CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023).

Background: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported. Methods: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs). Results: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%). Conclusion: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.

Solid-Liquid-Gas Three-Phase Indirect Electrolysis Enabled by Affinity Auxiliary Imparted Covalent Organic Frameworks.

The design of efficient heterogenous redox mediators with favorable affinity to substrate and electrolyte are much desired yet still challenging for the development of indirect electrolysis system. Herein, for the first time, we have developed a solid-liquid-gas three-phase indirect electrolysis system based on a covalent organic framework (Dha-COF-Cu) as heterogenous redox mediator for S-S coupling reaction. Dha-COF-Cu with the integration of high porosity, nanorod morphology, abundant hydroxyl groups and active Cu sites is much beneficial for the adsorption/activation of thiols, uniform dispersion and high wettability in electrolyte, and efficient interfacial electron transfer. Notably, Dha-COF-Cu as solid-phase redox mediator exhibits excellent electrocatalytic efficiency for the formation of value-added liquid-phase S-S bond product (yields up to 99%) coupling with the generation of gas-phase product of H2 (~1.40 mmol g-1 h-1), resulting in a powerful three-phase indirect electrolysis system. This is the first work about COFs that can be applied in three-phase indirect electrolysis system, which might promote the development of porous crystalline materials in this field.

Effect of Different Insertion Methods on LMA Protector-Related Complications: A Prospective Randomized Double-Blind Clinical Trail.

OBJECTIVE: The authors compared the effect of 2 insertion methods, namely the conventional laryngeal mask airway (LMA) insertion and the index finger-assisted LMA insertion, on the incidence of complications associated with LMA Protector insertion. METHODS: The authors enrolled 300 patients, who underwent painless bronchoscopy. The patients ranged in age between 18 and 75 and were classified as American Society of Anesthesiologists grade I to III. They were randomly divided into 2 groups: a control group of 150 patients and an assisted group comprising 150 patients. LMA was inserted using the conventional and index finger-assisted insertion methods in both groups, respectively. The primary outcome was postoperative complications, such as oral mucosal injury and pharyngeal pain. Secondary outcomes included the success rate of first-time insertion, the incidence rate of inverse folding of LMA tips, oropharyngeal leak pressure (OLP), and other postoperative complications. RESULTS: Compared with the conventional LMA insertion method, index finger-assisted LMA insertion can significantly reduce the incidence rate of oral mucosal injury and pharyngeal pain, with fewer insertion failures. There was a statistically significant difference between the 2 groups in the visual field grading before adjustment for LMA alignment (P<0.0001). The conventional insertion method increased the likelihood of inverse folding of LMA tips. When the conventional insertion method was utilized, there was a significant difference in airway pressure and tidal volume before and after alignment under a fiberoptic bronchoscope (P<0.0001), but no significant difference in visual field grading and respiratory mechanics-related indicators. CONCLUSIONS: Index finger-assisted insertion can significantly reduce the incidence rate of LMA Protector-related complications and inverse folding of LMA tips.

Design, Synthesis, Anti-TMV Activity, and Structure-Activity Relationships of Seco-pregnane C21 Steroids and Their Derivatives.

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study.

BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Investigating the causal relationship between gut microbiota and gastroenteropancreatic neuroendocrine neoplasms: a bidirectional Mendelian randomization study.

Background: The interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis. Methods: Two-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran's Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs. Results: We identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora. Conclusion: The present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

Retroperitoneal infantile hemangioma: a case report and literature review.

BACKGROUND: Retroperitoneal infantile hemangioma (RIH), a type of primary retroperitoneal tumors, are exceptionally rare in clinical practice. Infantile hemangiomas typically manifest on the skin's surface. RIHs are exceptionally rare and typically small. In adults, these tumors often manifest without specific clinical symptoms or detectable signs for a definitive diagnosis. This case report details a patient diagnosed with RIH. We recommend complete excision of the tumor after a comprehensive evaluation, followed by postoperative pathology, to achieve a conclusive diagnosis. We believe that managing critical retroperitoneal structures and vessels intraoperatively presents a significant challenge for all procedures involving primary retroperitoneal tumors. A 47-year-old male was diagnosed with gallstones and underwent surgery 3 months ago at other institution for unexplained nausea and vomiting. Follow-up imaging 2 months after surgery revealed a retroperitoneal mass below the left renal pole. Upon presentation to our hospital, the patient continued to experience intermittent nausea and vomiting, with no other significant symptoms or signs. Considering the patient's 8-year history of hypertension, a paraganglioma was initially suspected. We performed the laparoscopic mass resection after a detailed assessment. However, postoperative pathology revealed it a capillary hemangioma (old term)/infantile hemangioma. CONCLUSION: RIHs are exceedingly rare benign tumor. The possibility of malignancy should be ruled out, and surgical resection is recommended following a thorough evaluation, with the diagnosis confirmed through pathological examination.

[Proximal femoral nail antirotation combined with locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures].

OBJECTIVE: To investigate the effect of locking plate internal fixation for the treatment of proximal lateral femoral wall fracture. METHODS: From January 2021 to June 2022, 31 patients with intertrochanteric fractures and lateral wall fractures were treated. Among them, 15 patients were treated with proximal femoral nail antirotation (PFNA) fixation including 3 males and 12 females with an average age of (75.87±7.46) years old;the other 16 patients were treated with 3.5 mm pre-curved screw locking plate fixtion for lateral wall fracture including 4 males and 12 females with an average age of (76.15±9.47) years old. After surgery, the surgical index, tip-apical distance(TAD), postoperative standing weight-bearing time, and fracture reduction were compared between two groups. Postoperative hip function was evaluated according to Harris hip score. RESULTS: All patients were followed up for an average of (12±5) months ranging from 7 to 17 months. The immediate postoperative neck angle ranged from 111° to 132°(119.3±8.3)°. Fracture reduction results were excellent in 11 cases, fair in 2, worse in 1 in PFNA group;excellent in 12, fair in 3, worse in 1 in PFNA+locking plate group. One case of the PFNA group had a spiral blade cut out through the femoral head. There were significant differences in the time of operation, the amount of blood loss during the operation, the length of incision between two groups(P<0.05). There was no significant difference in TAD and postoperative standing weight-bearing time between two groups(P>0.05). There were significant differences in Harris scores at 6 months after surgery between two groups(P<0.05). CONCLUSION: The application of PFNA-assisted locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures is effective, and can restore the integrity of lateral wall, improve the stability of PFNA internal fixation, and reduce postoperative complications.

Preclinical ImmunoPET Imaging Using a Zr-89-Labeled Anti-CD146 Monoclonal Antibody for Diagnosis of Melanoma.

The aim of this study was to evaluate the preclinical efficacy of [89Zr]Zr-DFO-Ab253 as a novel positron emission tomography (PET) tracer for CD146-positive malignant melanoma imaging. Considering the high expression of CD146 in malignant melanoma, this study investigated the effect of different CD146 expression levels on the tumor uptake of [89Zr]Zr-DFO-Ab253. CD146 selectivity was investigated by using the CD146-positive human melanoma cell A375 and the CD146-negative human alveolar epithelial cell A549. The cell uptake of [89Zr]Zr-DFO-Ab253 tracers was investigated, and receptor-binding affinities were measured by radioactive enzyme-linked immunosorbent assay. Biodistribution studies and micro-PET imaging of the radiotracers were performed on mice bearing A375 and A549 xenografts under baseline and blocking conditions. An immunohistochemical test was performed using A375 and A549 tissue sections for CD146 expression level analysis. [89Zr]Zr-DFO-Ab253 was obtained with a high radiochemical yield (87.86 ± 4.66%) and a satisfactory radiochemical purity (>98.0%). The specificity and affinity of [89Zr]Zr-DFO-Ab253 were confirmed in melanoma A375 cells and in vivo PET imaging of A375 tumor models. [89Zr]Zr-DFO-IgG and A549 lung tumors were prepared as control radiotracers and negative models to verify the specificity of [89Zr]Zr-DFO-Ab253 on CD146. [89Zr]Zr-DFO-Ab253 has a Kd of 4.01 ± 0.50 nM. PET imaging and biodistribution showed a higher uptake of [89Zr]Zr-DFO-Ab253 in A375 melanomas than that in A549 tumors (42.1 ± 4.04% vs 7.87 ± 1.30% ID/g at 120 h, P < 0.05). A low tumor uptake of [89Zr]Zr-DFO-IgG was observed with uptakes of 1.91 ± 0.41 and 2.80 ± 0.14 ID%/g when blocked at 120 h. The radiation-absorbed dose was calculated to be 0.13 mSv/MBq. This study demonstrates the synthesis and preclinical evaluation of [89Zr]Zr-DFO-Ab253 and indicates that the novel tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma. It also provides feasibility for the development of integrated molecular probes for diagnosis and treatment based on the CD146 target.

Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

Morin Regulates M1/M2 Microglial Polarization via NF-κB p65 to Alleviate Vincristine-Induced Neuropathic Pain.

Background: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells. Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting. Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects. Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.

Constructing Functional Radiation-Resistant Thorium Clusters for Catalytic Redox Reactions.

When catalytic reactions are interfered with by radiation sources, thorium clusters are promising as potential catalysts due to their superior radiation resistance. However, there is currently very little research on the design synthesis and catalytic application of radiation-stable thorium clusters. In this work, we have elaborately engineered and fabricated three high-nuclear thorium cluster catalysts denoted as Th12L3-MA12, Th12L3-MA6-BF6, and Th12L3-Fcc12, which did not undergo any significant alterations in their molecular structures and compositions after irradiation with 690 kGy γ-rays. We systematically investigated the photocatalytic/thermocatalytic properties of these radiation-resistant thorium clusters for the first time and found that γ-rays could not alter their catalytic activities. In addition, it was found that ligand engineering could modulate the catalytic activity of thorium clusters, thus expanding the range of catalytic applications of thorium clusters, including reduction reactions (nitroarene reduction) and some oxidation reactions (N-heterocyclic oxidative dehydrogenation and diphenylmethane oxidation). Meanwhile, all of these organic transformation reactions achieved a >80% conversion and nearly 100% product selectivity. Radiation experiments combined with DFT calculations showed that the synergistic catalysis of thorium-oxo core and ligands led to the generation of specific active species (H+, O2•-, or tBuO/tBuOO•) and activation of substrate molecules, thus achieving superior catalytic performance. This work is not only the first to develop radiation-resistant thorium cluster catalysts to perform efficient redox reactions but also provides design ideas for the construction of high-nuclearity thorium clusters under mild conditions.

Association of Depression and Cognitive Performance in US Older Adults: A Secondary Analysis of Cross-Sectional Data Using NHANES 2013-2014.

INTRODUCTION: Depression has been associated with cognitive performance, but whether sociodemographic and clinical characteristics might influence this association is not well elaborated. This study aimed to further explore this relationship in older adults. METHODS: This cross-sectional study is based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. A total of 1,433 individuals with complete information on depressive symptoms and cognitive function variables were included in this study. Patient Health Questionnaire 9 (PHQ-9) score ≥10 as the cutoff to identify cases of depression in our study. We defined poor cognitive performance as a composite cognitive score <47. Logistic regression models were used to examine the association of depression with cognitive performance (model 1). We progressively adjusted the covariates as confounders (model 2: model 1 + age, and gender; model 3: model 2 + race, education level, family income, drinking, and smoking; model 4: model 3 + overweight, arthritis, hyperlipidemia, diabetes, hypertension, heart failure, coronary heart disease, heart attack, stroke, and cancer). We then conducted subgroup, interaction, and restricted cubic spline (RCS) analyses to examine this association. RESULTS: The prevalence of poor cognitive performance was 36.6% (53/145) in the depression group and 14.1% (182/1,288) in the non-depression group. In the fully adjusted model, depression was significantly associated with poor cognitive performance (adjusted odds ratio: 2.25; 95% confidence interval: 1.31-3.81). The results were robust to sensitivity analyses. Gender and education level may modify the association between depression and poor cognitive performance. RCS analysis revealed that the PHQ-9 score was related to poor cognitive performance in a nonlinear manner (p for nonlinearity <0.001), and exhibited a J-shaped curve. CONCLUSION: Depression is associated with poor cognitive performance in US older adults. Early recognition and treatment of depression may be potential intervention strategies to protect cognitive health.

Exposure to anti- and pro-smoking messages among adults in China: Results from the Global Adult Tobacco Survey, 2018.

SIGNIFICANCE: For decades, tobacco advertisements and promotions have been common in mass media and public places in China. In 2015, China amended the Advertising Law to prohibit the distribution of tobacco advertising, while also initiating waves of tobacco control media campaigns. This study investigates the associations between exposure to anti- and pro-smoking messages, smoking status, and people's smoking-related beliefs and willingness to support tobacco control policies. METHODS: A secondary data analysis was performed with the 2018 Global Adult Tobacco Survey of 19,376 adults aged ≥15 years in China. Anti- and pro-smoking message exposures were measured as the sum of sources (media or places) where respondents have seen the messages. Multivariable logistic regression analyses were conducted to examine the relationships among smoking status, message exposure, and the outcome variables (health harm beliefs, support for increasing tax on cigarettes, support for using part of the increased tax on tobacco control) controlling for smoking status and demographic differences. RESULTS: Overall, 63.3% of the respondents reported being exposed to anti-smoking messages from at least 1 source, while 18.1% were exposed to pro-smoking messages from at least 1 source. Adults who currently, formerly, and never smoked differed in their beliefs about smoking and willingness to support tobacco control policies. Greater reported exposure to anti-smoking messages was positively associated with belief that smoking is harmful, support for increased cigarette tax, and support for using increased tax revenue for tobacco control measures. Meanwhile, greater reported exposure to pro-smoking messages was negatively related to willingness to support cigarette tax increases. CONCLUSIONS: While national and local tobacco control campaigns in China have reached a large proportion of the adult population, there is still room for improvement. China might consider expanding anti-tobacco campaigns, as reported exposure to these messages is associated with increased public awareness of the health hazards of smoking and support for increasing cigarette taxes.

Single-molecule reconstruction of eukaryotic factor-dependent transcription termination.

Factor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.

The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

Intraoperative Glucose and Kidney Injury After On-Pump Cardiac Surgery: A Retrospective Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication after on-pump cardiac surgery, and previous studies have suggested that blood glucose is associated with postoperative AKI. However, limited evidence is available regarding intraoperative glycemic thresholds in cardiac surgery. The aim of this study was to explore the association between peak intraoperative blood glucose and postoperative AKI, and determine the cut-off values for intraoperative glucose concentration associated with an increased risk of AKI. METHODS: The study was retrospective and single-centered. Adult patients in West China Hospital of Sichuan University who underwent on-pump cardiac surgery (n = 3375) were included. The primary outcome was the incidence of AKI. Multivariable logistic analysis using restricted cubic spline was performed to explore the association between intraoperative blood glucose and postoperative AKI. RESULTS: The incidence of AKI in the study population was 18.0% (607 of 3375). Patients who developed AKI had a significantly higher peak intraoperative glucose during the surgery compared to those without AKI. After adjustment for confounders, the incidence of AKI increased with peak intraoperative blood glucose (adjusted odds ratio, 1.08, 95% confidence interval 1.03, 1.12). Furthermore, it was demonstrated that the possibility of AKI was relatively flat till 127.8 mg/dL (7.1 mmol/L) glucose levels which started to rapidly increase afterward. CONCLUSIONS: Increased intraoperative blood glucose was associated with an increased risk of AKI. Among patients undergoing on-pump cardiac surgery, avoiding a high glucose peak (i.e., below 127.8 mg/dL [7.1 mmol/L]) may reduce the risk of postoperative AKI.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).