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Abstract Background Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear. Methods This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group. Results As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5–42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively (p = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs (p = 0.021) and patients with L858R mutation (p = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0–4.0 was the only independent protective factor. Conclusions This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.

Many behavioural interactions in real life involve three individuals. When each individual has two alternative strategies, they can be abstracted into mathematical models by means of [Formula: see text] asymmetric games. In this paper, we explore a special class of [Formula: see text] asymmetric games satisfying fixed conditions. Firstly, we analyse two solitary interior equilibrium points and provide the judgement condition for their instability based on the Jacobi matrix local stability analysis method. Secondly, we analyse the interior equilibrium points that are continuously distributed within a line and probe into their stability conditions based on generalized Hamiltonian systems theory. Under the circumstances, the stable interior equilibrium point is surrounded by closed orbits in phase space, which presents an observable stable state where two strategies coexist and fluctuate in each of the three game populations. This work enriches the study of [Formula: see text] asymmetric games’ evolutionary dynamics.

Objective: In this study, we introduce a surgical procedure for multiple-quadrant hemorrhoid crisis, namely Lingnan surgery, and discuss its clinical efficacy and safety. Methods: We performed a retrospective analysis of patients with acute incarcerated hemorrhoids who underwent Lingnan surgery at the Anorectal Department of Yunan County Hospital of Traditional Chinese Medicine of Guangdong Province from 2017 to 2021. The baseline data, preoperative condition, and postoperative condition of each patient were recorded in detail. Results: A total of 44 patients were studied. There were no cases of massive hemorrhage, wound infection, wound nonunion, anal stenosis, abnormal anal defecation, recurrent anal fissure, or mucosal eversion within 30 days after surgery, and no recurrence of hemorrhoids and anal dysfunction occurred during the 6-month follow-up after surgery. The average operation time was 26.5 ± 6.2 min (17–43 min). The average length of hospital stay was 4.0 ± 1.2 days (2–7 days). In terms of postoperative analgesia, 35 patients took oral nimesulide, 6 did not use any analgesics, and 3 required nimesulide plus tramadol by injection. The mean Visual Analog Scale pain score was 6.8 ± 0.8 preoperatively and 2.9 ± 1.2, 2.0 ± 0.7, and 1.4 ± 0.6 at 1, 3, and 5 days postoperatively, respectively. The average basic activities of daily living score was 98.2 ± 2.6 (90–100) at discharge. Conclusion: Lingnan surgery is easy to perform and has obvious curative effects, providing an alternative to conventional procedures for acute incarcerated hemorrhoids.

Under the background that asymptomatic virus carriers have infectivity for an infectious disease, we establish a difference equations model with vaccination and virus testing in this paper. Assuming that the vaccine is 100% effective for susceptible people but cannot stop the infectivity of asymptomatic virus carriers, we study how to combine vaccination and virus testing at the beginning of an epidemic to effectively block the spread of infectious disease in different population sizes. By considering the daily processing capacity of the vaccine and daily proportion of testing, the corresponding numerical simulation results are obtained. It is shown that when vaccine availability and virus testing capacity are insufficient, a reasonable combination of the above two measures can slow down or even block the spread of infectious disease. Single virus testing or vaccination can also block the spread of infectious disease, but this requires a lot of manpower, material and financial resources. When the daily proportion of virus testing is fixed, the ratio of the minimum daily processing capacity of vaccines used to block the spread of infectious disease to the corresponding population size is rather stable. It demonstrates that effective protective measures of the same infectious disease in countries and regions with different population sizes can be used as a reference. These results also provide a certain reference for decision makers on how to coordinate vaccines and virus testing resources to curb the spread of such an infectious disease in a certain population size.

ABSTRACT Metabolism associated with energy production is highly compartmentalized in eukaryotic cells. During this process, transporters that move metabolites across organelle membranes play pivotal roles. The highly conserved ADP/ATP carrier (AAC) involved in ATP and ADP exchange between the mitochondria and cytoplasm is key to linking the metabolic activities in these 2 compartments. The ATP produced in mitochondria can be exchanged with cytoplasmic ADP by AAC, thus satisfying the energy needs in the cytoplasm. Toxoplasma gondii is an obligate intracellular parasite with a wide range of hosts. Previous studies have shown that mitochondrial metabolism helps Toxoplasma to parasitize diverse host cells. Here, we identified 2 putative mitochondria ADP/ATP carriers in Toxoplasma with significant sequence similarity to known AACs from other eukaryotes. We examined the ATP transport function of TgAACs by expressing them in Escherichia coli cells and found that only TgAAC1 had ATP transport activity. Moreover, knockdown of TgAAC1 caused severe growth defects of parasites and heterologous expression of mouse ANT2 in the TgAAC1 depletion mutant restored its growth, revealing its importance for parasite growth. These results verified that TgAAC1 functions as the mitochondrial ADP/ATP carrier in T. gondii and the functional studies demonstrated the importance of TgAAC1 for tachyzoites growth. IMPORTANCE T. gondii has an efficient and flexible energy metabolism system to meet different growth needs. ATP is an energy-carrying molecule and needs to be exchanged between organelles with the assistance of transporters. However, the function of TgAACs has yet to be characterized. Here, we identified 2 putative AACs of T. gondii and verified that only TgAAC1 had ATP transport activity with expression in the intact E. coli cells. Detailed analyses found that TgAAC1 is critical for the growth of tachyzoites and TgAAC2 is dispensable. Moreover, complementation with mouse ANT2 restored the growth speed of iTgAAC1, further suggesting TgAAC1 functions as a mitochondrial ADP/ATP carrier. Our research demonstrated the importance of TgAAC1 for tachyzoites growth.

Abstract Background We aimed to explore the prognostic utilities of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 (nCD64) index, in combination or alone, in septic patients. Methods We retrospectively included 349 septic patients (based on Sepsis 3.0 definition). The primary outcome was 28-day all-cause mortality. Cox regression model, receiver-operating characteristic (ROC) curve, reclassification analysis, Kaplan–Meier survival curves were performed to evaluate the predictive efficacy of the above parameters. Results CRP, nCD64 index were independent predictors of 28-day mortality for sepsis in the Cox regression model [CRP, HR 1.004 (95% CI 1.002–1.006), P

Background and Objective: Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its genetic growth potential in utero resulted by maternal, placental, fetal, and genetic factors. Previous studies have reported that IUGR is associated with a high incidence of neurological damage, although the precise causes of such damage remain unclear. We aimed to investigate whether cognitive impairment in rats with IUGR is related to pyroptosis of hippocampal neurons and determine the effect of early intervention with docosahexaenoic acid (DHA). Methods: Learning and memory function was assessed using the Morris water maze test. The morphological structure and ultrastructure of the hippocampus was examined via hematoxylin and eosin staining and electron microscopy respectively. The pyroptosis of hippocampal neuron was detected by gasdermin-D (GSDMD) immunofluorescence staining, mRNA and protein expression of nuclear localization leucine-rich-repeat protein 1 (NLRP1), caspase-1, GSDMD, and quantification of inflammatory cytokines interleukin (IL)-1β and IL-18 in the hippocampus. Results: IUGR rats exhibited decreased learning and memory function, morphological structure and ultrastructural changes in hippocampus compared to controls. IUGR rats also exhibited increased hippocampal quantification of GSDMD immunofluorescence staining, increased mRNA and protein expression of NLRP1, caspase-1, and GSDMD, and increased quantification of IL-1β and IL-18 in the hippocampus. Intervention with DHA attenuated these effects. Conclusion: Cognitive impairment in rats with IUGR may be related to pyroptosis of hippocampal neurons. Early intervention with DHA may attenuate cognitive impairment and reduce hippocampal pyroptosis in rats with IUGR.

Abstract In the present paper, based on the conditions that asymptomatic virus carriers are contagious and all symptomatic infected individuals wear masks, we study the impact of wearing masks in the susceptible and the asymptomatic virus carriers on the spread of infectious diseases by developing a differential equation model. At first, we give the existence, uniqueness, boundedness, and positivity of the solution as well as the basic reproduction number R 0 $R_{0}$ for the established model. Then, for two cases of wearing masks in the susceptible and the asymptomatic virus carriers where the proportion of wearing masks is fixed and the proportion of wearing masks changes with time, the results of the numerical simulation are shown in a series of pictures, and quantitative description of effects of the proportion of the population wearing masks, the protective effect of masks, and the time when they start wearing masks on the epidemic is given. Our results show that under the situation that the proportion of wearing masks is positively related to the confirmed new cases and new deaths, though the proportion will be close to 1 during the high incidence of patients, the effect on controlling the spread of such infectious diseases is far worse than the case of always maintaining a relatively higher proportion (≥0.66) of wearing masks.

SARS-CoV-2 is transmitted by contacting; however, the virus is so active that it can attach to objects and be transmitted from objects to humans via such contacting. The virus, which spreads through some living or inanimate-mediated processes, is more dangerous. On the basis of the routine contact transmission of infectious diseases, this paper further discusses the scope and efficiency of infectious diseases with indirect transmission. Through the study of two different transmission routes, the dynamic models of infectious diseases were constructed. The propagation of these two processes is theoretically studied using a differential equation model and stability analysis theory, and some actual virus propagation processes are simulated by numerical solutions. The prevention and control methods of infectious diseases are given, which lay the theoretical foundation for the discussion of related problems in practical application.

The spread of emerging self-limiting infectious diseases is closely related to medical resources. This paper introduces the concept of safe medical resources, i.e., the minimum medical resources that are needed to prevent the overburden of medical resources, and explores the impacts of medical resources on the spread of emerging self-limiting infectious diseases. The results showed that when the isolation rate of hospitalized patients who have mild infections is low, increasing the isolation rate of patients with severe infections requires safe more medical resources. On the contrary, when the isolation rate of hospitalized patients with mild infections is at a high level, increasing the isolation rate of patients with severe infections results in a decrease in safe medical resources. Furthermore, when the isolation rates of patients with mild and severe infections increase simultaneously, safe medical resources decrease gradually. That is to say, when the medical resources are at a low level, it is more necessary to improve the isolation rates of infected individuals so as to avoid the phenomenon of overburdened medical resources and control the spread of emerging infectious diseases. In addition, overwhelmed medical resources increase the number of deaths. Meanwhile, for different emerging self-limiting infectious diseases, as long as the recovery periods are the same, safe medical resources also remain the same.

Abstract Background The tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC). However, the effect of miR-1296-5p in ERBB2-positive breast cancers remains obscure. Methods Whether ERBB2 was the target gene of the miR-1296-5p was predicted by online software, and determined by dual-luciferase activity assay. miR-1296-5p expression levels were determined in breast cancer samples (114 breast cancer tissues and 30 adjacent normal tissues) by using qRT-PCR. The effect of miR-1296-5p and inhibition of ERBB2/mTORC1 signaling on the downstream target was assessed by Western blot. SK-BR-3 and BT-474 breast cancer cell line was transfected with miR-1296-5p mimic after which cell proliferation and apoptosis were determined by the clonogenic assay and the flow cytometry system, respectively. In addition, the chemotherapeutic drug sensitivity of SK-BR-3 and BT-474 cells transfected with miR-1296-5p mimic were determined by MTT assay. Results The luciferase assay carrying ERBB2 3′-untranslated region-based reporters expressed in SK-BR-3 and BT-474 cells suggested that ERBB2 was the target gene of miR-1296-5p. MiR-1296-5p was significantly decreased in breast cancer tissues compared to adjacent normal tissues. Moreover, it was declined in ERBB2-positive breast cancer samples compared with that in ERBB2-negative breast cancer tissues. Overexpressed miR-1296-5p reduced its target protein level and mTORC1/S6 activation, inhibited the proliferation of ERBB2-positive breast cancer cells and sensitized these cells to cisplatin and 5-fluorouracil-induced apoptosis. Conclusions Our findings suggest that miR-1296-5p is involved in the regulation of proliferation in breast cancer cells via targeting ERBB2/mTORC1 signaling pathway.

Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s). Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM) was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.

In this paper, we investigate the five-species Jungle game in the framework of evolutionary game theory. We address the coexistence and biodiversity of the system using mean-field theory and Monte Carlo simulations. Then, we find that the inhibition from the bottom-level species to the top-level species can be critical factors that affect biodiversity, no matter how it is distributed, whether homogeneously well mixed or structured. We also find that predators' different preferences for food affect species' coexistence.

In this paper a HBV infection model with impulsive vaccination is considered. By using fixed point theorem and stroboscopic map we prove the existence of disease-free T-periodic solution. Also by comparative theorem of impulsive differential equation we get the global asymptotic stability of the disease-free periodic solution and permanence of the disease. Numerical simulations show the influence of parameters on the dynamics of HBV, which provided references for seeking optimal measures to control the transmission of HBV.

We improve the traditional integrated pest management (IPM) control strategies and formulate three specific management strategies, which can be described by hybrid dynamical systems. These strategies can not only effectively control pests but also reduce the abuse of pesticides and protect the natural enemies. The aim of this work is to study how the factors, such as natural enemies optimum choice in the two kinds of different pests, timings of natural enemy releases, dosages and timings of insecticide applications, and instantaneous killing rates of pesticides on both pests and natural enemies, can affect the success of IPM control programmes. The results indicate that the pests outbreak period or frequency largely depends on the optimal selective feeding of the natural enemy between one of the pests and the control tactics. Ultimately, we obtain the only pest needs to be controlled below a certain threshold while not supervising pest .

Cyclically dominant systems are hot issues in academia, and they play an important role in explaining biodiversity in Nature. In this paper, we construct a five-strategy cyclically dominant system. Each individual in our system changes its strategy along a fixed direction. The dominant strategy can promote a change in the dominated strategy, and the dominated strategy can block a change in the dominant strategy. We use mean-field theory and cellular automaton simulation to discuss the evolving characters of the system. In the cellular automaton simulation, we find the emergence of spiral waves on spatial patterns without a migration rate, which suggests a new way to produce self-organized spatial patterns.