-O-β-D-glucoside,aloe emodin,rhein,cyperotundone,luteolin,α-cyperone,emodin,chrysophanol and emodin-3-methyl ether in Binglang Sixiao Pills.METHODS The analysis was performed on a 30℃thermostatic Kromasil C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of methanol-0.1%formic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.Subsequently,cluster analysis and principal component analysis were made.RESULTS Fifteen constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 96.00%-101.00%%with the RSDs of 0.50%-1.50%.Various batches of samples were clustered into two categories,and four principal components demonstrated the accumulative variance contribution rate of 90.004%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Binglang Sixiao Pills.

Objective:To investigate the effect of recombinant human prourokinase combined with tirofiban on cardiac func-tion and prognosis in patients with acute ST-segment elevation myocardial infarction(ASTEMI)undergoing emergency percutaneous coronary intervention(PCI).Methods:A total of 156 ASTEMI patients undergoing PCI treated in our hos-pital from June 2019 to December 2020 were selected.They were equally divided into control group(received tirofiban in-jection during emergency PCI)and study group(received recombinant human prourokinase injection based on control group)according to random number table method.Two groups received the same medication before and after emergency PCI.Thrombolysis in myocardial infarction(TIMI)flow,TIMI myocardial perfusion grade(TMPG)before and after PCI,cardiac function indexes before and one week after PCI,incidence of major adverse cardiovascular events(MACE)and adverse reactions within 1-year follow-up were compared between two groups.Results:After PCI,compared with control group,there were significant rise in proportions of TIMI flow grade 3(51.28％vs.83.00％)and TMPG grade 3(51.28％vs.84.62％),left ventricular ejection fraction(LVEF)one week after PCI[(44.26±3.45)％vs.(49.17±2.92)％],and significant reductions in left ventricular end-diastolic diameter(LVEDd)[(56.47±2.54)mm vs.(51.32±2.55)mm],left ventricular end-systolic diameter(LVESd)[(41.86±2.49)mm vs.(36.01±1.68)mm]one week after PCI,incidence rates of MACE(24.36％vs.7.69％)and adverse reactions(10.26％vs.1.28％)within 1-year fol-low-up in study group(P＜0.05 or＜0.01).Conclusion:Recombinant human prourokinase combined with tirofiban can significantly improve cardiac function,reduce the incidence rates of MACE and adverse reactions,and improve the prog-nosis in ASTEMI patients after PCI,which is worthy of clinical reference.

AIM:To investigate the molecular mechanism underlying ferroptosis induced by celastrol(Cel)in huamn pancreatic cancer cell line PANC-1.METHODS:The viability of PANC-1 cells was analyzed by MTT assay,and the effects of Cel on cell proliferation were analyzed using EdU and colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess and observe changes in lipid reactive oxygen species(ROS)levels,respectively,while the levels of malondialdehyde(MDA),glutathione(GSH)and Fe2+were measured using specific kits.The protein expression of glutathione peroxidase 4(GPX4)was evaluated by Western blot,and GPX4 ubiquitination was measured by immunoprecipitation.RESULTS:It was found that the viability,proliferation and colony formation in PANC-1 cells de-creased gradually as the concentration of Cel increased.Addition of Cel alone to the cells reduced both cell rounding and viability,while treatment with ferrostatin-1(Fer-1)alone or in combination with Cel had no effect on either cell morpholo-gy or viability.Fluorescence staining of lipid ROS with BODIPYTM 581/591 C11 followed by flow cytometry analysis showed significantly increased levels of green fluorescence indicative of oxidized lipid ROS,which were further increased after treatment of the cells with Cel.Treatment of the cells with both Cel and Fer-1 reduced the green fluorescence and lip-id ROS levels.Treatment with Cel also increased the levels of MDA and Fe2+,relative to the controls,which reducing the levels of GSH,while addition of both Cel and Fer-1 to the cells restored the levels of MDA,Fe2+,and GSH to those of the control group.CONCLUSION:Treatment with Cel reduces the proliferation of pancreatic cancer cells by inducing fer-roptosis through promoting the ubiquitination and degradation of GPX4.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective:Three-dimensional simulation modeling technology was used to conduct three-dimensional reconstruction, classification and measurement for the anatomic structures of colorectal canal, tumor and key blood vessels in patients with rectal cancer before operation. And the accuracy of the data and information obtained for the prediction of anastomotic tension, important types of vascular variant, positioning of anatomical landmarks, etc. in laparoscopic-assisted radical resection of rectal cancer, and the guiding effect of operation was evaluated.Methods:The clinical data of 50 patients with laparoscopic-assisted radical resection of rectal cancer treated in the General Surgery Department, Beijing Ditan Hospital Capital Medical University from January 2019 to February 2021 were analyzed retrospectively, including 31 males and 19 females, aged from 42 to 83 years old, with an average age of (62.72 ±15.21) years. The patients were divided into two groups according to whether the patients underwent three-dimensional simulation reconstruction before operation. The patients who underwent abdomen pelvic enhancement CT and further three-dimensional reconstruction before surgery were taken as reconstruction group ( n=24), and the patients who were only routinely performed abdomen pelvic enhancement CT before operation were taken as control group ( n=26). For the patients in the reconstruction group, the CT images were modeled by Mimics software before operation, and the key data such as the length of colorectal and tumor, the correlation length of rigid structure of pelvic wall, the length of inferior mesenteric artery (IMA) from the bifurcation point of left and right arteria iliaca communis, the type and proportion of IMA variation, the length of left colonic artery (LCA) from the beginning of IMA and the distance between LCA and IMV were measured, and the consistency correlation coefficient (CCC) was analyzed with the actual data obtained during operation. And then the accuracy of three-dimensional simulation modeling technology for surgical guidance was evaluated. MedCalc 19.0 software was used for statistical analysis. Results:In the reconstruction group, regarding the data of each dimension of the model (intestinal tract, pelvic cavity, blood vessels) and the corresponding structural measurements during the operation, the consistent correlation coefficient (CCC) evaluation was more than 0.9. One case was predicted to have free splenic flexure of colon and one case actually had free splenic flexure of colon. The prediction accuracy was 100%. The IMA variants in the reconstruction group were divided into 4 types, all of which were verified by operation. Compared with the control group, the operation time ( P=0.011) and the location time (IMA, P=0.043; LCA, P=0.007; IMV, P=0.034) of each vessel in the reconstruction group were shorter, and the amount of intraoperative blood loss was less ( P=0.017). Conclusion:The application of three-dimensional simulation modeling technology before operation is helpful for the operator to accurately predict the intraoperative anastomotic tension, the type of IMA variation and the related diameter length, based on which the accurate operation plan can be made to guide the operation.

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.
Female ; Humans ; Moxibustion ; Meridians ; Acupuncture Points ; Acupuncture Therapy ; Foot ; Genital Diseases, Female/therapy*

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care