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Objectives Investigate the correlation between the percentage of predicted forced expiratory volume in 1 s (FEV1%pred) and survival outcomes, namely relapse-free survival (RFS) and overall survival (OS), in patients diagnosed with operable early-stage non-small cell lung cancer (NSCLC).Design Prospective observational study.Setting Clinical settings in Xiangya Hospital, Central South University, Hunan, China.Participants From November 2014 to December 2019, 775 operable patients with NSCLC, median age 58 years (IQR 13) with 40.6% women, were consecutively enrolled and underwent preoperative FEV1 assessment. All participants were evaluated using the FEV1%pred assessment. Subsequent treatments and operative interventions followed established protocols for NSCLC.Results During the follow-up, which lasted a median of 40 months (range 1–85 months) and continued until December 2021, 202 patients either relapsed or died. Optimal FEV1%pred cut-off was identified using receiver operating characteristic analysis. Results revealed 110 and 71 relapses and deaths per 1000 person-years for patients with FEV1 values of

AbstractIntroduction This study aimed to investigate the association between cardiorespiratory fitness (CRF) and perioperative morbidity and long-term mortality in operable patients with early-stage non-small cell lung cancer (NSCLC).Patients and Methods This prospective study included consecutive patients with early-stage NSCLC who underwent presurgical cardiopulmonary exercise testing between November 2014 and December 2019 (registration number: ChiCTR2100048120). Logistic and Cox proportional hazards regression were applied to evaluate the correlation between CRF and perioperative complications and long-term mortality, respectively. Propensity score overlap weighting was used to adjust for the covariates. We performed sensitivity analyses to determine the stability of our results.Results A total of 895 patients were followed for a median of 40 months [interquartile range 25]. The median age of the patients was 59 years [range 26–83], and 62.5% were male. During the study period, 156 perioperative complications and 146 deaths were observed. Low CRF was associated with a higher risk of death (62.9 versus 33.6 per 1000 person-years; weighted incidence rate difference, 29.34 [95% CI, 0.32 to 58.36] per 1000 person-years) and perioperative morbidity (241.6 versus 141.9 per 1000 surgeries; weighted incidence rate difference, 99.72 [95% CI, 34.75 to 164.70] per 1000 surgeries). A CRF of ≤ 20 ml/kg/min was significantly associated with a high risk of long-term mortality (weighted hazard ratio, 1.98 [95% CI, 1.31 to 2.98], p

IntroductionThis study aimed to explore whether aerobic exercise (AE) can prevent fatal stress-induced myocardial injury.MethodsThirty C57BL/6J mice were divided into either a normal diet, high-fat diet, or high-fat diet plus AE (n=10 per group). The AE protocol consisted of eight weeks of swimming. At the end of the diet and AE interventions, the mice were stimulated with fatal stress caused by exhaustive exercise (forced weight-loaded swimming until exhaustion), after which cardiac function was evaluated using echocardiography, myocardial ultrastructure was examined using transmission electron microscopy, and myocardial apoptosis was assessed using western blotting and TUNEL. Mitophagy, mitochondrial biogenesis and dynamics, and activation of the macrophage migration inhibitor factor (MIF)/AMP-activated protein kinase (AMPK) pathway were evaluated using quantitative PCR and western blotting. Obesity phenotypes were assessed once per week.ResultsAE reversed high-fat diet-induced obesity as evidenced by reductions in body weight and visceral fat compared to obese mice without AE. Obesity exacerbated fatal stress-induced myocardial damage, as demonstrated by impaired left ventricular ejection fraction and myocardial structure. The apoptotic rate was also elevated upon fatal stress, and AE ameliorated this damage. Obesity suppressed mitophagy, mitochondrial fission and fusion, and mitochondrial biogenesis, and these effects were accompanied by suppression of the MIF/AMPK pathway in the myocardium of mice subjected to fatal stress. AE alleviated or reversed these effects.ConclusionThis study provides evidence that AE ameliorated fatal stress-induced myocardial injury in obese mice. The cardioprotective effect of AE in obese mice might be attributed to improved mitochondrial quality.

Aim We conducted a meta-analysis of published randomized controlled trials to compare the effectiveness and safety of eribulin versus paclitaxel for patients with breast cancer. Methods We systematically searched multiple databases including Cochrane, PubMed, Medline, and Embase. The primary outcomes analyzed were overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), and adverse events (AEs). These outcomes were evaluated using RevMan5.3 software. Results A total of 5 studies were included in the analysis. Compared to paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs not only extended the overall survival of patients but also improved the disease control rate (DCR) [risk ratio (RR) 0.98, (95% confidence intervals (CI): 0.70, 1.38), p = 0.92]. Hematological system diseases [RR 1.18 (95% CI: 1.07, 1.31), p = 0.002] were the most frequently observed adverse event with eribulin, while paclitaxel was more likely to cause nervous system lesion [RR 0.66 (95% CI: 0.54, 0.80), p < 0.0001]. Conclusion Compared with paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs can also prolong the PFS and OS of BC patients. Our recommendation is to use eribulin plus other chemotherapy drugs to treat advanced BC and to continuously monitor and manage the drug-related adverse events. Plain Language Summary In order to further explore the efficacy and safety of eribulin and paclitaxel in treating breast cancer, our study conducted the first meta-analysis on this topic. The objective was to compare the effectiveness of eribulin and paclitaxel and provide valuable insights for clinicians. Eribulin plus other chemotherapy drugs significantly prolonged OS or improved DCR in patients with BC, which was no statistical difference compared with paclitaxel (P＞0.05). Eribulin not only can be used as a first-line treatment for advanced breast cancer but also can be used to treat patients who are resistant to taxane, so the choice is wider. In terms of adverse drug reactions, Eribulin is easy to cause hematological system diseases, especially neutropenia, while paclitaxel is prone to cause nervous system lesions. Both of them can cause impaired digestive function and skin and hair damage. Our recommendation is to select appropriate chemotherapy drugs to treat different states of BC patients and to prevent and manage AEs after using drugs. [ABSTRACT FROM AUTHOR]

The macrophage migration inhibitory factor (MIF) expressed in hepatocytes can limit steatosis during obesity. Lipotoxicity in nonalcoholic fatty liver disease is mediated in part by the activation of the stress kinase JNK, but whether MIF modulates JNK in lipotoxicity is unknown. In this study, we investigated the role of MIF in regulating JNK activation and high-fat fostered liver lipotoxicity during simultaneous exercise treatment. Fifteen mice were equally divided into three groups: normal diet, high-fat diet, and high-fat and exercise groups. High-fat feeding for extended periods elicited evident hyperlipemia, liver steatosis, and cell apoptosis in mice, with inhibited MIF and activated downstream MAPK kinase 4 phosphorylation and JNK. These effects were then reversed following prescribed swimming exercise, indicating that the advent of exercise could prevent liver lipotoxicity induced by lipid overload and might correlate to the action of modulating MIF and its downstream JNK pathway. Similar detrimental effects of lipotoxicity were observed in in vitro HepG2 cells palmitic acid treatment. Suppressed JNK reduced the hepatocyte lipotoxicity by regulating the BCL family, and the excess JNK activation could also be attenuated through MIF supplementation or exacerbated by MIF siRNA administration. The results found suggest that exercise reduces lipotoxicity and inhibits JNK activation by modulating endogenous hepatic MIF in NAFLD. These findings have clinical implications for the prevention and intervention of patients with immoderate diet evoked NAFLD.

Abstract Background Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor. In addition to the main ATC type with classical histopathological features, the other morphological types of ATC include paucicellular variant, angiomatoid, lymphoepithelioma-like, and small-cell variant. However, an ATC variant with a chondrosarcomatous component has not been reported to date. Case presentation Computed tomography imaging of a 63-year-old male with a 2-month history of a cervical mass revealed a 4.5-cm lesion with heterogeneous enhancement in the left thyroid lobe and two smooth and homogeneous nodules in the right thyroid lobe. The patient underwent total thyroidectomy and cervical lymph node resection. Histologically, the tumor boundary in the left lobe was clear, with a few mitotically active, spindle sarcoma-like tumor cells observed in some areas. Immunohistochemically, these spindle cells were positive for vimentin and negative for cytokeratin, paired box-8, epithelial membrane antigen, calcitonin, thyroglobulin, and thyroid transcription factor-1. In other areas, abundant cartilage matrix production and irregularly shaped lobules of cartilage, often separated by fibrous bands, were observed. The chondrocytes appeared mildly/moderately atypical and contained enlarged, hyperchromatic nucleoli. One of the two nodules in the right thyroid lobe had a clear boundary and comprised some bland spindle cells in a prominently collagenous stroma with clear boundaries. The other nodule in the right thyroid lobe was completely enclosed within a thin, fibrous capsule and exhibited normofollicular and microfollicular architecture. The patient received adjuvant radiotherapy after the surgery and was free of any local or regional recurrence or distant metastases at the 8-month follow-up evaluation. Conclusions This unusual case of ATC with chondrosarcomatous differentiation is an important addition to the morphology spectrum of ATC types.

Objectives: This meta-analysis aims to investigate the diagnostic value of exercise stress testing (EST) for asymptomatic coronary artery disease (CAD) among patients with type 2 diabetes mellitus (T2DM) and to ascertain the influence of different variables on the sensitivity and specificity of EST.Background: Asymptomatic CAD occurs in >1 in five diabetes mellitus patients, and it is associated with an increased risk of complications. Methods for screening asymptomatic CAD in T2DM patients are still not unified.Methods: MEDLINE (via Ovid), Embase (via Ovid), Cochrane Library, SCOPUS, PubMed, Ovid, EBSCO ASP, and Web of Science were systematically searched on June 8 and 9, 2021, for diagnostic cohort and case-control studies. We included studies that used EST to screen for CAD in asymptomatic patients with T2DM, and that used coronary angiography to diagnose CAD and had reported the basic diagnostic indicators. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess study quality. The combined effect sizes were calculated by overall analysis and multiple variable effects were explored by regression analysis and subgroup analysis.Results: Nine groups of data from eight diagnostic cohort studies, totaling 515 participants, were included. Included studies showed a low risk of bias in most items, except for flow and timing. The combined sensitivity and specificity of EST for asymptomatic CAD in patients with T2DM were 55 (48 to 61%) and 66 (61 to 70%), respectively. When non-diagnostic tests were excluded, sensitivity increased to 73 (56 to 88%). The proportion receiving angiography also significantly affected sensitivity. No significant difference was found in the duration of diabetes or other additional risk factors.Conclusions: EST is a tool of moderate sensitivity and specificity to be used for the initial screening of asymptomatic CAD in T2DM. It has the advantage of being non-invasive, relatively inexpensive, easily available in most settings, and has no radiation associated with its use. Additional research with higher quality studies in which tests that are non-diagnostic are included and flow and timing is described clearly, will be important to further our understanding of EST for asymptomatic CAD detection in patients with T2DM.Systematic review registration: PROSPERO CRD42021259555.

Thyroid-like follicular renal cell carcinoma is a rare subtype of renal cell carcinoma that has only been recently recognized, as most cases involve a solid tumor in one kidney. In this study, we report a rare case of bilateral renal cell carcinoma wherein the tumor in the left kidney was diagnosed as clear cell carcinoma, while the tumor in right kidney as thyroid-like follicular renal cell carcinoma. The difference between this case and the ones described in previous reports is that thyroid-like follicular renal cell carcinoma showed cystic changes on imaging. This suggests that when renal cystic lesions are encountered, we should consider the possibility of such rare tumors.

The quality control research of traditional Chinese medicine (TCM) is lagged far behind the space of progress in modernization and globalization. Thus the concept of quality marker (Q-marker) was proposed recently to guide the quality investigations of TCM. However, how to discover and validate the Q-marker is still a challenge. In this paper, a system pharmacology based strategy was proposed to discover Q-marker of HuangQin decoction (HQD) to attenuate Intestinal Damage. Using this strategy, nine measurable compounds including paeoniflorin, baicalin, scutellarein, liquiritigenin, norwogonin, baicalein, glycyrrhizic acid, wogonin, and oroxylin A were screened out as potential markers. Standard references of these nine compounds were pooled together as components combination according to their corresponding concentration in HQD. The bioactive equivalence between components combination and HQD was validated using wound healing test and inflammatory factor determination experiment. The comprehensive results indicated that components combination is almost bioactive equivalent to HQD and could serve as the Q-markers. In conclusion, our study put forward a promising strategy for Q-markers discovery.