Intermediate occupation numbers for 5f electrons in a Pu and U mixed oxide.

In order to reveal the correlation effect on the electronic properties in particular 5f electron occupation numbers of Pu/U ions in a (Pu,U) mixed oxide-PuUO4, a first principles calculation is performed by using density functional theory (DFT) plus a dynamical mean field theory (DMFT) scheme with the spin-orbit coupling (SOC) and on-site Coulomb repulsion for correlation effect due to localized Pu/U 5f orbitals. Results demonstrate that Pu/U 5f electron occupation numbers in the ground state of PuUO4 are mainly composed of 5f4/5f5 and 5f2/5f3 configurations, and exhibiting the intermediate occupation (IO) numbers with average 5f occupation numbers of about nf = 4.879 and 2.423 for Pu and U ions, respectively, irrespective of different Pu and U lattice sites in PuUO4. Pu 5f j = 5/2 and j = 7/2 components are in moderately and weakly correlated states, respectively, while U 5f j = 5/2 and j = 7/2 manifolds are both in weakly correlated states. jj and LS coupling schemes are feasible for Pu and U 5f electrons, respectively. In order to directly compare with the experimental angle-resolved photoemission spectrum (ARPES), we also estimate the momentum-resolved electronic spectrum function for this system.

Catheter ablation of atrial fibrillation in situs inversus dextrocardia: Challenge, improved procedure, outcomes, and literature review.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF-CA) in patients with situs inversus dextrocardia (SID) can be challenging because of the contrary anatomy and associated anomalies. Cases and literature regarding AF-CA in SID are rare and provide little information. Our study aims to present an improved procedure, ablation strategies, and evaluate the safety and outcomes of AF-CA in patients with AF and SID. METHODS: A total of 10 patients with AF-SID (mean age, 60.4 ± 15.7 years; six paroxysmal AF, four persistent atrial fibrillation [PeAF]) were enrolled. For the improved procedure, images obtained by preacquired computed tomography and three-dimensional electroanatomical mapping, integrating intracardiac echocardiography, and x-ray imaging data are necessary to optimize the transseptal puncture and ablation procedure. RESULTS: All patients successfully underwent 13 AF-CA procedures without complications, including three patients received repeat procedures. However, two PeAF patients presented sick sinus syndrome (SSS) after the AF-CA procedure, and one underwent permanent pacemaker implantation therapy during hospitalization. During the follow-up period (6-72 months), the outcomes were not favorable: three patients (30%) maintained sinus rhythm (SR) after the initial procedure; after repeated procedures, the overall SR rate was 40% (four patients). CONCLUSION: With the improved strategy, AF-CA can be safely and effectively performed with low radiation exposure in patients with SID. However, the long-term outcomes were not favorable, even when managed at a tertiary center by a team of specialists. Moreover, patients with PeAF might also have masked SSS, which should be carefully considered.

[Distribution and major influencing factors of annual systolic blood pressure variability: results from a large cohort study].

OBJECTIVE: To investigate the distribution and major influencing factors of annual systolic blood pressure variability from a large population cohort. METHODS: In this prospective cohort study, data from Kailuan Group employees who attended all 4 physical examinations ( taken in June 2006 to October 2007, June 2008 to October 2009, June 2010 to October 2011, June 2012 to October 2013, respectively) were analyzed (32 959 males and 10 401 females, mean age: (48.2 ± 11.5) years old). Systolic blood pressure variability was defined as the standard deviation (SSD) and the coefficient of variation (SCV) of systolic blood pressure of 4 physical examinations. Multivariate linear regression analysis was used to determine the related influencing factors of SSD and SCV. RESULTS: (1) The mean of SSD and SCV for this cohort was 10.91 mmHg (1 mmHg = 0.133 kPa) and 8.34%, respectively. SSD and SCV increased in male and female with increasing age (both P < 0.001). (2) Multiple linear regression analysis showed that systolic blood pressure (ß = 0.225, P < 0.001), age (ß = 0.163, P < 0.001), fasting blood glucose (ß = 0.038, P < 0.001), the use of anti-hypertensive drugs (ß = 0.038, P < 0.001), sex (ß = 0.038, P < 0.001), smoking (ß = 0.025, P < 0.001), alcohol drinking (P = -0.022, P < 0.001), physical exercise (ß = -0.018, P = 0.001), high-sensitivity c-reactive protein (ß = 0.016, P = 0.001) body mass index (ß = -0.011, P = 0.018) were related to SSD. Age (ß = 0.139, P < 0.001), sex (ß = 0.055, P < 0.001), systolic blood pressure (ß = 0.047, P < 0.001), fasting blood glucose (P = 0.033, P < 0.001), drinking (ß = -0.030, P < 0.001), body mass index (ß = -0.026, P < 0.001), the use of anti- hypertensive drugs (ß = 0.026, P < 0.001), smoking (ß = 0.024, P < 0.001), physical exercise (ß = -0.015, P = 0. 001), high-sensitivity c-reactive protein (ß = 0. 014, P = 0. 001) were related to SCV. CONCLUSIONS: SSD and SCV increase with increasing age. Systolic blood pressure, age, fasting blood glucose, the use of anti-hypertensive drugs, sex, smoking, drinking, physical exercise, high-sensitivity c-reactive protein, body mass index are major influencing factors for SSD. Age, sex, systolic blood pressure, fasting blood glucose, alcohol drinking, body mass index, the use of anti-hypertensive drugs, smoking, physical exercise, high-sensitivity c-reactive protein are major influencing factors for SCV.

[Impact of CHA2DS2 VASc score on substrate for persistent atrial fibrillation and outcome post catheter ablation of atrial fibrillation].

OBJECTIVE: To explore if CHA2DS2 VASc score can predict substrate for persistent atrial fibrillation ( AF) and outcome post catheter ablation of AF. METHODS: From January 2011 to December 2012,116 patients underwent catheter ablation of persistent AF in our department and were enrolled in this study. CHA2DS2VASc score was calculated as follows: two points were assigned for a history of stroke or transient ischemic attack and age ≥ 75 and 1 point each was assigned for age ≥ 65, a history of hypertension, diabetes,recent cardiac failure, vessel disease, female. Left atrial geometry ( LA) was reconstructed with a 3.5 mm tip ablation catheter with fill-in threshold 10 in CARTO system. The mapping catheter was stabled at each endocardial location for at least 3 seconds for recording. The electrogram recordings at each endocardial location were analyzed with a custom software embedded in the CARTO mapping system. Interval confidence level (ICL) was used to characterize complex fractionated atrial electrograms (CFAEs) . As the default setting of the software, ICL more than or equal to 7 was considered sites with a highly repetitive CFAEs complex. CFAEs index was defined as the fraction of area of ICL more than or equal to 7 to the left atrial surface. The CFAEs index and outcome of catheter ablation among different CHA2DS2VASc groups were compared. RESULTS: Of the 116 patients, CHA2DS2VASc was 0 in 33 patients, 1 in 31 patients and ≥ 2 in 52 patients. Left atrial surface ((121.2 ± 18.9) cm2, (133.6 ± 23.8) cm2, (133.9 ± 16.1) cm2, P = 0.008), left atrial volume ((103.6 ± 24.8) ml, (118.3 ± 27.8) ml, (120.9 ± 20.9) ml, P = 0.005) and CFAEs index (44.6% ± 22.4%, 54.2% ± 22.2%, 58.7% ± 23.1%, P = 0.023) increased in proportion with increasing CHA2DS2VASc. ICLmax, ICLmin and CFAEs spatial distribution were similar among the three groups. During the mean follow-up of (13 ± 8) months, the recurrence rate were 36.4%, 35.5%, 55.8% among the three groups (P = 0.025). CONCLUSION: A high CHA2DS2VASc score is associated with extensive AF substrate and higher recurrence rate post catheter ablation of persistent AF.

Heart failure care in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. METHODS AND FINDINGS: Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. CONCLUSIONS: The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.

The impact of the COVID-19 epidemic on tuberculosis control in China.

BACKGROUND: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country. METHODS: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline. FINDINGS: The notified number of TB patients decreased sharply in the 1st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19. INTERPRETATION: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established. FUNDING: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).

Percutaneous treatment with drug-eluting stent vs bypass surgery in patients suffering from chronic stable angina with multivessel disease involving significant proximal stenosis in left anterior descending artery.

BACKGROUND: The aim of the present study was to compare the effects of drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in patients suffering from chronic stable angina with multivessel disease, involving significant proximal stenosis in the left anterior descending artery (LAD). METHODS AND RESULTS: All consecutive patients suffering from chronic stable angina with multivessel disease involving significant proximal LAD stenosis underwent DES implantation (n=600) or CABG (n=709) at our institution. At 2 years, the unadjusted mortality was significantly lower in the DES group than in the CABG group (2.2% vs 5.2%, P=0.004), but the adjusted risk of death was similar (odds ratio (OR) 0.74, 95%CI 0.28-1.97, P=0.555). Furthermore, both the adjusted rate of nonfatal myocardial infarction and cerebrovascular events was also comparable. However, the unadjusted and adjusted risk of major adverse cardiac cerebrovascular events in the DES was significantly higher than in the CABG (13.3% vs 9.6%, OR 2.71, 95%CI 1.56-4.74, P<0.001), which is probably attributed to the higher subsequent revascularization rate after DES implantation. CONCLUSIONS: DES showed comparable long-term mortality for the treatment of multivessel disease involving significant proximal stenosis in LAD in comparison with CABG.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.@*METHODS@#Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.@*RESULTS@#A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001).@*CONCLUSIONS@#In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Expression, refolding, and purification of a truncated human Delta-like1, a ligand of Notch receptors.

The Notch signaling pathway plays a pivotal role in proliferation, apoptosis, and cell fate specification in both embryonic and postnatal development, and is a potential therapeutic target for human diseases such as cancer. To express in Escherichia coli and purify soluble fragment of human Delta-like1 (hDll1), we cloned two extracellular fragments of hDll1 [hDll1 (127-225) and hDll1 (26-225)]. The hDll1 (127-225) fragment was successfully expressed in E. coli as a GST fusion protein (GST-hDll1). The GST-hDll1 protein, which was expressed as inclusion bodies after induction by IPTG, was refolded and purified simultaneously using affinity chromatography and size exclusion chromatography. The purified GST-hDll1 was of more than 95% purity, and had a molecular weight of 39kDa. Reporter assay showed that GST-hDll1 could activate a reporter gene that is dependent on Notch activation. Therefore, using the E. coli expression system and different chromatography systems, we successfully expressed, refolded, and purified a biologically active GST-hDll1, which might be potentially useful for therapy and studying the Notch pathway.

[DSC and FTIR study of adsorbed lysozyme on hydrophobic surface].

During a process of hen egg white lysozyme adsorption and folding on a moderately hydrophobic surface (PEG-600), the effects of salt((NH4)2SO4) concentrations, surface coverage and denaturant (guanidine hydrochloride, GuHCl) concentrations on thermal stability and the changes in the molecular conformation of adsorbed native and denatured lysozyme without aqueous solution were studied with a combination of differential scanning calorimetry (DSC) with FTIR spectroscopy. The results showed that temperature due to endothermic peaks was reduced and the disturbance increased at higher temperature with the increase in salt concentration and surface coverage of adsorbed protein. beta-Sheet and beta-Turn stucture increased while alpha-Helix structure decreased after the adsorption. The peaks corresponding to both C-C stretching frequency in 1400-1425 cm(-1) and amide I band frequency in 1650-1670 cm(-1) of adsorbed denatured lysozyme can be detected in FTIR spectra while that due to amide I band frequency of adsorbed native lysozyme almost can't be observed. Adsorption resulted in structural loss of adsorbed native lysozyme, whose performance was less stable.

Progress of venetoclax in treatment of hematologic malignancies / 白血病·淋巴瘤

The anti-apoptotic protein bcl-2, a key regulator of the intrinsic apoptotic pathway, is frequently overexpressed in cells of hematologic malignancies, and the small molecule inhibitor venetoclax that targets this apoptotic pathway has shown promising efficacy in the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma. The survival and prognosis of patients with acute myeloid leukemia who are of advanced age or who are unsuitable for strong induction chemotherapy because of comorbidities also have significantly improved, but some patients develop progressive drug resistance during the course of venetoclax treatment, which affects the efficacy of medical therapy. This article reviews the action mechanism, therapeutic progress and resistance mechanism of venetoclax in hematologic malignancies.

MXD1 regulates the imatinib resistance of chronic myeloid leukemia cells by repressing BCR-ABL1 expression.

Tyrosine kinase inhibitors have achieved unprecedented efficacy in the treatment of chronic myeloid leukemia (CML); however, imatinib resistance has emerged as a major problem in the clinic. Because the overexpression of BCR-ABL1 critically contributes to CML pathogenesis and drug resistance, targeting the regulation of BCR-ABL1 gene expression may be an alternative therapeutic strategy. In this study, we found that the transcriptional repressor MXD1 showed low expression in CML patients and was negatively correlated with BCR-ABL1. Overexpression of MXD1 markedly inhibited the proliferation of K562 cells and sensitized the imatinib-resistant K562/G01 cell line to imatinib, with decreased BCR-ABL1 mRNA and protein expression. Further investigation using reporter gene analysis showed that MXD1 significantly inhibited the transcriptional activity of the BCR-ABL1 gene promoter. Taken together, these data show that MXD1 functions as a negative regulator of BCR-ABL1 expression and subsequently inhibits proliferation and sensitizes CML cells to imatinib treatment.

Research progress of exosomes in the diagnosis and treatment of sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.

Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients.@*METHODS@#Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed.@*RESULTS@#14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.@*CONCLUSION@#VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.

Analysis of biochemical failure rate and its influencing factors in patients with high-risk localized prostate cancer after radical prostatectomy / 中华泌尿外科杂志

Objective:To analyze the biochemical failure rate and its predictive factors after radical prostatectomy (RP) in patients with high-risk localized prostate cancer.Methods:The data of 166 patients with high-risk localized prostate cancer who underwent RP surgery in Peking university cancer hospital from January 2015 to November 2021 were retrospectively reviewed. The average age was 65.4±6.2 years old, and the average body mass index (BMI) was 24.86±3.23 kg/m 2. The median prostate-specific antigen (PSA) was 19.84 (10.98, 44.47) ng/ml, PSA density was 0.68 (0.34, 1.32)ng/ml 2, and prostate volume was 31.20 (25.58, 40.23) ml. Biopsy pathology Gleason score according to the International society of Urological Pathology(ISUP) grade group: 18 cases of group 1, 33 cases of group 2, 30 cases of group 3, 51 cases of group 4, and 33 cases of group 5, 1 case was unknown. The percentage of puncture positive needles was (55.4±25.7)%, and the largest linear length of positive lesions was 80.0% (60.0%, 90.0%). Preoperative clinical stage : 14 cases in ≤T 2b stage, 117 cases in T 2c stage, 13 cases in T 3a stage and 22 cases in ≥T 3b stage; 157 cases in N 0 stage, 9 cases in N 1 stage. One hundred and three patients (62.0%) were assessed by traditional imaging and 63(38.0%) were assessed by PSMA PET-CT. The patients underwent laparoscopic radical prostatectomy. 64 patients (38.6%) received neoadjuvant therapy, including 37 received neoadjuvant therapy for 1-3 months, 23 for 4-6 months and 4 for over 6 months. The postoperative pathological characteristics, treatment and prognosis of the patients were analyzed. The primary endpoint was biochemical failure, including biochemical persistence(BCP, defined as PSA≥0.1ng/ml at 4-6 weeks after operation, and confirmed by re-examination at least 1 week interval) and biochemical recurrence(BCR, PSA falling below 0.1ng/ml after operation and then rising ≥0.2 ng/ml without adjuvant therapy or after the end of adjuvant treatment). Results:Compared with preoperative clinicopathological characteristics, 48(28.9%) cases had postoperative pathological ISUP upgrade, 98 (59.0%)cases had T stage upgrade, and 13 (7.8%) cases had N stage upgrade. The rate of positive margins was 53%, and apex margin was the most common positive site (65.9%). The postoperative PSA in 114 patients (68.7%) decreased to less than 0.1ng/ml, of which 74 patients didn't receive the therapy and 40 patients received adjuvant therapy. 52 patients (31.3%) had postoperative PSA more than 0.1ng/ml and among them, 51 cases received salvage treatment. 5 patients (3.0%) underwent PSA progression during adjuvant or salvage endocrine therapy and were considered to have castration resistance. After a median follow-up time of 25.5 (12.0, 40.0) months, 78 patients (48.4%, 78/161) experienced biochemical failure, including 49 BCP and 29 BCR, the median time of biochemical failure was 30.0 (95% CI 14.5-45.5) months. Adjuvant therapy could reduce the rate of BCR (31.1% and 15.8%, P=0.08). Baseline PSA, PSA density, proportion of pathological ISUP ≥4, proportion of pathological T stage ≥T 3a, adjuvant therapy, and positive surgical margins were significantly associated with biochemical failure ( P=0.034, 0.002, 0.004, 0.025, <0.001and 0.047). Multivariate Cox regression analysis showed that adjuvant therapy ( P<0.001, OR=0.12), PSA density ( P=0.03, OR=1.19) and positive surgical margins ( P=0.034, OR=1.80) were independent factors for biochemical failure. Conclusions:Patients with high-risk localized prostate cancer have a high rate of biochemical failure after RP and need to receive RP-based multimodal therapy. Adjuvant therapy, PSA density and positive surgical margins are independent factors associated with postoperative biochemical failure.

Effects of delayed ramelteon treatment on neurological function and tissue repair after cryogenic traumatic brain injury / 中国药理学通报

:Aim To study the effects of continuous dai¬ly administration of ramelteon starting at the subacute period of cryogenic traumatic brain injury (cTBI) on neurological function and brain tissue repair in mice. Methods Thirty male C57BL/6 mice were randomly divided into sham group, vehicle group and ramelteon treatment groups. The right sensory-motor cortex was damaged by pressing a copper probe precooled by liq¬uid nitrogen onto the skull. Ramelteon ( 10 nig 'kg-1 • d"1) was administered by gavage every day starting at different time points after cTBI (1 h, 1 d,3 d) until sacrifice on day 14. Beam walking test and open field test were used to evaluate the motor function. Toluidine blue staining was used to measure the infarct volume. Immunofluorescence was used to detect the expression of GAP-43 and synaptophysin in peri-infarct area. Mi¬croglia activation was detected using Iba-1. The area and thickness of glial scars were analyzed by detecting GFAP positive areas. Results All three treatment ( 1 h - 14 d, 1 - 14 d, and 3 - 14 d) significantly im¬proved cTBI induced motor dysfunction, reduced the infarct volume, elevated the expression of GAP -43 and synaptophysin, and decreased the area and thick¬ness of glial scar and microglia activation. In addition, all ramelteon treatment groups had similar effects on the above indexes. Conclusions Delayed ramelteon treatment can improve neurological dysfunction after cTBI,and the therapeutic time window can be delayed for up to three days after cTBI. Inhibiting glial scar formation and microglia activation, and promoting ax- onal regeneration and synaptogenesis may contribute to the beneficial effects of ramelteon.

Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials / 中国针灸

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

Effects of life satisfaction and shift work and their interaction on cumulative fatigue in petrochemical employees / 环境与职业医学

Background Cumulative fatigue without intervention will seriously threaten the physical and mental health of workers. Shift work and life satisfaction are strongly associated with fatigue accumulation. Objective To explore the effects of life satisfaction, shift work, and their interaction on cumulative fatigue in petrochemical employees, and to provide a scientific basis for preventing cumulative fatigue. Methods All staff of a petrochemical enterprise were selected by cluster sampling for a cross-sectional study from July to October 2021 in Jiangsu Province. A questionnaire designed by the project team was used to collect information on shift work; and life satisfaction and cumulative fatigue were investigated by the World Health Organization Five-item Well-Being Index and the Self-diagnosis Checklist for Assessment of Worker’s Fatigue Accumulation respectively. A logistic regression model was used to analyze the influences of life satisfaction and shift work on cumulative fatigue. Multiplicative and additive models were applied to analyze the interaction effect of life satisfaction and shift work. Results A total of 4066 questionnaires were returned, of which 3763 were valid, with an effective recovery rate of 92.5%. The percentage of cumulative fatigue in the petrochemical employees was 63.2% (2377/3763), and the percentages of low life satisfaction and shift work in the petrochemical employees were 53.6% (2016/3763) and 54.2% (2041/3763), respectively. The results of univariate analysis showed no significant difference in cumulative fatigue among different marital status groups (P=0.176), and there were statistically significant differences in cumulative fatigue among the petrochemical employees in different groups of age, gender, educational level, average monthly income, job title, length of service, working hours, night shift, smoking, drinking, physical exercise, life satisfaction, and shift work (P<0.001). After adjustment for covariates such as age, gender, educational level, average monthly income, job title, length of service, working hours, night shift, smoking, drinking, and physical activity, the unconditional logistic regression model showed that the risk of reporting cumulative fatigue in high life satisfaction participants was 0.129 (95%CI: 0.109, 0.154) times of that in participants of low life satisfaction; the risk of reporting cumulative fatigue in shift work participants was 3.792 (95%CI: 2.713, 5.300) times of that in no shift work participants; and the risk of reporting cumulative fatigue in participants with both high life satisfaction and shift work was 0.105 (95%CI: 0.081, 0.135) times of that in participants with low life satisfaction and shift work. The relative excess risk due to interaction, the attributable proportion due to interaction, and the synergy index of coexisting life satisfaction and shift work were −5.504 (95%CI: −7.247, −3.760), −4.728 (95%CI: −7.575, −1.880), and 0.029 (95%CI: 0.002, 0.351) respectively, which suggested that life satisfaction and shift work have an additive interaction effect on cumulative fatigue. A significant multiplicative interaction was also found between life satisfaction and shift work (OR=0.688, 95%CI: 0.476, 0.936). Conclusion Life satisfaction and shift work are the influencing factors of cumulative fatigue among petrochemical employees, and they interact with each other on the risk of cumulative fatigue. High life satisfaction can reduce the risk of accumulated fatigue associated with shift work.