Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective:This study compiled a comprehensive overview of the academic misconduct cases handled by the National Natural Science Foundation of China (NSFC) over the past decade, and took it as a representative to analyze the current situation of China′s academic research integrity to propose further enhancement suggestions.Methods:We collected data on academic misconduct cases notified by the NSFC between 2013 and 2022, and conducted a statistical analysis to gain insights into the time of occurrence, the way of discovery, the distribution of disciplines, the types of misconduct, and the handling measures of the NSFC.Results:Between 2013 to 2022, the Funding Committee notified 273 decisions regarding misconduct cases, indicating a general upward trend over time. Among the 158 cases with a labeled discovery pathway, the most common way was funding paper retraction by scientific journals, followed by reporting, and then review by the Funding Committee. The majority of individuals involved were from universities (44.81%) and hospitals affiliated with universities (45.45%). The top three most frequent types of misconduct were plagiarism, manipulation of reviews, and falsification. The Fund Committee's handling measures primarily involved in restrictions on applying for national funds within 2~7 years, notifications and criticisms, project withdrawals, and fund recoveries.Conclusions:Over the past ten years, the number of investigations of academic misconduct by the Fund Committee has been increasing, and the way of discovery has shifted from reporting and retraction by research journals to self-investigation by the Fund Committee. Biomedicine is a key field where misconduct occurs, and universities are the primary institutions where such cases are detected. Common causes of academic misconduct include plagiarism, manipulated peer review, and falsification. The foundation typically imposes punishments that restrict funding applications and issues public criticisms. To strengthen the academic integrity system, it is essential to establish and implement an early warning mechanism for academic integrity, reform the scientific research evaluation system, and establish an academic integrity management platform.

Objective:To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis.Methods:① Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. ② Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting.Results:① Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (μg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×10 9/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients ( n = 20) was significantly higher than that in the non-thrombocytopenia patients ( n = 37; μg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients ( r = -0.340, P = 0.010). ② Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×10 9/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/β-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. Conclusion:PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

Objective To evaluate the optimum compatibility of nalbufine combined with ropivacaine for patient-controlled epidural analgesia (PCEA) after cesarean section.Methods A total of 100 parturients who were at full term with a singleton fetus,aged 24-35 yr,with body mass index of 29-33 kg/m2,of American society of Anesthesiologists physical status Ⅱ,scheduled for elective cesarean section under combined spinal-epidural anesthesia,were divided into 4 groups (n =25 each) using a random number table method:sufentanil 0.5 μg/ml plus 0.15％ ropivacaine group (SR group),nalbufine at final concentration of 0.2 mg/ml plus 0.15％ ropivacaine group (N1 R group),nalbufine at final concentration of 0.4 mg/ml plus 0.15％ ropivacaine group (N2R group) and nalbufine at final concentration of 0.4 mg/ml plus 0.1％ ropivacaine group (N3Rgroup).PCEA solution was prepared correspondingly after surgery,and all the drugs were diluted to 100 ml in normal saline in each group.The PCA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Visual analog scale scores of incisional pain and anduterine contraction pain were maintained＜4.Ramsay sedation scores were recorded at 8,12,24 and 48 h after surgery.The total pressing times of PCEA were recorded within 48 h after surgery.The development of adverse reactions such as nausea,vomiting,skin itching,numbness of lower extremity,urinary retention and respiratory depression was recorded in the analgesia period.Venous blood samples were collected before surgery and at 24 and 48 h after surgery for determination of plasma prolactin concentrations,and the time of colostrum was recorded.Neonatal nerve and adaptive capacity was assessed and scored.Results Compared with group SR,the total pressing times of PCEA were significantly reduced in N2R and N3R groups (P＜0.05),and no significant change was found in the total pressing times of PCEA in group N1R (P＞0.05).Compared with group N1R,the total pressing times of PCEA were significantly reduced in N2R and N3 R groups (P＜0.05).There was no significant difference in the total pressing times of PCEA between group N2R and group N3R (P＞0.05).The Ramsay sedation score was 2 in four groups.There was no significant difference in numbness of lower extremity,plasma prolactin concentrations or neonatal nerve and adaptive capacity scores among four groups (P＞0.05).Conclusion Nalbufine at final concentraction of 0.4 mg/ml mixed with 0.1％ ropivacaine is the optimum compatibility when used for PCEA after cesarean section.

Objective To evaluate the clinical efficacy of modified Bascom cleft lift procedure in the treatment of chronic sinus.Methods Modified Bascom cleft lift procedure was performed in 53 patients admitted from Oct 2012 to Jul 2016.49 cases were male and 4 were female.The average age was (25.4± 2.3) years.Results All patients were satisfied with the operation.There were 49 cases of primary healing and 4 cases of incision complications.The average follow-up was (12.1 ±4.3) months,no recurrence was observed.Conclusion The modified Bascom cleft lift technique is effective and reliable,with less complications and a lower recurrence rate.

Objective To evaluate video-assisted anal fistula treatment (VAAFT) for Parks type Ⅱ anal fistula.Methods 40 Parks type Ⅱ anal fistula patients underwent VAAFT procedure from June 2015 to June 2017.Results were compared with 40 cases treated by incision and thread drawing.Results There was no significant difference between the two groups for curative effect,postoperative urinary retention,wound edema,bleeding and recurrence rate after 6 months of operation (90％ vs.95％,x2 =0.722,P =0.697;5％ vs.8％,x2 =0.213,P=1.0;2％ vs.8％,x2 =1.053,P=0.615;0 vs.5％,x2 =2.051,P =0.494;10％ vs.5％,x2 =0.721,P =0.675).Pain on first day and one week after operation in the VAAFT was less [(1.9±0.6) vs.(3.7±1.0),t =9.438,P=0.001;(0.9±0.7) vs.(1.9±0.8),t=6.269,P=0.001],hospital stay was shorter [8.4 ±1.3) d vs.(9.2 ±2.2) d,t =2.030,P=0.047],wound healing was faster [(27 ±8) dm.(38 ±6) d,t =7.328,P =0.001].The Jorge-Wexner incontinence score [(0.5±0.7) vs.(1.2±1.3),t =2.951,P=0.005] and the fecal incontinence severity index [(1.1±1.6) vs.(5.1 ±3.2),t =7.097,P=0.001] were lower in patients receiving VAAFT procedure.Conclusion Video-assisted anal fistula treatment is a safe and effective surgical method with the advantages of less trauma,and pain,quicker recovery and no damage to the anal sphincter.

Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from().(GenBank access number KU885950) is a 1530 bp cDNA with a 1041 bp open reading frame predicted to encode a 346-amino acid, 38.62 kDa protein. The polypeptide encoded by thecDNA was expressed and purified as a recombinant protein from() and showed SMT activity. The expression ofwas highly up-regulated incell suspension cultures treated with methyl jasmonate (MeJA). Tissue expression pattern analysis showed higher expression in the phellem layer compared to the other four organs (leaf, stem, xylem and phloem), which is about ten times that of the lowest expression in leaf. The results are meaningful for the study of sterol biosynthesis ofand will further lay the foundations for the research in regulating both the content of other main compounds and growth and development of