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*

The immune microenvironment plays a key role in the development and progression of tumors.In recent years,with the rapid advancement of high-throughput sequencing technologies,researchers have gained a deeper under-standing of the composition and function of immune cells in the tumor microenvironment.However,traditional bulk sequenc-ing technologies are limited in resolving heterogeneity at the single-cell level,constraining a comprehensive understanding of the complexity of the tumor microenvironment.The advent of single-cell RNA sequencing technology has brought new opportunities to uncover the heterogeneity of the immune microenvironment in lung cancer.Currently,T-cell-centered im-munotherapy in clinical settings is prone to side effects affecting prognosis,such as immunogenic drug resistance or immune-related pneumonia,with the key factor being changes in the interactions between immune cells and tumor cells in the tumor microenvironment.Single-cell RNA sequencing technology can reveal the origins and functions of different subgroups within the tumor microenvironment from perspectives such as intercellular interactions and pseudotime analysis,thereby discovering new cell subgroups or novel biomarkers,providing new avenues for uncovering resistance to immunotherapy and monitoring therapeutic efficacy.This review comprehensively discusses the newest research techniques and advancements in single-cell RNA sequencing technology for unveiling the heterogeneity of the tumor micro environment after lung cancer immunotherapy,offering insights for enhancing the precision and personalization of immunotherapy.

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.

Objective Using bioinformatics methods to study the immune infiltration mechanism of Primary Sj?gren's syndrome(pSS)and to explore potential target Chinese medicines,which can provide new directions for the clinical treatment of pSS.Methods Gene expression profile microarray dataset of pSS was downloaded from the GEO database,differential genes were screened using R software,and gene ontology(GO)and gene pathway enrichment(KEGG)enrichment analysis was performed on these differential genes.Protein interaction network analysis of differential genes was performed by applying the STRING database,key genes were screened by using Cytoscape,and ELISA for the verification of key genes expression.Immune infiltration and correlation of immune cells in pSS were calculated by CIBERSORT inverse convolution method in 22.Finally,the herbal prediction of key target genes was performed by using the Coremine Medical database.Results A total of 232 differential genes were obtained,of which 207 were up-regulated and 25 were down-regulated.GO was mainly enriched in:leukocyte mediated immunity,lymphocyte mediated immunity,leukocyte cell-cell adhesion,etc;KEGG was mainly enriched in Hematopoietic cell lineage,Primary immunodeficiency,Intestinal immune network for IgA production,Phagosome,Leishmaniasis.Ten key genes were screened:PTPRC,CD19,LCP2,CCR5 and CD69 etc.The hub genes expression in the pSS is the same as that of GSE40611.Immune infiltration showed that memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve were highly expressed in the pSS.Immune cell correlation analysis showed a positive correlation between initial Monocytes and T cells regulatory(Tregs),a positive correlation between Macrophages M1 and B cell na?ve,and a negative correlation between Plasma cells and T cells CD4 memory activated.COREMINE Medical predicted that Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,and Strychni may treat pSS.Conclusion The development and progression of pSS are the results of the combined involvement of multiple genes and pathways.Memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve may promote the development of pSS.The predicted Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,Strychni may be used as target herbs for the potential treatment of pSS.

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.

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Purpose: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. Materials and Methods: The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. Results: Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a.We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. Conclusion Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.

Objective:To analyze the epidemiological and clinical characteristics of human brucellosis in Enshi Tujia and Miao Autonomous Prefecture (Enshi Prefecture) of Hubei Province, and to provide a basis for prevention and control of local brucellosis.Methods:Using descriptive epidemiological methods, the data of reported cases of brucellosis in Enshi Prefecture from 2012 to 2019 (from the "Enshi Infectious Disease Reporting Information Management System" and the medical record system of hospitals in counties and cities within the jurisdiction of Enshi Prefecture) were collected, and the three distributions (population, time, region distributions) and clinical manifestations of human brucellosis cases were statistically described and analyzed.Results:A total of 78 brucellosis cases were reported in Enshi Prefecture from 2012 to 2019, with an average annual incidence rate of 0.193 5/100 000. Among the 78 cases of brucellosis reported, the sex ratio of men to women was 2.12∶1.00 (53∶25); the age of onset was mainly from 30 to 59 years old, accounting for 75.64% (59/78); the occupation was mainly farmer, accounting for 88.46% (69/78); the main contact animal was sheep, accounting for 80.77% (63/78). There were reported cases of brucellosis throughout the year, and the main onset months were May, June, September, November, and December, accounting for 55.13% (43/78) of the total number. From 2012 to 2019, all counties and cities in Enshi Prefecture except Xianfeng County and Hefeng County had reported cases. Among them, Lichuan City had the most cases, with 55 cases (70.51%). The main clinical manifestations of reported cases of brucellosis were fever, fatigue, hyperhidrosis, and muscle and joint pain, which accounted for 98.72% (77 cases), 89.74% (70 cases), 79.49% (62 cases), and 69.23% (54 cases), respectively.Conclusions:The majority of patients with brucellosis in Enshi Prefecture are young and middle-aged male farmers, with the highest incidence in Lichuan City. Relevant departments should increase the propaganda of brucellosis, increase the people's awareness of disease prevention, and strengthen the prevention and control measures of high-risk groups and regions to reduce the incidence of brucellosis.

Purpose: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. Materials and Methods: The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. Results: Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a.We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. Conclusion Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.

OBJECTIVE：To provide reference for the quality control of the leaves of Toricellia angulata . METHODS ：HPLC method was adopted. The determination was performed on Agela Promosil C 18 column with 0.2％ phosphoric acid solution-acetonitrile（gradient elution ）as mobile phase at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 35 ℃. The sample size was 10 μL. HPLC fingerprint of 10 batches of the leaves of T. angulata was established and similarity evaluation was conducted by using Similarity Evaluation System of TCM Chromatographic Fingerprint（2004 edition）. The chromatographic peak was identified by comparing with the chromatogram of reference substance. Cluster analysis ，PCA and PLS-DA were used to identify chemical patterns ，and the quality differential markers were screened. The contents of hyperoside and isoquercitrin were determined by the same HPLC. RESULTS ：The similarities of HPLC fingerprint of 10 batches of the leaves of T. angulata with control fingerprint were 0.923-0.983. A total of 11 common peaks were identified ，and the peaks 4 and 5 were hyperoside and isoquercitrin ，respectively. Results of cluster analysis ，PCA and PLS-DA showed that 10 batches of leaves of T. angulata could be divided into two categories ，Y10 was clustered into one category ，and others were clustered into one category. PLS-DA analysis showed that 6 common peaks （peaks 4，3，10，2，6 and 11） with variable importance projection （VIP）greater than 1 were selected. Average contents of hyperoside and isoquercitrin in 10 batches of the leaves of T. angulata were 0.47-6.97，0.21-1.87 mg/g，respectively. CONCLUSIONS ：Established HPLC fingerprint and the method for content determination are stable and reliable ，and can be used for the quality control of the leaves of T. angulata from different areas. Six quality differential markers including hyperoside in the leaves of T. angulata from different areas are qnyz202034） preliminarily screened.