ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

AIM: To investigate the efficacy of lacrimal duct laser dacryoplasty combined with intubation and postoperative meibomian gland treatment in patients with chronic dacryocystitis complicated by meibomian gland dysfunction.METHODS: Data were collected from 128 patients with chronic dacryocystitis complicated by meibomian gland dysfunction treated at Xi'an No.1 Hospital from March 2021 to December 2022. All patients underwent lacrimal duct laser dacryoplasty combined with intubation. Postoperatively, those patients were randomly divided into two groups: group A(64 cases, without meibomian gland treatment)and group B(64 cases, with meibomian gland treatment). The lacrimal intubation was removed at 3 mo after surgery to evaluate the patency rate of lacrimal irrigation. Additionally, changes in the ocular surface disease index(OSDI)score, non-invasive tear film break-up time, tear meniscus height, conjunctival hyperemia analysis, meibomian gland analysis, tear lipid layer thickness, tear ferning test, and conjunctival impression cytology were compared between the two groups.RESULTS: The lacrimal irrigation patency rates in the group A and group B were 78.1% and 81.2% respectively, with no statistically significant difference between the two groups(P>0.05); compared with the group A, group B showed a significant extension in non-invasive tear breakup time at 3 mo after surgery, and the OSDI score, conjunctival hyperemia analysis, tear ferning test and conjunctival impression cytology grading were all significantly decreased(all P<0.05), while there was no significant difference in tear meniscus height, tear lipid layer thickness and meibomian gland loss score between the two groups(all P>0.05).CONCLUSION: Comprehensive treatment for patients with chronic dacryocystitis combined with meibomian gland dysfunction have improved patients' comfort, tear film stability, and reduces local inflammatory response. It is important to simultaneously address ocular surface microenvironment abnormalities during surgical treatment to achieve satisfactory efficacy.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

Osteoporosis is an important cause of internal fixation loosening after spinal surgery.Cement-augmented pedicle screw instru-mentation(CAPSI)technique is the most widely used technique in clinical practice to improve the stability of pedicle screw,mainly applied in osteoporosis and revision surgery,which included conventional solid pedicles crews and fenestrated/cannulated pedicle screws technique.CAPSI technique may cause cement leakage and pulmonary embolism,and there is no consensus on its indications or technical points.Therefore,this article reviews the research progress of CAPSI,in order to provide relevant reference for clinical practice.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Perivascular adipose tissue(PVAT),attached to the adventitia,is a special functional layer of the vascular wall structure.PVAT exists around most blood vessels and is mainly composed of adipocytes,fibroblasts,stem cells,mast cells and nerve cells.PVAT not only participates in energy metabolism,but also has secretory function.It plays an important role in maintaining vascular structure and regulating vascular function.Atherosclerosis is a chro-nic metabolic syndrome characterized by endothelial dysfunction,lipid deposition,and inflammatory infiltration,which is closely associated with obesity.This paper reviews the role of PVAT in atherosclerosis.

Oral diseases are usually caused by external physical and chemical factors,the invasion of pathogens,dento-maxillofacial deformities and systemic diseases.Oral infections and orofacial pain triggered by oral diseases seriously reduce the quality of life.Pyroptosis is a kind of programmed cell death,which is characterized by swelling of the cell until the cell membrane ruptures,releasing the cell contents and activating a strong inflammatory response.Previous studies have shown that pyroptosis is widely involved in the occurrence and development of oral diseases.In this review,four types of cellular pyroptosis pathways are described in detail,including the canonical pathway,non-canonical pathway,caspase-3/8 mediated pathway and caspase independent pathway.Different pyroptosis pathways form complex signal networks,which regulate the functions of periodontal membrane cells,gingival fibroblasts,macrophages and other cells in the oral cavity,thus affecting the occurrence and development of oral diseases.This review summarizes the latest research about the pathways of pyroptosis and its roles in oral diseases,aiming to provide a theoretical basis and direction for searching effective methods to treat and prevent oral diseases.

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

Gut microbiome and their metabolites are closely related to human diseases, which influence the development of diseases by interacting with receptors. G protein-coupled receptor (GPCR) is a receptor superfamily that exists on the surface of cell membrane, which is involved in a wide range of human physiological activities. GPCR is currently considered as important drug targets. Traditional Chinese medicines (TCM) are characterized by multi-components, multi-targets, and multi-pathways. More and more studies have demonstrated that TCM can ultimately intervene in diseases by modulating gut microbiome and their metabolites, affecting their interactions with GPCR. This review discusses the status of gut microbiome and human diseases, the interactions of gut microbiome and their metabolites with GPCR, and the status of GPCR drug development. Based on the above contents, a new model of "TCM-gut microbiome panel-GPCR-disease" is proposed. The interactions between active ingredients of TCM, gut microbiome panel, and GPCR and their effects on disease are elucidated through multi-omics techniques. This review will provide new ideas for analyzing the pharmacological mechanism of TCM efficacy and searching for new targets of TCM.