Deletion of Tmem268 in mice suppresses anti-infectious immune responses by downregulating CD11b signaling.

Transmembrane protein 268 (TMEM268) is a novel, tumor growth-related protein first reported by our laboratory. It interacts with the integrin subunit ß4 (ITGB4) and plays a positive role in the regulation of the ITGB4/PLEC signaling pathway. Here, we investigated the effects and mechanism of TMEM268 in anti-infectious immune response in mice. Tmem268 knockout in mice aggravated cecal ligation and puncture-induced sepsis, as evidenced by higher bacterial burden in various tissues and organs, congestion, and apoptosis. Moreover, Tmem268 deficiency in mice inhibited phagocyte adhesion and migration, thus decreasing phagocyte infiltration at the site of infection and complement-dependent phagocytosis. Further findings indicated that TMEM268 interacts with CD11b and inhibits its degradation via the endosome-lysosome pathway. Our results reveal a positive regulatory role of TMEM268 in ß2 integrin-associated anti-infectious immune responses and signify the potential value of targeting the TMEM268-CD11b signaling axis for the maintenance of immune homeostasis and immunotherapy for sepsis and related immune disorders.

Upregulation of HLA-II related to LAG-3+CD4+ T cell infiltration is associated with patient outcome in human glioblastoma.

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)-1/PD ligand-1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte-activation gene 3 (LAG-3) binding to human leukocyte antigen-II (HLA-II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti-PD-1 treatment; however, the value of LAG-3-HLA-II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA-II in human GBM samples and the correlation with LAG-3+CD4+ T cell infiltration. Human leukocyte antigen-II was highly expressed in GBM and correlated with increased LAG-3+CD4+ T cell infiltration in the stroma. Additionally, HLA-IIHighLAG-3High was associated with worse patient survival. Increased interleukin-10 (IL-10) expression was observed in GBM, which was correlated with high levels of HLA-II and LAG-3+ T cell infiltration in stroma. HLA-IIHighIL-10High GBM associated with LAG-3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti-LAG-3 and anti-IL-10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA-II expression in GBM cells through tumor necrosis factor-α (TNF-α). Blocking TNF-α-dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell-tumor cell interactions, such as LAG-3-HLA-II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG-3-HLA-II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients.

Effects of Noise Damage on the Purinergic Signal of Cochlear Spiral Ganglion Cells in Guinea Pigs.

To observe the expression changes of P2 protein in cochlear spiral ganglion cells before and after noise injury, and to explore the relationship between the changes of purinergic receptors in spiral ganglion cells and noise-induced hearing loss, so that the signal transduction of purinergic receptors can be used to treat SNHL The target point provides a theoretical basis. The experimental animals were randomly divided into normal and experimental groups. The experimental group was given 120 dB white noise continuous exposure for 10 days and 3 h a day. The auditory brainstem response was measured before and after the noise exposure. After the noise exposure, the two groups of animals were collected. Do immunofluorescence staining, western blot, fluorescence real-time quantitative PCR to observe the expression of P2 protein. The average hearing threshold of the animals in the experimental group increased to 38.75 ± 6.44 dB SPL after 7 days of noise exposure, and the high-frequency hearing loss was lower and severe; the average hearing threshold increased to 54.38 ± 6.80 dB SPL after 10 days of noise exposure, and the hearing loss at 4 k Hz was relatively high. Light; Frozen sections of cochlear spiral ganglion cells and staining of isolated spiral ganglion cells found that P2X2, P2X3, P2X4, P2X7, P2Y2, and P2Y4 proteins were all expressed in cochlear spiral ganglion cells before noise exposure. Among them, P2X3 expression increased and P2X4, the down-regulation of P2Y2 expression was statistically significant (P < 0.05); Western blot and real-time quantitative PCR detection results showed that the expression of P2X3 was significantly increased after noise exposure than before noise exposure (P < 0.05), and P2X4 and P2Y2 were expressed after noise exposure The amount was significantly lower than before noise exposure (P < 0.05). (Figure. 4). After noise exposure, the expression of P2 protein is upregulated or downregulated. By affecting the Ca2+ cycle, the transmission of sound signals to the auditory center is blocked, which provides a theoretical basis for the signal transduction of purinergic receptors to become a target for the treatment of SNHL.

Genome editing in rice using CRISPR/Cas12i3.

The CRISPR/Cas type V-I is a family of programmable nuclease systems that prefers a T-rich protospacer adjacent motif (PAM) and is guided by a short crRNA. In this study, the genome-editing application of Cas12i3, a type V-I family endonuclease, was characterized in rice. We developed a CRIPSR/Cas12i3-based Multiplex direct repeats (DR)-spacer Array Genome Editing (iMAGE) system that was efficient in editing various genes in rice. Interestingly, iMAGE produced chromosomal structural variations with a higher frequency than CRISPR/Cas9. In addition, we developed base editors using deactivated Cas12i3 and generated herbicide-resistant rice plants using the base editors. These CRIPSR/Cas12i3-based genome editing systems will facilitate precision molecular breeding in plants.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response.

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), chemokines (e.g., MCP1/CCL2) and inflammatory cell (e.g., monocytes and neutrophils) infiltration. Moreover, it was found that the autophagy activity in Rnf115-/- livers was increased, which resulted in the removal of damaged mitochondria and hepatocyte apoptosis. However, the administration of adeno-associated virus Rnf115 or autophagy inhibitor 3-MA impaired autophagy and aggravated liver injury in Rnf115-/- mice with ALI. Further experiments proved that RNF115 interacts with LC3B, downregulates LC3B protein levels and cell autophagy. Additionally, Rnf115 deletion inhibited M1 type macrophage activation via NF-κB and Jnk signaling pathways. Elimination of macrophages narrowed the difference in liver damage between Rnf115+/+ and Rnf115-/- mice, indicating that macrophages were linked in the ALI induced by LPS/D-GalN. Collectively, for the first time, we have proved that Rnf115 inactivation ameliorated LPS/D-GalN-induced ALI in mice by promoting autophagy and attenuating inflammatory responses. This study provides new evidence for the involvement of autophagy mechanisms in the protection against acute liver injury.

Splicing mutations in AMELX and ENAM cause amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations are reported to be relevant to AI. However, the mechanism underlying AI caused by different mutations is still unclear. This study aimed to reveal the molecular pathogenesis in AI families with 2 novel pre-mRNA splicing mutations. METHODS: Two Chinese families with AI were recruited. Whole-exome sequencing and Sanger sequencing were performed to identify mutations in candidate genes. Minigene splicing assays were performed to analyze the mutation effects on mRNA splicing alteration. Furthermore, three-dimensional structures of mutant proteins were predicted by AlphaFold2 to evaluate the detrimental effect. RESULTS: The affected enamel in family 1 was thin, rough, and stained, which was diagnosed as hypoplastic-hypomature AI. Genomic analysis revealed a novel splicing mutation (NM_001142.2: c.570 + 1G > A) in the intron 6 of amelogenin (AMELX) gene in family 1, resulting in a partial intron 6 retention effect. The proband in family 2 exhibited a typical hypoplastic AI, and the splicing mutation (NM_031889.2: c.123 + 4 A > G) in the intron 4 of enamelin (ENAM) gene was observed in the proband and her father. This mutation led to exon 4 skipping. The predicted structures showed that there were obvious differences in the mutation proteins compared with wild type, leading to impaired function of mutant proteins. CONCLUSIONS: In this study, we identified two new splicing mutations in AMELX and ENAM genes, which cause hypoplastic-hypomature and hypoplastic AI, respectively. These results expand the spectrum of genes causing AI and broaden our understanding of molecular genetic pathology of enamel formation.

TyG index is a predictor of all-cause mortality during the long-term follow-up in middle-aged and elderly with hypertension.

BACKGROUND: The triglyceride and glucose (TyG) index has been found to be significantly associated with a higher risk of mortality. However, there has been a lack of studies exploring the specific relationship between the TyG index and all-cause and cardiovascular mortality among middle-aged and elderly with hypertension. METHODS: A total of 3,614 participants with hypertension were enrolled from the National Health and Nutrition Examination Survey. The TyG index was calculated using the formula log [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. The Cox proportional hazard ratios were used to evaluate the association between the TyG index and the risk of mortality. RESULTS: Over a follow-up period of 7.87 years, 991 all-cause death and 189 cardiovascular deaths occurred. Compared with the reference quartile, the multivariate-adjusted hazard ratios and 95% confidence intervals were 1.28 (1.07-1.53; p = .006) in the fourth quartile for all-cause mortality and 0.63 (0.42-0.96; p = .031) in the second quartile for cardiovascular mortality. Dose-response analysis indicated an L-shaped relationship. CONCLUSIONS: The TyG index exhibited an L-shaped association with the risk of all-cause mortality among middle-aged and elderly with hypertension.

CCL2 is a key regulator and therapeutic target for periodontitis.

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Closed reduction and percutaneous pinning for treatment of unstable lateral condyle fractures of the humerus in children.

Objective: In the past, obviously displaced lateral condyle fractures of the humerus in children were treated satisfactorily with open reduction and internal fixation (ORIF). However, in recent years, more studies have mentioned closed reduction and percutaneous pinning (CRPP) of these fractures. Methods: In this retrospective investigation, the radiographic and clinical results of patients with these fractures that were initially managed with CRPP were newly classified. We classified these fractures into three groups according to the degree and pattern of fracture displacement as identified on four radiographic images. In Type I, the fracture is unstable and displacement is ≥2 mm; In Type II degree I, the fracture is unstable and displacement is >2 mm, with single rotation of fragment; In Type II degree II, the fracture is unstable and displacement is >2 mm, with single rotation of fragment, with rotation of fragment and antero-proximal displacement; In Type III, the fracture is unstable and displacement is >2 mm, with posterior dislocation of elbow joint. We also designed an algorithm for closed reduction of these fractures according to this new classification. Results: We retrospectively analyzed the radiographic and clinical results of 37 unstable fractures (in 22 boys and 15 girls) that were treated with closed reduction. Twenty-one of 25 (84.0%) type I fractures, which could have been reduced to within 2 mm of residual displacement, were treated with closed reduction and pinning with 2 or 3 Kirschner wires (K wires). Three of 5 (60.0%) type II degree I, 3 of 4 (75.0%) type II degree II, and 3 of 3 (100%) type III fractures were treated with CRPP. In 4 of 25 (16.0%) type I, 2 of 5 (40.0%) type II degree I and 1 of 4 (25.0%) type II degree II fractures, closed reduction failed, so ORIF was implemented. There were no complications, such as nonunion, osteonecrosis of the capitellum, superficial or deep infection, malunion, cubitus varus or valgus, or early physeal arrest. Conclusion: Although the management of type III fractures may not be more difficult than type II fractures with a rotated fracture fragment, as elbow dislocations are usually easy reducible. This retrospective study showed that type III fractures should not be ignored as a lateral condyle fracture that can be cured with CRPP and that lateral humeral condyle fractures with obvious displacement and rotation can be initially treated with CRPP to achieve satisfactory recovery of the elbow. Kirschner wire (K wire) fixation is recommended to avoid reoperation or anesthesia for hardware removal.

Interrelation of Chronic Lung Disease and Cardiovascular Disease Based on Two National Prospective Cohort Studies.

BACKGROUND: Chronic lung diseases (CLDs) and cardiovascular diseases (CVDs) are the main chronic diseases responsible for a considerable burden of disease. This study aimed to estimate the interrelation of CLDs and CVDs using two Chinese national longitudinal cohort studies. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were used in this study with 15,052 and 9,765 participants, respectively. The Cox proportional risk model was used to estimate the interrelation between CLDs and CVDs. Mediating effects were performed to detect possible influencing pathways between CLDs and CVDs. RESULTS: The association of CLDs with CVDs was identified in 1,647 participants (10.9%) with newly diagnosed CVDs in CHARLS and 332 participants (11.6%) in CLHLS. The Cox proportional risk model showed that CLDs were a significant predictor of CVDs (HR 1.49, 95% CI 1.27-1.76) after adjusting for covariates, and the hazard ratios of stroke and CVDs excluding stroke were (HR 1.02, 95% CI 0.79-1.31) and (HR 1.76, 95% CI 1.46-2.13), respectively. These association were mediated by body mass index (BMI) and Center for Epidemiological Studies Depression Scale (CES-D-10) scores. No significant association was found in CHARLS and CLHLS regarding CVDs with CLDs. In CHARLS, CVDs was a significant predictor of CLDs (HR 1.40, 95% CI 1.09-1.79). CONCLUSIONS: Chronic lung disease was associated with increased incidence of CVDs in middle-aged and older people in the community population and vice versa. Body mass index and depressive symptoms might be mediated by the effect of CLD on CVD.

HnRNPK is involved in stress-induced depression-like behavior via ERK-BDNF pathway in mice.

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients.

Transcriptome and WGCNA reveal hub genes in sugarcane tiller seedlings in response to drought stress.

Drought stress can severely affect sugarcane growth and yield. The objective of this research was to identify candidate genes in sugarcane tillering seedlings in response to drought stress. We performed a comparative phenotypic, physiological and transcriptomic analysis of tiller seedlings of drought-stressed and well-watered "Guire 2" sugarcane, in a time-course experiment (5 days, 9 days and 15 days). Physiological examination reviewed that SOD, proline, soluble sugars, and soluble proteins accumulated in large amounts in tiller seedlings under different intensities of drought stress, while MDA levels remained at a stable level, indicating that the accumulation of osmoregulatory substances and the enhancement of antioxidant enzyme activities helped to limit further damage caused by drought stress. RNA-seq and weighted gene co-expression network analysis (WGCNA) were performed to identify genes and modules associated with sugarcane tillering seedlings in response to drought stress. Drought stress induced huge down-regulated in gene expression profiles, most of down-regulated genes were mainly associated with photosynthesis, sugar metabolism and fatty acid synthesis. We obtained four gene co-expression modules significantly associated with the physiological changes under drought stress (three modules positively correlated, one module negatively correlated), and found that LSG1-2, ERF1-2, SHKA, TIL, HSP18.1, HSP24.1, HSP16.1 and HSFA6A may play essential regulatory roles as hub genes in increasing SOD, Pro, soluble sugar or soluble protein contents. In addition, one module was found mostly involved in tiller stem diameter, among which members of the BHLH148 were important nodes. These results provide new insights into the mechanisms by which sugarcane tillering seedlings respond to drought stress.

Therapeutic effect of YiQi HuoXue BuShen decoction combined with Western medicine on hypertensive nephropathy: a meta-analysis.

OBJECTIVE: To comprehensively evaluate therapeutic effect of YiQi HuoXue BuShen decoction combined with Western medicine on hypertensive nephropathy. METHODS: The CNKI, WanFang, VIP, Chinese Biomedical Database (CBM), PubMed, Embase and Cochrane Library databases were searched to collect the randomized controlled trials (RCTs) of YiQi HuoXue BuShen decoction combined with Western medicine on hypertensive nephropathy, which were published as of March 10, 2023. Then, these articles were screened to extract and evaluate the data. Revman 5.3 was applied for data analysis. RESULTS: Eight RCTs involving 732 patients were included after screening. Comparing with Western medicine, YiQi HuoXue BuShen decoction combined with Western medicine enhanced the clinical effect [OR = 3.48, 95% CI: 2.12~5.73, P < 0.00001]; reduced 24-hour urine protein content [OR = -0.60, 95% CI: -0.92~-0.28, P = 0.0003], serum creatinine (Scr) [OR = -39.11, 95% CI: -44.72~-33.51, P < 0.00001], blood urea nitrogen (BUN) [OR = -2.51, 95% CI: -4.06~-0.95, P = 0.002], cystatin C (Cys-C) [OR = -0.30, 95% CI: -0.36~-0.25, P < 0.00001], Urine ß2-microglobulin [OR = -0.42, 95% CI: -0.87~-0.02, P = 0.06]; and enhanced creatinine clear rate (Ccr) [OR = 3.24, 95% CI: 1.85~4.64, P < 0.00001]. In addition, the combination treatment didn't increase the incidence of adverse reaction compared with western medicine [OR = 1.55, 95% CI: 0.61~3.95, P > 0.05]. CONCLUSIONS: The combination of Yiqi Huoxue Bushen decoction and western medicine can effectively improve the clinical symptoms and renal function of patients with hypertensive nephropathy and provide more theoretical basis for clinical application.

Meta-analysis of the clinical effect of Kanglaite injection-assisted gemcitabine plus cisplatin regimen on non-small cell lung cancer.

OBJECTIVE: To systematically evaluate the clinical effect of Kanglaite (KLT) injection-assisted gemcitabine plus cisplatin (GP) regimen on non-small cell lung cancer (NSCLC). METHODS: The CNKI, WanFang, VIP, Chinese Biomedical Database, PubMed, Embase and Cochrane Library databases were searched to collect the randomized controlled trials (RCTs), which evaluated the clinical effect of KLT combined with GP chemotherapy on NSCLC, published as of February 15, 2023. These articles were screened, extracted and evaluated. Revman 5.3 and STATA 17 were used for analysis, where the odds ratio (OR) was used as the statistic for the binary variables, and the mean difference (MD) was used as the statistic for the continuous variables. RESULTS: After selection, this meta-analysis included 27 RCTs and 2,579 patients. Comparing with GP chemotherapy, KLT combined with GP regimen enhanced the total response rate (OR=1.76, 95% CI: 1.49-2.06, P<0.00001), improved the Karnofsky (KPS) score (OR=2.03, 95% CI: 1.55-2.66, P<0.00001), decreased the adverse reactions, including gastrointestinal reactions (OR=0.41, 95% CI: 0.33-0.51, P<0.00001), leucopenia (OR=0.45, 95% CI: 0.35-0.58, P<0.00001), anemia (OR=0.47, 95% CI: 0.32-0.67, P<0.0001) and liver function damage (OR=0.52, 95% CI: 0.38-0.73, P<0.0001), as well as elevated immune level, including CD3+ (MD=8.51, 95% CI: 7.63-9.39, P<0.00001), CD4+ (MD=5.68, 95% CI: 5.08-6.27, P<0.00001) and CD4+/CD8+ (MD=0.41, 95% CI: 0.38-0.44, P<0.00001). CONCLUSIONS: Current evidence shows that the combination regimen of KLT with GP has shown promising results in increasing the response rate, improving the KPS score, enhancing the immune level, and reducing the incidence of adverse reactions in NSCLC patients. However, this conclusion needs to be further verified due to limitations such as the limited number of articles included in this paper and the variability in research methodology and quality among the included studies.

Effect of Dexmedetomidine on Postoperative Renal Function in Patients Undergoing Cardiac Valve Surgery Under Cardiopulmonary Bypass: A Randomized Clinical Trial.

OBJECTIVE: The effect of dexmedetomidine on postoperative renal function was investigated in patients undergoing cardiac valve surgery under cardiopulmonary bypass (CPB). DESIGN: A randomized controlled trial. SETTING: University teaching, grade A tertiary hospital. PARTICIPANTS: A total of 70 patients scheduled to undergo cardiac valve replacement or valvuloplasty under CPB were eligible and randomly divided into groups D (n = 35) and C (n = 35) between January 2020 and March 2021. INTERVENTIONS: Patients in group D were administered 0.6 µg/kg/h of dexmedetomidine intravenously from 10 minutes before anesthesia induction to 6 hours after surgery; normal saline was used instead of dexmedetomidine in group C. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of acute kidney injury (AKI). Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes (2012). It was 22.86% and 48.57% in groups D and C, respectively (p = 0.025). The secondary outcomes were intraoperative hemodynamics and various indices in serum. Ten minutes before CPB (T1), 10 minutes after CPB (T2), and 30 minutes after CPB (T3), mean arterial pressure in group D was lower than that in group C, with statistical significance (74.94 ± 8.52 v 81.89 ± 13.66 mmHg, p=0.013; 62.83 ± 11.27 v 71.86 ± 7.89 mmHg, p < 0.001; 72.26 ± 8.75 v 78.57 ± 8.83 mmHg, p = 0.004). At T1, the heart rate in group D was significantly lower than in group C (80.89 ± 14.04 v 95.54 ± 12.53 bpm, p=0.022). The tumor necrosis factor α, interleukin-6, C-reactive protein, and cystatin C levels in group D were lower than those in group C after the surgery (T4) and 24 hours after surgery (T5), with statistical significance. The duration of mechanical ventilation, intensive-care-unit stay time, and hospital stay time in group D were significantly shorter than in group C. The incidences of tachycardia, hypertension, nausea, and vomiting in group D were similar to those in group C. CONCLUSIONS: Dexmedetomidine may be considered as a way to reduce the incidence and severity of postoperative AKI in patients undergoing cardiac valve surgery under cardiopulmonary bypass.

Influence of accelerating storage of foxtail millet on the edible and cooking quality of its porridge: An insight into the structural alteration of the in-situ protein and starch and physicochemical properties.

This study aimed to elucidate the effect of the accelerating storage (40 °C, 10 weeks) of foxtail millet on the edible and cooking quality of its porridge. The structural alteration of the in-situ protein and starch in foxtail millet, as well as the physicochemical properties were investigated. Both the homogeneity and palatability of millet porridge were significantly improved after 8-week storage of millet, while its proximate compositions remained unchanged. Meanwhile, the accelerating storage increased the water absorption and swelling of millet by 20 % and 22 %, respectively. The morphological studies (using the SEM, CLSM and TEM) revealed that the starch granules in the stored millet became easier to swell and melt, leading to better gelatinization with a higher coverage extension in protein bodies. FTIR results showed that the protein hydrogen bonds in the stored millet became stronger and the starch ordered degree was reduced. Compared to the native foxtail millet, the peak, trough, final, and setback viscosity of the stored sample increased by 27 %, 76 %, 115 % and 143 %, respectively, while the onset, peak, and conclusion temperature increased by 0.80, 1.10 and 0.80 °C, respectively. Besides, the G' and G″ of the stored foxtail millet were significantly higher than its native counterpart.

AFG1-induced TNF-α-mediated inflammation enhances gastric epithelial cell injury via CYP2E1.

Aflatoxin G1 (AFG1), a member of the aflatoxin family with cytotoxic and carcinogenic properties, is one of the most common mycotoxins occurring in various agricultural products, animal feed, and human foods and drinks worldwide. Epithelial cells in the gastrointestinal tract are the first line of defense against ingested mycotoxins. However, the toxicity of AFG1 to gastric epithelial cells (GECs) remains unclear. In this study, we explored whether and how AFG1-induced gastric inflammation regulates cytochrome P450 to contribute to DNA damage in GECs. Oral administration of AFG1 induced gastric inflammation and DNA damage in mouse GECs associated with P450 2E1 (CYP2E1) upregulation. Treatment with the soluble TNF-α receptor sTNFR:Fc inhibited AFG1-induced gastric inflammation, and reversed CYP2E1 upregulation and DNA damage in mouse GECs. TNF-α-mediated inflammation plays an important role in AFG1-induced gastric cell damage. Using the human gastric cell line GES-1, AFG1 upregulated CYP2E1 through NF-κB, causing oxidative DNA damage in vitro. The cells were also treated with TNF-α and AFG1 to mimic AFG1-induced TNF-α-mediated inflammation. TNF-α activated the NF-κB/CYP2E1 pathway to promote AFG1 activation, which enhanced DNA cellular damage in vitro. In conclusion, AFG1 ingestion induces TNF-α-mediated gastric inflammation, which upregulates CYP2E1 to promote AFG1-induced DNA damage in GECs.

Tumor Necrosis Factor α-Dependent Lung Inflammation Promotes the Progression of Lung Adenocarcinoma Originating From Alveolar Type II Cells by Upregulating MIF-CD74.

Lung adenocarcinoma is the most common type of lung cancer. We recently reported that inflammation-driven lung adenocarcinoma (IDLA) originates from alveolar type (AT)-II cells, which depend on major histocompatibility complex (MHC) class II to promote the expansion of regulatory T cells. The MHC class II-associated invariant chain (CD74) binds to the macrophage migration inhibitory factor (MIF), which is associated with promoting tumor growth and invasion. However, the role of MIF-CD74 in the progression of lung adenocarcinoma and the underlying mechanisms remain unclear. We aimed to explore the role of MIF-CD74 in the progression of lung adenocarcinoma and elucidate the mechanisms by which tumor necrosis (TNF)-α-mediated inflammation regulates CD74 and MIF expression in IDLA. In human lung adenocarcinoma, CD74 was upregulated on the surface of tumor cells originating from AT-II cells, which correlated positively with lymph node metastasis, tumor origin/nodal involvement/metastasis stage, and TNF-α expression. MIF interaction with CD74 promoted the proliferation and migration of A549 and H1299 cells in vitro. Using a urethane-induced IDLA mouse model, we observed that CD74 was upregulated in tumor cells and macrophages. MIF expression was upregulated in macrophages in IDLA. Blocking TNF-α-dependent inflammation downregulated CD74 expression in tumor cells and CD74 and MIF expression in macrophages in IDLA. Conditioned medium from A549 cells or activated mouse AT-II cells upregulated MIF in macrophages by secreting TNF-α. TNF-α-dependent lung inflammation contributes to the progression of lung adenocarcinoma by upregulating CD74 and MIF expression, and AT-II cells upregulate MIF expression in macrophages by secreting TNF-α. This study provides novel insights into the function of CD74 in the progression of IDLA.