Objective:To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC).Methods:This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023.Results:A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss( M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions:The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.

Objective Explore the molecular mechanism by which long chain non-coding(lncRNA)MEG8 regulates the development of chronic obstructive pulmonary disease(COPD)mediated by miR-367-3p/phos-phatase and tensin homolog(PTEN).Methods Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the expression level of lncRNA MEG8 in 16HBE cells and clinical tissues of chron-ic obstructive pulmonary disease(COPD).MEG8 was overexpressed in 16HBE cells stimulated by cigarette smoke extract(CSE),and MEG8 or PTEN were simultaneously knocked down after the addition of miR-367-3p inhibitor,then MTT assay,flow cytometry,enzyme-linked immunosorbent assay,and immunoblotting were used to detect changes in cell apoptosis,proliferation,and levels of inflammatory factors.The targeting rela-tionships of MEG8,miR-367-3p,and PTEN was verified by using the dual luciferase reporting system.Results MEG8 expression was reduced in CSE stimulated 16HBE cells and COPD clinical tissue samples(P<0.05).Compared to the CSE group,overexpression of MEG8 stimulated apoptosis and inflammatory fac-tor interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-αlevels decreased(P<0.05)in 16HBE cells stimulated by CSE.The expression levels of proapoptotic proteins Bax,Caspase3,and Cleared caspase3 de-creased(P<0.05),and the expression level of apoptosis inhibitory factor Bcl-2 increased(P<0.05).The double luciferase Reporter gene experiment verified that MEG8 can target to inhibit miR-367-3p(P<0.05),and miR-367-3p can target to inhibit the expression of PTEN(P<0.05),thereby inhibiting the apoptosis and inflammatory response of 16HBE cells stimulated by CSE(P<0.05).Under CSE stimulation,compared to the Control group,the addition of miR-367-3p inhibitor significantly upregulated the protein expression level of PTEN in 16HBE cells(P<0.05),enhanced cell proliferation activity(P<0.05),reduced cell apoptosis(P<0.05),significantly downregulated the expression levels of proapoptotic proteins Bax,Caspase 3,and Cleared caspase 3(P<0.05),upregulated the expression level of anti apoptotic protein Bcl-2(P<0.05),and suppressed the inflammatory factor IL-1 β,IL-6 and TNF-α Knocking down MEG8 or PTEN can restore the protein expression level of PTEN(P<0.05),inhibit cell proliferation activity(P<0.05),reverse cell apoptosis caused by miR-367-3p inhibitor(P<0.05),and regulate apoptosis related proteins(P<0.05),and enhance the in-flammatory factor IL-1 β,IL-6 and TNF-α The level of(P<0.05).Conclusion MEG8 inhibits the apoptosis and inflammatory response of 16HBE cells stimulated by CSE by regulating miR-367-3p/PTEN molecular ax-is,and may provide a potential molecular target for the treatment of COPD.

Objective:To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC).Methods:This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023.Results:A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss( M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions:The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective:To investigate the allele distribution of aldehyde dehydrogenase 2 (ALDH2) gene polymorphism in elderly patients with type 2 diabetes mellitus (T2DM) and to analyze its correlation with the presence and severity of coronary stenosis.Methods:A total of 94 elderly patients with T2DM who were admitted to the Affiliated Hospital of Jining Medical University from March 2020 to March 2022 were selected as the observation group, and 50 age- gender-matched healthy subjects were selected as the control group. The observation group was further divided into stenosis group and non-stenosis group based on the presence of coronary stenosis. Clinical data were collected from all participants, and blood samples were taken for analysis. The ALDH2 gene polymorphism (rs671 locus) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The distribution of ALDH2 genotypes was observed in elderly patients with T2DM, and multivariate logistic regression analysis was used to identify independent factors associated with the development of coronary stenosis in elderly patients with T2DM. The degree of coronary stenosis was compared between patients with different genotypes.Results:The allele A frequency of ALDH2 gene (rs671 locus) was significantly higher in the observation group than in the control group ( P<0.05). The proportion of patients with diabetes duration≥5 years and smoking history in the stenosis group was significantly higher than that in the non-stenosis group (all P<0.05). Serum levels of glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the stenosis group than in the non-stenosis group, while high-density lipoprotein cholesterol (HDL-C) level was significantly lower in the stenosis group than in the non-stenosis group (all P<0.05). The proportion of ALDH2 genotypes AA and allele A frequency were significantly higher in the stenosis group than in the non-stenosis group (all P<0.05). Long duration of diabetes, low HDL-C level, and ALDH2 genotypes AA were independent risk factors for the development of coronary stenosis in elderly patients with T2DM (all P<0.05). The proportion of patients with three or more coronary artery lesions in the stenosis group with genotype AA was significantly higher than that in the stenosis group with genotypes GG and GA (all P<0.05). Conclusions:ALDH2 gene polymorphism is associated with the development of T2DM in elderly patients, and allele A carriers may have a higher risk of developing coronary stenosis and more severe disease severity.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective To investigate the clinical significance of biochemical markers in EBC and serum in patients with bronchial asthma and chronic obstructive pulmonary disease overlap syndrome(ACOS). Methods We selected Patients with chronic airway inflammatory diseases in our hospital,These patients underwent clinical trial after the stable phase,including 18 ACOS patients,22 asthma patients,24 COPD patients and 20 healthy non-smokers in the same period.8-isoPG and other inflammatory factors levels in EBC and serum were measured in the selected patients. A comparative analysis was performed. Results The levels of EBC 8-isoPG in the ACOS group were significantly higher than those in the healthy control group,The levels of serum and EBC 8-isoPG in the ACOS group were significantly higher than the asthma group and the COPD group(P < 0.05). The level of 8-isoPG in EBC was not related to age,smoking index,weight,and FEV1value(P>0.05).Conclusions Inflam-matory factors including 8-isoPG,are involved in chronic inflammation in lung tissues of patients with ACOS. 8-isoPG in EBC may have potential value in identifying ACOS from COPD and asthma as biomarkers and deserve further study.

Objective To observe the effect of Yunnanbaiyao combined with gelatin sponge on wound healing in patients with post-extraction hemorrhage.Methods 72 patients received dental extraction were selected,and they were divided into observation group (Yunnanbaiyao + gelatin sponge) and control group (gelatin) according to the digital table,each group in 36cases.The hemostasis after treatment and the improvement of pain after 12h and 24h after treatment were observed.The wound healing was observed in the two groups after 7 days of treatment.Results After treatment,the total effective rate was 91.67％ in the observation group and 69.44％ in the control group.The effective rate of hemostasis in the observation group was significantly higher than that of the control group(x2 =7.32,P =0.007).The VAS scores of the observation group at 12 h (t =23.44,P =0.000) and 24h (t =22.86,P =0.000) after pack treatment obviously decreased;The VAS scores of the control group at 12h(t =19.87,P =0.000) and 24h (t =18.47,P =0.000) after pack treatment obviously decreased;The VAS scores of the observation group at 12h and 24h after pack treatment was lower than those of the control group,the differences were statistically significant(t =7.03,5.03,all P =0.000).The wound healing of the observation group was improved after 7d treatment(t =8.12,P =0.00);The wound healing of the control group was improved after 7d treatment(t =5.39,P =0.00);The wound healing of the observation group was better than that of the control group,the differences were statistically significant (t =2.88,P =0.005).Conclusion Yunnanbaiyao combined with gelatin sponge can relieve the bleeding symptoms after tooth extraction,promote wound healing,reduce the patients' pain.

To explore a new strategy for the transformation of antibacterial activity of fluoroquinolone into antitumor activity,twelve new title compounds,1-ethyl-6-fluoro-7-(4-methyl-pipreazin-1-yl)-quinolin-4-one-3-carboxylicacid (5-arylidene-2-thioxo-1,3-thiozolidin-2,4-dione-3-yl) amides (6a-61),were designed and synthesized with an amide group and a rhodanine unsaturated ketone moiety as an isostere and modified group,respectively,from pefloxacin (1).Their structures were characterized by elemental analysis and spectral data.The in vitro antitumor activity of the title compounds against Hep-3B,Capan-1 and L1210 cell lines exhibited more significant potency than pefloxacin.The compounds with aromatic heterocyclic or flurophenyl displayed comparable activity to the comparasion doxorubicin.Thus,rhodanine unsaturated ketone hybrided amide group as an isostere of the C-3 carboxylic acid group appears to be an alternative route for further design of antitumor fluoroquinolone.