To screen the targets related to the metabolic enzymes involved in the cholesterol synthesis pathway that inhibits the polarization of macrophages towards M1 phenotype, and verify the intervention effects and underlying mechanisms in colorectal cancer cells.

Mouse colorectal cancer MC38 cells were divided into control group (si-NC) and experimental groups (the expression of enzymes in cholesterol synthesis pathway was interfered with siRNA for corresponding targets). RT-qPCR was used to detect the mRNA levels of corresponding targets in MC38 cells after transfection. After peritoneal macrophages were extracted from male C57BL/6 mice (6 weeks old, weighing 13~18 g), the macrophages were then treated with the conditioned media of MC38 cells transfected with different siRNAs for 48 h. RT-qPCR was employed to detect the mRNA levels of IL-1β, IL-6 and TNF-α in the macrophages so as to evaluate the effect of the culture media on the M1 polarization. MC38 cells were divided into control groups (OE-NC and sh-NC), farnesyl-diphosphate farnesyltransferase 1 (FDFT1) overexpression group (OE-FDFT1) and FDFT1 knockdown group (sh-FDFT1). RT-qPCR was applied to detect the mRNA expression of FDFT1, and Western blotting was conducted to measure the protein level of FDFT1. C57BL/6 mice were subjected randomly to construct a subcutaneous tumor-bearing model and a model of intraperitoneal metastatic tumor (n=5) respectively. The growth of tumor mass was then measured. Flow cytometry was used to observe the proliferation and apoptosis of MC38 cells, and Transwell assay to detect migration ability of MC38 cells. Five C57BL/6 macrophage-depleted mice (established with injection of clodronate liposome suspension through tail vein) received intraperitoneal implantation to construct a metastasis model, and then the obtained tumor masses were then weighted.

Compared with MC38 cells after si-NC transfection, the mRNA levels of corresponding targets in MC38 cells in the experimental groups were significantly reduced (P<0.05). Significant increases were found in the mRNA levels of IL-1β, IL-6 and TNF-α of the macrophages with FDFT1 interference than the control cells (P<0.05). There were no statistical differences in the proliferation, apoptosis and migration of MC38 cells in the control group (OE-NC and sh-NC) and the cells of the FDFT1 overexpression group and FDFT1 knockdown group (P>0.05). In both the subcutaneous tumor-bearing model and the model of intraperitoneal metastatic tumor, the mass weight was significantly heavier in the OE-FDFT1 group than the OE-NC group (P<0.01), and was notably smaller in the sh-FDFT1 group than the sh-NC group (P<0.01). For the macrophage-depleted mouse tumor model, no remarkable change was observed in the tumor weight between the OE-FDFT1 group and the OE-NC group as well as the sh-FDFT1 group and the sh-NC group.

FDFT1, the metabolic enzyme in the cholesterol synthesis pathway of colorectal cancer tumor cells, is a potential target for tumor immunotherapy targeting macrophages, which promotes tumor progression by regulating macrophages.

To explore the role and mechanism of warm malate ringer’s solution (MR) in resuscitation of the lethal triad caused by severe trauma.

A rat model of severe trauma was established in SPF-grade SD rats (half male and half female, weighing 200~220 g) using combined multiple injuries and hemorrhagic shock, and the rats were randomly divided into 8 groups (n=8): Sham group, only arterial and venous catheterization; Trauma (Tra) groups with different time points (10, 30, 60, 90, 120, 180 min) and a Trauma group that were observed without any treatment for 180 min after model establishment. The changes of activated clotting time (ACT), reaction time (R), maximum amplitude (MA), and rate of blood clot formation (Angle) at different time points were detected by using thromboelastography, and tail bleeding, core body temperature and arterial blood gas parameters, were also observed and detected. The plasma von Willebrand Factor (vWF) level, mitochondrial respiratory control ratio in pulmonary venous endothelium, and expression levels of vascular endothelial cadherin (VE-Cadherin), peroxisome proliferator activating receptor gamma coactivator 1α (PGC1α), dynamin-related protein 1 (Drp1), p-Drp1, and mitofusin 2 (Mfn2) were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction. Another group of SD rats were randomly divided into severe trauma group (no treatment for 180 min after injury), and MR solution at room temperature and at 37 ℃ groups. MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma. Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.

Compared with the Sham group, the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values (P<0.05), shortened MA and decreased Angle values (P<0.05), extended tail bleeding time (P<0.05), lower partial pressure of carbon dioxide (PCO₂) and HCO{}_{\mathrm{3}}^{-} and base excess (BE) levels (P<0.05), and continuously increasing K⁺ (P<0.05) and decreasing Na⁺ (P<0.05) and Ca²⁺ levels (P<0.05). Additionally, plasma vWF level (P<0.05) and protein levels of VE-cadherin, PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced (P<0.05), the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury (P<0.05). MR solution resuscitation shortened tail bleeding time (P<0.05), increased core body temperature (P<0.05), elevated plasma vWF level (P<0.05), increased protein levels of VE-cadherin, PGC1α and Mfn2 (P<0.05), and decreased that of p-Drp1 protein expression (P<0.05) when compared with the rats at 180 min after severe traumatic injury. The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.

Warm MR solution significantly improves the lethal triad in rats after severe trauma, which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

‍To investigate the prognostic factors affecting survival in patients with natural killer T-cell lymphoma (NKTL), and then develop a prognostic model for predicting their overall survival (OS) based on random survival forest (RSF) algorithm.

Demographic and clinical pathological data of NKTL patients were collected from the SEER database during 2000 and 2020. The patients were divided into a training cohort (n=471) and a validation cohort (n=203) in a 7∶3 ratio. Cox regression analysis was performed to identify prognostic factors affecting OS, and a nomogram model was constructed based on the obtained factors. Meanwhile, RSF algorithm was used to determine prognostic factors affecting OS to build the RSF model. The models were evaluated using receiver operating characteristic (ROC) curve, calibration curve, decision curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI), and the predictive performances of the 2 models were compared. Risk scores for each patient were calculated using the 2 models. Then the patients were divided into high- and low-risk groups based on the median risk score, and survival curve was plotted for comparison.

Ann Arbor stage, age, radiotherapy, combined treatment, and type of disease were identified as significant prognostic variables associated with OS. In the validation cohort, the area under the ROC curve (AUC) for the nomogram model at 1, 3, and 5 years was 0.745, 0.771, and 0.748, respectively, while the AUC for the RSF model was 0.764, 0.792, and 0.761 at the same time points. ROC curve analysis indicated that both models demonstrated good accuracy and discrimination in predicting OS. Calibration curve analysis showed a strong consistency between the predicted and actual OS for both models. Both models effectively stratified the patients into poor and favorable prognosis groups, with the OS of patients in the poor prognosis group being significantly shorter than that of the favorable prognosis group (P<0.000 1). Decision curve analysis revealed that the net benefit of the RSF model was superior to that of the nomogram model. Compared to the nomogram model, the NRI for the RSF model was 0.184 (95%CI: 0.098~0.267, P<0.01), and the IDI was 0.300 (95%CI: 0.241~0.359, P<0.01). Overall, the RSF model demonstrated superior predictive capability than the nomogram model.

Ann Arbor stage, age, radiotherapy, combined treatment, and type of disease are prognostic factors affecting the prognosis of NKTL patients. Our RSF model demonstrates strong predictive capability for the prognosis of NKTL patients and can effectively assess patient outcomes.

‍To investigate the role and mechanism of bergapten in treating osteoarthritis (OA) based on network pharmacology, molecular docking and in vitro experiments.

‍The functional targets of bergapten and the related targets of OA disease were obtained by searching Super-Pred, Swiss Target Prediction, Drug Bank. The obtained targets were intersected with Venny2.1.0, protein-protein interaction (PPI) analysis was performed using the STRING database, and molecular docking was conducted by AutoDock Vina. Subsequently, human chondrocyte C28/I2 cells were subjected in the following validation experiments. After the cells were treated with 0~50 μmol/L bergapten for 24, 48 or 72 h, CCK-8 assay, RT-qPCR and immunofluorescence assay were used to detect the proliferation and apoptosis, and the expression of the molecules related to proliferation, inflammation and senescence (senescence associated secretory phenotype, SASP). Senescence β-galactosidase (SA-β-Gal) staining kit was employed to detect the change of SA-β-Gal level in the cells.

There obtained 145 potential targets of bergapten for OA. PPI analysis revealed 4 potential core targets, HSP90AA1, EGFR, HIF1A, and PIK3CA, and they could form relatively stable complex with bergapten. CCK-8 assay showed that 10 μmol/L bergapten treatment for 48 h resulted in the highest proliferative activity of C28/I2 cells (P<0.05). Immunofluorescence assay, RT-qPCR and Western blotting indicated that bergapten treatment induced significant increases in the expression of cell proliferation markers such as PCNA, CCND1 and CCNE1 (P<0.05), while decreases in the expression of apoptosis markers Caspase3 and BAX (P<0.05). Meanwhile, the expression levels of IL-1β-induced inflammatory factors IL-6 and TNF-α were reduced, while those of anti-inflammatory factors IL-4 and IL-10 were elevated after bergapten treatment (P<0.05). The levels of SASP factors, such as P16, P21, MMP9 and MMP13 were also significantly declined (P<0.05). SA-β-Gal staining displayed that the level of SA-β-Gal in C28/I2 cells was significantly enhanced after IL-1β induction (P<0.05), while bergapten treatment could decrease the positive cell rate of the staining (P<0.05).

Bergapten can reduce the expression of SASP factors such as IL-6, TNF-α, P16, P21, MMP9 and MMP13 in IL-1β-stimulated chondrocytes, and thus exerts its anti-inflammatory and anti-aging effects in delaying the progression of OA.

‍To investigate the role and mechanism of paeoniflorin （PF） in sepsis-associated acute kidney injury （SA-AKI） in mice.

Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice （6~8 weeks old，weighing 20~25 g） were randomly divided into Control group，model group，PF group （intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration），and β-catenin specific agonist BML284 group （10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration）. The renal histopathological changes were observed by HE staining and Paller scoring. ELISA was used to determine the contents of serum creatinine （Scr），neutrophil gelatinase-associated lipocalin （NGAL） and lactate，and renal contents of hexokinase 2 （HK2），lactate dehydrogenase A （LDHA），IL-1β and IL-18. Western blotting was performed to detect the expression of total β-catenin，p-β-catenin^Y654，nucleus β-catenin and c-Myc.

Compared with the Control group，the LPS group showed obviously damaged renal tissue，higher Paller score （P<0.05），increased serum Scr and NGAL levels （P<0.05），elevated renal contents of aerobic glycolytic indexes such as HK2，LDHA and serum lactate，as well as contents of IL-1β and IL-18 （P<0.05），and enhanced expression of total β-catenin，p-β-catenin^Y654，nucleus β-catenin and c-Myc in the renal tissue （P<0.05）. PF treatment attenuated the renal tissue damage，decreased Paller score （P<0.05），reduced serum Scr and NGAL levels （P<0.05），HK2，LDHA and serum lactate levels，and contents of IL-1β and IL-18 in renal tissues （P<0.05），and down-regulated the renal expression of total β-catenin，p-β-catenin^Y654，nucleus β-catenin and c-Myc when compared with the levels in the model group （P<0.05）. While，addition of BML284 reversed above effects of PF treatment with significant differences （P<0.05）.

PF can alleviate SA-AKI，and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway，thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

To investigate the protective effect of β-glucan (BG) against intestinal ischemia reperfusion (II/R) injury by regulating the secretion of glucagon-like peptide-1 (GLP-1).

Male C57BL/6 mice (6~8 weeks old) were subjected, and finally, the experiments had sham group, II/R group, II/R+BG group (0.1 mg/mL BG in drinking water for 2 weeks before modeling), II/R+liraglutide (LLT, GLP-1 analogue) group (0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling), and II/R+BG+Ex9-39 (GLP-1R antagonist) group (intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling). After modeling, HE staining was used to observe intestinal morphological changes, and RT-qPCR and Western blotting were employed to evaluate the molecules (Occludin, ZO-1 and Claudin-1) related to intestinal barrier damage. The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay, respectively, and RT-PCR for the molecules related to GLP-1 expression (Gcg, Pcsk1/2, GIP and Foxa2). The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules.

II/R induced significant decreases in the mRNA levels of Occludin, ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice (P<0.05). While, the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group (P<0.05). BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice, and improved the mRNA expression of GLP-1-related molecules (P<0.05). The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score, with statistical difference in comparison with the II/R group (P<0.05). GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage, with notably differences in the expression of Occludin, ZO-1 and Claudin-1 and Chiu's score (P<0.05).

BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.

‍To investigate the effect and mechanism of dexmedetomidine （Dex） pretreated pericytes （Dex-PCs） on acute lung injury （ALI） in septic mice.

Mouse model of sepsis-ALI was established with intraperitoneal injection of lipopolysaccharide （LPS） at a dose of 10 mg/kg. A total of 96 C57BL/6J mice were randomly divided into sham operation （Sham） group，ALI group，PC treatment group and Dex-PCs treatment group. The mice of the PCs and Dex-PCs groups received a tail venous injection of 5×10⁵ PC cells，respectively，whereas those of the Sham and ALI groups received equal volume of normal saline. Flow cytometry，immunofluorescence assay，whole-body volume tracing system and ELISA were used to observe the changes in the colonization of PCs，pulmonary vascular permeability，lung function，serum TNF-α and IL-6 levels，as well as the survival rate and survival time of mice at 72 h after LPS stimulation. After PCs and Dex-PCs were exposed to 10 μg/mL LPS，the level of intracellular reactive oxygen species （ROS） was measured.

‍Compared with the Sham group，the ALI group had increased permeability of pulmonary vascular endothelial cells，extensive extravasation of Evans blue，severely destructed of lung tissue structure and massive inflammatory cell infiltration，higher lung wet/dry weight ratio，elevated serum TNF-α and IL-6 levels，and declined lung function，and no mice survived for 72 h after modeling （P<0.05）. Both PC cell treatment effectively alleviated the pulmonary vascular endothelial leakage，reduced Evans blue content per unit tissue，improved lung pathological structure，lung function and inflammatory responses，and significantly improved the survival rates in the PC group and the Dex-PC group （P<0.05）. What’s more，the therapeutic effect of Dex-PC cells was significantly better than that of the PC cells （P<0.05）. LPS stimulation induced ROS accumulation greatly in PCs，but no such effect was observed in the PCs after Dex pretreatment （P<0.05）.

‍Dex pretreatment significantly enhances PCs’ protective effect on pulmonary vascular endothelial barrier functions in septic mice，which may be due to its enhancing anti-oxidative capacity of PCs.

To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF，constructed using reverse genetics （RG） technology，in combination with chemotherapy drug，gemcitabine （GEM），against pancreatic cancer cells.

The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study. The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay，transmission electron microscopy，and viral replication assay. CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses ［multiplicities of infection （MOI）：0，0.1，1.0，3.0］ on the survival rate of pancreatic cancer cell lines （Panc02，PANC-1，SW1990，BxPC-3） and normal pancreatic ductal epithelial cells （HPDE6-C7） after treatment for 24，48 or 72 h. Using a subcutaneous tumor-bearing mouse model of pancreatic cancer，36 female C57BL/6 mice （6 weeks old） were randomly divided into PBS group，recombinant oncolytic virus group，GEM group，and the combined treatment group，with 9 mice in each group. PBS （100 μL/animal） or OvFlu-GM-CSF virus （1×10⁷ PFU/100 μL） was given to the mice of the corresponding groups through intratumoral injection，while GEM （100 mg/kg） was injected intraperitoneally，once per 3 days，for totally 9 times. Changes in tumor volume and survival rate were monitored. Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues. HE staining was performed to observe the pathological changes in major organs （heart，liver，lungs，kidneys and brain），and the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the safety of the recombinant oncolytic virus.

The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 2⁸，typical morphological features of influenza virus，and can selectively replicate within pancreatic cancer cells. At the cellular level，the viruses demonstrated a significant selective cytotoxic effect on Panc02，PANC-1，SW1990，and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0，when compared to 48 h post-infection and MOI=0 （P<0.01）. The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time （P<0.01），but the viruses showed no significant effect on normal pancreatic ductal epithelial cells （HPDE6-C7）. In the pancreatic cancer tumor-bearing mouse model，the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment （P<0.01），and enhanced the infiltration of T cells in the tumor tissues. No obvious pathological changes were observed in the above-mentioned major organs. Additionally，there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group，GEM group，and OvFlu-GM-CSF+GEM group compared to the PBS group.

RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF，when combined with the chemotherapeutic agent GEM，enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host’s anti-tumor immune response.

To investigate the influencing factors of pain during ultrasound-guided puncture sclerotherapy in the treatment of ovarian chocolate cyst (OEC).

A retrospective cohort study was conducted on 209 OEC patients undergoing ultrasound-guided puncture sclerotherapy in our department from September 2021 to September 2023. Demographic data, medical history and surgical information were collected. According to surgical approach, they were divided into transabdominal surgery group (n=57) and transvaginal surgery group (n=152). Pain scores were assessed at 5 surgical time points: needle insertion, irrigation, displacement, sclerosis, and needle withdrawal. Pain scores were compared between the 2 groups at each surgical moment. According to the pain scores at the moments of needle insertion and replacement, the patients were divided into the no/mild pain group (pain score ≤3) and the moderate/severe pain group (pain score ≥4), and the related factors of the incidence of moderate/severe pain were analyzed.

There was no statistical difference in intraoperative pain between different surgical approaches (transabdominal/transvaginal) in treating OEC under the guidance of ultrasound. At the moment of needle insertion, significantly higher incidence of moderate/severe pain was observed in the patients with a body mass index (BMI) >23.9 kg/m² than those with BMI ≤23.9 kg/m², and those with a history of dysmenorrhea than those without (P<0.05). At the time point of displacement, BMI and history of dysmenorrhea had no correlation with the incidence of moderate/severe pain. Age, obstetric history, mode of delivery, time of menarche, menstrual volume, history of pelvic surgery, history of combined adenomyosis, size of cysts, duration of surgery, and surgical approach had no notable impacts on intraoperative pain.

Different surgical approaches for ultrasound-guided puncture sclerotherapy of OEC have no effect on pain levels at various surgical moments. From the aspect of humanistic care, transabdominal puncture should be preferred. During needle insertion and displacement, particular attention should be given to the overweight patients and those with a history of dysmenorrhea, and appropriate pain intervention measures should be formulated.

To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease （CKD） and healthy controls.

A total of 8 CKD patients admitted in Department of Nephrology of our hospital，and another 5 age- and gender-matched healthy individuals were recruited in this study. Fresh fecal samples were collected from the CKD patients and healthy controls. ITS DNA sequencing was employed to determine the composition of intestinal fungi，and then bioinformatics analysis was applied to compare the differences in fungal community diversity，structure，and function between the 2 groups.

There were no statistical differences between the 2 groups in terms of age，gender composition，BMI，and so forth. The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups （P<0.01）. So was in the Beta diversity between them （P<0.01）. The relative abundance of Candida was increased significantly （P<0.01），while those of Cladosporium and Penicillium were decreased in the CKD group （P<0.05）. LEfSe analysis revealed that Candida was significantly enriched in CKD patients，whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.

The composition of intestinal fungi in CKD patients is different from that in healthy individuals，exhibiting characteristic changes. Dysfunction of gut fungal flora may promote the progression of CKD. Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.