Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

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.

OBJECTIVE: To investigate early clinical efficacy of unilateral biportal endoscopy technique for the treatment of lumbar postoperative adjacent segmental diseases. METHODS: Fourteen patients with lumbar postoperative adjacent segmental diseases were treated with unilateral biportal endoscopy technique from June 2019 to June 2020. Among them, there were 9 males and 5 females, aged from 52 to 73 years old, and the interval between primary and revision operations ranged from 19 to 64 months. Adjacent segmental degeneration occurred after lumbar fusion in 10 patients and after lumbar nonfusion fixation in 4 patients. All the patients received unilateral biportal endoscopy assisted posterior unilateral lamina decompression or unilateral approach to the contralateral decompression. The operation time, postoperative hospital stay and complications were observed. The visual analogue scale (VAS) of low back pain and leg pain, Oswestry Disability Index (ODI), modified Japanese Orthopaedic Association (mJOA) score were recorded before operation and at 3 days, 3 months, and 6 months after operation. RESULTS: All procedures were successfully completed. Surgical duration ranged from 32 to 151 min. Postoperative CT showed adequate decompression and preservation of most joints. Out of bed walking 1 to 3 days after surgery, postoperative hospital stay was 1 to 8 days, and postoperative follow-up was 6 to 11 months. All 14 patients returned to normal life within 3 weeks after surgery, and VAS, ODI, and mJOA scores improved significantly at 3 days and 3, 6 months after surgery. One patient occurred cerebrospinal fluid leak after operation, received local compression suture, and the wound healed after conservative treatment. One patient occurred postoperative cauda equina neurologic deficit, which was gradually recovered about 1 month after rehabilitation therapy. One patients advented transient pain of lower limbs after surgery, and the symptoms were relieved after 7 days of treatment with hormones, dehydration drugs and symptomatic management. CONCLUSION Unilateral biportal endoscopy technique has a good early clinical efficacy in the treatment of lumbar postoperative adjacent segmental diseases, which may provide a new minimally invasive, non-fixation option for the treatment of adjacent segment disease.
Male ; Female ; Humans ; Middle Aged ; Aged ; Spinal Stenosis/surgery* ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Treatment Outcome ; Decompression, Surgical/methods* ; Spinal Fusion/methods* ; Retrospective Studies

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K _d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

OBJECTIVE: To explore the clinical value and safety of unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion by muscle-splitting approach treatment of recurrent lumbar disc herniation. METHODS: The clinical data of 51 patients with recurrent lumbar disc herniation treated from June 2012 to December 2017 were retrospectively analyzed. There were 32 males and 19 females, aged 34 to 64 years with an average of (51.11± 7.28) years. Lesions invoved L RESULTS: There was no statistical difference in operation time between two groups ( CONCLUSION Muscle-splitting approach is feasible for thetreatment of recurrent lumbar disc herniation with pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion. Compared with the median incision approach, the muscle-splitting approach has the advantages of small incision, less trauma, less bleeding, rapid recovery. Also it can protect multifidus and do not increase the incidence of serious complications. Thus, it can be used as a choice for fixation and fusion of recurrent lumbar disc herniation.
Adult ; Female ; Humans ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Middle Aged ; Muscles ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion ; Treatment Outcome

In this study, three new germacranolide sesquiterpenes (1-3), together with six related known analogues (4-9) were isolated from the whole plant of Carpesium cernuum. Their structures were established by a combination of extensive NMR spectroscopic analysis, HR-ESIMS data, and ECD calculations. The anti-leukemia activities of all compounds towards three cell lines (HEL, KG-1a, and K562) were evaluated in vitro. Compounds 1-3 exhibited moderate cytotoxicity with IC
Antineoplastic Agents, Phytogenic/pharmacology* ; Asteraceae/chemistry* ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Phytochemicals/pharmacology* ; Sesquiterpenes, Germacrane/pharmacology*

Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.

A high performance liquid chromatography( HPLC) method was established for the fast,and precise determination of ten nucleosides in Fritillariae Cirrhosae Bulbus and its counterfeits. Then multivariate statistical analyses,such as clustering analysis,principal component analysis( PCA),and Fisher' s linear discriminant analysis( LDA),were conducted to establish a discriminant function model for an integrated analysis. The results indicated that data acquisition time of a single sample was shortened within 16 min by the HPLC method. In the range of 5-1 000 mg·kg~(-1),the mass concentrations of all nucleosides exhibited good linear relationships with the corresponding peak areas( R2> 0. 999). The spiked recoveries were in the range of 93. 83%-108. 9% with RSDs of0. 12%-1. 3%( n = 5). The limit of quantitation( LOQ) was 0. 98-4. 13 mg·kg~(-1). As revealed by the clustering analysis,Fritillariae Cirrhosae Bulbus and the counterfeits could be discriminated into two clusters based on the content of nucleosides. Fisher's LDA could achieve this discrimination,while PCA dimension reduction failed. The accuracy of the discriminant function model established on the screened characteristic indicators reached 97. 5%. The present study proposed a new identification method of Fritillariae Cirrhosae Bulbus with one-dimensional indicators,which is simple,accurate,and reliable. It can provide a scientific basis for further optimizing the identification techniques for Fritillariae Cirrhosae Bulbus and inspiration for quality control strategy development of Chinese medicinal materials.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Fritillaria ; Nucleosides ; Plant Roots

Aim To investigate the influence of different concentrations of dextran sulfate sodium (DSS) and administration approaches on the establishment of mouse model of acute ulcerative colitis(UC). Methods Mice were randomly divided into the normal control group, 3% DSS free drinking group, 4% DSS free drinking group, 30% DSS intragastric administration group and 40% DSS intragastric administration group. The amount and average dosage of intaken DSS by mice in free drinking group were measured and the intragastric administration group were given the same dosage. The survival rate, disease activity index (DAI), the lengths and pathological changes of colon were observed, and the coefficients of variation of each indicator described above were compared among the groups. Results Except for the normal control group, other groups developed experimental UC. Among these four approaches, 3% DSS solution free drinking showed appropriate incidence, higher animal survival rate and operability and lower cost, while there was no significant difference in the coefficients of variation of DAI between 3% DSS solution free drinking group and the others. Conclusion 3% DSS solution free drinking has more advantages in the establishment of a murine model with acute UC than other approaches.

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm² vs. 1.4(1.1-1.9)mm², all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Aged ; Coronary Angiography ; Humans ; Inflammation ; Male ; Middle Aged ; Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Retrospective Studies ; ST Elevation Myocardial Infarction/surgery* ; Stroke Volume ; Thrombolytic Therapy ; Ventricular Function, Left