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Guojun Zhang,1 Chuan Yang,2 Caixia Zhao,1 Feng Xian,3 Dong Qing,1 Qiyu Guo,1 Junmei Song,1 Xilin Liu,1 Jun Bie1 1Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Oncology, Guangyuan Central Hospital, Guangyuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Jun Bie, Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Hongguang Road, Shunqing District, Nanchong, People’s Republic of China, Email 78593860@qq.comBackground: The neutrophil-to-lymphocyte ratio (NLR) has been shown to have prognostic value in several common cancers. This study aimed to investigate the prognostic value of NLR in patients with advanced oesophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT).Methods: A retrospective analysis was performed on 158 patients with advanced ESCC who received dCRT from January 2012 to December 2018. The NLR for different treatment stages was calculated based on laboratory test results. The Kaplan–Meier (KM) method and Cox proportional regression model were used to analyse the relationship between NLR and overall survival (OS).Results: The mean NLR of 158 patients with ESCC was 3.403 ± 2.479. The pre-treatment NLR cut-off was 4.839, and patients were divided into the low NLR group (NLR < 4.839) and the high NLR group (NLR ≥ 4.839). NLR in patients with ESCC was related to N stage (P < 0.05). The KM analysis showed that the median OS of all enrolled patients was 29.3 months, the median OS periods of patients in the high and low NLR groups were 15.6 and 35.8 months, respectively, and the OS of the low NLR group was better than that of the high NLR group (P < 0.001). In the multivariate analysis, NLR was an independent prognostic factor that affects the prognosis of patients with ESCC receiving dCRT. Furthermore, patients who maintained a high NLR before and after treatment showed worse clinical outcomes than the other groups.Conclusion: Our findings suggest that NLR can effectively assess the prognosis of patients with advanced ESCC undergoing dCRT.Graphical Abstract: Keywords: oesophageal squamous cell carcinoma, radiochemotherapy, neutrophil-to-lymphocyte ratio

OBJECTIVE: Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1 inhibitor combined with transcatheter arterial chemoembolization (TACE), has been widely used in the treatment of HCC. However, there remains a contentious debate regarding the clinical value of the TACE and camrelizumab combination. This study seeks to investigate the efficacy and safety of this combination treatment regimen in patients with HCC. MATERIALS AND METHODS: The related studies were retrieved from four online databases, including PubMed, Cochrane Library, EMBASE, and Web of Science, up to June 1, 2023. The selection of studies was based on screening of titles, abstracts, and full-texts. The primary efficacy outcomes included complete response (CR), objective response rate (ORR), and disease control rate (DCR), while safety outcomes evaluated all treatment-related adverse events (AEs). Additionally, secondary outcomes such as overall (OS) and progression-free survival (PFS) were extracted for further survival analysis. The quality of the included trials was assessed using the MINORS tool. Publication bias was evaluated through funnel plot and Egger"s test. RESULTS: A total of 17 publications involving 1,377 cases were included. The pooled CR rate, ORR, and DCR of the patients treated with TACE plus camrelizumab had a pooled CR rate of 8% (95% CI: 0.01-0.15, p=0.03), ORR of 47% (95% CI: 0.42-0.52, p<0.00001) and DCR of 82% (95% CI: 0.77-0.88, p<0.00001), respectively. Compared with a control group that did not receive TACE or camrelizumab, the pooled RR of CR rate, ORR, and DCR were 1.61 (95% CI: 1.27-2.04, p<0.0001), 1.56 (95% CI: 1.19-2.05, p=0.001) and 1.55 (95% CI: 1.19-2.03, p=0.001), respectively. Besides, the combination regimen can prolong the OS (HR=2.60, 95% CI: 2.25-3.02, p<0.00001) and PFS (HR=4.90, 95% CI: 1.94-12.38, p=0.0008). However, the incidence of treatment-related AEs was relatively high (77%), with 29% for grade 3 AEs. The most common AEs observed were pain (47%), fever (46%), hepatic function abnormalities (44%), hypoalbuminemia (39%), and hypertension (37%). The combination treatment did not increase the incidence of AEs compared to the control group, except for the hand-foot skin reaction (RR=0.85, 0.74-0.97, p=0.01), hepatic encephalopathy (RR=4.29, 2.51-7.35, p<0.00001) and nausea (RR=1.35, 1.13-1.61, p=0.001). CONCLUSIONS: Combination therapy of TACE plus camrelizumab has shown notable clinical benefits, improved survival, and a manageable safety profile in patients with HCC, but it is essential to monitor and manage the specific toxicities, especially for the camrelizumab-related AEs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The triplet regimen based on the programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a novel therapeutic strategy for hepatocellular carcinoma. We conducted a meta-analysis to evaluate the efficacy and safety of the triplet therapeutic regimen in the treatment of hepatocellular carcinoma. MATERIALS AND METHODS: We searched scientific literature databases and clinical trial databases through October 31, 2022, for required studies. The pooled hazard ratio (HR) was used to analyze the of overall survival (OS), progression-free survival (PFS), and the pooled relative risk (RR) was used to analyze the of objective response rate (ORR), disease control rate (DCR), mortality rate (MR), and adverse events (AEs) through random or fixed effects model, 95% confidence interval (CI) was determined for all outcomes. Qualities of the included literature were assessed by MINORS Critical appraisal checklist. Funnel plot was used to assess publication bias in the included studies. RESULTS: Five studies (3 single-arm and 2 non-randomized comparative trials), including 358 cases were enrolled. Meta-analysis showed that the pooled ORR, DCR, and MR were 51% (95% CI: 34%-68%), 86% (95% CI: 69-102%), and 38% (95% CI: 18-59%), respectively. Compared with triplet regimen, the single or dual-combination treatments had shorter OS (HR=0.53, 95%: 0.34-0.83 via univariate analysis; HR=0.49, 95%: 0.31-0.78 via multivariable analysis) and PFS (HR=0.52, 95%: 0.35-0.77 via univariate analysis; HR=0.54, 95%: 0.36-0.80 via multivariable analysis). Common AEs to triplet regimens included skin reaction (17%), nausea/vomiting (27%), fatigue (23%), while severe AEs (10%), fever (18%), diarrhea (15%), and hypertension (5%) without statistically significant differences. CONCLUSIONS: In the treatment of hepatocellular carcinoma, PD1/PDL1 inhibitors combined radiotherapy and antiangiogenic drugs achieved better survival benefits than alone or dual-combination regimens. In addition, the triple-combination therapy has tolerable safety. [ABSTRACT FROM AUTHOR]

Trials to improve oocyte developmental competence under metabolic stress by using antioxidants may start before or after oocyte maturation. In the present conceptual study, we aimed to identify the most efficient timing of antioxidant application in relation to a metabolic insult using a bovine in vitro embryo production model. Pathophysiological concentrations of palmitic acid (PA) were used to induce metabolic stress during oocyte maturation or embryo development. Trolox (TR; antioxidant) treatment prior to, during or after the PA insult was tested to evaluate the protective, neutralising and rescuing capacity of TR respectively. Changes in embryo developmental competence, mitochondrial activity, reactive oxygen species (ROS) concentrations, blastocyst cell allocation and apoptosis and cell stress-related gene expression were monitored. The improvement in developmental capacity was most obvious when oocytes were preloaded with TR before the PA insult. This protective effect could be explained by the observed combination of increased mitochondrial activity with reduced ROS production. This resulted in blastocysts with normal cell counts and apoptosis, as well as increased nuclear factor erythroid 2-related factor 2 (NRF2) expression (a marker for redox regulatory processes) and normalised the expression of the mitochondrial transcription factor A (TFAM), a marker of mitochondrial biogenesis. These results indicate that 'pretreatment' of oocytes with antioxidants produces embryos that seem to be more resilient to a metabolic stress insult. Suboptimal nutrition and metabolic health can increase oxidative stress in oocytes and embryos, thereby affecting fertility. The strategic use of antioxidants protects oocytes against metabolic stress insults during embryo development. These findings highlight the importance of the timing of antioxidant treatment with the aim of protecting and safeguarding oocyte and embryo quality, and improving fertility. [ABSTRACT FROM AUTHOR]

Abstract Background Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. As a transboundary animal disease, the prevention and control of FMD are important. This study was based on spatial multi-criteria decision analysis (MCDA) to assess FMD risk areas in mainland China. Ten risk factors were identified for constructing risk maps by scoring, and the analytic hierarchy process (AHP) was used to calculate the criteria weights of all factors. Different risk factors had different units and attributes, and fuzzy membership was used to standardize the risk factors. The weighted linear combination (WLC) and one-at-a-time (OAT) were used to obtain risk and uncertainty maps as well as to perform sensitivity analysis. Results Four major risk areas were identified in mainland China, including western (parts of Xinjiang and Tibet), southern (parts of Yunnan, Guizhou, Guangxi, Sichuan and Guangdong), northern (parts of Gansu, Ningxia and Inner Mongolia), and eastern (parts of Hebei, Henan, Anhui, Jiangsu and Shandong). Spring is the main season for FMD outbreaks. Risk areas were associated with the distance to previous outbreak points, grazing areas and cattle density. Receiver operating characteristic (ROC) analysis indicated that the risk map had good predictive power (AUC=0.8634). Conclusions These results can be used to delineate FMD risk areas in mainland China, and veterinary services can adopt the targeted preventive measures and control strategies.

OBJECTIVE: Myeloma severely threatens public health, and molecular targeting treatment becomes the future perspective. Dual specificity phosphatases (DSUP) protein has multiple functions including modulating cell proliferation, differentiation, aging, and apoptosis. Whether DUSP can regulate myeloma cell is unclear. This study thus aimed to investigate the effect of DUSP on myeloma cell line RPMI8226 cell aging and provide evidence for the clinical treatment of myeloma. MATERIALS AND METHODS: H2O2-induced aging model of myeloma cell line RPMI8226 was generated. DUSP over-expression plasmid or specific siRNA was transfected by liposome. Western blot was used to detect the expression of DUSP in RPMI8226 cells. Cell aging condition was evaluated by β-galactosidase assay. Aging proteins P53 and P16 expression levels, the activation of TLR4 signal pathway were tested by immunoblotting. TLR4 signal pathway was then suppressed by Vertepor- fin for testing RPMI8226 cell aging. RESULTS: Growing levels of DUSP, aging proteins P53 and P16, with inhibition of TLR4 signal pathway were found in the H2O2-induced aging model of myeloma cell line RPMI8226. Transfection of DUSP over-expression plasmid or siRNA potentiated or inhibited the aging of RPMI8226 cells induced by H2O2 and suppressed or enhanced TLR4 signal pathway, respectively. Verteporfin, an inhibitor of TLR4, increased the level of P53 and aging of RPMI8226 cells. CONCLUSIONS: DUSP facilitates H2O2-induced aging of myeloma cell line RPMI8226 and suppresses TLR4 expression, which provides academic basis for clinical intervention. [ABSTRACT FROM AUTHOR]

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia. [ABSTRACT FROM AUTHOR]

Jihadist networks have become a serious threat to Europe' s internal security and are therefore a policy priority. But what do we know about these networks and how should we counter them? This study focuses on the modus operandi of jihadist networks between 2000 and 2013 and gives an empirical insight in the organizational structures, activities, and involvement mechanisms of jihadist networks in the Netherlands. The data are derived from 28 police investigations, 51 interviews with police investigators, public prosecutors, lawyers, imams, and staff members from Asylum and Detention Centers. The findings show how jihadist networks have changed over the years and how this development has affected the way jihadists operate. [ABSTRACT FROM AUTHOR]

We assessed the diagnostic performance of both ultra-high-resolution (UHR) and high-resolution (HR) modes of photon-counting detector (PCD)-CT within the confines of standard pre-TAVI CT scans, as well as the performance of UHR mode adjusted specifically for coronary imaging, using quantitative coronary angiography (QCA) as the reference. We included 60 patients undergoing pre-TAVI planning CT scans. Patients were divided into 3 groups: 20 scanned in HR mode, 20 in UHR mode, and 20 in adjusted UHR mode, on a dual-source PCD-CT. The adjusted UHR mode employed a lower tube voltage (90 kV vs. 120 kV) and a higher image quality level (65 vs. 34) to enhance coronary artery visualization. Patients underwent invasive coronary angiography as part of clinical routine. CCTA and QCA were reviewed to assess CAD presence defined as stenosis ≥ 50% in proximal and middle coronary segments. We included 60 patients (mean age 79 ± 7 years; 39(65%) men). Mean heart rate during scanning was 72 ± 13 bpm. Median coronary calcium score was 973 [379-2007]. QCA identified significant CAD in 24 patients (40%): 9 patients scanned with HR mode, 10 patients with the UHR mode, and 5 patients with the UHR adjusted mode. Per-patient area under the curves were 0.57 for HR, 0.80 for UHR, and 0.80 for adjusted UHR, with no significant differences between the scan modes, and per-vessel the area under the curves were 0.73 for HR, 0.69 for UHR, and 0.87 for adjusted UHR, with significant differences between UHR and adjusted UHR (p = 0.04). UHR and adjusted UHR modes of dual source PCD-CT show potential for improved sensitivity and negative predictive value for detecting CAD in patients undergoing pre-TAVI scans, however, no statistically significant difference from HR mode was observed., (© 2024. The Author(s).)