Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.

Hypoxic pulmonary hypertension(HPH)is a kind of chronic high-altitude sickness disease,which is also the initiation link of high-altitude sickness such as pneumocardial disease and high-altitude pulmonary edema.Its main features are persistent vasoconstriction and irreversible remodeling of blood vessels.HPH has greatly impacted the health of people in the plat-eau section.As a typical representative of ethnic medicine,Zang medicine embodies the wisdom of the Zang people in their long-term struggle against diseases.Adapting to local conditions for a long time,Zang medicine has unique advantages in the treatment of HPH.By reviewing the pathogenesis of HPH and the research of single Zang medicine and the complex prescription of Zang medicine in the treatment of HPH,this article aims to provide a theoretical basis for the physiological and pathological research of HPH and to provide a reference for the clinical application of Zang medicine.

Objective:To investigate the correlation between triglyceride-glucose (TyG) index on admission and unfavorable outcomes of patients with moderate-to-severe traumatic brain injury (msTBI) at 6 months postinjury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 277 patients with msTBI admitted to Affiliated Jiangyin Hospital of Nantong University from January 2019 to December 2022, including 208 males and 69 females, aged 18-88 years [(57.0±15.1)years]. Glasgow Coma Scale (GCS) scores on admission were 3-8 points in 168 patients and 9-12 points in 109. According to the Glasgow Outcome Scale-Extended (GOSE) assessment at 6 months after injury, there were 121 patients with unfavorable outcomes (GOSE≤4 points) and 156 with favorable outcomes (GOSE≥5 points). The following indicators of the patients were recorded, including gender, age, history of diabetes, cause of injury, admission GCS, GCS motor score (GCSM), pupillary light reflex, worst Marshall CT classification within the first 24 hours after admission, admission TyG index, Mean Amplitude of Glycemic Excursions (MAGE) within 24 hours after admission, GCSM decline≥2 points within 72 hours after admission, craniotomy or not after admission, and prognosis, etc. TyG index served as the exposure variable focused in this study, which was calculated with fasting triglycerides and fasting blood glucose within 24 hours after admission. The 6-month prognosis of the patients was designated as the outcome variable of the study. After the patients were divided into different groups according to the three quantiles of the TyG index and unfavorable or favorable outcomes, the univariate analysis was conducted on watch variables, and variables with statistically significant differences were included in directed acyclic graphs (DAGs) for further identification of confounding variables. Factors which were found with no statistical significance in the univariate analysis but might affect insulin resistance after injury according to the authors′ previous researches were also included in the DAGs analysis. Three Logistic regression models were designed (Model 1 without correction, Model 2 with core variables of International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) corrected, and Model 3 with confounding variables screened by DAGs corrected) to analyze whether the TyG index was an independent risk factor for the prognosis of msTBI patients. The optimal Logistic regression model was selected and then restricted cubic spline (RCS) was employed to investigate the relationship between the TyG index and the unfavorable outcomes.Results:The univariate analysis suggested that there were significant differences in gender, history of diabetes, MAGE, GCSM decline, and prognosis among the three quantiles of the TyG index ( P<0.05 or 0.01). Significant differences in age, history of diabetes, GCSM, pupillary light reflex, Marshall CT classification, TyG index, MAGE and GCSM decline were observed between unfavorable and favorable outcome groups ( P<0.05 or 0.01). The results of Logistic regression analysis that identified the confounding variables that influenced the correlation between the TyG index and unfavorable prognosis with DAGs suggested that a high TyG index level was significantly correlated with unfavorable outcomes in msTBI patients. Moreover, Model 3 that was corrected with confounding variables screened by DAGs had an optimal goodness-of-fit and adaptability. Model 3-based further RCS analysis indicated that the risk of unfavorable outcomes following msTBI may increase approximately linearly with the increase in TyG index within a certain range (TyG index<9.79). Conclusions:A high TyG index level on admission is the identified as an independent risk factor for unfavorable outcomes of patients with msTBI at 6 months postinjury. As the TyG index level increases, the risk of unfavorable outcomes also rises and may show a linear increasing trend within a certain range (TyG index<9.79).

Objective To analyze the timeliness of the start time of the first elective operation in a hospital and observe its impact on the operating room cost.Methods Make statistics and analysis on the opening of the first operation in a hospital,record the on-time opening rate of the first operation,analyze the reasons for the delay in the opening time of the first operation,formulate corresponding intervention measures and set up a"management team to improve the efficiency of operating room use".The on-time rate of the first operation,operation,cost control and the satisfaction of surgeons and patients were compared before and after the operation.Results The overall punctuality rate of the first operation was 53.74％,among which the colorectal sur-gery department had the highest punctuality rate of 63.16％,while the minimally invasive surgery department had the lowest punctuality rate of 45.45％.The main reasons for the delay of first operation(35.29％),failed anesthesia(30.88％),and the termination of the operation(17.65％);compared with before implementation,higher overtime time of nurses,shorter opening time and expected time,decreased interval between operation(P＜0.05),lower frequency of centralized delivery and unnecessa-ry consumables cost within 1 month after implementation(P＜0.05),and higher satisfaction of patients and physicians after im-plementation(P＜0.05).Conclusion By improving the first elective operation on time,can effectively reduce the cost of the operating room,shorten the nurse overtime time,at the same time improve the satisfaction of doctors and patients,and improve the management efficiency of the operating room,the first operation on time improved,interval time and unnecessary consumables costs are significantly reduced,optimize the use efficiency of the operating room resources.

Ischemic stroke is one of the important causes of disability and death among middle-aged and elderly people in China,and there are many complicated problems from diagnosis to treatment.At present,vascular recanalization has become the most important treatment for ischemic stroke.However,the prognosis of patients is still not ideal after vascular recanalization treatment alone.At the same time,the therapeutic effect of neuroprotective drugs targeting a single target is still not significant.Annexin A5 has many biological functions,such as anticoagulation,anti-inflammation,protection of neuron survival and so on,and can be used for neuroprotective therapy such as reducing reperfusion injury after cerebral vascular recanalization.Annexin A5 can be used in the diagnosis of stroke and the construction of targeted vectors because of its close binding with phosphatidylserine.The authors summarized the multiple functions of Annexin A5,and analyzes its possible effects on ischemic stroke,so as to provide reference for the follow-up study.

Both morbidity and mortality of gastric cancer are in the front rank among malignant tumors.At present,enhanced CT is served as an important imaging method for preoperative diagnosis and assessment of gastric cancer,but it is mostly based on morphological evaluation and unable to perform quantitative analysis.The functional imaging technology represented by energy spectral CT and CT perfusion imaging has a variety of quantitative parameters,which is expected to make up for the shortcomings of conventional CT.The review introduces the basic principles of energy spectral CT and CT perfusion imaging,and summarizes their applications in the diagnosis,pathological classification,grading,staging and efficacy prediction of gastric cancer,aiming to improve the understanding of functional CT imaging for the pretreatment assessment in gastric cancer.

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract,and they are also genetically heterogeneous tumors.c-KIT gene or PDGFRA gene mutation is the main driving factor leading to its occurrence,and it is also one of the key factors affecting the treatment and prognosis of patients with GISTs.Imaging examination is non-invasive and can display tumors from multiple angles and directions,making it the main method for preoperative evaluation of GISTs.With the continuous development of imaging technology,non-invasive and definite genotyping of GISTs by imaging methods before surgery plays a positive role in the selection of targeted drugs and doses for patients and the evaluation of targeted treatment efficacy.This article reviews the imaging progress on the genotype of GISTs and the efficacy of targeted therapy.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.
Mice ; Animals ; Receptor, trkB/metabolism* ; Neurons/metabolism* ; Signal Transduction