To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

Objective To analyze the case data of farmers' foodborne disease surveillance reports in Guizhou Province from 2022 to 2024, and to provide reference for the precise prevention and control of foodborne diseases among farmers in Guizhou Province. Methods Case data of foodborne disease surveillance reports of farmers were systematically collected from 2022 to 2024 in Guizhou Province. Descriptive epidemiological methods were used to analyze the temporal, geographical, and demographic distribution of foodborne diseases among farmers, along with their primary clinical symptoms and pathogen detection results. Results From 2022 to 2024, a total of 22,882 cases of foodborne diseases were reported among farmers in Guizhou Province. The majority of clinical symptoms (97.81%) were related to the digestive system, with summer being the peak season. While females outnumbered males, the gender difference was statistically insignificant (P >0.05). The 36-55 age group accounted for the highest proportion (38.83%), with Zunyi City (34.89%) and Qiandongnan Prefecture (23.21%) reporting the most cases. Fungal products were the most frequently reported suspected food items (26.96%), and home-made preparation was the primary processing method (58.63%). A total of 1 210 fecal samples were collected through active monitoring with an overall detection rate of 13.22%. Norovirus showed the highest detection rate (9.92%, 120/1 210). Statistically significant differences were observed among different seasons, age groups, regions, types and processing methods of suspected food exposure, and pathogen detection rates (P <0.001). Conclusion Foodborne disease prevention and control among farmers in Guizhou Province should focus on the risks of wild mushroom poisoning in summer and homemade foods, and continuously improve farmers' awareness of the dangers of foodborne diseases and food safety.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Objective To investigate the effects of early statin therapy on collateral circulation,responsible vessel improvement,and thromboxane B2(TXB2)/prostaglandin F1(PGF1α)in acute ischemic stroke with large vessel occlusion(AIS-LVO).Methods From May 2021 to May 2023,105 AIS-LVO patients treated with statins within 3 days of admission were selected as the statin group from the Neurology Department of Taiyuan Iron and Steel(Group)General Hospital.Concurrently,105 early AIS-LVO patients not treated with statins were selected as the non-statin group.The study compared symptom scores[National Institutes of Health Stroke Scale(NIHSS),modified Rankin Scale(mRS),Swallowing Standard Assessment(SSA),and Functional Oral Intake Scale(FOIS)scores],responsible vessel improvement,TXB2/PGF1α levels,and endothelial function indicators[basic fibroblast growth factor(bFGF)and circulating endothelial cells(CECs)].Results Af-ter 1 and 2 weeks,the statin group showed lower NIHSS,mRS,and SSA scores,and higher FOIS scores compared to the non-statin group(P<0.02).The statin group demonstrated higher rates of responsible vessel velocity increase,collateral circulation compensation,and superior CTA collateral circulation grading(P<0.05).At 1 and 2 weeks,the statin group had lower TXB2 and TXB2/PGF1α levels,and higher PGF1α levels compared to the non-statin group(P<0.02).The statin group showed lower bFGF levels and higher CECs levels(P<0.02).After 3 months,the statin group had a higher proportion of mRS scores of 0～2(P<0.05).Conclusion Early statin therapy in AIS-LVO patients can improve responsible vessel blood flow and endothelial function,regulate TXB2/PGF1α levels,promote collateral circulation compensation,and enhance swallowing and neurological function recovery.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Objective:To investigate the efficacy of tiotropium bromide combined with bilevel positive airway pressure (BiPAP) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by type 2 respiratory failure and its effects on serum level of inflammatory factors in patients.Methods:A total of 90 patients with AECOPD complicated by type 2 respiratory failure admitted to the Department of Respiratory Medicine, The Affiliated Qingdao Third People's Hospital of Qingdao University from June 2021 to June 2023 were included in this study. This study used a randomized controlled design. The patients included were divided into a control group and an observation group ( n = 45/group) using a random number table method. The control group was given conventional treatment in addition to mechanical ventilation using a BiPAP respirator. Patients in the control group used the spontaneous/timed (S/T) mode, which automatically switched between spontaneous breathing and time-controlled ventilation. The observation group received inhalation treatment with tiotropium bromide in addition to the treatment provided to the control group. The efficacy and serum levels of inflammatory factors (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-6) were compared between the two groups. Results:After treatment, the mMRC (Modified Medical Research Council) Dyspnoea Scale score and chronic obstructive pulmonary disease assessment test score in the observation group were (1.40 ± 0.35) and (12.42 ± 2.57), respectively. These values were significantly lower than those in the control group [(2.62 ± 0.55), (19.05 ± 3.13), t = -4.05, -3.65, both P < 0.05]. After treatment, the acute physiology and chronic health evaluation Ⅱ score in the observation group was (13.85 ± 1.24), which was significantly lower than that in the control group [(18.24 ± 1.58), t = -3.92, P < 0.05]. After treatment, oxygen saturation and partial pressure of oxygen in the observation group were (95.18 ± 5.82) % and (84.37 ± 5.54) mmHg (1 mmHg = 0.133 kPa), respectively. These values were significantly higher than those in the control group [(91.42 ± 5.79) %, (72.41 ± 4.79) mmHg, t = 3.99, 3.96, both P < 0.05]. Partial pressure of carbon dioxide in the observation group was (34.37 ± 1.97) mmHg, which was significantly lower than that in the control group [(41.68 ± 2.19) mmHg, t = -3.72, P < 0.05]. After treatment, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 levels in the observation group were (13.18 ± 1.43) mg/L, (8.42 ± 1.26) ng/L, and (9.18 ± 1.05) ng/L, respectively. These values were significantly lower than those in the control group [(19.28 ± 2.36) mg/L, (15.76 ± 1.73) ng/L, (19.38 ± 1.61) ng/L, t = -4.22, -5.23, -6.18, all P < 0.05]. The total response rate in the observation group was significantly higher than that in the control group [91.11% (41/45) vs. 73.33% (33/45), χ2 = 5.86, P < 0.05). Conclusions:Inhalation treatment with tiotropium bromide combined with mechanical ventilation using a BiPAP respirator can effectively reduce the severity of dyspnea and alleviate clinical symptoms in patients with AECOPD complicated by type Ⅱ respiratory failure. This combination therapy reduces hypoxia and carbon dioxide retention, diminishes inflammatory response, and enhances overall clinical efficacy.

Subunit 5B of constitutively photomorphogenic 9 signalosome(CSN5B)is an inhibitory factor for the biosynthesis of vitamin C in the L-galactose synthesis pathway in plants.To create mutants with richer vitamin C in tomato fruits,a dual-target vector of pKSE402-SlCSN5Bwas constructed and trans-formed into the breeding parent of 1912.Based on the molecular biological assay and DNA sequencing,17 transgenic positive lines were determined,and 6 lines of them were genetically mutated at the target site of SlCSN5B,with an editing efficiency of 35.3％.Among the mutants,2 lines were homozygous mu-tants,csn5b-6 with 180 bp deletion and csn5b-8 with 3 bp deletion.The biological traits of two types of deficiency homozygotes without exogenous T-DNA insertion derived from the T1 generation were observed,and there were no significant differences in phenotypes of the plant and fruit.Through physiological tes-ting of red-ripe fruits from T,generation lines of csn5b-6,the GMPase activity and the vitamin C content significantly increased by 43％and 37.8％,respectively,the content of hydrogen peroxide significantly decreased by 25.9％,and the content of soluble solids did not obviously change,compared with the wild type.There were no significant differences in plant traits and physiological characteristics between T1 gen-eration lines of csn5b-8 and the wild type.Based on gene expression analysis and protein structure predic-tion,the results showed that the gene of SlCSN5B normally transcribed,and the loss of large peptide seg-ments of CSN5B encoded by SlCSN5B caused changes in its structure to affect functioning,which led to an increase of vitamin C content in the line of csn5b-6-1 1.The findings suggest that the vitamin C content of tomato fruit can be improved by CRISPR/Cas9-mediated SlCSN5B gene editing,which provides the valuable resources for high-quality breeding in tomato.

Periodontitis, a common chronic inflammatory disease, progressively damages the supporting tissues of teeth, ultimately resulting in tooth loss. The rising incidence of periodontitis in adults has prompted researchers to observe a frequent co-occurrence of mental health disorders (such as anxiety disorders, depression disorders) in patients undergoing periodontitis onset and treatment. The existence of severe periodontitis can even aggravate the mental and psychological disorders of patients. Furthermore, the long-term fast-paced, high-pressure modern life is easy to cause a series of psychological problems, in turn affecting the occurrence and development of periodontitis. At present, researchers have reported the correlation between periodontitis and anxiety disorders/depression disorders. However, due to the lack of systematic understanding, most of them are clinical investigations or epidemiological statistics without deep mechanism studies. In view of the above problems, this article elucidates the bidirectional relationship between periodontitis and depression/anxiety disorders in recent years by examining recent epidemiological findings, exploring potential bidirectional pathogenic mechanisms, and discussing current treatment strategies. Ultimately, this review seeks to provide new perspectives for improving both oral and mental health outcomes in patients affected by periodontitis and anxiety/depression disorders.

Genetics,which provides important theoretical knowledge for the cultivation of students majo-ring in biology,is a discipline that studies the law of biological heredity and variation.In the era of high-ly advanced information technology,the blended online and offline teaching model has progressively been integrated into university classrooms,which seamlessly merges offline teaching with"Internet+"and greatly improves the outcomes and effectiveness of student learning and teacher instruction.Taking the genetics course as a platform,this paper first examines the complementary features of online and offline teaching methods.Then,the genetic teaching model that was carried out through various online platforms and resources were designed and optimized from purely online instruction and blended online-offline in-struction respectively.The assessment and evaluation methodologies were also enhanced.The findings of the investigation on the impact of teaching practices showed that a notable enhancement in students'en-thusiasm for learning genetic courses was achieved.This was reflected in the fact that an increasing num-ber of students selected genetic-related topics in science and innovation competitions.Meanwhile,com-pared with the non-implementation of blended teaching reform,students'academic performance in genet-ics courses has also been significantly improved,with a total score of about 5-6 points.The implementa-tion of the innovative blended teaching model will further enhance the efficiency of classroom teaching in-novation and talent training.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude