Metastasis is a key cause of death in tumor patients, and a number of tumor patients have comorbid psychosomatic abnormalities and are in a state of chronic stress. Chronic stress affects the release of many kinds of hormones and neurotransmitters, such as epinephrine, norepinephrine, dopamine, glucocorticoids, cortisol, sex hormones, etc., through the hypothalamus–pituitary–adrenal axis and sympathetic nervous system. These substances can act on the β-adrenergic receptor, glucocorticoid receptor, etc., on tumor cells, immune cells, and other cells in the tumor microenvironment and promote the tumor progression and metastasis by directly enhancing the invasive and metastatic ability of tumor cells, inducing the formation of the immunosuppressive microenvironment and promoting tumor angiogenesis and other pathways. Antipsychotic drugs, β-blockers, and glucocorticoid receptor antagonists have inhibitory effects on chronic stress-mediated tumor metastasis and have achieved certain clinical efficacy. Relevant studies have been carried out on traditional Chinese medicine decoctions and monomers, which can inhibit tumor metastasis by modulating the immune microenvironment and reversing chronic stress-mediated hormonal changes. The psychological problems of tumor patients have gradually received attention, and the development of new anti-metastatic drugs based on the mechanism of action of chronic stress in promoting tumor progression and metastasis provides new ideas for the improvement of the overall efficiency of tumor prevention and treatment.

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics* ; Wnt Signaling Pathway/drug effects* ; Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neoplasm Metastasis/prevention & control* ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Neutrophil Infiltration/drug effects* ; Down-Regulation/drug effects* ; Cell Movement/drug effects* ; beta Catenin/genetics* ; Apoptosis/drug effects* ; Mice, Inbred C57BL ; Male ; Neoplastic Cells, Circulating/drug effects*

Lung cancer is the leading cause of cancer-related deaths worldwide,with metastasis being the primary cause of mortality in lung cancer patients,and its prevention and control efficacy remain limited.In recent years,immunothera-py has emerged as a promising direction for overcoming the bottleneck of metastasis.Macrophages,as essential components of innate immunity,participate in the entire process of tumor initiation and progression.Tumor-associated macrophages(TAMs)represent the most abundant immune population in the tumor microenvironment(TME),displaying both anti-tumor M1-like and pro-tumor M2-like phenotypes.The latter promotes tumor invasion and metastasis,angiogenesis,lymphangiogenesis,immune suppression,and reactivation of dormant disseminated tumor cells(DTCs),thereby facilitating tumor metastasis.In recent years,traditional Chinese medicine(TCM)has shown significant efficacy in inhibiting tumor metastasis and has been extensively validated.It exerts anti-tumor effects by reducing the recruitment of TAMs,inhibiting M2-like polarization,and modulating cytokines and proteins in the TME.This paper reviews the relationship between TAMs and lung cancer metastasis,elucidates the targets and mechanisms of TCM in regulating TAMs to prevent and treat lung cancer metastasis,aiming to pro-vide insights into lung cancer prevention and treatment.

Abstract OBJECTIVE To analyze the differences in adverse drug reactions between newborns using medium/long chain fat emulsions and multiple types of oil fat emulsions, and to explore potential risk factors. METHODS A retrospective cohort study was conducted using data from newborns who used medium/long chain fat emulsions or multiple oil fat emulsions from January 2020 to June 2023. The China Hospital Pharmacovigilance System(CHPS) was used to retrieve adverse reaction information and evaluate it. Four hundred and ninety-nine newborns in the medium/long chain fat emulsion group and 1 940 newborns in the multiple oil fat emulsion group were included. Using logistic regression and stratified analysis to explore the safety differences between groups and the risk factors that affect the occurrence of adverse reactions. RESULTS The total incidence of adverse reactions in the medium/long chain fat emulsion group was 19.24%, with common adverse reactions including fever(5.81%), decreased hemoglobin(3.01%), increased blood pressure(2.40%) and hypoglycemia(2.40%); The total incidence of adverse reactions in the group of multiple oil fat emulsions was 36.44%, with a very common adverse reaction being fever(10.57%); common adverse reactions include decreased hemoglobin(8.97%), decreased blood pressure(3.20%), and increased blood pressure(3.09%); rare adverse reactions include liver dysfunction(0.05%), splenomegaly(0.05%) and cyanosis (0.05%). In univariate analysis, the risk of fever, decreased hemoglobin, and increased blood sugar in the group of multiple oil fat emulsions was higher than that in the medium/long chain fat emulsion group(P<0.05), but this association did not show statistical differences in the overall multivariate analysis. Furthermore, a stratified factor analysis based on gestational age found that the risk of fever and decreased hemoglobin in the group of multiple oil fat emulsions was significantly higher than that in the medium/long chain fat emulsion group in extremely premature infants. The corresponding OR(95%CI) were 6.437(1.327, 31.227) and 5.066(1.089, 23.570), respectively, with no significant differences observed in other gestational age stratification. CONCLUSION The risk of using medium/long chain fat emulsions in newborns is similar to that of using multiple types of oil fat emulsions. However, in extremely premature infants, the risk of fever and decreased hemoglobin in multiple types of oil fat emulsions is higher than that in medium/long chain fat emulsions. It is recommended to regularly monitor indicators such as body temperature, hemoglobin, and blood pressure, and do a good job in drug vigilance.

Objective:To evaluate the accuracy of airway ultrasonic parameters in predicting difficult mask ventilation (DMV) in obese patients.Methods:Ninety-six patients of both sexes, aged >18 yr, with body mass index of 28- <40 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective surgery under general anesthesia with endotracheal intubation, were selected. The airway was evaluated at 1 day before surgery to record the thyromental distance, modified Mallampati classification and upper lip bite test classification. Before anesthesia induction, the mandibular condylar motion, longitudinal cross-sectional area and transverse diameter of the tongue were measured by ultrasound, and the tongue volume was calculated. Mask ventilation was performed after anesthesia induction, DMV classification was recorded, DMV was defined as DMV classification Ⅲ and Ⅳ, and the patients were divided into non-DMV group (NDMV group) and DMV group. Spearman correlation analysis was used to analyze the correlation between each parameter and DMV, the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of each parameter in predicting DMV, and the cut-off value was determined based on the principle of Jorden index at maximum. Results:Ninety-six patients were finally included in the study, with 64 patients in NDMV group and 32 patients in DMV group. Compared with NDMV group, the increase in age, modified Mallampati grade, upper lip biting test grade, longitudinal cross-sectional area of tongue, transverse diameter of tongue and volume of tongue were significantly increased, and the thyromental distance and mandibular condylar motion were decreased in DMV group ( P<0.05). Age ( r=0.283), modified Mallampati grade ( r=0.668), upper lip biting test classification ( r=0.826), tongue longitudinal cross-sectional area ( r=0.598), tongue transverse diameter ( r=0.578) and tongue volume ( r=0.707) were positively correlated with DMV ( P<0.01), and thyromental distance ( r=-0.623) and mandibular condylar motion ( r=-0.666 ) were negatively correlated with DMV ( P<0.05). The area under curve (95% confidence interval) of tongue longitudinal cross-sectional area, tongue transverse diameter, tongue volume, and mandibular condylar motion for DMV prediction were 0.870 (0.780-0.961), 0.858 (0.768-0.948), 0.937 (0.864-1.000), 0.912 (0.835-0.990), respectively ( P<0.01), and the predicted cut-off values were 22.61 cm 2, 4.29 cm, 100.60 cm 3 and 1.18 cm, respectively, the sensitivity was 90%, 83%, 90% and 90%, respectively, the specificity was 80%, 80%, 95% and 95%, respectively. Conclusions:Tongue volume and mandibular condylar motion measured by ultrasound are highly accurate in predicting DMV in obese patients. Tongue volume> 100.60 cm 3 or mandibular condylar motion< 1.18 cm suggests a high risk of DMV.

Objective To explore the effect of immune senescence on lung cancer metastasis and reveal the mechanism of Fuzheng traditional Chinese medicine Jinfukang in the prevention and treatment of the metastasis. Methods A lung metastasis model of Lewis lung cancer cells was established in C57BL/6 mice with different ages (15 months, 6 months, and 2 months). Mice in the 6-month-old group were given Jinfukang intragastrically for 42 days. Pulmonary metastasis was analyzed by in vivo imaging, anatomical microscopic observation, and HE staining. The proportion of memory T cells and NK cells in peripheral blood was detected by flow cytometry. Results The lung metastatic tumor formation rate of 15-month-old and 6-month-old mice was significantly higher than that of 2-month-old mice (all P < 0.05). Abundance of CD4+T cells in peripheral blood was positively correlated with age (2-month-old vs. 6-month-old, P=0.041; 2-month-old vs.15-month-old, P=0.041; 6-month-old vs.15-month-old, P=0.953). The abundance of NK cells was negatively correlated with age (2-month-old vs. 6-month-old, P=0.009; 2-month-old vs.15-month-old, P=0.009; 6-month-old vs. 15-month-old, P=0.574). However, the survival time of mice in the Jinfukang group was longer (P > 0.05) and the level of NK cells in peripheral blood was significantly higher (P=0.029) than those in the normal saline group. Conclusion Immune senescence can promote the metastasis of lung cancer. The prolongation of the survival time of mice administered with Jinfukang may be related to delaying immune senescence and increasing the number of NK cells.

Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.

Metastasis is the main factor leading to the death of patients with lung cancer, and active prevention is the key to improve the efficacy of treatment. Circulating tumor cells (CTCs) play an important role in initiating metastasis. They trigger a series of metastatic cascade reactions at the moment of shedding from the primary focus, and finally colonize and proliferate in the distant target organs. In recent years, the detection technology of lung cancer CTCs has been continuously optimized. It can not only count CTCs, but also identify different subsets. CTCs detection of lung cancer can be used for early screening, the prediction of prognosis after surgery and chemoradiotherapy and the evaluation of curative effect of targeted immunotherapy. Dynamic monitoring of tumor heterogeneity is helpful to adjust personalized treatment plan and achieve the accurate treatment of cancer. Tian Jianhui's research group established the world's first circulating tumor cell line of human lung adenocarcinoma, integrated it into the theory of "positive deficiency and toxin" in the subclinical core pathogenesis of lung cancer, and actively promoted the construction of a specific research platform for lung cancer, in order to improve the research, prevention and control efficiency of lung cancer metastasis.

Objective: To investigate the application value of real-time virtual sonography(RVS)in the diagnosis and treatment of complicated hepatolithiasis. Methods: The retrospective and descriptive study was conducted. The clinical data of 10 patients with complicated hepatolithiasis who were admitted to Hunan Provincial People′s Hospital between October 2017 and March 2018 were collected. There were 3 males and 7 females, aged from 40 to 69 years, with an average age of 57 years. Patients received abdominal color Doppler ultrasound examination, magnetic resonance cholangiopancreatography, and upper abdominal spiral computed tomography (CT) thinly scanning + enhanced examination. Data of CT examination were imported into RVS. RVS was used to locate hepatolithiasis, relationship between stones and vessels, anatomy of bile ducts and vessels in hepatic hilus. Surgical methods included RVS-guided hilar cholangiotomy, biliary stricturoplasty, bilateral hepatojejunostomy, hepatic segmentectomy (lobectomy), and hepatolithotomy. Observation indicators: (1) surgical and postoperative situations; (2) typical case analysis; (3) follow-up. Follow-up using outpatient examination was performed to detect residual stones up to June 2019. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results: (1) Surgical and postoperative situations: 10 patients underwent RVS-guided surgeries successfully for complicated hepatolithiasis, with successful match in RVS (difference between CT images and ultrosound images <2 mm). No residual stone was identified by choledochoscope during operation. The operation time and volume of intraoperative blood loss were 285 minutes (range, 210-360 minutes) and 200 mL (range, 100-600 mL), respectively. No blood transfusion was needed during the operations. The duration of hospital stay was 20.5 days (range, 14.0-29.0 days). There was no perioperative death. One patient had postoperative biliary leakage and abdominal infection, and was cured after conservative treatment. (2) Typical case analysis: the tenth patient, female, 60 years old, was diagnosed with complicated hepatolithiasis, and was prepared to undergo hepatolithotomy+ quadrate lobectomy and hilar cholangioplasty+ bilateral hepatojejunostomy. Preoperative CT images and intraoperative color Doppler ultrasound images of the patient were fused and matched on the sagittal section of the portal vein and the cross section of the right branch of portal vein, and stones and important vessels were marked on the images. After accurate positioning, a curette was used to remove the stones. Removal of biliary stones through hepatic parenchyma and peripheral dilated bile ducts was conducted at the site where stones obviously existed. After the stones were removed, the intrahepatic bile duct and hilar bile duct merged. The left end of the bile duct split was confirmed by real-time ultrasound. After location of portal vein was determined by ultrasound, vascular plastic surgery was perfomed to avoid stenosis. (3) Follow-up: 10 patients were followed up for 6-12 months, with a median follow-up time of 8 months. One of 10 patients was suspected residual stones at the right peripheral hepatic anterior lobe by postoperative angiography at 2 months after surgery, and was not removed stones by choledochoscope. The patient had no recurrent symptoms after T-tube removal. The other 9 patients had no residual stones. Conclusion RVS applied in complicated hepatolithiasis is helpful for the precise intraoperative diagnosis, and the surgical treatment can be safe and effective.

Objective To investigate the effects of phosphcreatine preconditioning on lung injury induced by renal ischemia-reperfusion (IR) in rats.Methods Forty-five SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 180-220 g, were randomly divided into 3 groups using a random number table:sham operation group (group S), renal IR group (group IR), and phosphcreatine preconditioning group (group PCr), 15 cases in each group.The rats in group S recieved dissoci ation of renal pedicles and right nephrectomy, on top of which renal IR model was prepared in group IR and group PCr.phosphcreatine 150 mg/kg was injected in group PCr for 30 minutes before ischemia, where as rats in group S and group I/R recieved the normal saline at the same time.The blood samples were obtained from left ventricle at 6 hours after reperfusion, the arterial blood gas analysis was performed in order to determined the oxygen partial pressure (PaO2).Serum levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were also determined.Fluo 3-AM staining and flow cytometry were used to measure the concentration of alveolar macrophage calcium ions.The lung tissue was obtained with HE staining for determination of microscope examination of pathologic changes, and weight/dry (W/D) ratio were also determined.The lung tissue cell apoptotic rate was measured by Annexin V/PI apoptosis detection reagent staining and flow cytometry.Fluo 3-AM staining and flow cytometry were used to measure the concentration of alveolar macrophage calcium ions.Results Compared with group S, the histopathological demages, W/D ratio, lung tissue cell apoptotic rate, the serum levels of MDA and the concentration of alveolar macrophage calcium ions were signifcant increased (P<0.05), whereas the PaO2 and the activity of SOD were signifcantly decreased in group IR and group PCr (P<0.05).Compared with group IR, the histopathological demages, W/D ratio, lung tissue cell apoptotic rate, the serum levels of MDA and the concentration of alveolar macrophage calcium ions were signifcant decreased (P<0.05), whereas the PaO2 and the activity of SOD were signifcantly increased in group PCr (P<0.05).Conclusion Phosphcreatine preconditioning can attenuate lung injury induced by renal I/R, the mechanism is related to inhabit oxidative stress, and reduce cell apopotosis and calcium overload.