A real-world pharmacovigilance study of amivantamab-related cardiovascular adverse events based on the FDA adverse event reporting system (FAERS) database.

Amivantamab is the first dual-specificity antibody targeting EGFR and MET, which is approved for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. Cardiovascular toxicities related to amivantamab have not been reported in the CHRYSALIS study. However, the occurrence of cardiovascular events in the real world is unknown. To comprehensively investigate the clinical characteristics, onset times, and outcomes of cardiovascular toxicities associated with amivantamab. The Food and Drug Administration Adverse Event Reporting System (FAERS) database from 1st quarter of 2019 to the 2nd quarter of 2023 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with amivantamab. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage trans-formation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. A total of 20,270,918 eligible records were identified, among which 98 records were related to cardiovascular events associated with amivantamab. 4 categories of cardiovascular events exhibited positive signals: venous thrombotic diseases, abnormal blood pressure, arrhythmia, and pericardial effusion. Venous thrombotic diseases and abnormal blood pressure were the two most common signals. The median time to onset (TTO) for cardiovascular AEs was 33 days. The cumulative incidence within 90 days was 100% for cardiac failure, 75% for stroke, 63.16% for arrhythmia, 50% for sudden death, and 44.18% for venous thrombotic diseases. Death accounted for 16.3% of all cardiovascular AEs associated with amivantamab. The mortality rates for Major Adverse Cardiovascular Events (MACE) were up to 60%. This pharmacovigilance study systematically explored the cardiovascular adverse events of amivantamab and provided new safety signals based on past safety information. Early and intensified monitoring is crucial, and attention should be directed towards high-risk signals.

[Effects of Four Amendments on Fertility and Labile Organic Carbon Fractions of Acid Purple Soil].

The aim of this study was to explore the effects of four amendments on soil fertility and labile carbon fraction characteristics of acid purple soil, so as to provide scientific basis for nutrient management and carbon storage stability in purple soil. Field experiments were carried out, and six treatments were set up:no fertilization (CK), only chemical fertilizer (F), lime + chemical fertilizer (SF), organic fertilizer + chemical fertilizer (OM), biochar + chemical fertilizer (BF), and vinasse biomass ash + chemical fertilizer (JZ). The contents of soil organic matter, pH, available nutrients, soil integrated fertility index (IFI), dissolved organic carbon (DOC), microbial biomass carbon (MBC), particulate organic carbon (POC), their effective rates, and soil carbon pool management index (CPMI) under different treatments were studied to clarify their relationships. The results showed that:① the application of amendments significantly increased soil pH and the contents of organic matter, alkali-hydrolyzed nitrogen, available phosphorus, and available potassium (P<0.05). The OM and JZ treatments had the most significant increase in soil comprehensive fertility index (P<0.05), with increases of 1.96 and 0.77 and 170.43% and 66.96%, respectively. ② Compared with those in the control treatment, the contents of POC, MBC, and DOC in JZ and OM increased by 110.30% and 84.81%, 61.08% and 46.56%, and 195.87% and 141.67%, respectively. The application of amendments significantly increased the soil carbon pool index (CPI) and CMPI (P<0.05), in which the OM treatment showed the most significant increase, with soil CPI and CMPI values increasing by 107.34% and 90.75% compared with those of the control, respectively. ③ Soil organic carbon and its labile fractions were positively correlated with IFI (P<0.05), and redundancy analysis showed that there were significant differences among different treatments. The interpretation rates of soil IFI, pH, and available potassium to organic carbon and its components reached significant levels, and the order of interpretation rates was IFI(74.6%)>pH (11.7%)>AK(6.5%). The application of vinasse biomass ash and organic fertilizer to acid purple soil had the most significant effect on improving soil fertility and soil quality and was conducive to promoting the accumulation and activation of soil carbon fractions.

Practical effect of different teaching modes in teaching gastrointestinal surgery nursing.

BACKGROUND: With the continuous development and progress of medical technology, the position of surgical nursing in the field of clinical medicine is becoming increasingly prominent. As an important branch of the surgical field, the nursing requirements and difficulty of gastrointestinal surgery are also increasing. In order to improve the teaching quality of nursing care in gastrointestinal surgery, many educators and researchers are actively exploring new teaching methods. Among them, the teaching method case-based learning (CBL), scene-simulated learning (SSL), task-based learning (TBL), combining self-evaluation and training mode is considered as an effective method. This method aims to help students to better master knowledge and skills and improve their comprehensive quality by cultivating their self-evaluation ability. AIM: To explore the practical effect of CBL-SSL-TBL combined with training mode and student self-assessment in nursing teaching of gastrointestinal surgery. METHODS: Seventy-one nursing interns in our hospital from December 2020 to December 2021 were selected. According to different teaching modes, they were divided into observation group CBL-SSL-TBL combined with training mode combined with student self-assessment and control group (conventional teaching mode), of which 36 were in observation group and 35 were in control group. The results of operational skills, theoretical knowledge, nursing students' satisfaction, learning effectiveness questionnaire and teaching effect were compared between the two groups. RESULTS: Compared between the two groups, the operational skills and theoretical knowledge scores of the observation group were higher than those of the control group, and the difference was statistically significant (P < 0.05). Compared between the two groups, the total satisfaction ratio of the observation group was higher than that of the control group, the difference was statistically significant (P < 0.05). Compared between the two groups, the observation group was lower than the control group in the questionnaire results of learning efficacy, and the difference was statistically significant (P < 0.05). Compared between the two groups, the proportion of thinking ability, subjective initiative and understanding of theoretical knowledge in the observation group was higher than that in the control group, the difference was statistically significant (P < 0.05). CONCLUSION: The use of CBL-SSL-TBL combined with training mode and student self-assessment in gastrointestinal surgery nursing teaching can improve the operational skills of nursing interns, theoretical knowledge and satisfaction scores of nursing students, improve the results of learning efficiency questionnaire and teaching effect, which can be popularized in clinical teaching.

A qualitative study on the clinical safety and user experiences of female condoms for anal intercourse among men who have sex with men in Shanghai, China.

Objective: This qualitative study aimed to understand the clinical safety, efficacy, and receptiveness of using the female condom (FC) during anal intercourse among men who have sex with men (MSM). Methods: Subjects for this study were recruited from a two-group crossover trial among MSM in Shanghai. The trial consisted of two phases, each including the use of condoms (FC vs. male condom), questionnaires, and in-depth one-on-one interviews. The two phases were separated by a washout period of 4 weeks. The minimum sample size for this study was determined in accordance with the principle of "information saturation." The qualitative data were organized and analyzed using ATLAS.ti version 7. Results: A total of 26 participants from the MSM population were recruited for this study, with 10 assuming the insertive role (i.e., "1"), 8 assuming the receptive role (i.e., "0"), and 8 being versatile (i.e., "0.5"). Each participant completed the crossover trial comprising two phases. The cumulative usage of FCs and male condoms (MCs) amounted to 115 and 127 times, respectively. During the reported sexual encounters, no participants reported incidents of condom rupture, slippage, or other malfunctions. A few participants reported experiencing slight chafing pain, primarily put forward by "0" participants. Apart from those reports, no instances of bleeding, swelling, or allergic reactions were reported. The efficiency of FC in disease prevention, the sexual partner's willingness to use FC, the freshness of FC, and positive sexual experiences were the main reasons for the consistent use of FC for anal sex. Discomfort and pain during sexual activity, the loose design and thick material of FCs, and difficulties in placing FCs were the major obstacles to FC use among MSM. The elements referring to the forehead exhibited varied in importance among "1,", "0," and "0.5" participants. Regarding the willingness to use the FC in the future anal intercourse, 61.54% of participants expressed a positive inclination, 23.08% were uncertain, and 15.38% stated that they would not. "A better sense of security during anal sex" was the main factor affecting willingness among "0" participants and "the sexual pleasure that the FC brought" among "1" participants. Improving the design and technology of FCs and increasing the frequency of use and practice might improve the use skills, which will favor the willingness to use FCs among the MSM population. Conclusion: FCs received positive user feedback from study participants, but distinctions were found in individuals in different sexual roles. Large-scale quantitative studies are needed to evaluate the clinical safety of the FC and its effectiveness in preventing the transmission of STDs during anal intercourse.

Health Service Utilization and Its Associations with Depression and Sexual Risk Behaviors Among Transgender Women in Shanghai, China.

Purpose: Given the limited research on health care utilization among transgender women in China, we described the use of primary health care and gender-affirming health care, and the associations between utilization of gender-affirming health care and depression and sexual risk behaviors. Methods: We conducted a cross-sectional survey in 2017 among a purposive sample of transgender women in Shanghai, China (N=199). We examined correlates of health care utilization and its association with depression and sexual risk behaviors with Chi-square (χ2), Fisher's exact tests, and analysis of variance. Results: The majority of the sample (78.5%) only had physician appointments when having an illness, while about one-fifth of the sample had physician appointments for yearly checkups. Nineteen out of 199 participants (9.5%) received gender-affirming surgery, among which only five used hormone therapy prescribed by a doctor (26.3%). Receiving some form of gender-affirming surgery was associated with higher depression scores [Welch's F(2, 12.22)=4.16, p=0.04], engagement in sex work (p=0.001), having 7 or more male sexual partners in the last 30 days (p=0.003), lifetime unprotected sex with a man (p=0.050), and unprotected sex with a main partner (p=0.043). Compared with transgender women who received both breast augmentation and vulvo-vaginoplasty (mean=5.86), those who received breast augmentation only (mean=12.33) scored higher on depression (p=0.04). Conclusions: Access to gender-affirming health care is low among transgender women in this study. The utilization of gender-affirming surgery is associated with depression and sexual risk behaviors. Findings suggest China should establish national guidelines on transgender-related health care and set up more clinics to provide consultation and services for the transgender population in China.

[Mechanism of Zhongfeng Xingnao Decoction in improving microcirculatory disorders in cerebral hemorrhage based on network pharmacology and molecular docking techniques].

This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components ß-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100ß), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1ß(IL-1ß), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.

The impact of anxiety, depression, and social support on the relationship between HIV-related stigma and mental health-related quality of life among Chinese patients: a cross-sectional, moderate-mediation study.

BACKGROUND/OBJECTIVE: People living with HIV (PLWH) are prone to mental health problems and evidence indicates that HIV-related stigma can negatively impact mental health-related quality of life. This study explored potential mechanisms between HIV-related stigma and mental health-related quality of life, specifically whether anxiety or depression mediates, and whether social support moderates, the relationship. METHOD: A total of 1197 Chinese PLWH participated in the study. The Berger HIV Stigma Scale, the Hospital Anxiety and Depression Scale (HADS), the 12-item Brief Health Survey (SF-12), and the Multidimensional Scale of Perceived Social Support (MSPSS) were employed. RESULTS: HIV-related stigma was negatively associated with mental health-related quality of life. Anxiety and depression partially mediated the relationship between HIV-related stigma and mental health-related quality of life; social support played a moderating role. CONCLUSIONS: The mental health-related quality of life in PLWH was shown to be indirectly affected by HIV-related stigma through anxiety and depression in China. The negative impact of HIV-related stigma decreased with increased social support.

Enhancing Mental Health and Medication Adherence Among Men Who Have Sex With Men Recently Diagnosed With HIV With a Dialectical Behavior Therapy-Informed Intervention Incorporating mHealth, Online Skills Training, and Phone Coaching: Development Study Using Human-Centered Design Approach.

BACKGROUND: Mental health problems are common among men who have sex with men (MSM) living with HIV and may negatively affect medication adherence. Psychosocial interventions designed to address these urgent needs are scarce in China. Incorporating behavioral health theories into intervention development strengthens the effectiveness of these interventions. The absence of a robust theoretical basis for interventions may also present challenges to identify active intervention ingredients. OBJECTIVE: This study aims to systematically describe the development of a mobile health-based intervention for MSM recently diagnosed with HIV in China, including the theoretical basis for the content and the considerations for its technological delivery. METHODS: We used intervention mapping (IM) to guide overall intervention development, a behavioral intervention technology model for technological delivery design, and a human-centered design and cultural adaptation model for intervention tailoring throughout all steps of IM. RESULTS: The dialectical behavior therapy (DBT)-informed intervention, Turning to Sunshine, comprised 3 components: app-based individual skills learning, group-based skills training, and on-demand phone coaching. The theoretical basis for the intervention content is based on the DBT model of emotions, which fits our conceptualization of the intervention user's mental health needs. The intervention aims to help MSM recently diagnosed with HIV (1) survive moments of high emotional intensity and strong action urges, (2) change emotional expression to regulate emotions, and (3) reduce emotional vulnerability, as well as (4) augment community resources for mental health services. Technological delivery considerations included rationale of the medium, complexity, and esthetics of information delivery; data logs; data visualization; notifications; and passive data collection. CONCLUSIONS: This study laid out the steps for the development of a DBT-informed mobile health intervention that integrated app-based individual learning, group-based skills training, and phone coaching. This intervention, Turning to Sunshine, aims to improve mental health outcomes for MSM newly diagnosed with HIV in China. The IM framework informed by human-centered design principles and cultural adaptation considerations offered a systematic approach to develop the current intervention and tailor it to the target intervention users. The behavioral intervention technology model facilitated the translation of behavioral intervention strategies into technological delivery components. The systematic development and reporting of the current intervention can serve as a guide for similar intervention studies. The content of the current intervention could be adapted for a broader population with similar emotional struggles to improve their mental health outcomes.

Anti-cerebral ischemic neuronal injury mechanism of Zhenlong Xingnao capsules: role of the Notch/NF-κB signaling pathway.

OBJECTIVE: To investigate the anti-cerebral ischemia-reperfusion injury (CIRI) effect and mechanism of Zhenlong Xingnao capsules based on Notch/NF-κB signaling pathway. METHODS: The rat model of middle cerebral artery occlusion (MCAO) was established using the Longa suture occlusion method, and 70 rats were divided into sham-operated, model, low dose Zhenlong Xingnao capsule group (125 mg/kg Zhenlong Xingnao capsule solution) and high dose Zhenlong Xingnao capsule group (250 mg/kg Zhenlong Xingnao capsule solution), low dose Zhenlong Xingnao capsule + neurogenic site notch homologous protein 1 (Notch1) antibody (Jagged1 group, 125 mg/kg capsule solution + 25 mg/kg Jagged1 solution), high dose Zhenlong Xingnao capsule + Jagged1 group (250 mg/kg capsule solution + 25 mg/kg Jagged1 solution), and Jagged1 group (25 mg/kg Jagged1 solution). The learning and memory abilities (behavioral score, spontaneous movement, and rotarod test), neurological function score, inflammatory factors and oxidative stress levels [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)] in hippocampal tissue, and Bcl-2, Bax, and Caspase-3 mRNA levels were measured by reverse transcription quantitative polymerase chain reaction, and Notch1/NF-κB signaling pathway-related protein expression was assessed by Western blot. RESULTS: The low and high dose interventions of Zhenlong Xingnao capsules significantly improved the learning and memory abilities of MCAO rats, reduced the neurological impairment scores, improved the levels of IL-6, TNF-α, MDA, GSH-Px, SOD, and inhibited the expression levels of Notch1, p-NF-κB p65, and Hes-1 proteins. However, the protective effect of Zhenlong Xingnao capsules on neurons in rat brain tissue could be reduced after treatment with Jagged1. CONCLUSIONS: Zhenlong Xingnao capsules can promote neuronal repair during ischemia-reperfusion, and its mechanism may be related to inhibiting the activation of Notch/NF-κB signaling pathway and reducing inflammation and oxidative stress response.

Attitude of undergraduate nursing interns in regard to death and the influencing factors.

OBJECT: To explore the influencing factors of attitudes about death among undergraduate nursing interns. METHODS: The study subjects were selected from the full-time fourth year undergraduate nursing interns in Jiangxi University of Technology from January to March 2021 by convenience sampling method. The general information questionnaire was designed by our hospital, and attitude towards death referred to the Chinese version of Death Attitude Depiction Scale (Revised) (DAP-R). Univariate and multivariate Logistic regression analysis was performed on the factors that may affect nursing interns. RESULTS: A total of 210 nursing undergraduate interns were investigated in this study. The total score of DAP-R scale was (89.27±7.26) with a range of 72 and 112. Dimensions were ordered according to the average scores for the items of natural acceptance, escaping from death, fear, approaching acceptance and fleeing acceptance. Univariate and multivariate logistic regression analyses were conducted to analyze the factors that might affect the attitude. Items with statistical significance in univariate analysis, including religious belief, death of the patients cared for during the internship, reading the books related to death and the family's open discussion on the topic of death were entered into the regression model (all P<0.05). The formula of DAP-R total score prediction model was as follows: DAP-R total score = 62.980 + 3.056 * religious belief + 4.381 * death of patients cared for during internship + 5.727 * reading books on death + 3.531 * family open discussion on the topic of death. CONCLUSION: The undergraduate nursing interns in our school have a good attitude towards death, but still exhibit a negative attitude in fearing death.

Corrigendum: Distinct patterns of fasting plasma glucose and lipid profile levels over time in adults tested positive for HIV on HAART in Shanghai, China, revealed using growth mixture models.

[This corrects the article DOI: 10.3389/fmed.2022.1071431.].

Case Report: A long-term survival case of diffuse large B-cell lymphoma with left ventricular infiltration and spinal cord compression.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and may occur with lymph node and/or extranodal involvement. However, DLBCL with intracardiac mass is exceedingly rare. In the reported literature, the intracardiac infiltration of DLBCL mostly involves the right ventricle. Lymphoma that invades the heart has an aggressive nature, with symptoms that are easily ignored initially and can lead to multiple complications in severe cases, resulting in a poor prognosis. Early screening and diagnosis may significantly improve the survival rate. Early diagnosis may significantly improve outcomes. Case summary: We presented a 68-year-old woman with back pain. PET/CT suggested increased FDG metabolism in the left ventricle, right adrenal gland, right erector spinae intramuscularis, multiple bones and multiple lymph nodes. Contrast-enhanced ultrasound showed a left ventricular apical mass with ventricular septum thickening. Cardiac MRI suggested a 1.6*1.1*2.1 cm mass in the apical-central portion of the left ventricle. Biopsy of the right neck mass confirmed the pathologic diagnosis of diffuse large B-cell lymphoma. However, before the pathologic diagnosis was confirmed, the patient was paralyzed due to spinal cord compression caused by the progression of bone metastases. Subsequently, pathology confirmed the diagnosis of diffuse large B-cell lymphoma, and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was treated immediately as first-line therapy. In addition, glucocorticoids and mannitol dehydration were administered to relieve the symptoms of spinal cord compression. After 8 cycles of R-CHOP, the tumor at all sites had almost complete regression. The patient was able to walk normally and had no tumor-related symptoms. Conclusions: We present a case of DLBCL with a very high tumor load that involved multiple organs, including the left ventricle, but exhibited no cardiac-related symptoms. The combination of various imaging modalities is valuable for the diagnosis of cardiac infiltration. The mass in the left ventricle almost completely regressed after R-CHOP treatment, and no recurrence has occurred in the 5 years of follow-up so far.

Lenvatinib as second-line treatment in patients with unresectable hepatocellular carcinoma: A retrospective analysis.

Objective: The purpose of this study is to determine the efficacy and safety of lenvatinib as second-line therapy in Chinese patients with unresectable hepatocellular carcinoma (HCC). Methods: We performed a retrospective analysis of Chinese patients with unresectable HCC who received second-line treatment of lenvatinib at three institutions from November 2018 to February 2022. Demographic and clinicopathologic characteristics, data on the treatment regimens were obtained from medical records. Tumor response was evaluated every 4-6 weeks by modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: In total, 50 patients with unresectable HCC who received second-line treatment of lenvatinib were enrolled in this study. The objective response rate (ORR) was 18.0% and the disease control rate (DCR) was 74.0%, respectively. The duration of response (DoR) was 6.0 months. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 8.5 months, respectively. Patients who received ICIs combined with anti-angiogenic inhibitors as first-line therapy, achieving CR/PR at first-line therapy, with PFS≥6months at first-line therapy had a higher DCR. Univariate and multivariate analysis showed that AFP (ng/ml)<400, absence of extrahepatic metastasis, Child-Pugh A, tumor number<3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, CR/PR to first-line therapy, and PFS≥6months at first-line therapy were independent factors of favorable PFS. Univariate analysis showed that absence of extrahepatic metastasis, tumor number<3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, and PFS≥6months at first-line therapy were significantly associated with longer OS. Multivariate analysis showed that absence of extrahepatic metastasis, Child-Pugh A, tumor number<3, CR/PR to first-line therapy and PFS≥6months at first-line therapy were independent prognostic factors of OS. The majority of AEs were grade 1-2, and were reversible. Grade 3/4 AEs occurred in 12 patients (24.0%) and were mostly connected with hand-foot skin reactions (10.0%), and 10 patients had lenvatinib dose reductions. Two toxicity-related treatment interruptions were attributed to grade 3 hand-foot skin reaction, and grade 4 proteinuria, respectively. Conclusion: This study confirms the efficacy and safety of lenvatinib as second-line therapy after progression on sorafenib or ICIs combined with anti-angiogenic inhibitors.

RIOK3 promotes pancreatic ductal adenocarcinoma cell invasion and metastasis by stabilizing FAK.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive cancer, characterized by a high metastatic burden. RIO Kinase 3 (RIOK3) has been shown to promote invasion and metastasis of PDAC by cytoskeleton remodeling, but the exact mechanism is still unknown. In this study, we analyzed transcriptome sequencing data from RIOK3 stable knockdown PANC-1 cells and TCGA-PDAC data and discovered that RIOK3 was substantially related to focal adhesion signaling in PDAC. Additionally, silencing RIOK3 dramatically decreased Focal Adhesion Kinase (FAK) protein expression and phosphorylation (Tyr397 and Tyr925 sites). Immunoprecipitation assay verified the interaction of RIOK3 and FAK. Furthermore, RIOK3 considerably increased the protein stability of FAK protein but not FAK-Y925F protein. The biological function of RIOK3 in increasing PDAC cell invasion and migration was shown to be dependent on FAK activation. Moreover, we discovered that RIOK3 mutations were mainly characterized by amplification. RIOK3 mRNA was found to be significantly elevated in PDAC tissues and was associated with a poor prognosis. Furthermore, RIOK3 mRNA was significantly upregulated in later T-stage, pre-existing lymph node metastases, and later pathological stage samples. Overall, our study found that RIOK3 promotes PDAC cell invasion and metastasis by stabilizing FAK protein expression and upregulating its phosphorylation. This also provides a new target for therapeutic modalities targeting FAK.

Quality Evaluation of Ideological and Political Education in Universities Based on BP Neural Network.

At present, there are some problems in the research of curriculum ideological and political quality evaluation, such as insufficient theme attention, insufficient theoretical research, incomplete data collection, and so on. This study aims to use the BP neural network in the ideological and political quality evaluation system so that the system can more comprehensively and accurately reflect the actual situation of students and point out the direction for the development of students' ideological and political education. The construction of this system can provide a very considerable and accurate way for the quality evaluation of ideological and political education of college students and especially solves the problems of human subjective, factor errors, and the setting of evaluation index weights in the evaluation system.

Prognostic Significance of NLR, PLR, LMR and Tumor Infiltrating T Lymphocytes in Patients Undergoing Surgical Resection for Hilar Cholangiocarcinoma.

Objective: This study evaluated the prognostic significance of preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and tumor-infiltrating lymphocytes (TILs), and whether these preoperative blood inflammatory indicators were associated with TILs in hilar cholangiocarcinoma (HCCA). Methods: A total of 76 patients with HCCA who underwent radical resection were included. Data on their clinicopathologic characteristics, perioperative features, and survival outcomes were analyzed. The optimal cutoff levels for the NLR, PLR and LMR were defined by using the web application Cut-off Finder. The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were examined by immunohistochemical. The association of the number of CD3+, CD4+ and CD8+ T cells infiltration in the local tumor microenvironment with preoperative NLR, PLR and LMR level was analyzed. Survival curves were calculated using the Kaplan-Meier estimate. Univariate and multivariate logistic regression models were used to identify factors associated with overall survival. Results: The optimal cutoff value of preoperative NLR, PLR and LMR was 2.00, 117.60, and 4.02, respectively. NLR was significantly negatively correlated with CD3+ and CD8+ T cell infiltration, but not with CD4+ T cells. PLR had no correlation with CD3+, CD4+, or CD8+ T cell infiltration, while LMR had a significantly positive correlation with CD3+ T cells infiltration but not with CD4+ or CD8+ T cells. In the multivariate logistic regression model, T stage, lymph node metastasis, CA19-9 and LMR were independent risk factors associated with overall survival (OS). Survival curves indicated that HCCA patients with low CD3+ T cells infiltration and low preoperative LMR live shorter than others. Conclusions: LMR played as an independent factor for predicting the survival in patients with HCCA after R0 radical resection. A high LMR was associated with an accumulation of CD3+ T cells in HCCA.

The in vitro and in vivo antibacterial activities of uniflorous honey from a medicinal plant, Scrophularia ningpoensis Hemsl., and characterization of its chemical profile with UPLC-MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica, honey has been used as a traditional medicine in treatment against mucositis, tinea, hemorrhoids and psoriasis. In complementary medicine, due to its significant antimicrobial activity, honey has been widely used as a remedy for skin wounds and gastrohelcosis for thousands of years. AIM OF THE STUDY: This study is aimed at exploring the antimicrobial activity and mechanisms of honey sourced from medicinal plants, and revealing the composition-activity relationship, to facilitate their complementary and alternative application in the therapy of bacterial infectious diseases. MATERIALS AND METHODS: Eight kinds of medicinal plant-derived uniflorous honey, native to China, were gathered. Their antimicrobial activities were evaluated in vitro, and then in vivo with the systemically infected mouse model and the acute skin infection model. SYTOX uptake assay, scanning electron microscopy, DNA binding assay, and quantitative real-time PCR, were carried out to elucidate the antibacterial mechanisms. This was followed by an investigation of the componential profile with the UPLC-MS/MS technique. RESULTS: It was found that Scrophularia ningpoensis Hemsl. (figwort) honey (S. ningpoensis honey) exhibited broad-spectrum and the strongest antibacterial potency (MICs of 7.81-125.00%, w/v), comparable to manuka honey. In the in vivo assays, S. ningpoensis honey significantly decreased the bacterial load of the muscles under the acute MRSA-infected skin wounds; the sera level of TNF-α in the S. aureus and P. aeruginosa-infected mice decreased by 45.38% and 51.75%, respectively, after the treatment of S. ningpoensis honey (125 mg/10 g). It was capable of killing bacteria through disrupting the cell membranes and the genomic DNA, as well as down-regulating the expression of genes associated with virulence, biofilm formation and invasion, including icaA, icaD, eno, sarA, agrA, sigB, fib and ebps in S. aureus, and lasI, lasR, rhlI, rhlR and algC in P. aeruginosa. Apart from H2O2, some other nonperoxide compounds such as adenosine, chavicol, 4-methylcatechol, trehalose, palmitoleic acid and salidroside, might play a vital role in the antibacterial properties of S. ningpoensis honey. CONCLUSIONS: This is the first study to thoroughly investigate the antibacterial activity, mode of action, and componential profile of S. ningpoensis honey. It suggested that S. ningpoensis honey might be a potential supplement or substitute for manuka honey, for the prevention or treatment of bacterial infections. It will facilitate the precise application of medicinal plant-sourced honey, provide a new thread for the development of antibacterial drugs, and assist in the distinction of different kinds of honey.

USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma.

Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) through K48-linked deubiquitination, and in turn, this stabilization increases acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) expressions. In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments. In HCC, high expression of USP22 positively correlates with PPARγ, ACLY or ACC expression, and associates with a poor prognosis. Taken together, we identify a USP22-regulated lipogenesis mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition.