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Chronic hepatitis B is one of the common infectious diseases in the world, with a wide epidemic range and strong contagiousness, which is difficult to completely eradicate. From July 2020 to April 2022, 142 patients with hepatitis B who were admitted to tertiary hospitals were selected and randomly divided into 2 cases, with 71 cases per case. The control group adopts a conventional model, and the observation group implements a nursing model based on the control group. The management capacity and quality of life before and after the two groups of care were compared. 94 patients with chronic hepatitis B who were admitted to the hospital from July 2020 to April 2022 were selected, and 47 cases were divided into the control group and observation group according to the admission time. The control group is given a conventional model, and the observation group is given a nursing model on the basis of the control group. Both groups of patients observed anxiety self-assessment scale (SAS), depression self-assessment scale (SDS), short life span scale (SF-36) scores, and treatment conditions before and after the intervention, to explore the application of nursing model in the management of hepatitis B patients in tertiary hospitals and its impact on patient quality of life. Based on study’s precare outcomes, there was no statistically significant difference between the self-administered scale (PIH) score and the quality of life measurement summary scale (QOL-BREF) score ( P > 0.05 ) between the two groups. After one month of care, both groups had lower PIH scores than before care, and QOL-BREF scores were higher than before care ( P < 0.05 ). After one month of treatment, the PIH score of the observation group was significantly reduced, and the QOL-BREF score after one month of treatment was significantly higher than that of the control group ( P < 0.05 ). The SAS and SDS scores in the observation group were lower than those in the control group, and the quality of life scores and treatment compliance were higher than those in the control group, and the difference was statistically significant ( P < 0.05 ). Conclusions. The nursing model can effectively improve the management and quality of life of hepatitis B patients. It also had a significant positive effect on the therapeutic capacity and quality of life of patients with hepatitis B and improved patient compliance behavior and quality of life.

Brain imaging studies have shown insula-related functional and structural abnormalities in patients with obesity. Laparoscopic sleeve gastrectomy is currently an effective procedure for treating obesity, which promotes acute recovery of brain functional and structural abnormalities in obese patients. The aim of this study was to investigate the long-term impact of laparoscopic sleeve gastrectomy on insula-related structural and functional connectivity.Diffusion tensor imaging and resting-state functional magnetic resonance imaging were employed to investigate laparoscopic sleeve gastrectomy-induced changes in insula-related structural connectivity and corresponding resting-state functional connectivity in 25 obese patients prior to (PreLSG) and 12 months post-surgery (PostLSGResults showed significant increases in fractional anisotropy and axial diffusivity between the right insula and anterior cingulate cortex, and higher fractional anisotropy of left insula-putamen, left insula-caudate and anterior cingulate cortex-right posterior cingulate cortex/precuneus at PostLSG12 compared with PreLSG. There were significant negative correlations between axial diffusivity of right insula-anterior cingulate cortex and body mass index, and fractional anisotropy of right insula-anterior cingulate cortex with scores on external eating at PostLSG12. Anxiety and depressive status ratings were negatively correlated with fractional anisotropy of left insula-putamen at PostLSG12. In addition, there was a significant decrease in resting-state functional connectivity between left insula and left caudate.These findings demonstrate long-term changes in insula-related structural and functional connectivity abnormalities promoted by laparoscopic sleeve gastrectomy, which highlight its strong association with long-term weight loss and improvement in eating behaviors.

Anti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants.Eight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed.Eight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed.Rituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease.

BACKGROUND: Middle cerebral artery (MCA) occlusion is extremely common, especially unilateral artery, which can result in a significant incidence of cerebral infarction. OBJECTIVE: To assess the value of whole-brain computed tomography perfusion (CTP) imaging combined with dynamic CT angiography (dCTA) in the evaluation of pial collateral circulation in patients with MCA occlusion. METHODS: Whole-brain CTP and dCTA images were acquired in 58 patients with unilateral MCA occlusion. All patients were divided into three groups according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score (by CTA). The CTP parameters were analysed, including relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transit time (rMTT), and relative time to peak (rTTP). Patients were followed up with the modified Rankin scale (mRS). All cases in this study were confirmed by DSA. RESULTS: The CTP parameters of the MCA blood supply area on the affected side of patients with different degrees of stenosis were significantly different from those on the unaffected side. There are significant differences in the CTP parameters and openings of the Willis circle in patients with different degrees of stenosis. Significant differences were found in the number of patients with good prognosis. CONCLUSIONS: Whole-brain CT perfusion combined with dynamic CTA can structurally and functionally evaluate the establishment of pial collateral circulation and its effect on cerebral hemodynamic changes.

BACKGROUND AND OBJECTIVES: Patients with monoclonal gammopathy and concomitant kidney diseases are frequently found in clinical practice. Some of them are diagnosed with monoclonal gammopathy of renal significance (MGRS) due to the presence of monoclonal Ig–related kidney injuries. This study aimed to investigate the histopathologic spectrum and clinical characteristics associated with MGRS in a large cohort of patients with monoclonal gammopathy and biopsy-proven kidney diseases from a single Chinese nephrology referral center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients who presented with monoclonal gammopathy (monoclonal spike on serum and/or urine immunofixation tests) and underwent kidney biopsy in the Peking University First Hospital from January 1, 1999 to December 31, 2020 were enrolled in this retrospective study. Patients with malignant hematologic diseases were excluded. Clinical and laboratory data were collected from the electronic medical record system. Comparisons of patients with and without MGRS and with and without amyloidosis were performed. The clinical characteristics associated with MGRS were identified using multivariable logistic regression. RESULTS: A total of 700 patients with monoclonal gammopathy and kidney biopsy were identified. Thirteen patients with repeat kidney biopsies were analyzed separately. For the remaining 687 patients with one kidney biopsy, 261 patients (38%) had MGRS lesions, and the rest (426 patients, 62%) had non-MGRS kidney diseases. Ig-related amyloidosis accounted for the most MGRS cases (n=164, 63%), followed by monoclonal Ig deposition disease (n=23, 9%) and thrombotic microangiopathy (n=22, 8%). In the non-MGRS group, membranous nephropathy was the most common diagnosis (n=171, 40%). In the multivariable logistic regression model, the presence of abnormal serum free light chain ratio, older age, and greater proteinuria were independently associated with MGRS. CONCLUSIONS: Monoclonal Ig amyloidosis is the leading cause of MGRS in Chinese patients with monoclonal gammopathy. The presence of abnormal free light chain ratio, older age, and greater proteinuria were associated with MGRS.

Although extensive efforts have been paid to identify reliable predictors for renal outcomes of diabetic kidney disease (DKD) patients in type 2 diabetes mellitus (T2DM), there are still only a limited number of predictive factors for DKD progression. Increasing evidence reported the role of the overactivated complement system in the pathogenesis of DKD. Whether renal complement depositions are associated with renal outcomes of DKD in T2DM is of interest.A total of 213 biopsy-proven DKD patients with T2DM were retrospectively recruited. Clinical and pathological data of the patients were analyzed. Kaplan-Meier analysis and Cox regression analysis were performed to explore predictors of end-stage renal disease (ESRD).During a median follow-up of 23.0 (12.0, 39.0) months, 100/213 (46.9%) patients progressed to ESRD. C3c and C1q deposition were observed in 133/213 (62.4%) and 45/213 (21.1%) patients, respectively. Kaplan-Meier analysis revealed patients with C3c or C1q deposition had significantly worse renal outcomes compared with those without C3c or C1q deposition (p = .001 and p .001, respectively). Univariate and multivariate Cox regression analysis demonstrated proteinuria (per 1 g/24 h increase, hazard ratio [HR] 1.134, 95% confidence interval [CI] [1.079, 1.191], p .001), interstitial fibrosis and tubular atrophy score (score 2 and 3 vs. 0 and 1, HR 3.925, 95% CI [1.855, 8.304], p .001), and C3c deposition (per 1+ increase, HR 1.299, 95% CI [1.073, 1.573], p = .007) were independent predictors for ESRD in DKD patients with T2DM.C3c deposition in the kidney was associated with worse renal outcomes and was an independent predictor for ESRD in DKD patients with T2DM.背景: 尽管已经付出了大量努力来确定糖尿病肾病(DKD)合并2型糖尿病(T2DM)患者肾脏结局的可靠预测因子, 但DKD进展的预测因子仍然有限。越来越多的证据表明, 过度激活的补体系统在DKD的发病机制中起着重要作用。T2DM患者肾脏补体沉积是否与DKD的肾脏预后有关值得关注。 方法: 回顾分析213例经手术病理证实的DKD合并T2DM患者的临床资料。对患者的临床和病理资料进行分析。采用Kaplan-Meier分析和Cox回归分析探讨终末期肾病(ESRD)的预测因子。 结果: 中位随访23.0(12.0, 39.0)个月, 100/213(46.9%)患者进展为ESRD。C3c和C1q沉积分别为62.4%(133/213)和21.1%(45/213)。Kaplan-Meier分析显示, C3c或C1q沉积的患者与无C3c或C1q沉积的患者相比, 肾脏结局明显差(分别为p=0.001和p0.001)。单因素和多因素COX回归分析显示, 蛋白尿(每增加1g/24小时, HR 1.134, 95%CI[1.079, 1.191], p0.001), 间质纤维化和肾小管萎缩积分(2和3分 vs. 0和1分, HR 3.925, 95%CI[1.855, 8.304], p0.001)和C3c沉积(每增加1+, HR 1.299, 95%CI[1.073, 1.573], p=0.007)是DKD合并T2DM患者ESRD的独立预测因子。 结论: 肾内C3c沉积与肾脏结局不良相关, 是DKD合并T2DM患者ESRD的独立预测因子。.

To analyze the clinical manifestations, pathological characteristics, therapeutic effect and prognosis of diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL).A total of 45 inpatients were eligible for criteria of histologic transformation from FL to DLBCL from January 2010 to January 2021, and their clinical characteristics, diagnosis, treatment and efficacy were collected and analyzed retrospectively.Among the 45 patients, transformation occurred at diagnosis in 27 cases, during " watch and wait " phase in 7 cases and after treatment of FL in 11 cases. The median age was 56 years old (ranged from 27 to 76 years), with 23 male and 22 female. The transformations were observed in 8 cases with low-grade and 37 cases with high-grade FL. Extranodal involvement was present in 26 cases, including bone marrow infiltration in 16 cases. There were 17 cases with anemia and 32 cases met the GELF criteria of high tumor burden. B symptoms were present in 12 cases. There were 38 cases with Ki-67≥50%. The germinal center B-cell-like (GCB) subtype of DLBCL was observed in 43 cases. Efficacy was evaluated in 45 cases. The OR, CR and PR rate were 80.0%, 60.0% and 20.0%, respectively. The OR,CR rate of patients received R-CHOP was higher than those of patients received other regimens (86.11% vs 55.55%,The OR and CR rates are higher in early transformation group of patients with DLBCL transformed from FL. Patients with anemia, B symptoms, POD24, and high-risk score have poor prognosis. IPI score is the independent prognosis factor for OS.滤泡性淋巴瘤转化的弥漫大B细胞淋巴瘤患者临床特征分析.分析滤泡淋巴瘤（FL）转化的弥漫大B细胞淋巴瘤（DLBCL）患者的临床表现、病理、疗效及预后的特点.选择并回顾性分析2010年1月至2021年1月符合条件的45例FL转化为DLBCL的患者，总结其临床特点、诊断、治疗方法和疗效.45例患者中，诊断时即发生转化的27例，选择观察等待之后发生转化的7例，FL治疗后发生转化的11例；男23例，女22例；中位年龄56(27-76)岁。低级别转化8例，高级别转化37例，26例出现结外侵犯，骨髓累及16例，贫血17例，高肿瘤负荷（GELF标准）32例, 伴B症状12例，Ki-67≥50%患者38例。43例转化为GCB型DLBCL。45例患者可评价疗效，所有患者初始化疗疗效评估总有效率（ORR）为80.0%，完全缓解（CR）率为60.0%，部分缓解（PR）率20%；R-CHOP和其他方案组患者ORR分别是86.11%和55.55%（FL转化为DLBCL患者诊断时即转化组ORR及CR率高；患者贫血及B症状、POD24及高危组预后差；IPI评分是影响OS的独立预后因素.

The overall therapeutic outcome of acute myeloid leukemia (AML) is poor, and relapse and refractory are the main reasons for treatment failure. Leukemia cells of relapsed and refractory AML (R/R-AML) patients are usually resistant to conventional chemotherapy, and new treatment regimens are urgently needed to further improve the survival rate and prolong the survival time of these patients.There are no recommended unified treatment regimens other than entering clinical trials.At present,the main options are salvage chemotherapy and hematopoietic stem cell transplantation (HSCT), and HSCT is the only possible cure for R/R-AML, but the prognosis of most of these patients is still poor.In recent years,the treatment status of AML has progressed rapidly, and the new therapies are emerging, many new drugs have become the research focus. Some progress has been made in improving chemosensitivity and overcoming chemoresistance by combining the new drugs with the original chemotherapeutic drugs, which provide a new treatment option and improve the overall prognosis for R/R-AML patients. This article will review the current treatment status and the latest progress in new drug research of R/R-AML.复发难治性急性髓系白血病治疗现状及新药进展.急性髓系白血病（AML）总体治疗效果差，复发难治是其治疗失败的主要原因。复发难治性AML（R/R-AML）患者白血病细胞通常对常规化疗耐药，亟需新的治疗方案以进一步提高患者生存率及延长生存期。对于R/R-AML，除进入临床试验外，尚无推荐的统一治疗方案，目前主要以挽救化疗和造血干细胞移植（HSCT）为主，HSCT是目前唯一可能治愈的方法，但该类患者大多数预后仍差。近年来AML的治疗进展迅速，新的治疗方案层出不穷，多种新药成为研究的热点，并通过与原有化疗药物联合使用提高化疗敏感性、克服化疗耐药，取得了一定的进展，为R/R-AML患者的治疗提供了新的选择，改善了患者的整体预后。本文将对R/R-AML的治疗现状及新药研究最新进展作一综述。.

Background Due to the blood-brain barrier, plasma is not an ideal source to evaluate the genetic characteristics of central nervous system tumors. Thus, cerebrospinal fluid (CSF) is becoming an alternative biopsy type to evaluate the genetic landscape of intracranial tumors. We aimed to explore the genetic profiles of CSF-derived circulating tumor DNA (ctDNA) to predict intracranial tumor responses and monitor mutational evolution during the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases. Methods We conducted a prospective study of 92 newly diagnosed NSCLC patients with brain metastases. Paired CSF and plasma samples were collected at baseline, 8 weeks after treatment initiation, and disease progression. All samples underwent next-generation sequencing of 425 cancer-related genes. Results At baseline, the positive detection rates of ctDNA in CSF, plasma, and extracranial tumors were 63.7% (58/91), 91.1% (82/90), and 100% (58/58), respectively. A high level of genetic heterogeneity was observed between paired CSF and plasma, while concordance in driver mutations was also observed. A higher number of unique copy number variations was detected in CSF-ctDNA than in plasma. ctDNA positivity of CSF samples at baseline was associated with poor outcomes (HR=2.565, P=0.003). Moreover, patients with ≥ 50% reductions in the concentrations of CSF ctDNA after 8 weeks of treatment had significantly longer intracranial progression-free survivals (PFS) than patients with < 50% reductions in CSF ctDNA concentrations (13.27 months vs 6.13 months, HR=0.308, P=0.017). A ≥ 50% reduction in CSF ctDNA concentrations had better concordance with radiographic intracranial tumor responses than plasma. A ≥ 50% reduction in plasma ctDNA concentrations was also associated with longer extracranial PFS (11.57 months vs 6.20 months, HR=0.406, P=0.033). Based on clonal evolution analyses, the accumulation of subclonal mutations in CSF ctDNA was observed after 8 weeks of treatment. The clonal mutations that remained in more than 80% in CSF after 8 weeks also predicted shorter intracranial PFS (HR=3.785, P=0.039). Conclusions CSF ctDNA exhibited unique genetic profiles of brain metastases, and dynamic changes in CSF ctDNA could better predict intracranial tumor responses and track clonal evolution during treatment in NSCLC patients with brain metastases. Trial registration ClinicalTrials.gov identifier: NCT 03257735.

To evaluate the influence of congestive heart failure (CHF) on safety and efficacy of left atrial appendage closure (LAAC) in non-valvular atrial fibrillation (NVAF) patients.A total of 401 patients who consecutively underwent LAAC with Watchman and LAmbre devices were divided into CHF (85 cases) and non-CHF (316 cases) groups. Comparisons between groups were performed against data.No significant differences were found in implantation success and periprocedural complication rates between the two groups. During a mean 2.2 years of follow-up, the incidence rate of thromboembolism, major bleeding, device-related thrombus, and non-cardiovascular death was comparable. However, patients with CHF had significantly increased risk of all-cause death (Implantation of atrial appendage occluder is effective and safe in NVAF patients with CHF. The increased risk of mortality and combined efficacy endpoints in patients with CHF versus non-CHF after LAAC may be associated with the high risk of CHF itself.

The resistance to cisplatin, the most common platinum chemotherapy drug, may confine the efficacy of treatment in epithelial ovarian cancer patients. Aberrant expression of inhibitor of apoptosis proteins set the stage for resistance to cisplatin in EOC; besides, chemosensitivity in EOC can be chalked up to dysregulation of specific miRNAs. Herein, we investigated whether there is a potential correlation between miR-874-3p and the X-chromosome-linked inhibitor of apoptosis, a member of the IAP protein family in cisplatin-resistant EOC cells. The lower expression of miR-874-3p was found in SKOV3-DDP cells; it was also in association with cisplatin-resistance in EOC cells. XIAP was found to contribute to developing platinum resistance and is an authentic target for miR-874-3p in SKOV3-DDP cells. Consistently, restoration of miR-874-3p expression reversed cisplatin resistance in such cells by modulating XIAP and NF-κB/Survivin signaling pathway. Besides, siRNA knock down of XIAP in SKOV3-DDP cells had an anti-migratory effect like those with miR-874 overexpression. Importantly, the enforced expression of XIAP rescued SKOV3-DDP cells from the cytotoxic effects of miR-874-3p. Finally, miR-874-3p sensitized EOC cells to cisplatin-induced apoptosis, at least in part, through targeting XIAP. The cytotoxic effects of miR-874-3p can be attributed to the targeting XIAP in cisplatin-resistant EOC cells. We believe that the combination of cisplatin with miR-874-3p may make a potential strategy to reverse cisplatin resistance.

Dysregulated secretion in neutrophil leukocytes associates with human inflammatory disease. The exocytosis response to triggering stimuli is sequential; gelatinase granules modulate the initiation of the innate immune response, followed by the release of pro-inflammatory azurophilic granules, requiring stronger stimulation. Exocytosis requires actin depolymerization which is actively counteracted under non-stimulatory conditions. Here we show that the actin nucleator, WASH, is necessary to maintain azurophilic granules in their refractory state by granule actin entrapment and interference with the Rab27a-JFC1 exocytic machinery. On the contrary, gelatinase granules of WASH-deficient neutrophil leukocytes are characterized by decreased Rac1, shortened granule-associated actin comets and impaired exocytosis. Rac1 activation restores exocytosis of these granules. In vivo, WASH deficiency induces exacerbated azurophilic granule exocytosis, inflammation, and decreased survival. WASH deficiency thus differentially impacts neutrophil granule subtypes, impairing exocytosis of granules that mediate the initiation of the neutrophil innate response while exacerbating pro-inflammatory granule secretion.

Bladder cancer is one of the most common malignant tumors of the urinary system, with high morbidity and mortality. At present, the survival rates and prognosis of patients with bladder cancer are still relatively low; thus, there remains a need to improve prognosis by identifying novel targets. Kinesins (kinesin superfamily proteins) are a series of microtubule‐based motor proteins that mediate various types of cellular processes. Kinesin family member 3A (KIF3A) is critical for cytoplasm separation in mitosis, and it has been reported to be misexpressed in multiple types of cancer. However, its effects on the progression and development of bladder cancer remain unclear. Herein, we report that KIF3A is highly expressed in human bladder cancer. We identified a significant correlation between KIF3A and clinical features, including clinical stage (P = 0.047), pathological tumor status (P = 0.045), lymph node status (P = 0.041) and metastasis (P = 0.035). KIF3A expression was also correlated with poor prognosis of patients with bladder cancer. Our results further indicated that KIF3A ablation resulted in cell cycle arrest; blocked the proliferation, migration and invasion of bladder cancer cells in vitro; and restrained tumor growth in mice in a microtubule‐dependent manner. In summary, our findings suggest that KIF3A is a potential therapeutic target for bladder cancer., We found that kinesin family member 3A (KIF3A) was highly expressed in human bladder cancer tissues. Our results further indicated that KIF3A ablation resulted in cell cycle arrest and blocked the proliferation, migration and invasion of bladder cancer cells in a microtubule‐dependent manner. Importantly, our findings indicate that KIF3A could serve as a promising therapeutic target for bladder cancer treatment.

Pien-Tze-Huang, one of the most famous and widely used Chinese medicinal prescriptions in China, consists of Notoginseng Radix et Rhizoma, Bovis Calculus, Fel Serpentis, and Moschus.The prescription can clear heat and remove toxin, cool blood and resolve blood stasis, and relieve swelling and pain.Characterizing the chemical composition can facilitate the construction of the quality standard and the research on the effective compounds and action mechanism of Pien-Tze-Huang.Therefore, this study used direct infusion(DI)-MS/MS~(ALL) method to rapidly and accurately reveal the chemical composition of Pien-Tze-Huang.The principle of chemical composition profiling of Chinese medicinal prescriptions lies in the MS~1-MS~2 dataset construction, followed by structural annotation based on MS/MS spectra and summarizing of mass fragmentation pathways.MS/MS~(ALL) owns unique mass spectrometric separation ability via applying gas phase fractionation which enables MS~1 ion cohort successively enter the collision cell and acquire MS~2 spectrum for each precursor ion current with a width of m/z=1.Because DI can provide desired measurement time, MS/MS~(ALL) is able to acquire MS~2 spectrum for each compound individually except for the compounds which share identical nominal molecular weight, even isomers.A total of 52 compounds were identified in Pien-Tze-Huang, including 16 saponins, 24 bile acids, 9 fatty acids, 2 saccharides, and 1 other compound.DI-MS/MS~(ALL) can simultaneously identify the compounds with different polarities in a short time, which is superior to LC-MS.This study provides a powerful tool for the rapid chemome profiling of Chinese medicinal prescriptions.

Objective Effect of physical exercise on pregnant women currently has become a hot topic in prenatal health care. In this study, A meta-analysis was conducted on account of Randomized Controlled Trial (RCT). It focused on evaluating the effect of physical exercise intervention on blood pressure so that could provide certain evidence for health care during pregnancy. Methods Results of relevant studies were retrieved from PubMed, Embase, Web of Science and the Cochrane Library, and all of these included studies were evaluated according to the Cochrane collaboration’s tool for assessing the risk of bias. Stata 15.1 was used for meta-analysis, and mean difference (MD) was used as statistic for pooled analysis. The effect values were combined by conventional meta-analysis and Bayesian meta-analysis respectively, and the consistency of pooled results was considered as well. Results A total of 18 RCT studies were included in the quantitative analysis. The conventional meta-analysis showed differences in blood pressure between intervention group and control group (P CI: -5.13, -1.25) and 2.14 mmHg (95% CI: -4.26, -0.03) lower than that of control group, respectively. Bayesian meta-analysis showed that both systolic and diastolic pressure among intervention group decreased by 3.34 mmHg (95% CrI: -5.15, -1.56) and 2.14 mmHg (95% CrI: -3.79, − 0.50), respectively. Subgroup analysis supported that as long as healthy pregnant women participated in exercises, their blood pressure could be slightly regulated, while hypertension susceptible pregnant women significantly lowered blood pressure. Conclusion Exercise intervention during pregnancy is beneficial to lower or normalize blood pressure, and this research provides clues for follow-up studies.

Tricuspid regurgitation (TR) is a well-known complication after permanent pacemaker implantation. The aim of this study was to compare the degree of TR and the relationship of lead position across the tricuspid valve (TV) between patients with right ventricular apical (RVA) and non-RVA pacing determined by three-dimensional echocardiography.Conventional and three-dimensional echocardiography was performed in 284 patients to determine the change in TR severity following permanent pacemaker implantation. Transvenous lead locations were based on fluoroscopic images. This was a retrospective study, and the selected pacing mode was not randomized.RVA pacing had more frequent severe TR (37.9% vs 25.7%, P = .03) compared with non-RVA pacing. Severe TR occurred in 9.7%, 12.6%, and 58.8% of patients when the lead passed through the middle, between the commissures, and impinging the TV leaflets, respectively. Non-RVA leads were more likely to be positioned in the middle of the TV (30.3% vs 12.1%, P .01) and had the lowest chance of leaflet impingement (33.6% vs 51.5%, P .01) compared with RVA leads. RVA pacing was associated with worsening of grade ≥2 TR severity compared with non-RVA pacing (42.4% vs 27.6%, P .01). A TV lead passage angle of -15° to 15° minimized TR.Pacing-induced TR is more prevalent with RVA than non-RVA pacing. Preferential lead impingement on the TV leaflet, as determined by TV lead passage angle, can explain the development and progression of pacing-induced TR.

In this paper, a novel acidic polysaccharide (CPS-1) was successively prepared from Gynostemma pentaphyllum using hot water isolation method to explore its antitumor and antioxidant activities. Structural characteristics of CPS-1 were evaluated by SEM, HPGPC, HPAEC-PAD, FT-IR, and NMR. The results indicated: CPS-1 was mainly composed of Ara, Gal, Glc, Xyl, Man, GalA and GlcA in a molar ratio of 1.23:2.14:0.67:0.2:0.29:0.16:0.04 with molecular weight of 3297 kDa. Combining with the results of FT-IR and NMR, it was inferred that CPS-1 was mainly possessed the five main linkages including α-D-Ara, α-D-Gal, α-D-Man, α-D-Xyl and β-D-Glc. Furthermore, MTT results exhibited that the IC50 value of CPS-1 for inhibitive effect on SPC-A-1 and MGC-803 cells for 24 h were 284.36 and 365.27 μg/mL, respectively. Microscopic observations showed that the cells exhibited significant apoptotic characteristics, such as cell shrinkage, the decreased of cell adherence and the appearance of apoptotic bodies. It was shown that CPS-1 had significant anti-tumor activity. In addition, the ability of CPS-1 to scavenge superoxide radical, ABTS and DPPH radicals was also enhanced with the increased of concentration. Therefore, it was revealed that CPS-1 might be used as a natural anticancer and antioxidant component.

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J Virol 86:12441–12442 CAS Article Google Scholar Zou L, Zhou J, Li H, Wu J, Mo Y, Chen Q, Fang L, Wu D, Ke C (2012) Human adenovirus infection in children with acute respiratory tract disease in Guangzhou, China. APMIS 120:683–688 Article Google Scholar Download references This study was supported by Doctor Research Startup Foundation of Changzhi Medical College (BS201912, BS201921), Key Project of Qinghai Health and Family Planning Commission (2017-wjzd-08) and Qinghai Thousand People Plan. Department of Basic Medical Sciences, Changzhi Medical College, Changzhi, 046000, China Juan Yu Department of Public Health and Preventive Medicine, Changzhi Medical College, Changzhi, 046000, China Huaxiang Rao Center of Hygiene Inspection, Qinghai Center for Disease Control and Prevention, Xining, 810007, China Juan Yu & Shengcang Zhao Institute for Communicable Disease Control and Prevention, Qinghai Center for Disease Control and Prevention, Xining, 810007, China Huaxiang Rao You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Huaxiang Rao. The authors declare that they have no conflict of interest. This study was approved by the Ethics Committee of Qinghai Center for Disease Control and Prevention, the related procedures were performed according to the guideline of National Influenza Surveillance Program (Edition 2017). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain...

The edible mushroom Grifola frondosa has been used as a functional food for diseases prevention and therapy in Asian countries. In the present work, an acid-soluble polysaccharide (GFAP) was prepared from Grifola frondosa under room temperature and hydrochloric acid solution treatment, and its inhibitory effects on H22 and HepG2 cells were investigated. Results of MTT indicated that GFAP could effectively suppress proliferations of HCC cells, dose-dependently. Microscopic observation results demonstrated that GFAP-treated HCC cells showed apoptotic characteristics like membrane blebbing, chromatin condensed, nucleus pycnosis and fragmentation. Annexin V-FITC/PI staining and cell cycle distribution results showed that GFAP could induce the apoptosis of H22 and HepG2 cells via arresting them in G1 and S phases respectively. Rh123, JC-1 staining and western blotting results suggested that GFAP could significantly increase the permeability of mitochondrial membrane of HCC cells, and upregulated the expressions of Bax, cytochrome c, cleaved-caspase-3 and cleaved-caspase-9, which indicated that GFAP could trigger apoptosis of HCC cells through mitochondria apoptotic pathway in a caspases-dependent pattern. Our data demonstrated that GFAP holds great application prospect as a safe and effective antitumor drug for hepatocellular carcinoma therapy.

Patient-reported outcomes (PROs) have been widely accepted in western countries. However, limited attention has been given to PROs in China due to a lack of research on the agreement between doctors’ and patients’ reports of adverse events. This study aims to reveal the perception gap of chemotherapy-induced adverse events between doctors and cancer patients in China. An observational study was administered at Sun Yat-Sen University Cancer Center (SYSUCC). Totally, 200 adult cancer patients undergoing chemotherapy participated. Patient reports were collected by nurses via telephone. Doctor reports were collected by nurses based on their medical records. The agreement between doctors and patients was analyzed by Cohen’s κ. Agreement between doctors and patients varied among different symptoms: 0.26 for nausea/vomiting, 0.49 for constipation, 0.63 for diarrhea, 0.65 for general pain, and 0.76 for rash. Doctors’ underreporting rates were 70% for nausea/vomiting, 50% for diarrhea, 38% for rash, 33% for constipation, and 29% for general pain. The perception gap of chemotherapy-induced adverse events between doctors and patients exists in China, especially regarding subjective symptoms. Introduction of PROs in both clinical trials and routine clinical practice should be considered in China.

Aim: Long noncoding RNA (lncRNA) B3GALT5-AS1 has been reported as a biomarker for cancer monitoring. This research aims to identify serum long noncoding RNA B3GALT5-AS1 as a new biomarker for the diagnosis of colorectal cancer (CRC) and evaluate its clinical value. Materials & methods: Serum B3GALT5-AS1 expression levels were measured by quantitative real-time PCR. Results: The level of B3GALT5-AS1 in CRC patients was significantly lower than that of healthy patients (p < 0.0001). Further exploration validated that high serum B3GALT5-AS1 level was related to tumor node metastasis (TNM) stage (p = 0.008) and histological differentiation (p = 0.027). Compared with the healthy control group, AUCROC of serum B3GALT5-AS1 in the CRC group was 0.762 with 95% CI: 0.698–0.826 (p < 0.0001). Conclusion: B3GALT5-AS1 may be served as a diagnostic marker for distinguishing CRC patients from healthy people.

Objectives: To improve the infection control and prevention practices against coronavirus disease 2019 (COVID-19) in radiology department through loophole identification and providing rectifying measurements. Methods: Retrospective analysis of 2 cases of health-care-associated COVID-19 transmission in 2 radiology departments and comparing the infection control and prevention practices against COVID-19 with the practices of our department, where no COVID-19 transmission has occurred. Results: Several loopholes have been identified in the infection control and prevention practices against COVID-19 of the 2 radiology departments. Loopholes were in large part due to our limited understanding of the highly contagious coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is characterized by features not observed in other SARS viruses. We recommend to set up an isolation zone for handling patients who do not meet the diagnostic criteria of COVID-19 but are not completely cleared of the possibility of infection. Conclusions: Loopholes in the infection control and prevention practices against COVID-19 of the 2 radiology departments are due to poor understanding of the emerging disease which can be fixed by establishing an isolation zone for patients not completely cleared of SARS-CoV-2 infection.

To investigate the performance of the combined hepatocyte fraction (HepF) and apparent diffusion coefficient (ADC) values to stage hepatic fibrosis (HF) in patients with hepatitis B/C.A total of 281 patients with hepatitis B/C prospectively underwent gadoxetate disodium-based T1 mapping and diffusion-weighted imaging. HepF was determined from pre and postcontrast T1 mapping with pharmacokinetics. The independent predictors of the HF stage (S0-4) were identified from HepF, ADC, conventional T1-based parameters, and age using a logistic regression analysis. The performances of independent and combined predictors in diagnosing various HF stages were compared by analyzing receiver operating characteristic curves. The intraclass correlation coefficient (ICC) was used to assess the interobserver reproducibility of each predictor.In total, 167 patients with various stages of HF were included. All measurements had excellent interobserver agreement (ICC ≥ 0.75). The hepatic relative enhancement, HepF ,and ADC values were significantly different among various HF stages (p 0.05). The HepF and ADC were independent predictors of S0, S1, S2 , and S3 disease (p 0.05). T1The combined predictor of HepF and ADC shows acceptable performance for staging HF.

Stable propagation of epigenetic information is important for maintaining cell identity in multicellular organisms. However, it remains largely unknown how mono-ubiquitinated histone H2A on lysine 119 (H2AK119ub1) is established and stably propagated during cell division. In this study, we found that the proteins RYBP and YAF2 each specifically bind H2AK119ub1 to recruit the RYBP-PRC1 or YAF2-PRC1 complex to catalyse the ubiquitination of H2A on neighbouring nucleosomes through a positive-feedback model. Additionally, we demonstrated that histone H1-compacted chromatin enhances the distal propagation of H2AK119ub1, thereby reinforcing the inheritance of H2AK119ub1 during cell division. Moreover, we showed that either disruption of RYBP/YAF2-PRC1 activity or impairment of histone H1-dependent chromatin compaction resulted in a significant defect of the maintenance of H2AK119ub1. Therefore, our results suggest that histone H1-dependent chromatin compaction plays a critical role in the stable propagation of H2AK119ub1 by RYBP/YAF2-PRC1 during cell division.

Disruption of copper homeostasis is associated with a number of severe diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Wilson’s disease, and Menkes syndrome. Given this association, the detection and capture of Cu2+ in biological fluids and tissues may provide a new direction for the diagnosis and treatment of related disorders. The current analytical approaches, however, are challenging due to the high cost, complexity, and long time required to prepare and analyze samples. Here, we report a novel salen ligand, namely N,N’-(1,2-phenylene)bis(1-(1H-imidazol-4-yl)methanimine) (pimi), which can readily detect and concurrently capture Cu2+ from aqueous as well as biological mediums. Pimi can selectively and specifically detect Cu2+ from biofluid and cellular samples with rapid ccresponse time (

2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times.DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation.Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.

Cryoglobulinemia encompasses a group of diseases with circulating aberrant Igs, which can cause systemic cryoglobulinemic vasculitis, including cryoglobulinemic glomerulonephritis. The complexities of different types and changing etiologies of cryoglobulinemias determine its heterogeneous clinical manifestations and diagnostic difficulties. In this issue of Kidney International, Javaugue et al. have emphasized the diagnostic points of cryoglobulinemic glomerulonephritis and hematological disorders as the major culprits of noninfectious cryoglobulinemic glomerulonephritis in a large cohort.

Background Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. Methods ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Results We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. Conclusions In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.

ObjectivesTo investigate the relationship among baseline health-related quality of life (HRQoL), early changes in HRQoL from baseline to completion of the first cycle of chemotherapy, and prognosis in patients with advanced lung cancer.DesignThis was a prospective, observational study.SettingThe study was conducted in a national cancer centre in South China.ParticipantsA total of 243 patients with chemo-naïve with advanced lung cancer were enrolled.InterventionNone.Primary and secondary outcome measuresThe Functional Assessment of Cancer Therapy-Lung was used to assess HRQoL at baseline and at the end of the first cycle of chemotherapy. The Trial Outcome Index (TOI) and Lung Cancer Scale (LCS) were calculated as predictive indicators. Response to treatment was evaluated as per the Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1. Survival data were gathered from follow-up to September 2019.ResultsPatients with 5-point or greater decreases in TOI (65% vs 48%, adjusted risk ratio (aRR)=2.19, 95% CI 1.09 to 4.41) or 2-point or greater decreases in LCS (72% vs 48%, aRR=3.29, 95% CI 1.50 to 7.22) from baseline to completion of the first cycle of chemotherapy were more likely to show stable or progressive disease than those whose HRQoL had improved. Baseline TOI ≤54 (80.0% vs 69.9%, adjusted hazard risk (aHR)=1.36, 95% CI 1.01 to 1.84) and LCS ≤21 (77.6% vs 72.5%, aHR=1.36, 95% CI 1.01 to 1.83) were associated with higher risk for death compared with TOI>54 and LCS>21. Area under the curve analysis indicated that early changes in LCS and baseline LCS scores could better predict response to treatment and overall survival than the corresponding TOI values.ConclusionsHigher pretreatment HRQoL scores could predict longer survival, while declining HRQoL values could predict unfavourable treatment outcome among patients with advanced lung cancer. The use of the LCS is recommended for the routine collection of patient-reported HRQoL.Trial registration numberNCT01914120.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

To observe the effect of umbilical moxibustion on phlegm damp constitution and intestinal flora, and explore the mechanism of umbilical moxibustion in improving phlegm damp constitution.A total of 60 subjects with phlegm damp constitution were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given TCM health guidance, such as diet and exercise; on the basis of the control group, umbilical moxibustion was applied in the observation group, 7 moxa cones each time, 2 times a week for 8 weeks. Before and after intervention, the indexes (transformation score of phlegm damp constitution, body mass, body mass index [BMI], waist circumference, hip circumference, heart rate and blood pressure) related to phlegm damp constitution were recorded in the two groups. The intestinal flora was detected with 16S rDNA sequencing technology in the two groups.After intervention, the transformation score of phlegm damp constitution, body mass, BMI, waist circumference and hip circumference were decreased compared before intervention in the observation group (Umbilical moxibustion may reshape the intestinal flora by up-regulating the relative abundance of

The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine.A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented.Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications.Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.

Amyloid light‐chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single‐cell level of CD3+ T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara‐BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8+ T cells. In particular, we found the presence of CD8+ BM resident memory T cells (TRM) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara‐BCD, these TRM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara‐based therapy in patients with AL amyloidosis promotes anti‐tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis., We performed scRNA‐seq of T cells in patients with AL amyloidosis before and after daratumumab‐based therapy and observed prominent changes in CD8+ T cells after treatment. In particular, we found the presence of CD8+ bone marrow resident memory T cells (TRM) with high expression of inhibitory molecules in AL patients at diagnosis. After daratumumab‐based treatment, these TRM cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression.

Polysaccharides from the Polygala tenuifolia Willd. have been shown multiple biological activities, however the structural feature and immunomodulatory activity are still rarely reported. In this study, a polysaccharide was obtained by purification, and its structural characteristics and immune activity were analyzed. The polysaccharide was a homogeneous macromolecular polysaccharide with smooth flat flakes surface structure and molecular weight of 2.34 × 10

Currently, the primary treatments for fungal keratitis (FK) are drugs and surgery. However, drug treatment has low efficacy and many side effects, and surgical treatment is costly. Therefore, it is critical to develop a new method of FK treatment. This report describes a 56-year-old male patient with FK who was treated with a combination of traditional Chinese medicine (TCM) and Western medicine with noticeable results and few side effects.The main symptoms were blurred vision in the right eye and pain. On the corneal surface, a large area of ulcer with a turbid margin was visible, along with an oral ulcer. Additionally, the patient was afraid of corneal transplantation due to financial constraints.The case was diagnosed as FK. In vivo confocal microscopy is the first choice for the diagnosis of this condition. Corneal ulcer was infiltrated with numerous inflammatory cells and dendritic fungal hyphae, as determined by in vivo confocal microscopy.Early in his illness, the patient was treated with only Western medicine, which resulted in poor outcomes and severe adverse reactions. Corneal transplantation was recommended by the first hospital. The patient was later transferred to our hospital for treatment with TCM decoction.After 21 days of treatment, the corneal ulcer of the patient became shallower, his vision improved, and his discomfort disappeared. Due to financial concerns, the patient and his family requested early discharge, so no follow-up disease information was obtained. However, when analyzing the disease development process in the hospital, the combination of TCM and Western medicine had obvious effects and a high level of safety.This case report shows that TCM is safe and effective in the treatment of FK and is worthy of promotion. However, in practice, we found that TCM is better for patients with early FK, so early diagnosis of FK is crucial.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

In this study, we aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals from the central region of the Qinghai-Tibetan Plateau. Toward this, small mammals were captured using snap traps in Yushu City and Nangqian County, West China, and the spleen tissue was used for Bartonella culture. The suspected positive colonies were evaluated using polymerase chain reaction (PCR) amplification and by sequencing the citrate synthase (gltA) gene. We discovered that 31 out of the 103 small mammals tested positive for Bartonella, with an infection rate of 30.10%. Sex differences between the mammals did not result in a significant difference in infection rate (χ2 = 0.018, P = 0.892). However, there was a significant difference in infection rates in different small mammals (Fisher’s exact probability method, P = 0.017) and habitats (χ2 = 7.157, P = 0.028). Additionally, 31 Bartonella strains belonging to three species were identified, including B. grahamii (25), B. japonica (4) and B. heixiaziensis (2), among which B. grahamii was the dominant epidemic strain (accounting for 80.65%). Phylogenetic analyses showed that most of the B. grahamii isolates identified in this study may be closely related to the strains isolated from Japan and China. Genetic diversity analyses revealed that B. grahamii strains had high genetic diversity, which showed a certain host and geographical specificity. The results of Tajima’s test suggested that the B. grahamii followed the progressions simulated by a neutral evolutionary model in the process of evolution. Overall, a high prevalence and genetic diversity of Bartonella infection were observed in small mammals in the central region of the Qinghai-Tibetan Plateau. B. grahamii as the dominant epidemic strain may cause diseases in humans, and the corresponding prevention and control measures should be taken into consideration in this area.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) has been frequently overexpressed in many types of malignancy, suggesting its oncogenic function. It recognizes phosphorylated serine or threonine (pSer/Thr) of a target protein and isomerizes the adjacent proline (Pro) residue, thereby altering folding, subcellular localization, stability, and function of target proteins. The oncogenic transcription factor, Nrf2 harbors the pSer/Thr-Pro motif. This prompted us to investigate whether Pin1 could bind to Nrf2 and influence its stability and function in the context of implications for breast cancer development and progression. The correlation between Pin1 and Nrf2 in the triple-negative breast cancer cells was validated by RNASeq analysis as well as immunofluorescence staining. Interaction between Pin1 and Nrf2 was assessed by co-immunoprecipitation and an in situ proximity ligation assay. We found that mRNA and protein levels of Pin1 were highly increased in the tumor tissues of triple-negative breast cancer patients and the human breast cancer cell line. Genetic or pharmacologic inhibition of Pin1 enhanced the ubiquitination and degradation of Nrf2. In contrast, the overexpression of Pin1 resulted in the accumulation of Nrf2 in the nucleus, without affecting its transcription. Notably, the phosphorylation of Nrf2 at serine 215, 408, and 577 is essential for its interaction with Pin1. We also identified phosphorylated Ser104 and Thr277 residues in Keap1, a negative regulator of Nrf2, for Pin1 binding. Pin1 plays a role in breast cancer progression through stabilization and constitutive activation of Nrf2 by competing with Keap1 for Nrf2 binding.

To conduct a head-to-head comparison in terms of image quality and diagnostic confidence between an individualized post-trigger delay and a conventional fixed post-trigger delay in bolus tracking abdominal multiphase CT.Abdominal multiphase CT was performed in 104 patients with either of the two bolus tracking strategies: an individualized post-trigger delay (group A) and fixed post-trigger delay of 11 s (group B). All CT scan parameters and contrast media protocol parameters were consistent between the two groups. Quantitative parameters (organs and blood vessels enhancement, image noise, signal-to-noise ratios [SNRs] and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (overall image quality and diagnostic confidence) were compared. Quantitative and qualitative image quality for the two groups were compared using the Mann-Whitney U and independent sample t test. Degrees of agreement between two radiologists were evaluated using the Kappa analysis.In the arterial phase (AP), images of group A provided higher attenuation (P ≤ 0.001). Although SNRs of liver, pancreas and aorta were similar in AP between the two groups, CNRs of liver, pancreas and portal vein in group A were significantly higher than those in group B (all P values ≤ 0.002). The overall subjective image quality and diagnostic confidence between the two groups were similar (P = 0.809; P = 0.768).Compared to a fixed post-trigger delay using bolus tracking, application of an individualized post-trigger delay can optimize the objective image quality in arterial phase without compromising diagnostic quality in abdominal multiphase CT.

Beneficial effects of parent-administered pediatric tuina on ADHD in children have been reported in previous studies, but no rigorously designed randomized controlled trials (RCTs) have been conducted on it.To assess the feasibility and preliminary effects of parent-administered pediatric tuina for ADHD symptoms in preschoolers.This project was a two-arm, parallel, open-label, pilot RCT. Sixty-four participants were randomized into two groups at a 1:1 ratio. Parents in the parent-administered tuina group (n = 32) attended an online training program on pediatric tuina for ADHD and conduct this intervention on their children at home. Parents in the parent-child interaction group (n = 32) attended an online training about progressive muscle relaxation exercise and carried out parent-child interactive physical activities with their children at home. Both interventions were carried out every other day during a two-month intervention period, with each manipulation for at least 20 min. Feasibility outcomes included recruitment rate, consent rate, participants' adherence, retention rate, and adverse event. Outcomes were assessed at baseline, week 4, and week 8. The primary outcome measure was the Swanson, Nolan, and Pelham parent scale (SNAP); the secondary outcomes included preschool anxiety scale, children's sleep habits questionnaire, and parental stress scale. A mixed-method process evaluation embedded within the outcome evaluation was performed.The recruitment rate was 12.8 per month. The consent rate was 98.5%. Good adherence was shown from the parent logbook. Four participants withdraw from the study. No severe adverse event was reported. For the SNAP total score, both groups showed improvement with moderate within-group effect size (Cohen's d0.5, all p0.001) and the between-group effect size was minimal (dThe study design and the parent-administered pediatric tuina intervention were feasible. Parent-administered pediatric tuina provided beneficial effects on improving core hyperactivity/impulsivity symptoms in preschool children. Parents perceived improvements on children's appetite and sleep quality. Further large-scale are warranted.

In the present study, the previously obtained macromolecuar-weight Astragalus polysaccharide (average molecular weight of 1.61 × 10

The aim of this study was to investigate laparoscopic sleeve gastrectomy (LSG)-induced changes in connectivity between regions involved with reward/antireward and cognitive control and the extent to which these changes persist after surgery and predict sustainable weight loss.Whole-brain local functional connectivity density (lFCD) was studied in 25 participants with obesity who underwent resting-state functional MRI before (PreLSG), 1 month after (PostLSGLSG significantly increased lFCD in the mediodorsal thalamic nucleus (MD) and in the habenula (Hb) at PostLSGThe findings highlight the importance of reward and interoceptive regions as well as that of regions mediating negative emotions in the long-term therapeutic benefits of LSG.

IntroductionAs the most common complication of diabetes mellitus (DM), diabetic nephropathy (DN) was initially considered to begin with proteinuria preceding the progression of renal insufficiency. This clinical paradigm has been questioned in the late decades, as many DM patients without proteinuria have progressive renal insufficiency. However, the characteristics of nonproteinuric DN were not fully clear yet.Patients and MethodsA total of 390 patients with renal biopsy-proven DN in our center were retrospectively recruited in the current study. Clinical and histopathological data of the patients were analyzed. We used propensity score-matching methods to address the imbalance of age, sex, and diabetes duration for comparative analyses.ResultsAmong all the renal biopsy-proven DN patients with renal biopsy proven DN, 18 patients were classified as nonproteinuric DN. Compared with 36 propensity score-matched proteinuric DN patients, diabetic retinopathy (DR) was less frequent in nonproteinuric DN patients (38.9% vs. 66.4%, pConclusionsCompared with proteinuric DN patients, DR was less frequent in nonproteinuric DN patients. Nonproteinuric DN patients had better renal outcomes than proteinuric DN patients.

The advent of three-dimensional echocardiography (3DE) enables detailed evaluation of the tricuspid valve (TV) apparatus; nonetheless, the clinical value of preoperative 3DE is unknown in patients undergoing tricuspid annuloplasty (TA). The aim of this study was to evaluate the prognostic value of TV geometric parameters and leaflet coaptation status evaluated by 3DE in patients undergoing TA.A total of 122 patients who underwent TA during left-sided heart valve surgery were prospectively evaluated. Detailed 3DE was performed before surgery. Adverse outcome was defined as the occurrence of heart failure requiring hospital admission or all-cause mortality following TA.A total of 33 adverse events (17 heart failures and 16 deaths) occurred during a median follow-up of 36 months. Tethering volume (hazard ratio = 1.32; 95% CI = 1.05-1.66; P = .01) and ratio of total leaflet length to closure length (hazard ratio = 1.07; 95% CI = 1.03-1.12; P .01) were associated with adverse events after adjustment for age, sex, and tricuspid regurgitation vena contracta width. Receiver-operator characteristic curve analysis revealed that tethering volume (area under curve = 0.73) and ratio of total leaflet length to closure length (area under curve = 0.75) were most associated with adverse events at 1-year follow-up. The presence of either a large tethering volume or a low ratio of total leaflet length to closure length was predictive of an adverse outcome 1 year following TA.Our study suggests that 3DE-derived TV tethering volume and ratio of total leaflet length to closure length are important preoperative measures associated with adverse events in patients undergoing TA.

PURPOSE The purpose of this study was to assess the diagnostic and prognostic value of serum progastrin-releasing peptide (ProGRP) in patients with gastric cancer (GC). MATERIALS AND METHODS A total of 150 patients with GC (89 males and 61 females) were recruited, including those with stage I (n=28), stage II (n=33), stage III (n=50), and stage IV (n=39) disease; 50 healthy controls and 66 patients with benign gastric diseases were also enrolled. Levels of serum ProGRP, carcinoembryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) were measured in all subjects. RESULTS Serum ProGRP levels were significantly higher in GC patients than in controls (p

BACKGROUND The aim of this study was to identify the nosocomial infection (NI) risk factors in neonatal Intensive Care Units (NICU). MATERIAL AND METHODS Databases (PubMed, Embase, Cochrane, VANFUN, CNKI, and VTTMS) were searched using index words to find relevant studies published before November 2018. Meta-analyses of relative risk (RR) were performed for the identification of risk factors. RESULTS Data from 22 cohort studies (2270 infants with and 21 605 infants without NI) were included in the meta-analysis. Infant weight of

Selenium compounds have been widely investigated as novel anticancer agents due to high efficacy and selectivity against cancer cells in recent years. This study aimed to research the potential inhibitory effects of seleno-β-lactoglobulin (Se-β-Lg) on HepG2 cells in vitro. MTT results demonstrated that the synthetized Se-β-Lg exhibited strong antitumor activity on HepG2 cells with few side effects on human normal cells (LO2) and relatively weaker cytotoxic effects compared to inorganic selenium (SeO2). Scanning electron microscope (SEM), hoechst 33342/PI double staining, annexin V-FITC/PI staining and cell cycle detection results showed that Se-β-Lg could induce the apoptosis of HepG2 cells via arresting them in S and G2/M phases and lead to the obvious morphological changes (loss of adhesion, cell shrinkage, and membrane blebbing, membrane permeabilities and DNA fragmentation). Besides, JC-1 staining, western blotting (WB) and polymerase chain reaction (PCR) results showed that Se-β-Lg could gradually destroy the mitochondrial membrane potential of HepG2 cells, and finally resulting in the mitochondria-dependant apoptosis via up-regulation of Bax, Cytochrome c, Caspase-3 and down-regulation of Bcl-2. Our data could provide a theoretical basis for practical application of Se-β-Lg in food and drug industries.