Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

Development and Validation of a Novel Nomogram for Predicting Perioperative Acute Kidney Injury Following Isolated Off-Pump Coronary Artery Bypass Grafting Surgery.

BACKGROUND: The aim of this work was to create a novel model for predicting acute kidney injury (AKI) after off-pump coronary artery bypass graft (OPCABG). METHODS: The individuals who underwent OPCABG were randomly separated into a derivation group and a validation group, at a 7:3 ratio. The primary outcome was AKI under the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. To optimize feature selection and construct a nomogram, both least absolute shrinkage and selection operator regression (LASSO) and logistic regression analysis were utilized. The nomogram was assessed in various ways: with the C-index, calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA). RESULTS: The use of an intra-aortic balloon pump (IABP), systolic blood pressure, smoking and baseline serum creatinine were identified as independent impact factors. The C-index of the nomogram was 0.733 (95% confidence interval (CI) = 0.669-0.791) and 0.786 (95% CI = 0.693-0.878) in the training and validation groups, respectively. The area under the curve (AUC) of the internal validation was 0.715 using bootstrapping with 1000 replicates. The calibration plot revealed that the predicted outcomes aligned well with the observations. DCA and CICA suggested that the model had clinical benefit. CONCLUSION: The nomogram that relied on clinical characteristics proved to be a dependable instrument to predict AKI after OPCABG. This model is conveniently applicable in clinical settings and will be a valuable resource for assessing timely medical measures to mitigate risk.

Effect of ultra-mini percutaneous nephrolithotomy and ShuoTong ureteroscopy on the stress response, inflammatory indices, and urokinase level in patients with polycystic kidney disease complicated with renal calculus.

This study aimed to explore the effects of ultra-mini percutaneous nephrolithotomy (UMP) combined with ShuoTong ureteroscopy on the stress response, inflammation indicators and urokinase levels in patients with polycystic kidney disease and kidney stones. In this study, 42 patients with polycystic kidney disease and kidney stones diagnosed and treated in our hospital from February 2018 to February 2021 were selected as the research objects. They were randomly divided into the control group and the study group, with 21 cases in each group, and the control group adopted Ultra-mini percutaneous nephrolithotomy treatment; the study group was combined with ShuoTong ureteroscopy on the basis of the control group, and compared and analyzed the stress response, inflammation indexes, urokinase level, renal function, complications and stone clearance rate of the two groups of patients. After treatment, the average operation time, channel establishment time, hemoglobin decline, number of puncture channels, and hospital stay in the study group were significantly shorter than those in the control group (P<0.05); after treatment, the reduction in CRP and PCT in the study group was significantly higher than that in the control group The increase of Ang I and Ang II in the control group was significantly lower than that in the control group (P<0.05); the improvement of PGE2, NO, and LPO levels in the study group was significantly higher than that in the control group after treatment (P<0.05); the study group TH, Cys- The levels of C and ß2-MG were significantly lower than those of the control group; the UK levels of the study group were significantly lower than those of the control group (P<0.05); the complication rate of 14.29% in the study group after treatment was significantly lower than that of the control group 33.33%; the study group The stone clearance rate of 95.24% was significantly higher than that of the control group 80.95% (P<0.05). In general, UMP combined with ShuoTong ureteroscopy is used to treat polycystic kidney with kidney stones, accurately determine the tip position of the needle sheath, ensure that the needle sheath enters the collection system to adjust its position, reduce patient stress and inflammation, improve safety and feasibility, and is worthy of clinical practice Promote applications.

Increased Insular Connectivity and Enhanced Empathic Ability Associated with Dance/Music Training.

Dance and music are expressive art forms. Previous behavioural studies have reported that dancers/musicians show a better sensorimotor ability and emotional representation of others. However, the neural mechanism behind this phenomenon is not completely understood. Recently, intensive researches have identified that the insula is highly enrolled in the empathic process. Thus, to expand the knowledge of insular function associated with empathy under the dance/music training background, we mapped the insular network and its associated brain regions in 21 dancers, 20 musicians, and 24 healthy controls using resting-state functional connectivity (FC) analysis. Whole brain voxel-based analysis was performed using seeds from the posterior insula (PI), the ventral anterior insula (vAI), and the dorsal anterior insula (dAI). The training effects of dance and music on insular subnetworks were then evaluated using one-way analysis of variance ANOVA. Increased insular FC with those seeds was found in dancers/musicians, including PI and anterior cingulated cortex (ACC), vAI and middle temporal gyrus (MTG) and middle cingulated cortex (MCC), and dAI and ACC and MTG. In addition, significant associations were found between discrepant insular FC patterns and empathy scores in dancers and musicians. These results indicated that dance/music training might enhance insular subnetwork function, which would facilitate integration of intero/exteroceptive information and result in better affective sensitivity. Those changes might finally facilitate the subjects' empathic ability.

Resveratrol Attenuates the Cytotoxicity Induced by Amyloid-ß1-42 in PC12 Cells by Upregulating Heme Oxygenase-1 via the PI3K/Akt/Nrf2 Pathway.

Oxidative stress and cytotoxic damage induced by amyloid beta (Aß) have been considered pivotal in the pathogenesis of Alzheimer's disease (AD) and may represent a target for treatment. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal to protect against multiple injuries, and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of the PI3K/Akt pathway, can bind to HO-1. Resveratrol, a natural polyphenol derived from grapes, has been widely reported to have diverse antioxidative effects against AD, but the mechanisms have not been fully elucidated. The present study aims to investigate the effects of resveratrol on Aß1-42-induced cytotoxicity in PC12 cells and to explore the potential mechanisms of these effects. PC12 cells were cultured and treated with Aß1-42. Oxidative stress was assessed by measuring malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels. After treating with resveratrol at different concentrations (0, 10, 20, 40 µM) and for different durations (24, 48, 72 h), the generation of MDA, GSH, and SOD were detected; cell viability was assessed by MTT assay. The production of reactive oxygen species (ROS) was determined using an ROS Assay Kit. Western blotting was used to detect the protein expression. Our studies showed that pretreatment with resveratrol could reduce Aß1-42-induced oxidative stress in PC12 cells by inhibiting the generation of MDA and ROS and increasing the production of SOD and GSH. Resveratrol markedly attenuated the Aß1-42-induced loss in cell viability in PC12 cells in both a dose- and time-dependent manner. More importantly, resveratrol stimulated the activation of HO-1, Nrf2, PI3K, and phosphorylated Akt. Notably, the neuroprotective effects of resveratrol were eliminated by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), Nrf2 small interfering RNA (siRNA), and the PI3K/Akt inhibitor LY294002. Taken together, the findings suggest that the cytoprotection of resveratrol against the cytotoxicity induced by Aß1-42 in PC12 cells is through the upregulation of HO-1 expression via the activation of the PI3K/AKT/Nrf2 intracellular signaling pathway, which might provide novel insights for understanding the mechanism of the neuroprotective effect of resveratrol as an anti-AD drug.

Lower serum uric acid levels in cerebral amyloid angiopathy: a pilot study.

Cerebral amyloid angiopathy (CAA) is a common degenerative disease presenting intracerebral hemorrhage (ICH) in older people. Uric acid (UA) is a natural antioxidant, and may have a beneficial role in neurodegenerative diseases. Nevertheless, the role of UA in CAA remains unknown. In the present study, we compared serum UA levels in CAA-associated ICH patients (n = 82) and age/sex-matched controls (n = 82). Serum UA levels in possible CAA were significantly decreased when compared with healthy controls (232.68 ± 77.70 vs. 309.42 ± 59.83 µmol/L; p < 0.001). Furthermore, UA levels in patients clinically diagnosed as probable CAA were significantly lower than those in patients diagnosed as possible CAA (193.06 ± 56.98 vs. 232.68 ± 77.70 µmol/L; p = 0.014). These differences were still significant after adjusting for renal function and dyslipidemia (p < 0.001 and p = 0.002, respectively). However, there were no associations between serum UA levels and the distribution of hemorrhagic lesion, as well as neurological impairment. Our observations indicate that serum UA levels were decreased in CAA patients. UA might play a neuroprotective role in CAA and serve as a potential biomarker for reflecting the severity of Aß deposition.

Glypican-3, a novel prognostic marker of hepatocellular cancer, is related with postoperative metastasis and recurrence in hepatocellular cancer patients.

Metastasis/recurrence has been the most fundamental characteristic of hepatocellular cancer (HCC) and the ultimate cause of most HCC-related deaths. However, there are still a limited number of reliable tumor markers that can be used to predict the possibility of metastasis/recurrence in an HCC patient after operation. Recently, much evidence has shown that glypican-3 (GPC3) can be a useful tool to identify the early development of HCC, but little research has been done to test its usefulness as a prognostic marker related to post-operative metastasis/recurrence in HCC patients. In this study, the expression of GPC3 and its relationship with clinicopathological factors were determined by immunohistochemical analysis in 61 primary HCC patients. The potential prognostic value of GPC3 was investigated by comparing the survival time between HCC patients with high and low GPC3 expression. The results demonstrated that GPC3 expression was closely related with metastasis/recurrence in an HCC patient who can receive the operation. The risk of metastasis/recurrence after surgery in an HCC patient with high GPC3 expression was increased to 3.214 as compared to that of an HCC patient with low GPC3 expression. Survival analysis showed that HCC patients with high GPC3 expression had a significantly shorter overall survival time than HCC patients with low GPC3 expression (P=0.003). Further, multivariate analysis showed that GPC3 expression was a significant, independent prognostic parameter (P=0.030) for HCC patients. Overall, the study indicates that GPC3 might be a valuable marker closely related with prognosis and post-operative metastasis/recurrence in HCC patients.

Dual-vessel intervention treatment for massive hemoptysis caused by lung cavitary lesions.

PURPOSE: To evaluate the outcome of dual-vessel intervention (DVI), including bronchial or pulmonary arterial embolization (B/PAE), in managing massive hemoptysis caused by cavitary lung lesions (with or without aspergilloma) and identify cavitary angiographic features influencing DVI procedures. METHOD: A retrospective analysis of the medical records and angiograms of 15 patients who underwent DVI for massive hemoptysis was performed. RESULTS: The most frequent causes of cavitary lung lesions were tuberculosis (TB) (8/15, 53%) and bronchiectasis (6/15, 40%). Eight patients were diagnosed with aspergilloma (8/15, 53%). In all, 24 systemic arteries, including the orthotopic and ectopic bronchial arteries and 1 pulmonary artery branch, were embolized in 16 procedures. Clinical success and immediate cessation of hemoptysis were achieved in 12 patients (80%). Hemoptysis was controlled in 10 patients (67%) and recurred in 2 patients (17%), while 1 patient (7%) required repeat embolization. The bronchopulmonary fistula (shunting) rate was 73.3% (11/15). The average fistula emergence time was 1.28 ± 1.27 s (M ± SD), and the average vessel diameter was 3.974 ± 1.57 mm. There were no significant differences in angiographic features, clinical success, or recurrence of cavitary lesions with or without aspergilloma. The complication rates were low, with only transient chest pain and ventricular arrhythmia reported. CONCLUSIONS: BAE is an effective and safe procedure for most cavitary lesions causing massive hemoptysis, and DVI is needed under certain circumstances. High bronchopulmonary fistula rates and early fistula emergence times were observed for cavitary lesions. The DVI strategy depends on the culprit vessel diameter, fistula type, and fistula emergence time.

Effects of fermentation medium on cigar filler.

The addition of medium during industrial fermentation can improve the quality of cigar tobacco leaves after agricultural fermentation. In this study, the cigar filler tobacco "Brazilian Frogstrips YA14" was used as the test material to determine the contents of main chemical components in cigar tobacco leaves after fermentations with the additions of water (control group) and a medium (test group), and the changes in the community structure and abundances of bacteria on tobacco leaves during the fermentation process were analyzed. The results of the study were as follows: 1) During the fermentation process, the protein content of tobacco leaves fluctuated slightly, basically stabilized at 19%-20%. 2) Under the impact of the medium, the total content of main amino acids in tobacco leaves showed a downward trend, and the difference of which between the control group and the test group was the most obvious on the fourth day of fermentation. 3) The change trend of the content of petroleum ether extract in cigar leaves for the control group was not obvious, and the content of petroleum ether extract in the tobacco leaves for the test group decreased by 12.4% under the impact of the medium. 4) After fermentation, the relative content of saturated fatty acids for the control group and the test group all increased, while the relative content of unsaturated fatty acids all decreased. 5) After the addition of the medium, the diversity of bacteria on tobacco leaves changed significantly, the number of OTUs in tobacco leaves increased, and the bacterial community structure changed. This research indicates that after adding the medium to ferment cigar filler, the changes of bacterial community and dominant bacterial group on cigar tobacco leaves have impacts on the contents of chemical components in tobacco leaves, and the fermentation with the addition of medium has a positive effect on improving the quality of tobacco leaves.

Minimally invasive versus open radical resection surgery for hilar cholangiocarcinoma: Comparable outcomes associated with advantages of minimal invasiveness.

BACKGROUND: Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial. METHODS: To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed. RESULTS: Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien-Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001). CONCLUSIONS: The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more.

Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD: A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS: Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS: LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

BACKGROUND: The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up. METHODS: Data of 3,068 patients from March 2011 through June 2019 was retrospectively extracted from The Provincial National Cardiac Database of Xiangya Second Hospital. The activities considered (and costs calculated) were outpatient consultations, hospital admissions, and drug treatment. Quality of life (QoL) questionnaires were also carried out to assess whether concomitant AFib correction procedures increase risk in patients, or improve patient's QoL. RESULTS: A total of 3,068 patients completed the questionnaires at a minimum of one time-point during the follow-up. The total cost was combined to obtain incremental costs per quality-adjusted life-years (QALYs). The total costs of the AFib catheter ablation group were remarkably higher compared to surgery as usual group. The incremental cost-effectiveness ratio was $76,513,227 (¥542,287,667) per QALY, with an acceptability line graph for cost at 43%. CONCLUSIONS: AFib is an extraordinarily costly and worrisome public health problem. Precision medicine is vital as it provides a platform for the clinical translation of targeted interventions that are designed to help treat and prevent AFib. Thus, to improve the QoL expectancy outcome(s), both therapeutic and surgical interventions should be aimed at addressing the underlying heart disease rather than restoring sinus rhythm.

Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation.

Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.

Sheng Guoguang's Stage Treatment of Metabolic Associated Fatty Liver Disease Based on"Earth-obstructing and Wood-stagnation,Phlegm and Blood Stasis" / 中国中医药信息杂志

Metabolic associated fatty liver disease has become the most important chronic liver disease in China.Its mechanism is not completely clear.Professor Sheng Guoguang examines the symptoms and seek the cause,treats the disease by stages from the perspective of"earth-obstructing and wood-stagnation,phlegm and blood stasis",summarizes the core pathogenesis of each stage,and prescribes drugs for the pathogenesis.In the early stage,the disease is mainly caused by earth-obstructing and wood-stagnation and phlegm and blood stasis and the corresponding treatment method should be activating spleen to eliminate depression,relieving phlegm and promoting blood circulation,with common use of modified Sizhu Decoction combined with Erchen Decoction.In the middle stage,phlegm and blood stasis transform into heat are the main pathogenesis,and the appropriate treatment is clearing liver and purging fire,and relieving phlegm and promoting blood circulation,with common use of modified Xiaochaihu Decoction combined with Erchen Decoction.In the late stage,weakness of the internal organs is the main pathogenesis,and it is appropriate to nourish liver and fortify the spleen,tonifying the kidney and consolidate the root,supplementing with reducing phlegm and activating blood circulation,with common use of modified Yiguan Decoction combined with Liujunzi Decoction in modification,which has achieved confirmed clinical efficacy.

Theoretical Connotation and Mechanism of Regulating Mental Activity by Dredging Collaterals in Treatment of Psycho-cardiological Diseases via Brain-derived Neurotrophic Factor / 中国实验方剂学杂志

The incidence of psycho-cardiological diseases， i.e.， cardiovascular diseases combined with psychological disorders， is increasing year by year. Brain-derived neurotrophic factor （BDNF） plays a role in the pathogenesis of such diseases. According to the theory of collateral diseases， our team innovates the concept of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases and summarizes the concepts of "heart of Qi and collaterals" and "heart of vessels and collaterals". We believe that obstructed collaterals and disturbed mental activity run through the whole course of psycho-cardiological diseases， being the core pathogenesis. BDNF closely related to the core pathogenesis can regulate nerve and vascular inflammation， alleviate oxidative stress， and mediate a variety of signaling pathways， thereby promoting the survival and repair of nerve cells and vascular endothelial cells to regulate emotion and protect the heart. Therefore， BDNF is one of the potential biomarkers for clinical treatment of psycho-cardiological diseases. Collateral obstruction caused by blood stasis is specifically manifested as collateral deficiency， blood stasis， and Qi stagnation in collaterals. It can easily lead to inflammation， free radical generation， and antioxidant system changes in the patients with psycho-cardiological diseases， which can cause oxidative stress damage， affect the BDNF level， and result in mental disorders， such as anxiety and depression. Disturbed mental activity is mainly caused by the disturbance in the heart of Qi and collaterals， which is specifically manifested as the disturbance of the mind and liver soul. It is prone to cause anxiety or depression symptoms， which is closely related to the BDNF-mediated abnormal activation of neural circuits， nerve injury， and inflammation. This article elaborates on the theoretical connotation and pathological mechanism of regulating mental activity by dredging collaterals in the treatment of psycho-cardiological diseases from the perspective of BDNF， aiming to provide new ideas for the prevention and treatment of psycho-cardiological diseases and collateral diseases.

A proteomic landscape of pharmacologic perturbations for functional relevance / 药物分析学报

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AF. To test a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model. METHODS: Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg x kg(-1) x d(-1) in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography. RESULTS: Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (r(s) = 0.90 961, P < 0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM. CONCLUSIONS: Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.

Textual Research and Modern Clinical Application of Famous Classical Formula Maimendongtang / 中国实验方剂学杂志

ObjectiveTo systematically review the ancient and modern literature about Maimendongtang, so as to provide a scientific basis for the modern clinical application and preparation research and development of Maimendongtang. MethodThe Chinese Medical Code (version 5) was searched with "Maimendongtang" as the keyword. The modern clinical studies of Maimendongtang were retrieved from CNKI with “Maimendongtang” as the keyword and the time interval from January 1, 1975 to December 31, 2022. The articles involving the main symptoms, herb composition, dosage, and decocting and medication methods of Maimendongtang were selected and screened according to the inclusion and exclusion criteria. Finally, the information including the book name, indications, herbs, dosage, and decocting and medication methods were included to summarize the ancient and modern application of Maimendongtang. ResultA total of 357 publications of Maimendongtang were included, involving 115 ancient books. Maimendongtang was first published in the Synopsis of the Golden Chamber by ZHANG Zhongjing in the Han dynasty. It is composed of Ophiopogonis Radix, Pinelliae Rhizoma, Ginseng Radix et Rhizoma, Semen Oryzae Sativae, Jujubae Fructus, and Glycyrrhizae Radix et Rhizoma. Despite the slight changes during the inheritance by later generations, the indications, herb composition, dosage, and decocting and medication methods of this formula were generally consistent with those in the Synopsis of the Golden Chamber. A total of 182 modern articles were included to analyze the clinical application of Maimendongtang. This formula was mainly used to treat respiratory system diseases, digestive system diseases, tumor-related diseases, etc. ConclusionAccording to the textual research on the ancient and modern literature, the composition, dosage, indications, and decocting and medication methods of Maimendongtang are basically consistent with those recorded in the Synopsis of the Golden Chamber. The modern clinical application not only follows the main indications but also expands the clinical application scope of this formula, which is mainly used to treat patients with the syndrome of yin deficiency of lung and stomach. The modern clinical application of Maimendongtang has promoted the inheritance and innovation of classic famous prescriptions and provided a scientific basis for the drug research and development.

Total arterialized coronary artery bypass grafting: short-and mid-term clinical outcomes / 中华胸心血管外科杂志

Objective:To evaluate the safety of total artery coronary artery bypass grafting(CABG) in patients with coronary heart disease and the short- and mid-term clinical outcomes.Methods:A retrospective analysis of the clinical data of 100 patients who underwent CABG treatment in the First Affiliated Hospital of Guangxi Medical University from January 2016 to July 2021. Of these, 50 patients were selected for comparison(TACR) with the left internal thoracic artery and radial artery(RA) as grafts. However, the left internal thoracic artery and the great saphenous vein were used as grafts in other 50 patients were selected as controls(NCR). The clinical data of preoperative, perioperative, and postoperative(3 months, 6 months, 1 year and 5 years) for two groups were compared.Results:In the perioperative period, TACR group was inferior to the control in both operation time and 24 h postoperative drainage. But the peak value of hypersensitive troponin T was lower than that of NCR. There was no significant difference between the two groups in terms of mechanical ventilation time and perioperative mortality. There was no significant difference between the two groups in terms of left ventricular ejection fraction(LVEF), recurrent angina, left ventricular end-diastolic diameter and recurrent myocardial infarction at 3 and 6 months after operation. LVEF in TACR was better than that in NCR at 1 year and 5 years postoperatively.Conclusion:The clinical effect of CABG with RA as bridge vessel carried out in our center is obvious. TACR is safe and feasible due to its good mid-term efficacy and is not likely to cause postoperative complications.