First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial.

There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator's discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1-63.4), while the disease control rate was 87.5% (95%CI 67.6-97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2-9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients.

Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning: A case report.

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

The emerging role of cysteine-rich peptides in pollen-pistil interaction.

Unlike early land plants, flowering plants have evolved a pollen tube that transport a pair of non-motile sperm cells to the female gametophyte. This process, known as siphonogamy, was first observed in gymnosperms and later become prevalent in angiosperms. However, the precise molecular mechanisms underlying the male-female interactions remain enigmatic. From the pollen grain's landing on the stigma to gametes fusion, the male part needs to pass various tests: How does the stigma distinguish between compatible and incompatible pollen? What mechanisms guide pollen tube towards the ovule? What factors trigger pollen tube rupture? How is polyspermy prevented? And how does the sperm cell ultimately reach the egg? Successful male-female communications is essential for surmounting these challenges, with cysteine-rich peptides (CRPs) playing a pivotal role in these dialogues. In this review, we summarize the characteristics of four distinct classes of CRPs and then we systematically review the recent progresses of the role of CRPs in four crucial stages of pollination and fertilization. Finally, we conclude by considering the potential applications of this knowledge in crop breeding, and suggesting avenues for future research.

A rare pediatric patient of anti-IgLON5 encephalitis with epileptic seizures as the first symptom.

BACKGROUND: Anti-IgLON5 encephalitis was a rare neurological and heterogeneous disorder, which was mainly found in adults. Epileptic seizures related to anti-IgLON5 disease were rarely reported. METHODS: Neural antibodies associated with autoimmune encephalitis in serum and cerebrospinal fluid (CSF) were tested using cell-based assays (CBA) with immunofluorescence double staining. The antibodies in serum were further confirmed by tissue-based assay (TBA) with rat brain and kidney tissue. RESULTS: We reported a pediatric case presented with epileptic seizures, cognitive impairments, and sleep disorders. Autoantibody screening showed anti-IgLON5 antibody IgG (1:100+) and anti-NMDAR antibody IgG (1:10+) in the serum. She was diagnosed as anti-IgLON5 encephalitis. Her conditions improved rapidly by treated with intravenous immunoglobulin and high dose intravenous methylprednisolone. CONCLUSION: We described the second pediatric case with anti-IgLON5 encephalitis, who was also the first presented with epileptic seizures as the initial presentation. Anti-IgLON5 encephalitis might have mild manifestations. For patients with new onset seizures associated with cognitive impairments and sleep disturbances, anti-IgLON5 antibody should be tested as early, even in children.

Exploring drug repositioning possibilities of kinase inhibitors via molecular simulation.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

Increasing the frequency of plant-based food intake in daily diets reduces the risk of cardiovascular disease among elderly Chinese: a cohort study.

Objective: There is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption. Methods: This study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011-2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results. Results: This study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise. Conclusion: The PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.

Single particle characteristics and ice nucleation potential of particles collected during Asian dust storms in 2021.

Dust storms have great impacts on air quality and climate. Dust can influence cloud microphysical properties and determine their radiative forcing and precipitation. Asian dust storms (ADS) are important sources of global aerosol. However, the physiochemical characteristics of dust from ADS at a single particle level are less understood, and the exact particles that can serve as ice nucleating particles (INPs) remain unclear. Here, we present the physicochemical properties and ice nucleation ability of dust particles collected in Beijing during two major ADS in March 2021. The particles from two ADS were classified into Illite, Kaolinite, Feldspar, Quartz, Chlorite, Mixed-dust, and Non-dust particles, which contributed 28.6 % ± 3.3 %, 20.0 % ± 3.9 %, 12.3 % ± 2.3 %, 11.1 % ± 2.8 %, 9.8 % ± 0.8 %, 13.7 % ± 1.8 %, and 4.4 % ± 1.7 % in number, respectively. On average, the ADS particles formed ice crystals via deposition ice nucleation from relative humidity with respect to ice (RHice) of 112 % ± 1 % at 250 K to 154 % ± 15 % RHice at 205 K. Part of the samples also formed ice via immersion freezing between 230 K and 250 K. Among the 149 identified INPs, Clay-like particles (Chlorite, Illite, and Kaolinite) contributed 71.1 % ± 6.2 % in number and followed by Mixed-dust-like particles (16.9 % ± 8.7 %) and Feldspar-like particles (10.4 % ± 6.3 %). Enrichment factor of each particle type in INPs is calculated as the ratio of its number fractions in INPs and the aerosol population. It ranges from 0.6 ± 0.7 to 1.3 ± 2.2. The contribution of each particle type to INP was correlated with its fraction in the population. These results imply that each particle type can serve as INP. Clay-like particles are the dominant INPs during the ADS. We conducted ice nucleation kinetic analysis and provided parameterizations of heterogeneous ice nucleation rate coefficient and contact angle for ADS. These parameterizations can be used in the modeling study to evaluate the impact of ADS in atmospheric ice crystal formation in clouds.

Radiomics Models Derived From Arterial-Phase-Enhanced CT Reliably Predict Both PD-L1 Expression and Immunotherapy Prognosis in Non-small Cell Lung Cancer: A Retrospective, Multicenter Cohort Study.

RATIONALE AND OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) and programmed cell death-ligand 1 (PD-L1) is a companion biomarker. This study aims to use baseline arterial-phase enhanced CT (APECT) to construct efficient radiomic models for predicting PD-L1 expression and immunotherapy prognosis in NSCLC. MATERIALS AND METHODS: We extracted radiomics features from the baseline APECT images of 204 patients enrolled in a published multicenter clinical trial that commenced on August 23, 2018, and concluded on November 15, 2019 (ClinicalTrials.gov: NCT03607539). Of these patients, 146 patients from selected centers were assigned to the training cohort. The least absolute shrinkage and selection operator (LASSO) method was used to reduce dimensionality of radiomics features and calculate tumor scores. Models were created using naive bayes, decision trees, XGBoost, and random forest algorithms according to tumor scores. These models were then validated in an independent validation cohort comprising 58 patients from the remaining centers. RESULTS: The random forest algorithm outperformed the other methods. In the three-classification scenario, the random forest model achieving the area under the curve (AUC) values of 0.98 and 0.94 in the training and validation cohorts, respectively. In the two-classification scenario, the random forest model achieved AUCs of 0.99 (95%CI: 0.97-1.0, P < 0.0001) and 0.93 (95%CI: 0.83-0.98, P < 0.0001) in the training and validation cohorts, respectively. Furthermore, patients classified as PD-L1 high-expression by this model can predict treatment response (AUC=0.859, 95%CI: 0.7-0.96, P < 0.001) and improved survival (HR=0.2, 95%CI: 0.08-0.53, P = 0.001) only in validation sintilimab arm. CONCLUSION: Radiomics models based on APECT represent a potential non-invasive approach to robustly predict PD-L1 expression and ICI treatment outcomes in patients with NSCLC, which could significantly improve precision cancer immunotherapy.

Undescribed polyketides from endophytes associated with the critically endangered conifer Abies beshanzuensis.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

Effect of different inhalant allergens on T-cell subsets in adults with bronchial asthma.

OBJECTIVE: We analyzed the impact of different inhalant allergens on T-lymphocyte subsets in patients diagnosed with bronchial asthma. METHODS: The study included 57 bronchial asthma patients and 22 healthy controls. Asthma patients were categorized into dust mite, animal hair, pollen, and mold groups. Flow cytometry was used to measure the cells in the case group and control group. These T-lymphocyte subset markers were evaluated among patients with bronchial asthma caused by different allergens as well as between the case group and control group. RESULTS: Peripheral blood CD4+ T-cells, CD8+ T-cells, CD4/CD8 ratio, and Th17/Treg ratios were all higher in the case group than in the control group (p < 0.05). Peripheral blood T-lymphocyte subsets were compared among the four groups, and it was found that there were statistical differences in the Th17/Treg ratio among the four groups (p < 0.05). There were no significant differences observed among the four groups in terms of CD3+ cells, CD4+ cells, CD8+ cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, Th9 cells, and Th22 cells. Further pairwise comparison was made, and the results suggested that the peripheral blood Th17/Treg ratio in the pollen mixed group was lower than that in the dust mite mixed group, animal hair mixed group, and mold mixed group (p < 0.05). CONCLUSION: Patients with bronchial asthma show varied T-lymphocyte subset responses to different inhalant allergens. Elevated CD4+ T cells and Th17 cells in peripheral blood could indicate asthma risk. However, small sample size may introduce bias to these findings.

Therapeutic application of decellularized porcine small intestinal submucosa scaffold in conjunctiva reconstruction.

The objective of this study was to investigate the biological feasibility and surgical applicability of decellularized porcine small intestinal submucosa (DSIS) in conjunctiva reconstruction. A total of 52 Balb/c mice were included in the study. We obtained the DSIS by decellularization, evaluated the physical and biological properties of DSIS in vitro, and further evaluated the effect of surgical transplantation of DSIS scaffold in vivo. The histopathology and ultrastructural analysis results showed that the scaffold retained the integrity of the fibrous morphology while removing cells. Biomechanical analysis showed that the elongation at break of the DSIS (239.00 ± 12.51%) were better than that of natural mouse conjunctiva (170.70 ± 9.41%, P < 0.05). Moreover, in vivo experiments confirmed the excellent biocompatibility of the decellularized scaffolds. In the DSIS group, partial epithelialization occurred at day-3 after operation, and the conjunctival injury healed at day-7, which was significantly faster than that in human amniotic membrane (AM) and sham surgery (SHAM) group (P < 0.05). The number and distribution of goblet cells of transplanted DSIS were significantly better than those of the AM and SHAM groups. Consequently, the DSIS scaffold shows excellent biological characteristics and surgical applicability in the mouse conjunctival defect model, and DSIS is expected to be an alternative scaffold for conjunctival reconstruction.

A case of variant of GBS with positive serum ganglioside GD3 IgG antibody.

BACKGROUND: Acute bulbar palsy-plus (ABPp) syndrome is an unusual variant of Guillain-Barré syndrome (GBS). Anti-GT1a and anti-GQ1b antibodies have been reported in patients with ABPp, but without reports related to GD3 antibodies. METHODS: Clinical data of a patient diagnosed as ABPp syndrome were reviewed clinically. And we summarized the GBS patients with ABP and facial paralysis reported in the literature. RESULTS: We reported a 13-year-old girl presented with asymmetric bifacial weakness, bulbar palsy and transient limb numbness, and had positive serum IgG anti-GD3 antibody. Through reviewing the GBS patients with ABP and facial paralysis reported previously, we found that facial palsy could be unilateral or bilateral. The bilateral facial palsy could present successively or simultaneously, and could be symmetrical or asymmetrical. Other common symptoms included ophthalmoplegia, sensory abnormality and ataxia. IgG anti-GT1a and IgG anti-GQ1b antibodies were the most frequent. Most of the patients had full recovery within two weeks to one year of follow-up. CONCLUSIONS: We reported a patient with asymmetric bifacial palsy and bulbar palsy, which seemed to fit the diagnosis of ABPp syndrome. This was the first report of ABPp variant of GBS with positive serum ganglioside GD3 IgG antibody.

Two Mn(II)-Bridged Silverton-Type [UMo12O42]8- Polyoxometalates with Catalytic Activity for the Synthesis of Pyrazoles.

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

Zinc supplementation alleviates oxidative stress to inhibit chronic gastritis via the ROS/NF-κB pathway in a mouse model.

Zinc (Zn) is an important trace element; it is involved in the regulation and maintenance of many physiological functions in organisms and has anti-inflammatory and antioxidant properties. Chronic gastritis is closely associated with damage to the gastric mucosa, which is detrimental to the health of humans and animals. There are few studies on the effects of zinc on, for example, gastric mucosal damage, oxidative stress, inflammation and cell death in mice. Therefore, we established in vivo and in vitro models of inflammatory injury and investigated the effects of zinc supplementation in C57BL/6 mice and Ges-1 cells and examined the expression of factors associated with oxidative stress, inflammation and cell death. In this study, the results of in vivo and in vitro experiments showed that reactive oxygen species (ROS) levels increased after sodium salicylate exposure. Malondialdehyde levels increased, the activity of the antioxidant enzymes catalase and superoxide dismutase decreased, and the activity of glutathione decreased. The NF-κB signaling pathway was activated, the levels of proinflammatory factors (TNF-α, IL-1ß, and IL-6) increased, and the expression of cell death-related factors (Bax, Bcl-2, Caspase3, Caspase7, Caspase9, RIP1, RIP3, and MLKL) increased. Zinc supplementation attenuated the level of oxidative stress and reduced the level of inflammation and cell death. Our study indicated that sodium salicylate induced the production of large amounts of reactive oxygen species and activated the NF-κB pathway, leading to inflammatory damage and cell death in the mouse stomach. Zinc supplementation modulated the ROS/NF-κB pathway, reduced the level of oxidative stress, and attenuated inflammation and cell death in the mouse stomach and Ges-1 cells.

A transthyretin-like protein acts downstream of miR397 and LACCASE to regulate grain yield in rice.

Increasing grain yield is a major goal of breeders due to the rising global demand for food. We previously reported that the miR397-LACCASE (OsLAC) module regulates brassinosteroid (BR) signaling and grain yield in rice (Oryza sativa). However, the precise roles of laccase enzymes in the BR pathway remain unclear. Here, we report that OsLAC controls grain yield by preventing the turnover of TRANSTHYRETIN-LIKE (OsTTL), a negative regulator of BR signaling. Overexpressing OsTTL decreased BR sensitivity in rice, while loss-of-function of OsTTL led to enhanced BR signaling and increased grain yield. OsLAC directly binds to OsTTL and regulates its phosphorylation-mediated turnover. The phosphorylation site Ser226 of OsTTL is essential for its ubiquitination and degradation. Overexpressing the dephosphorylation-mimic form of OsTTL (OsTTLS226A) resulted in more severe defects than did overexpressing OsTTL. These findings provide insight into the role of an ancient laccase in BR signaling and suggest that the OsLAC-OsTTL module could serve as a target for improving grain yield.

Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors.

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

Global climate change: Effects of future temperatures on emergency department visits for mental disorders in Beijing, China.

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

Research progress of acupuncture regulating ERK signaling pathway in the treatment of depression. / 针刺调控ERKä¿¡å·é€šè·¯æ²»ç–—æŠ‘éƒç—‡çš„ç ”ç©¶è¿›å±•.

Acupuncture treatment for depression has definite therapeutic efficacy, and its mechanism has been extensively studied. The extracellular regulatory protein kinase(ERK) signaling pathway is involved in the development and progression of depression. This article reviewed and summarized the research progress on the regulation of the ERK signaling pathway by acupuncture in the treatment of depression in recent years, focusing on the physiological activation and regulatory mechanism of the ERK signaling pathway, its association with the occurrence of depression, and the mechanisms through which acupuncture activates the ERK signaling pathway to treat depression (including enhancing neuronal synaptic plasticity, promoting the release of neurotrophic factors, and inhibiting neuronal apoptosis). Future research could explore the relationship between the ERK pathway and other pathways, investigate other brain regions besides the prefrontal cortex and hippocampus, examine differences in regulatory mechanisms between male and female patients, assess the effects of different acupuncture techniques on the ERK pathway, and increase efforts to explore mechanism of synaptic plasticity regulation, so as to provide reference for the clinical application and mechanism sludy of acupuncture in depression treatment.