Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Exploring the mechanism of Lianhuaqingwen (LHQW) in treating chronic bronchitis based on network pharmacology and experimental validation.

BACKGROUND: Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis. METHODS: The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets. RESULTS: A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein-protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways. CONCLUSION: This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.

Gastrointestinal cancer surgery in the elderly: The effects of preoperative oral nutritional supplements - A retrospective study.

BACKGROUND AND OBJECTIVES: The current study aimed to explore the effect of nutritional prehabilitation on the clinical prognosis of elderly patients undergoing abdominal cancer surgery. METHODS AND STUDY DESIGN: A retrospective study was conducted, where participants were divided into two groups based on whether they received oral nutritional supplementation at the first outpatient visit. The nutritional prehabilitation group (n=41) adopted a nutritional prehabilitation mode (a standard energy intake of 25-30 kcal/kg· d was recommended). While the control group (n=55) received routine care. All patients underwent laparoscopic surgery according to the National Comprehensive Cancer Network (NCCN) guidelines. Changes in nutritional status, complications, psychological status, symptoms, hospitalization days, and expenditures were compared between the two groups. RESULTS: Both groups of patients experienced weight loss. However, the decline in body weight in the prehabilitation group was less than that in the control group (-1.88 vs. -2.56 kg, p < 0.001). In the comparison of nutritional prehabilitation group and control group, significant improvements were observed in the Hospital Anxiety Scale scores (5 vs. 5, p = 0.01) and MD Anderson Symptom Inventory scores (3 vs. 0, p < 0.001) respectively. The infection rate in the nutritional prehabilitation group was lower than that in the control group (17.1% vs. 36.4%, p = 0.04). Additionally, patients in the nutritional prehabilitation group had significantly fewer hospitalization days at discharge (14.3 vs. 17.1 days, p = 0.03). CONCLUSIONS: In elderly patients undergoing abdominal cancer surgery, a nutritional prehabilitation model may help maintain better physical and mental status, reduce infection rates, and shorten hospitalization days.

Nasogastric tube feeding improves nutritional status and physical state in esophageal cancer patients during chemoradiotherapy: a retrospective study.

OBJECTIVE: To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. METHODS: EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. RESULTS: The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). CONCLUSIONS: EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..

Comparison of diagnosis-related group based reimbursement and case-mix index within hospitalized patients before and after modified malnutrition diagnosis.

BACKGROUND AND OBJECTIVES: Lack of professional and accurate diagnosis of malnutrition led to a reduction in Diagnosis Related Group (DRG) payment and a decrease in Case-Mix Index (CMI). The aim of this study was to explore the effects of adding a proper nutritional diagnosis and modifying complication groups on DRG payment and CMI. METHODS AND STUDY DESIGN: Retrospective analysis was performed on patients ad-mitted to the hospital from January to June 2022 who had received a nutritional assessment. Patients were diagnosed as well-nourished, mild malnutrition, moderate malnutrition or severe malnutrition according to patient-generated subjective global assessment (PG-SGA) scores within 24 hours of admission. CMI and DRG hospital internal control standards were recalculated and compared with the original values. RESULTS: A total of 254 patients were enrolled, including 40 patients with mild malnutrition, 74 patients with moderate malnutrition and 122 patients with severe malnutrition. Of all subjects, 111 changed complication groups. The median of the DRG hospital internal control standard (12006.09 vs. 13797.19, p=0.01) and the median of CMI (0.91 vs. 1.04, p=0.026) were significantly higher than those before the diagnostic change. In patients with inflammatory bowel disease (IBD), the CMI value, hospital control standard of DRG, and the classification of DRG were significantly different from those before diagnosis revision (p<0.001). CONCLUSIONS: Fully identification and correct coding of malnutrition cases are conducive for hospitals to receive appropriate DRG compensation, and further contribute to the improvement of medical quality and the economic sustain-ability of hospitals.

The associations between lipid profiles and visceral obesity among gastrointestinal cancer patients: a cross-sectional study.

BACKGROUND: Visceral obesity is associated with cancer incidence and prognosis. Altered lipid profiles are frequently seen in visceral obese patients. The blood test of lipid profiles is more convenient and has no radical side effects than computed tomography (CT), which is presently the most accurate way to measure visceral fat area. This article aims to investigate the associations between lipid profiles and visceral obesity in gastrointestinal cancer patients. METHODS: In total, 399 patients newly diagnosed with gastrointestinal cancer were enrolled in this observational study. Lipid profiles were obtained from blood samples, and visceral fat mass area (VFA) was measured by CT. VFA ≥ 100 cm2 was considered visceral obesity. The area under the receiver operating characteristic curve (AUROC) was utilized to evaluate the prognostic powers of lipid parameters for viscerally obese gastrointestinal cancer patients. RESULTS: Patients who had visceral obesity had higher triglyceride (TG) levels (1.20 ± 0.60 vs. 0.87 ± 0.57 mmo/L, P < 0.001), total cholesterol (TC) levels (3.57 ± 0.84 vs. 3.40 ± 0.82, P = 0.044), and low-density lipoprotein (LDL-C) levels (2.08 ± 0.66 vs. 1.94 ± 0.66, P = 0.047) and lower high-density lipoprotein (HDL-C) levels (0.88 ± 0.24 vs. 1.00 ± 0.26, P < 0.001) than those in the normal group. TG was positively correlated with VFA (r = 0.299, P < 0.001), while HDL-C was inversely correlated with VFA (r = -0.237, P < 0.001). TG and HDL-C had predictive capacity for visceral obesity at cutoff levels of 0.92 mmol/L (AUROC 0.700, 95% CI, 0.653-0.745, P < 0.001) and 0.98 mmol/L (AUROC 0.700, 95% CI, 0.585-0.682, P < 0.001), respectively. TG > 0.92 mmol/L with HDL-C < 0.98 mmol/L was linked with an increased risk of visceral obesity (OR = 4.068, 95% CI, 2.338-7.079, P < 0.001). CONCLUSIONS: Lipid profiles were significantly correlated with VFA. Gastrointestinal cancer patients with TG > 0.92 mmol/L and HDL-C < 0.98 mmol/L were at elevated risk of visceral obesity in the Chinese population. Identifying visceral obesity and taking proper actions in gastrointestinal cancers are helpful for overall tumor prognosis.

Overexpression of PsnSuSy1, 2 genes enhances secondary cell wall thickening, vegetative growth, and mechanical strength in transgenic tobacco.

KEY MESSAGE: Two homologs PsnSuSy1 and PsnSuSy2 from poplar played largely similar but little distinct roles in modulating sink strength, accelerating vegetative growth and modifying secondary growth of plant. Co-overexpression of them together resulted in small but perceptible additive effects. Sucrose synthase (SuSy) acts as a crucial determinant of sink strength by controlling the conversion of sucrose into UDP-glucose, which is not only the sole precursor for cellulose biosynthesis but also an extracellular signaling molecule for plants growth. Therefore, modification of SuSy activity in plants is of utmost importance. We have isolated two SuSy genes from poplar, PsnSuSy1 and PsnSuSy2, which were preferentially expressed in secondary xylem/phloem. To investigate their functions, T2 tobacco transgenic lines of PsnSuSy1 and PsnSuSy2 were generated and then crossed to generate PsnSuSy1/PsnSuSy2 dual overexpression transgenic lines. SuSy activities in all lines were significantly increased though PsnSuSy1/PsnSuSy2 lines only exhibited slightly higher SuSy activities than either PsnSuSy1 or PsnSuSy2 lines. The significantly increased fructose and glucose, engendered by augmented SuSy activities, caused the alternations of many physiological, biochemical measures and phenotypic traits that include accelerated vegetative growth, thickened secondary cell wall, and increased stem breaking force, accompanied with altered expression levels of related pathway genes. The correlation relationships between SuSy activities and many of these traits were statistically significant. However, differences of almost all traits among three types of transgenic lines were insignificant. These findings clearly demonstrated that PsnSuSy1 and PsnSuSy2 had similar but little distinct functions and insubstantial additive effects on modulating sink strength and affecting allocation of carbon elements among secondary cell wall components.

Carbendazim Resistance of Fusarium graminearum From Henan Wheat.

Fusarium head blight, also called scab, is caused by Fusarium graminearum and is one of the most important destructive diseases of wheat. The frequency of carbendazim resistance in 1,132 isolates of F. graminearum recovered from fields in different regions of Henan Province in 2016, 2017, and 2018 was determined. A total of 31 F. graminearum isolates resistant to carbendazim were detected, including 30 moderately resistant isolates and one highly resistant isolate. The frequency of resistance of F. graminearum isolates to carbendazim was 2.7%. The range of effective concentration (EC50) values of 1,101 sensitive isolates and 30 moderately resistant isolates was 0.08 to 0.98 µg ml-1 and 2.73 to 13.28 µg ml-1, respectively. The mean ± SD EC50 value was 0.55 ± 0.13 µg ml-1 and 5.61 ± 2.58 µg ml-1, respectively. The EC50 value of the highly resistant isolate was 21.12 µg ml-1. Point mutation types of the carbendazim-resistant isolates were characterized by cloning the ß2-tubulin gene of 31 resistant isolates. Three point mutation types at amino acids F167Y, E198Q, and E198L in the ß2-tubulin gene of resistant isolates were identified. Among 31 resistant isolates, the frequency of point mutation types in F167Y, E198Q, and E198L of the ß2-tubulin gene was 71.0, 25.8, and 3.2%, respectively. The data indicate that F. graminearum has developed resistance to carbendazim in Henan Province, and single point mutations at amino acid F167Y were the predominant type of mutation detected.

[Research progress of mitochondrial fission and fusion related proteins].

Mitochondria are an essential component of multicellular life and play important roles in the health of the cells and the body. Mitochondria can produce energy by oxidative phosphorylation, mediate calcium and reactive oxygen signal transduction, and regulate cell apoptosis. Recent studies indicate that mitochondria continually change their shapes and distribution by fission and fusion, which are collectively termed mitochondrial dynamics. Mitochondrial dynamics play critical roles in maintaining mitochondrial function. This review focuses on the structure and biological functions of mitochondrial fission and fusion related proteins in mammal cells.

Perineural dexamethasone does not enhance the analgesic efficacy of ultrasound-guided subcostal transversus abdominis plane block during laparoscopic cholecystectomy.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efficacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the analgesic efficiency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who underwent laparoscopic cholecystectomy. METHODS: Sixty patients who underwent laparoscopic cholecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the first-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at specific intervals. RESULTS: Compared to group I, the first-time requirement of rescue-analgesia in groups II and III was significantly delayed (403.0+/-230.9, 436.0+/-225.3 vs 152.3+/-124.7, P<0.01). Compared with those in group I, patients in groups II and III were associated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no significant difference in the variables mentioned above between groups II and III (P>0.05). CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efficacy for the patients undergoing laparoscopic cholecystectomy.

TiO(2) nanospheres: a facile size-tunable synthesis and effective light-harvesting layer for dye-sensitized solar cells.

A facile route to synthesize amorphous TiO2 nanospheres by a controlled oxidation and hydrolysis process without any structure-directing agents or templates is presented. The size of the amorphous TiO2 nanospheres can be easily turned from 20 to 1500 nm by adjusting either the Ti species or ethanol content in the reaction solution. The phase structure of nanospheres can be controlled by hydrothermal treatment. The TiO2 nanospheres show excellent size-dependent light-scattering effects and can be structured into a light-harvesting layer for dye-sensitized solar cells with a quite high power conversion efficiency of 9.25 %.

Transcriptome sequencing and screening of genes related to the MADS-box gene family in Clematis courtoisii.

The MADS-box gene family controls plant flowering and floral organ development; therefore, it is particularly important in ornamental plants. To investigate the genes associated with the MADS-box family in Clematis courtoisii, we performed full-length transcriptome sequencing on C. courtoisii using the PacBio Sequel third-generation sequencing platform, as no reference genome data was available. A total of 12.38 Gb of data, containing 9,476,585 subreads and 50,439 Unigenes were obtained. According to functional annotation, a total of 37,923 Unigenes (75.18% of the total) were assigned with functional annotations, and 50 Unigenes were identified as MADS-box related genes. Subsequently, we employed hmmerscan to perform protein sequence similarity search for the translated Unigene sequences and successfully identified 19 Unigenes associated with the MADS-box gene family, including MIKC*(1) and MIKCC (18) genes. Furthermore, within the MIKCC group, six subclasses can be further distinguished.

Greenhouse Gas Emissions during Oil Shale Crushing and Its Main Controlling Factors: A Contrast Study of Oil Shale in Yaojie and Fushun Areas, China.

Geological bodies are important sources of greenhouse gas (GHG) emissions. Organic-rich oil shale in sedimentary basins is a good gas source rock, the GHG in which will be released into the atmosphere during crushing to affect climate change. Quantitative calculations of GHG emissions during oil shale crushing were carried out on oil shales from the Yaojie (YJ) and Fushun (FS) mining areas in China. Organic geochemistry, X-ray diffraction, and pore structure analysis experiments, as well as the relationship between storage time and GHG emissions, were analyzed to investigate the main controlling factors of GHG release in different types of oil shales. The results showed that the CH4 and CO2 released from the YJ oil shale were 0.002-0.145 mL/g and 0.011-0.054 mL/g, respectively; the CH4 and CO2 released from the FS oil shale were 0.0001-0.0008 mL/g and 0.002-0.045 mL/g, respectively. Residual CH4 release was closely related to total organic carbon (TOC) and maturity: the CH4 released from the organic-rich and mature YJ oil shale was much higher than that of the FS oil shale, which is relatively organic-lean and immature. The control factors of the released CO2 vary in different regions: CO2 released from the YJ oil shale was somewhat affected by the TOC, while that released from the FS oil shale was mainly controlled by carbonate minerals and their contributing pores. The results of pore structure and organic maceral analyses indicated that both organic and inorganic pores of the YJ oil shale are occupied by asphaltenes, forming a key gas preservation mechanism of residual CH4 and CO2 as solutes dissolved in asphaltenes. In addition, CO2 has a greater absorptive capacity than CH4 and is therefore more difficult to release during the same crushing time. As oil shale is stored for longer periods, residual CH4 will be preferentially released to the atmosphere, while residual CO2 will be released in large quantities during crushing.

Association of systemic immune-inflammation index with malnutrition among Chinese hospitalized patients: a nationwide, multicenter, cross-sectional study.

Background: Systemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients. Design: From August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used. Results: The prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p < 0.001). A positive association was observed between higher SII and the risk of malnutrition in both before and after adjustment models compared to the first quartile (Q3 vs. Q1, OR = 1.27, 95%CI: 1.15-1.40; Q4 vs. Q1, OR = 1.83, 95%CI: 1.67-2.00). However, a significant reduction in prevalence was observed when SII was in the second quartile (Q2 vs. Q1, OR < 1), as indicated by a restricted cubic spline with a U trend (p for nonlinear <0.001). According to the CONUT score, the prevalence of individuals with normal nutritional status decreased with increasing SII, while the occurrence of three different degrees of malnutrition generally increased. The Kappa value between the two diagnostic methods was 0.23, and the merged data observed an area under the ROC curve of 0.73 (95%CI: 0.714-0.742). Conclusion: The U-shaped association between SII and the prevalence of malnutrition was observed. Both lower and higher SII levels (either continuous or categorical variable) were significantly associated with an increased risk of malnutrition.

Corrigendum: Association of systemic immune-inflammation index with malnutrition among Chinese hospitalized patients: a nationwide, multicenter, cross-sectional study.

[This corrects the article DOI: 10.3389/fnut.2024.1375053.].

Phenolic Compounds and Antioxidant Capacity Comparison of Wild-Type and Yellow-Leaf gl1 Mutant of Lagerstroemia indica.

BACKGROUND: The yellow-leaf gl1 mutant of Lagerstroemia indica exhibits an altered phenylpropanoid metabolism pathway compared to wild-type (WT). However, details on the metabolites associated with leaf color variation, including color-specific metabolites with bioactive constituents, are not fully understood. METHODS: Chemical and metabolomics approaches were used to compare metabolite composition and antioxidant capacity between the gl1 mutant and WT leaves. RESULTS: The mutant exhibited an irregular xylem structure with a significantly lower phenolic polymer lignin content and higher soluble phenolic compounds. Untargeted metabolomics analysis identified phenolic compounds, particularly lignans, as key differential metabolites between gl1 and WT, with a significant increase in the mutant. The neolignan derivative balanophonin-4-O-D-glu was identified as a characteristic metabolite in the gl1 mutant. The soluble phenolic compounds of the gl1 mutant exhibited higher FRAP, ABTS, DPPH, and hydroxyl radical scavenging activity than in WT. Correlation analysis showed a positive relationship between antioxidant capacity and phenolic compounds in L. indica. CONCLUSIONS: Metabolites associated with leaf color variation in the L. indica yellow-leaf gl1 mutant demonstrated high antioxidant capacity, particularly in scavenging hydroxyl radicals.

Hypothalamic FTO promotes high-fat diet-induced leptin resistance in mice through increasing CX3CL1 expression.

Long-term consumption of a high-fat diet (HFD) disrupts energy homeostasis and leads to weight gain. The fat mass and obesity-associated (FTO) gene has been consistently identified to be associated with HFD-induced obesity. The hypothalamus is crucial for regulating energy balance, and HFD-induced hypothalamic leptin resistance contributes to obesity. FTO, an N6-methyladenosine (m6A) RNA methylation regulator, may be a key mediator of leptin resistance. However, the exact mechanisms remain unclear. Therefore, the present study aims to investigate the association between FTO and leptin resistance. After HFD or standard diet (SD) feeding in male mice for 22 weeks, m6A-sequencing and western blotting assays were used to identify target genes and assess protein level, and molecular interaction changes. CRISPR/Cas9 gene knockout system was employed to investigate the potential function of FTO in leptin resistance and obesity. Our data showed that chemokine (C-X3-C motif) ligand 1 (CX3CL1) was a direct downstream target of FTO-mediated m6A modification. Furthermore, upregulation of FTO/CX3CL1 and suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus impaired leptin-signal transducer and activator of transcription 3 signaling, resulting in leptin resistance and obesity. Compared to wild-type (WT) mice, FTO deficiency in leptin receptor-expressing neurons of the hypothalamus significantly inhibited the upregulation of CX3CL1 and SOCS3, and partially ameliorating leptin resistance under HFD conditions. Our findings reveal that FTO involved in the hypothalamic leptin resistance and provides novel insight into the function of FTO in the contribution to hypothalamic leptin resistance and obesity.

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer.

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.

[Routine western medicine treatment plus qishen yiqi dripping pill for treating patients with chronic heart failure: a systematic review of randomized control trials].

OBJECTIVE: To systematically review the safety and efficacy of Qishen Yiqi Dripping Pill (QYDP) as a complementary treatment for chronic heart failure (CHF) patients. METHODS: CNKI, VIP, Wanfang Data, PubMed and Cochrane Library were retrieved for papers on randomized control trials of treating CHF patients by routine western medical treatment plus QYDP. The quality of inclusive literatures was assessed by methods from Cochrane Handbook. Valid data were extracted and analyzed by Meta-analysis using RevMan 5.1.0 Software. RESULTS: Totally 17 trials and 1840 patients in line with standard were included. Results of Meta-analysis showed, compared with the routine Western medical treatment group, additional use of QYDP could decrease re-admission rate [RR = 0.52, 95% CI (0.33, 0.81), P = 0.004] and the mortality rate, improve the clinical efficacy [RR = 1.18, 95% CI (1.12, 1.25), P < 0.01] and cardiac function [RR = 1.18, 95% CI (1.10, 1.27),P < 0.01], increase left ventricular ejection fraction (LVEF) [WMD = 5.57, 95% CI (4.16, 6.97), P < 0.01] of CHF patients. Subgroup analysis of LVEF showed that additional use of QYDP could further improve LVEF [ WMD = 8.34, 95% CI (6.23, 10.45), P < 0.01] of CHF patients and increase the distance of their 6-min walk test [WMD = 94.39, 95% CI (71.89, 116.89), P < 0.01]. But there was no statistical difference in plasma brain natriuretic peptide (BNP) between the two groups. No obvious adverse reaction and liver or kidney damage was reported during the trial. CONCLUSIONS: Compared with the Western medical treatment, additional use of QYDP was safe and could further improve clinical efficacy. However, larger and high-quality clinical trials are necessary for further evidence.