Association between triglyceride-glucose related indices and mortality among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). RESULTS: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Carbon Nanofiber-Based Sandwich Free-Standing Cathode for High-Performance Lithium-Sulfur Batteries.

Challenges including rapid capacity degradation and reduced Coulombic efficiency due to the shuttle effect have hindered the commercial viability of lithium-sulfur (Li-S) batteries. A novel sandwich-structured electrode with an optimized electrode structure and current collector interface design was presented as a free-standing positive electrode for Li-S batteries. Fabricated via a simple slurry coating process, the electrode embedded multiwalled carbon nanotubes within carbon nanofiber composite films (PCNF/T). Owing to the superior conductivity and reduced weight in comparison to both carbon nanofibers (PCNF) and the conventional aluminum foil current collector (Al), the PCNF/T electrode exhibited diminished polarization and accelerated redox reaction kinetics. Thus, it delivers an initial discharge capacity of 990.23 mA h g-1 at 0.5 C. Even after 400 cycles, while retains a reversible capacity of 707.45 mA h g-1, corresponding to a minimal capacity degradation rate of merely 0.07% per cycle. Notably, the electrode exhibits a capacity retention of 619.81 mA h g-1 after 400 cycles at 1 C, with a capacity decay rate of only 0.08% per cycle. This study presents an innovative approach to developing a new free-standing cathode for high-performance Li-S batteries.

Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and meta-analysis of efficacy and safety outcomes.

Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Clinical significance of dynamic variation of low cholesterol and its prognostic value in patients with pyogenic liver abscesses: a retrospective study.

BACKGROUND: Serum lipids variations are closely related to the sepsis progression; however, their value for patients with pyogenic liver abscesses (PLA) has rarely been studied. We investigated the serum lipid level variations in patients with PLA and its predictive value to the disease. METHODS: The study included 328 patients with PLA hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021; 35 (10.67%) in the severe group (SG) and 293 (89.33%) in the non-severe group (nSG). Their clinical records were analyzed retrospectively, and dynamic curves were drawn to clarify the changes in different indicators during the course of the disease. RESULTS: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) in the SG were significantly lower than those in nSG (P < 0.001). Total cholesterol (TC) at baseline (OR = 0.184, P < 0.001) was an independent risk factor for severe patients and had the highest predictive value, with an area under the curve of 0.859 and a cut-off value of 2.70 mmol/L (sensitivity = 94.3%, specificity = 63.5%). For patients who met the criteria for drainage surgery, TC, HDL-C and LDL-C levels continued to decrease with antibiotic therapy alone before drainage and began to increase after the surgery. CONCLUSIONS: Low TC level on admission is an independent risk factor for the progression of severe illness in PLA patients, with the highest predictive value surpassing other routine clinical indices. Abscess drainage should be performed as soon as possible for patients whose TC continues to decline after medical treatment.

The Spliceosome Factor EFTUD2 Promotes IFN Anti-HBV Effect through mRNA Splicing.

Methods: Using a CRISPR/Cas9 gene-editing system, EFTUD2 single allele knockout HepG2.2.15 cells were constructed. Subsequently, the HBV biomarkers in EFTUD2+/- HepG2.2.15 cells and wild-type (WT) cells with or without IFN-α treatment were detected. And the EFTUD2-regulated genes were then identified using mRNA sequence. Selected gene mRNA variants and their proteins were examined by qRT-PCR and Western blotting. To confirm the effects of EFTUD2 on HBV replication and IFN-stimulated gene (ISG) expression, a rescue experiment in EFTUD2+/- HepG2.2.15 cells was performed by EFTUD2 overexpression. Results: IFN-induced anti-HBV activity was found to be restricted in EFTUD2+/- HepG2.2.15 cells. The mRNA sequence showed that EFTUD2 could regulate classical IFN and virus response genes. Mechanistically, EFTUD2 single allele knockout decreased the expression of ISG-encoded proteins, comprising Mx1, OAS1, and PKR (EIF2AK2), through mediated gene splicing. However, EFTUD2 did not affect the expression of Jak-STAT pathway genes. Furthermore, EFTUD2 overexpression could restore the attenuation of IFN anti-HBV activity and the reduction of ISG resulting from EFTUD2 single allele knockout. Conclusion: EFTUD2, the spliceosome factor, is not IFN-inducible but is an IFN effector gene. EFTUD2 mediates IFN anti-HBV effect through regulation of gene splicing for certain ISGs, including Mx1, OAS1, and PKR. EFTUD2 does not affect IFN receptors or canonical signal transduction components. Therefore, it can be concluded that EFTUD2 regulates ISGs using a novel, nonclassical mechanism.

CDN1163 alleviates SERCA2 dysfunction-induced pulmonary vascular remodeling by inhibiting the phenotypic transition of pulmonary artery smooth muscle cells.

BACKGROUND AND PURPOSE: Substitution of Cys674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) causes SERCA2 dysfunction which leads to activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway accelerating cell proliferation of pulmonary artery smooth muscle cells (PASMCs) followed by significant pulmonary vascular remodeling resembling human pulmonary hypertension. Based on this knowledge, we intend to investigate other potential mechanisms involved in SERCA2 dysfunction-induced pulmonary vascular remodeling. EXPERIMENTAL APPROACH: Heterozygous SERCA2 C674S knock-in (SKI) mice of which half of cysteine in 674 was substituted by serine to mimic the partial irreversible oxidation of C674 were used. The lungs of SKI mice and their littermate wild-type mice were collected for PASMC culture, protein expression, and pulmonary vascular remodeling analysis. RESULTS: SERCA2 dysfunction increased intracellular Ca2+ levels, which activated Ca2+-dependent calcineurin (CaN) and promoted the nuclear translocation and protein expression of the nuclear factor of activated T-lymphocytes 4 (NFAT4) in an IRE1α/XBP1s pathway-independent manner. In SKI PASMCs, the scavenge of intracellular Ca2+ by BAPTA-AM or inhibition of CaN by cyclosporin A can prevent PASMC phenotypic transition. CDN1163, a SERCA2 agonist, suppressed the activation of CaN/NFAT4 and IRE1α/XBP1s pathways, reversed the protein expression of PASMC phenotypic transition markers and cell cycle-related proteins, and inhibited cell proliferation and migration when given to SKI PASMCs. Furthermore, CDN1163 ameliorated pulmonary vascular remodeling in SKI mice. CONCLUSIONS AND IMPLICATIONS: SERCA2 dysfunction promotes PASMC phenotypic transition and pulmonary vascular remodeling by multiple mechanisms, which could be improved by SERCA2 agonist CDN1163.

'What is already known' l The dysfunction of SERCA2 promotes PASMC hyperproliferation and pulmonary vascular remodeling through activation of the IRE1α/XBP1s pathway.'What this study adds' l The dysfunction of SERCA2 activates the Ca²⁺-dependent CaN-mediated NFAT4 pathway to promote the PASMC phenotypic transition.l Revitalization of SERCA2 suppresses PASMC phenotypic transition and pulmonary vascular remodeling caused by SERCA2 dysfunction.'Clinical significance' l SERCA2 dysfunction-induced pulmonary vascular remodeling involves more than one mechanism, implicating that more drugable targets are to be discovered.l SERCA2 is a potential therapeutic target for preventing pulmonary vascular remodeling.

The aluminum distribution and translocation in two citrus species differing in aluminum tolerance.

BACKGROUND: Many citrus orchards of south China suffer from soil acidification, which induces aluminum (Al) toxicity. The Al-immobilization in vivo is crucial for Al detoxification. However, the distribution and translocation of excess Al in citrus species are not well understood. RESULTS: The seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck] and 'Shatianyou' [Citrus grandis (L.) Osbeck], that differ in Al tolerance, were hydroponically treated with a nutrient solution (Control) or supplemented by 1.0 mM Al3+ (Al toxicity) for 21 days after three months of pre-culture. The Al distribution at the tissue level of citrus species followed the order: lateral roots > primary roots > leaves > stems. The concentration of Al extracted from the cell wall (CW) of lateral roots was found to be about 8 to 10 times higher than in the lateral roots under Al toxicity, suggesting that the CW was the primary Al-binding site at the subcellular level. Furthermore, the Al distribution in CW components of the lateral roots showed that pectin had the highest affinity for binding Al. The relative expression level of genes directly relevant to Al transport indicated a dominant role of Cs6g03670.1 and Cg1g021320.1 in the Al distribution of two citrus species. Compared to C. grandis, C. sinensis had a significantly higher Al concentration on the CW of lateral roots, whereas remarkably lower Al levels in the leaves and stems. Furthermore, Al translocation revealed by the absorption kinetics of the CW demonstrated that C. sinensis had a higher Al retention and stronger Al affinity on the root CW than C. grandis. According to the FTIR (Fourier transform infrared spectroscopy) analysis, the Al distribution and translocation might be affected by a modification in the structure and components of the citrus lateral root CW. CONCLUSIONS: A higher Al-retention, mainly attributable to pectin of the root CW, and a lower Al translocation efficiency from roots to shoots contributed to a higher Al tolerance of C. sinensis than C. grandis. The aluminum distribution and translocation of two citrus species differing in aluminum tolerance were associated with the transcriptional regulation of genes related to Al transport and the structural modification of root CW.

Association of Elongation Factor Tu GTP-binding Domain-containing 2 Gene (EFTUD2) Polymorphism with the Risk of Hepatitis B Virus Infection.

BACKGROUND: The elongation factor Tu GTP-binding domain-containing 2 gene (EFTUD2) participates in antiviral immune responses. However, the association between genetic polymorphisms of EFTUD2 and hepatitis B virus (HBV) infection susceptibility has not been well-studied. We analyzed the relationship between single nucleotide polymorphisms (SNPs) of EFTUD2 and HBV infection susceptibility and clarified the potential function. METHODS: In total, 448 control subjects and 379 patients with chronic HBV infection from Zhangjiagang First People's Hospital (Jiangsu, China) were enrolled. Sequenom iPLEX assay was used to detect genotypes of four SNPs (rs1071682, rs2277617, rs2289674, and rs3809756). Dual-luciferase reporter vectors with wild-type A and mutant-type C alleles of EFTUD2 rs3809756 were transfected into HepG2 cells to explore effects on transcription activity. RESULTS: Only rs3809756 was significantly associated with HBV infection susceptibility (P < .05). The risk of HBV infection was higher in individuals carrying the rs3809756-CC genotype than in those carrying the rs3809756-AA genotype (odds ratio [OR] = 1.945, 95% confidence interval [CI] = 1.129-3.351, P = .017). Subgroup analysis based on the dominant model revealed that rs3809756-AC and rs3809756-CC carriers had a significantly higher risk of HBV infection than rs3809756-AA carriers among patients who were male (OR = 1.732, 95% CI = 1.218-2.464, P = .002), were aged ≥47 years (OR = 1.502, 95% CI = 1.050-2.148, P = .026), or without liver cirrhosis (OR = 1.407, 95% CI = 1.077-1.838, P = .012). In the dual-luciferase reporter assay, the relative luciferase activity of rs3809756-C was significantly lower than that of rs3809756-A (P < .05). CONCLUSION: EFTUD2 rs3809756A>C was associated with HBV infection susceptibility and might be involved in the downregulation of promoter activity.

Identifying the spatial heterogeneity in the effects of the construction land scale on carbon emissions: Case study of the Yangtze River Economic Belt, China.

Low-carbon emissions are a major research focus to solve the problem of global warming and an important area that China needs to focus on to achieve high-quality development. Construction land scale is a non-negligible factor affecting carbon emissions. However, carbon emission impacts of county-scale spatial heterogeneity in construction land scale are under addressed in contemporary research. To address this gap, this paper took 1042 counties in China's Yangtze River Economic Belt (YREB) and developed datasets of the influencing factors including the construction land scale, GDP, secondary industry output proportion in GDP, residential population, and fixed asset investment. After comparing the ordinary least squares and geographically weighted regression (GWR) models, we applied GWR for more in-depth analyses. The global regression model results showed that the effect of the scale of construction land on carbon emissions was exceedingly significant and that the directions of the impacts coincided with the predictions. Further, local regression model results showed that construction land scale had significant spatial heterogeneity in the impact on carbon emissions and most counties (69.58%) showed significant positive correlations. The counties with significant construction land scale impacts on carbon emissions were concentrated and contiguous in spatial distribution and spatially clustered areas varied, with the clearest impact in the downstream region. The findings help to further identify the spatial heterogeneity of construction land scale impacts on carbon emissions, which provides evidence-based and theoretical support for policymakers to develop spatially differentiated emission reduction measures.

Transcutaneous Electrical Acustimulation Improved the Quality of Life in Patients With Diarrhea-Irritable Bowel Syndrome.

BACKGROUND AND AIM: Patients with diarrhea-dominant irritable bowel syndrome (IBS-D) experience abdominal pain and reduced quality of life and need effective treatments. This study aimed to evaluate whether transcutaneous electrical acustimulation (TEA) at two acupuncture points, LI4 and ST36, could improve pain and quality of life of patients with IBS-D. MATERIALS AND METHODS: A total of 42 patients with IBS-D who met the Rome IV criteria were randomly divided into two groups: TEA and sham-TEA. TEA was performed through acupoints Hegu (LI4) and Zusanli (ST36) for one hour twice daily for one month, using previously established parameters; sham-TEA was delivered in the same way as TEA but without actual electrical current stimulation. RESULTS: The sham-TEA group showed a significantly higher rate of drop-out than the TEA group (29% vs 0%, p = 0.021). TEA, but not sham-TEA, significantly improved quality of life (before: 78.55 ± 9.62, after: 85.97 ± 9.49, p < 0.0001). Both TEA and sham-TEA reduced abdominal pain; however, TEA was more potent than sham-TEA (p = 0.014). The IBS symptom severity scale score was reduced by both TEA and sham-TEA. Autonomic functions assessed by plasma norepinephrine and pancreatic polypeptide were not altered with TEA, nor was interleukin 10 or interleukin 6. CONCLUSIONS: TEA at LI4 and ST36 improves abdominal pain and quality of life of patients with IBS-D, probably mediated by mechanisms other than autonomic function or inflammatory cytokines.

Photosynthetic Characteristics and Chloroplast Ultrastructure Responses of Citrus Leaves to Copper Toxicity Induced by Bordeaux Mixture in Greenhouse.

Bordeaux mixture (Bm) is a copper (Cu)-based pesticide that has been widely used for controlling citrus scab and citrus canker. However, frequent spraying of Bm is toxic to citrus. To our knowledge, few studies are available that discuss how the photosynthetic characteristics and chloroplast ultrastructure of citrus leaves are affected by Cu toxicity induced by excessive Bm. In the study, two-year-old seedlings of Citrus grandis (C. grandis) and Citrus sinensis (C. sinensis), which were precultured in pots, were foliar-sprayed with deionized water (as control) or Bm diluted 500-fold at intervals of 7 days for 6 times (4 times as recommended by the manufacturer) to investigate the leaf Cu absorption, photosynthesis, chloroplast ultrastructure and antioxidant enzymatic activities. Bm foliar-sprayed 6 times on citrus seedlings increased the leaf Cu content, decreased the photosynthetic pigments content and destroyed the chloroplast ultrastructure, which induced leaf chlorosis and photosynthetic inhibition. A lower Cu absorption, a higher light photon-electron transfer efficiency, a relative integrity of chloroplast ultrastructure and a promoted antioxidant protection contributed to a higher photosynthetic activity of C. grandis than C. sinensis under excessive spraying of Bm. The present study provides crucial references for screening and selecting citrus species with a higher tolerance to Cu toxicity induced by excessive Bm.

The role of lyases, NblA and NblB proteins and bilin chromophore transfer in restructuring the cyanobacterial light-harvesting complex‡.

Phycobilisomes are large light-harvesting complexes attached to the stromal side of thylakoids in cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of phycobilisomes contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching (Nb) proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B which imply that the situation is more complex than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: (i) NblA and NblB can interfere with chromophorylation as well as chromophore detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction; (ii) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers; (iii) while NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; (iv) they promote synergistically the lyase-catalyzed chromophorylation of the ß-subunit of the major rod component, CPC; and (v) they modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with lyases in remodeling the phycobilisomes to balance the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.

Inactivation of cysteine 674 in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 causes retinopathy in the mouse.

Diabetic retinopathy is a multifactorial microvascular complication, and its pathogenesis hasn't been fully elucidated. The irreversible oxidation of cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) was increased in the type 1 diabetic retinal vasculature. SERCA2 C674S knock-in (SKI) mouse line that half of C674 was replaced by serine 674 (S674) was used to study the effect of C674 inactivation on retinopathy. Compared with wild type (WT) mice, SKI mice had increased number of acellular capillaries and pericyte loss similar to those in type 1 diabetic WT mice. In the retina of SKI mice, pro-apoptotic proteins and intracellular Ca2+-dependent signaling pathways increased, while anti-apoptotic proteins and vessel density decreased. In endothelial cells, C674 inactivation increased the expression of pro-apoptotic proteins, damaged mitochondria, and induced cell apoptosis. These results suggest that a possible mechanism of retinopathy induced by type 1 diabetes is the interruption of calcium homeostasis in the retina by oxidation of C674. C674 is a key to maintain retinal health. Its inactivation can cause retinopathy similar to type 1 diabetes by promoting apoptosis. SERCA2 might be a potential target for the prevention and treatment of diabetic retinopathy.

Advances in HBV infection and replication systems in vitro.

BACKGROUND: Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently closed circular DNA (cccDNA) in host cells after HBV infection, current antiviral drugs cannot eradicate HBV. Therefore, the development of an active cell culture system supporting HBV infection has become the key to studying HBV and developing effective therapeutic drugs. MAIN BODY: This review summarizes the significant research achievements in HBV cell culture systems in vitro, including embryonic hepatocytes and primary hepatocytes, which support the virus infection process most similar to that in the body and various liver tumor cells. The discovery of the bile-acid pump sodium-taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has advanced our understanding of HBV biology. Subsequently, various liver cancer cells overexpressing NTCP that support HBV infection have been established, opening a new door for studying HBV infection. The fact that induced pluripotent stem cells that differentiate into hepatocyte-like cells support HBV infection provides a novel idea for the establishment of an HBV cell culture system. CONCLUSION: Because of the host and tissue specificity of HBV, a suitable in vitro HBV infection system is critical for the study of HBV pathogenesis. Nevertheless, recent advances regarding HBV infection in vitro offer hope for better studying the biological characteristics of HBV, the pathogenesis of hepatitis B, the screening of anti-HBV drugs and the mechanism of carcinogenesis.

Inactivation of cysteine 674 in the SERCA2 accelerates experimental aortic aneurysm.

Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is vital to maintain intracellular calcium homeostasis. SERCA2 cysteine 674 (C674) is highly conservative and its irreversible oxidation is upregulated in human and mouse aortic aneurysms, especially in smooth muscle cells (SMCs). The contribution of SERCA2 and its redox C674 in the development of aortic aneurysm remains enigmatic. Objective: Our goal was to investigate the contribution of inactivation of C674 to the development of aortic aneurysm and the mechanisms involved. Approach and results: Using SERCA2 C674S knock-in (SKI) mouse line, in which half of C674 was substituted by serine 674 (S674) to represent partial irreversible oxidation of C674 in aortic aneurysm, we found that in aortic SMCs the replacement of C674 by S674 resulted in SMC phenotypic modulation. In SKI SMCs, the increased intracellular calcium activated calcium-dependent calcineurin, which promoted the nuclear translocation of nuclear factor of activated T-lymphocytes (NFAT) and nuclear factor kappa-B (NFκB), while inhibition of calcineurin blocked SMC phenotypic modulation. Besides, the replacement of C674 by S674 accelerated angiotensin II-induced aortic aneurysm. Conclusions: Our results indicate that the inactivation of C674 by causing the accumulation of intracellular calcium to activate calcineurin-mediated NFAT/NFκB pathways, resulted in SMC phenotypic modulation to accelerate aortic aneurysm, which highlights the importance of C674 redox state in the development of aortic aneurysms.

Systemic immune-inflammation index predicted overall survival and radiosensitivity in advanced non-small-cell lung cancer.

Aim: To evaluate the predictive significance of systemic immune-inflammation index (SII) on overall survival (OS) and radiosensitivity in advanced non-small-cell lung cancer. Materials & methods: Kaplan-Meier analysis and Cox proportional hazard models were used to assess the prognostic value of SII. Results: The optimal cutoff for SII was 555.59, with an area under the curve of 0.782 (sensitivity: 76.6%, specificity: 71.9%, 95% CI: 0.730-0.833), respectively. Median OS (p < 0.001) in the low SII group (32.8 months) was better than the OS in the high SII group (8.5 months). SII-low group statistically exhibited a better radiosensitivity. Conclusion: SII was an independent prognostic factor for OS and predictive factor for radiosensitivity. Higher level of SII associated with poorer OS and poorer radiosensitivity.

Conversion Surgery for Unresectable Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

For patients with unresectable advanced gastric cancer, induction chemotherapy could down-stage primary tumors, resulting in conversion surgery becoming possible. However, the feasibility and therapeutic benefit of conversion surgery remains controversial. Therefore, this meta-analysis aimed to systematically review and investigate the efficacy of conversion surgery followed by chemotherapy for unresectable AGC.

Radiosensitivity nomogram based on circulating neutrophils in thoracic cancer.

AIM: To evaluate the prediction ability of neutrophils and develop a nomogram on radiosensitivity in thoracic cancer patients. METHODS: We retrospectively reviewed 398 lung and esophageal cancers patients who received external-beam radiotherapy or concurrent chemoradiotherapy as first-line therapy. RESULTS: Logistic regression model showed that patients with low levels of neutrophil counts and/or TGF-ß1 exhibited better radiation sensitivity. Furthermore, a nomogram was created to predict radiotherapy sensitivity. The combination of neutrophil count and TGF-ß1 level was an independent prognostic factor for lung and esophageal cancers patients. CONCLUSION: The study developed a nomogram based on the levels of circulating neutrophils and TGF-ß1. The prediction value in radiosensitivity and protumorigenic effect of neutrophils might owe to N2 tumor-associated neutrophils.

Needleless Transcutaneous Neuromodulation Accelerates Postoperative Recovery Mediated via Autonomic and Immuno-Cytokine Mechanisms in Patients With Cholecystolithiasis.

BACKGROUND: Postsurgical gastrointestinal disturbance is clinically characterized by the delayed passage of flatus and stool, delayed resumption of oral feeding, dyspepsia symptoms, and postsurgical pain. This study was designed 1) to evaluate the effects of needleless transcutaneous neuromodulation (TN) on postoperative recovery; 2) to investigate mechanisms of the TN involving autonomic functions in postoperative patients after removal of the gallbladder. METHODS: Sixty patients scheduled for laparoscopic cholecystectomy (LC) were randomized to TN (n = 30) and sham-TN (n = 30). TN was performed via acupoints ST36 and PC6 for 30 min twice daily from 24 hours before surgery to 72 hours after surgery. Sham-TN was performed using the same parameters at nonacupoints. RESULTS: 1) Compared to sham-TN, TN shortened time to first flatulence (38.9 ± 4.0 vs. 24.9 ± 2.4 hour, p = 0.004) and time to defecation (63.1 ± 4.5 vs. 42.5 ± 3.1 hour, p < 0.001). 2) Compared to sham-TN, TN increased the percentage of normal pace-making activity (66.2 ± 2.2 vs. 73.8 ± 2.3%, p = 0.018). 3) TN enhanced vagal activity. Compared to that 24 hours before surgery, surgery decreased vagal activity (HF) (0.41 ± 0.02 vs. 0.34 ± 0.02, p = 0.043) 3 hours after the operation. Compared to sham-TN, TN increased HF (0.45 ± 0.02 vs. 0.52 ± 0.02, p = 0.045) 72 hours after the operation. Further, HF was negatively correlated with time to defecation and serum norepinephrine. 4) Surgery increased serum IL-6 (1.1 ± 0.1 before surgery vs. 2.9 ± 0.7 pg/mL, p = 0.041) 72 hours after the operation, which was reduced to baseline by TN (0.9 ± 0.1). CONCLUSIONS: In conclusion, the proposed needleless TN accelerates postoperative recovery after LC, possibly mediated via the autonomic and immune-cytokine mechanisms. Needleless and self-administrable TN may be an easy-to-implement and low-cost complementary therapy for postoperative recovery.

Prognostic significance of long non-coding RNA MALAT1 for predicting the recurrence and metastasis of gallbladder cancer and its effect on cell proliferation, migration, invasion, and apoptosis.

The objective of this study is to explore the role of MALAT1 as a molecular indicator in predicting the recurrence, metastasis, and prognosis of gallbladder cancer (GBC) and its effect on the proliferation, invasion, migration, and apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first constructed to transfect the GBC-SD cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was applied to detect MALAT1 expression. CCK-8 assay, flow cytometry, and Transwell assay were applied to testify the cell proliferation, cell cycle, apoptosis, invasion, and migration. A receiver operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to analyze the independent influencing factors of GBC patients' survival status. ROC curve results showed that the MALAT1 expression could be a predictor of the GBC recurrence, metastasis, and prognosis. According to the COX regression analysis, MALAT1 expression, tumor size, and TNM stage were independent influencing factors of GBC patients' survival condition. Compared with the GBC-SD cells transfected with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher apoptosis rates, weakened proliferation, migration, and invasion. In conclusion, our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for evaluating the recurrence, metastasis, and prognosis of GBC patients. We also demonstrate how the overexpression of MALAT1 confers an oncogenic function in GBC.