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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.

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.

It has been demonstrated that the propagation of information and awareness regarding a disease can assist in containing the outbreak of epidemics. Previous models for this coevolving usually introduced the dependence between these two processes by setting a lower but time-independent infection rate for individuals with awareness. However, a realistic scenario can be more complicated, as individual vigilance and the adopted protective measures may depend on the extent of the discussion on the disease, whereas individuals may be irrational or lack relevant knowledge, leading to improper measures being taken. These can introduce a time-varying dependence between epidemic dynamics and awareness prevalence and may weaken the effect of spreading awareness in containing a pandemic. To better understand this effect, we introduce a nonlinear dependence of the epidemic infection rate on awareness prevalence, focusing on the effect of different forms of dependence on the coevolving dynamics. We demonstrate that a positive correlation between vigilance and awareness prevalence can enhance the effect of information spreading in suppressing epidemics. However, this enhancement can be weakened if some individuals are irrational. Our results demonstrate the importance of rational behavior in the strategy of containing epidemics by propagation of disease information.

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.

Background: The role of minute ventilation/carbon dioxide production (VE/VCO2) slope, a ventilation efficiency marker, in predicting short-term and long-term health outcomes for patients with nonsmall-cell lung cancer (NSCLC) undergoing lung resection has not been well investigated. Material and Methods: This prospective cohort study consecutively enrolled NSCLC patients who underwent a presurgical cardiopulmonary exercise test from November 2014 to December 2019. The association of VE/VCO2 slopewith relapse-free survival (RFS), overall survival (OS), and perioperative mortality was evaluated using the Cox proportional hazards and logistic models. Covariates were adjusted using propensity score overlap weighting. The optimal cut-off point of the VE/VCO2 slope was estimated using the receiver operating characteristics curve. Internal validation was completed through bootstrap resampling. Results: A cohort of 895 patients [median age (interquartile range), 59 (13) years; 62.5% male] was followed for a median of 40 (range, 1-85) months. Throughout the study, there were 247 relapses or deaths and 156 perioperative complications. The incidence rates per 1000 person-years for relapses or deaths were 108.8 and 79.6 among patients with high and low VE/VCO2 slopes, respectively [weighted incidence rate difference per 1000 person-years, 29.21 (95% CI, 7.30-51.12)]. A VE/VCO2 slope of greater than or equal to 31 was associated with shorter RFS [hazard ratio for relapse or death, 1.38 (95% CI, 1.02-1.88), P= 0.04] and poorer OS [hazard ratio for death, 1.69 (1.15-2.48), P=0.02] compared to a lower VE/VCO2 slope. A high VE/VCO2 slope increased the risk of perioperative morbidity compared with a low VE/VCO2 slope [odds ratio, 2.32 (1.54-3.49), P< 0.001]. Conclusions: In patients with operable NSCLC, a high VE/VCO2 slope was significantly associated with elevated risks of poorer RFS, OS, and perioperative morbidity. [ABSTRACT FROM AUTHOR]

Huangqin decoction (HQD), a traditional Chinese medicine (TCM), has been widely used to treat gastrointestinal syndrome in China for thousands of years. Chemotherapy drug irinotecan (CPT-11) is used clinically to treat various kinds of cancers but limited by its side effects, especially delayed diarrhea. Nowadays, HQD has been proved to be effective in attenuating the intestinal toxicity induced by CPT-11. HQD consists of four medicinal herbs including Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. Due to its complexity, the role of each herb and the multi-herb synergistic effects of the formula are poorly understood. In order to quantitatively assess the compatibility effects of HQD, mass spectrometry-based untargeted metabolomics studies were performed. The serum metabolic profiles of rats administered with HQD, single S. baicalensis decoction, S. baicalensis-free decoction and baicalin/baicalein combination were compared. A time-dependent trajectory upon principal component analysis was firstly used to visualize the overall differences. Then metabolites deregulation score and relative area under the curve were calculated and used as parameters to quantitatively evaluate the compatibility effects of HQD from the aspect of global metabolic profile and the specifically altered metabolites, respectively. The collective results indicated that S. baicalensis played a crucial role in the therapeutic effect of HQD on irinotecan-induced diarrhea. Both HQD and SS decoction regulated glycine, serine and threonine pathway. This study demonstrated that metabolomics was a promising tool to elucidate the compatibility effects of TCM or combinatorial drugs.

Loop closure detection is a crucial part of VSLAM. However, the traditional loop closure detection algorithms are difficult to adapt to complex and changeable scenes. In this paper, we fuse Gist features, semantic features and appearance features of the image to detect the loop closures quickly and accurately. Firstly, we take advantage of the fast extraction speed of the Gist feature by using it to screen the loop closure candidate frames. Then, the current frame and the candidate frame are semantically segmented to obtain the mask blocks of various types of objects, and the semantic nodes are constructed to calculate the semantic similarity between them. Next, the appearance similarity between the images is calculated according to the shape of the mask blocks. Finally, based on Gist similarity, semantic similarity and appearance similarity, the image similarity calculation model can be built as the basis for loop closure detection. Experiments are carried out on both public and self-filmed datasets. The results show that our proposed algorithm can detect the loop closure in the scene quickly and accurately when the illumination, viewpoint and object change. [ABSTRACT FROM AUTHOR]

We focus on the propagation properties of a single-cycle laser pulse through a two-level medium by numerically solving the full-wave Maxwell–Bloch equations. The counter-rotating terms in the spontaneous emission damping are included such that the equations of motion are slightly different from the conventional Bloch equations. The counter-rotating terms can considerably suppress the broadening of the pulse envelope and the decrease of the group velocity rooted from dispersion. Furthermore, for incident single-cycle pulses with envelope area 4 π , the time delay of the generated soliton pulse from the main pulse depends crucially on the carrier-envelope phase of the incident pulse. This can be utilized to determine the carrier-envelope phase of the single-cycle laser pulse.

Objective: To estimate association between androgen receptor (AR) gene polymorphisms and testicular germ cell tumor (TGCT) susceptibility.Materials and Methods: Systematic search of studies on the association between AR gene polymorphisms and TGCT susceptibility was conducted. Odds ratios and 95% confidence intervals were used to pool effect size.Results: For CAG repeat, no evidence was found for association between (>25 vs. ≤25), (>25 vs. 21-25), (<21 vs. 21-25), (others vs. 21-25), (>23 vs. ≤23), (<21 vs. ≥21), (<21 vs. ≥21)'s some subgroups and TGCT susceptibility, which showed stability. In (>24 vs. ≤24), (>24 vs. 21-24), (<21 vs. 21-24), and (others vs. 21-24) and almost all of their subgroups, increased TGCT risk was found without sensitivity analysis. For GGN, no statistical change of TGCT risk was found in (<23 vs. ≥23), (<23 vs. 23), which showed stability. For single nucleotide polymorphism (SNP) rs6152 G > A, rs1204038 G > A and rs2361634 A > G, no statistical change was found without sensitivity analysis.Conclusions: GGN repeat number <23 may not be associated with TGCTs susceptibility. However, there was insufficient data to fully confirm association in GGN repeat number >23, CAG repeat number, SNP rs6152, rs1204038, and rs2361634. [ABSTRACT FROM AUTHOR]

Huangqin decoction (HQD), a traditional Chinese medicine (TCM), has been widely used to treat gastrointestinal syndrome in China for thousands of years. Chemotherapy drug irinotecan (CPT-11) is used clinically to treat various kinds of cancers but limited by its side effects, especially delayed diarrhea. Nowadays, HQD has been proved to be effective in attenuating the intestinal toxicity induced by CPT-11. HQD consists of four medicinal herbs including Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. Due to its complexity, the role of each herb and the multi-herb synergistic effects of the formula are poorly understood. In order to quantitatively assess the compatibility effects of HQD, mass spectrometry-based untargeted metabolomics studies were performed. The serum metabolic profiles of rats administered with HQD, single S. baicalensis decoction, S. baicalensis-free decoction and baicalin/baicalein combination were compared. A time-dependent trajectory upon principal component analysis was firstly used to visualize the overall differences. Then metabolites deregulation score and relative area under the curve were calculated and used as parameters to quantitatively evaluate the compatibility effects of HQD from the aspect of global metabolic profile and the specifically altered metabolites, respectively. The collective results indicated that S. baicalensis played a crucial role in the therapeutic effect of HQD on irinotecan-induced diarrhea. Both HQD and SS decoction regulated glycine, serine and threonine pathway. This study demonstrated that metabolomics was a promising tool to elucidate the compatibility effects of TCM or combinatorial drugs. [ABSTRACT FROM AUTHOR]

Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs' homeostasis. [ABSTRACT FROM AUTHOR]