As the longest and most widely distributed pair of nerves in the brain,the vagus nerve is involved in the regulation of many systems and organs.Recent studies have found that the vagus nerve may be involved in the occurrence of a variety of neuropsychiatric diseases by regulating the release of neurotransmitters(such as norepinephrine,5-hydroxytryptamine,gamma-aminobutyric acid and acetylcholine)and regulating the immune system and gut-brain axis.This article focuses on the regulatory mechanisms of the vagus nerve on neurotransmitters,immune system function,and the gut-brain axis,as well the therapeutic advances in vagus nerve stimulation for neurological and psychi-atric diseases such as epilepsy,depression and anxiety disorders.

Objective:To analyze the relationship between blood urea nitrogen (BUN)/albumin (ALB) ratio (B/A) and prognosis of patients undergoing percutaneous coronary intervention (PCI) guided by ultrasound before operation.Methods:A total of 116 patients who underwent PCI under the guidance of intra-coronary ultrasound in Xianyang Central Hospital from February 2020 to December 2022 were retrospectively selected as the observation group, and 120 healthy people in the same period were selected as the control group. All patients were followed up for 1 year after surgery, and 116 patients were divided into poor prognosis group ( n=33) and good prognosis group ( n=83), taking major adverse cardiovascular events (MACE) as the end point during follow-up. The levels of BUN and ALB in peripheral blood of all subjects were detected after admission, and B/A was calculated. The basic data, biochemical indexes and B/A of each group were analyzed and compared. The predictive value of preoperative BUN, ALB and B/A on postoperative MACE in patients with PCI guided by intra-coronary ultrasound was analyzed by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was used to evaluate the related influencing factors of postoperative MACE in patients with PCI guided by intra-coronary ultrasound. Results:The left ventricular end-diastolic inner diameter (LVEDD), N-terminal B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme (CK-MB), BUN and B/A in the observation group were higher than those in the control group, and left ventricular ejection fraction (LVEF) and ALB were lower than those in the control group (all P<0.05). NT-proBNP, CK-MB, BUN and B/A in the poor prognosis group were higher than those in the good prognosis group, and LVEF and ALB were lower than those in the good prognosis group (all P<0.05). ROC curve results showed that the AUC of peripheral blood BUN, ALB and B/A predicting postoperative MACE in patients with PCI guided by intra-coronary ultrasound were 0.833(95% CI: 0.783-0.883), 0.859(95% CI: 0.809-0.909) and 0.922(95% CI: 0.872-0.972). Multivariate logistic regression analysis showed that LVEF [ OR(95% CI)=1.952(1.317-2.895)], NT-proBNP [ OR(95% CI)=2.625(1.643-4.193)], BUN [ OR(95% CI)=3.353(1.922-5.851)], ALB [ OR(95% CI)=3.792(2.049-7.018)] and B/A [ OR(95% CI)=3.277(2.000-5.370)] were all the influencing factors of postoperative MACE in patients undergoing PCI guided by intra-coronary ultrasound ( P<0.05). Conclusions:The level of B/A in patients with PCI guided by intra-coronary ultrasound increased before surgery, and the high level of B/A is a risk factor for postoperative MACE, which can be used as a biological index to evaluate the postoperative MACE in patients with PCI guided by intra-coronary ultrasound.

With the rapid global population aging, multimorbidity is becoming a more serious public health problem, to which medical researchers have paid close attention. A standardized definition of multimorbidity is essential for relevant research. However, there is a lack of consensus on the definition of multimorbidity, which makes it difficult to compare results among studies and replicate important findings. Based on the conceptual comparison, this paper summarizes the key dimensions of the definition of multimorbidity, including the number and types of conditions, the granularity of classification, methods for obtaining outcomes, and settings and objectives of research. It also discusses the inherent relationships among the dimensions and their impact on research results, and introduces the characteristics of the commonly used condition lists in current multimorbidity definition research. By suggesting areas for improvement in the multimorbidity definition system, it aims to enhance the understanding of multimorbidity research and achieve consensus on the definition, thereby facilitating further multimorbidity research.

Objective To investigate the association between plasma homocysteine(Hcy)level and coronary artery calcification(CAC)and its clinical predictive efficacy.Methods A total of 172 patients who underwent coronary CT angiography North China University of Science and Technology Affiliated Hospital from April 2019 to May 2021 and CAC score(CACS)＞0 were enrolled.According to the CACS value,the subjects were divided into mild calcification group(n=136)and severe calcification group(n=36),and the clinical characteristics of two groups were compared and analyzed.Multivariate Logistic regression model was used to screen the independent influencing factors of CAC severity,and a prediction model was constructed based on the Hcy detection value.The clinical diagnostic value was evaluated by the receiver operating characteristic(ROC)curve.Results There were significant differences in Hcy,white blood cell count,triglyceride and magnesium ion levels between two groups(P＜0.05).Multivariate Logistic regression analysis showed that Hcy,white blood cell count and magnesium ion level were independent risk factors for the progression of CAC.Furthermore,a regression model based on Hcy was constructed and ROC curve was fitted to evaluate its predictive efficacy.The results suggested that the predictive model had the best performance when the critical value of Hcy was set at 27.4μmol/L:the sensitivity was 55.6％,the specificity was 97.1％,and the area under the curve was 0.765.Conclusion Hcy serves as an independent risk factor for the severity of CAC and can effectively predict the progression of CAC with high accuracy.

Objective:To explore and verify the value of neoadjuvant rectal (NAR) score in predicting the prognosis of patients with middle and low locally advanced rectal cancer.Methods:A retrospective analysis of 207 patients with middle and low locally advanced rectal adenocarcinoma who received neoadjuvant radiotherapy and chemotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2015 to December 2021 was performed. The neoadjuvant radiotherapy regimen was pelvic external irradiation of 45-50.4 Gy, 1.8 Gy/f, 5 times per week and concurrent oral capecitabine chemotherapy on days 1-14 and 22-36 during radiotherapy. Total mesorectal excision (TME) was then performed. The NAR score was calculated based on the initial clinical stage and postoperative pathological stage, and divided into the low (<8), medium (8-16) and high (>16) layers, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences in DFS and OS among different NAR score layers were compared using the log-rank test. Some patients received consolidation chemotherapy during the interval between concurrent radiotherapy-chemotherapy and surgery, even the total neoadjuvant therapy (TNT) model. Subgroup analysis was further used to verify the predictive value of the NAR score in the strengthened neoadjuvant therapy model.Results:The median follow-up of all patients was 46.0 months (range: 19.5-88.0 months), the 3-year DFS was 79.2%, and the 3-year OS was 87.4%. Univariate analysis found that the NAR score had a significant impact on the 3-year DFS and OS. The 3-year DFS of patients with low, medium, and high NAR scores were 90.3%, 86.1% and 58.7% ( P<0.001), and the 3-year OS were 94.4%, 91.7% and 74.6%, ( P<0.001), respectively. Subgroup analysis showed that the predictive value of the NAR score also applied to the strengthened neoadjuvant therapy model. The 3-year DFS of patients with low, medium, and high NAR scores were 86.9%, 83.8% and 68.3% ( P=0.044), and the 3-year OS were 92.9%, 90.7% and 85.4% ( P=0.029), respectively. Conclusion:The NAR score can effectively predict the prognosis of patients with middle and low locally advanced rectal adenocarcinoma, whether using neoadjuvant therapy or strengthened neoadjuvant therapy followed by TME surgery.

Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.

Objective To investigate the effects of exosomes (Exo) derived from high glucose-stimulated glomerular mesangial cells (GMC) on the kidneys of C57BL/6 mice and the intervention mechanism of Tongluo Yishen Formula (TLYSF). Methods The rat GMC were divided into a normal glucose group (NG, with 5.6 mmol/L glucose) and a high glucose group (HG, with 30 mmol/L glucose). After 24 hours of culture, the supernatant was collected, and exosomes were extracted using the ultracentrifugation method. The exosomes were then identified by transmission electron microscopy and Western blot analysis. Male C57BL/6 mice were divided into three groups: NO-Exo group, NG-Exo group, and HG-Exo group. These groups were respectively administered tail vein injections of PBS buffer, exosomes derived from GMC cultured in normal glucose, and exosomes derived from GMC cultured in high glucose, three times a week for a total of 8 weeks. After 8 weeks, the mice in the HG-Exo group were randomly divided into three subgroups: the HG-Exo group [gavaged with saline], the HG-Exo+TLYSF group [gavaged with TLYSF at 34.32 g/(kg.d)], and the HG-Exo + VAL group [gavaged with valsartan suspension at 10.4 mg/(kg.d)], and the intervention lasted for 4 weeks. Urinary microalbumin (mALb), urinary N-acetyl-β-D-aminoglucosidase (NAG), glycated hemoglobin (HbA1c), serum creatinine (Scr) and urea nitrogen (BUN) were detected. Transmission electron microscopy was used to observe the ultrastructure of renal tissues. TUNEL was used to detect the DNA damage of renal tissue cells. Immunofluorescence was used to detect the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and wilms tumor 1(WT-1). RT-PCR was used to detect the mRNA levels of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin-1 beta (IL-1β), miR-200c-3p and miR-148a-3p. Western Blot was employed to detect the protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 and IL-1β. Results Compared with the NG-Exo group, mice in the HG-Exo group exhibited significantly increased levels of mALb, urinary NAG, Scr and BUN. Transmission electron microscopy revealed ruptured podocyte membranes and swollen mitochondria. The positive rate of cells stained by the TUNEL increased, with elevated optical density of NLRP3 and decreased optical density of WT-1. Additionally, there was a significant increase in the level of NLRP3, caspase-1, IL-1β mRNA, as well as miR-200c-3p and miR-148a-3p. The protein expression of NLRP3, ASC, caspase-1, and IL-1β also increased. Compared with HG-Exo group, mice in the HG-Exo+TLYSF group showed decreased levels of mALb, urinary NAG, Scr, and BUN. The podocyte membranes were relatively intact, and mitochondrial damage was alleviated. The positive rate of cells stained by the TUNEL decreased, along with a reduction in the optical density of NLRP3 and an increase in the optical density of WT-1. Furthermore, the mRNA expression levels of NLRP3, caspase-1, IL-1β, miR-200c-3p, and miR-148a-3p were all downregulated to varying degrees. The protein expression levels of NLRP3, ASC, caspase-1, and IL-1β also decreased. Conclusion Exosomes derived from GMC stimulated by high glucose can damage the kidneys of mice and induce podocyte pyroptosis. TLYSF may ameliorate podocyte pyroptosis by downregulating the expression of exosomal miR-200c-3p and miR-148a-3p and inhibiting the activation of the NLRP3/ASC/caspase-1 pathway.
Animals ; Exosomes/ultrastructure* ; Glucose/pharmacology* ; Male ; Podocytes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Mesangial Cells/metabolism* ; Pyroptosis/drug effects* ; Rats ; MicroRNAs/genetics*

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Anxiety and fear,as common symptoms of psychiatric disorders,remain inadequately understood in terms of their pathogenesis.Changes in immune inflammation are considered to play a significant role in both the pathological and physiological processes associated with these mental illnesses.In recent years,it has been demonstrated that stress can regulate immune inflammation through multiple pathways,including the regulation of the autonomic nervous system,the hypothalamic-pituitary-adrenal axis,indoleamine 2,3-dioxygenase and its metabolite kynurenine,and the gut-brain axis.These pathways are implicated in the onset and treatment of anxiety and fear-related mental illnesses.This article focuses on the relationships between anxiety and fear-related mental illnesses and immune inflammatory responses.