Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective To explore the efficacy of negative pressure ureteral access sheath combined with disposable flexible ureteroscope(UAS+FRUS)in the treatment of renal calculi of 2-3 cm,so as to provide reference for the treatment.Methods A retrospective analysis was conducted on 130 cases of renal calculi of 2-3 cm treated with surgery in Xiamen Third Hospital during Sep.2021 and Sep.2023,including 68 cases with UAS+FRUS and 62 cases with super-mini percutaneous nephrolithotripsy(SMP).The perioperative indexes and stone-clearance rate(SFR)were compared between the two groups.Results All operations were successful.There were no statistically significant differences in the total SFR and incidence of complications(5.88％vs.9.67％)between the two groups 3 days(88.24％vs.90.32％)and 1 month(91.18％vs.93.55％)after surgery(P＞0.05).For patients with lower calyceal calculi with infundibulopelvic angle(IPA)＜45°,the SFR of the UAS+FRUS group was significantly lower than that of the SMP group(57.14％vs.100％,P＜0.05).The UAS+FRUS group had a longer operation time than the SMP group[(104.94±8.79)minutes vs.(77.98±6.60)minutes,P＜0.001],higher hospitalization costs[(23 112.82±1152.34)yuan vs.(21 975.84±1512.24)yuan,P＜0.001],less postoperative decrease in hemoglobin[(6.71±2.07)g/L vs.(9.81±4.80)g/L,P＜0.001],and shorter postoperative hospitalization time[(3.28±0.51)d vs.(5.58±0.71)d,P＜0.001].The UAS+FRUS group had lower postoperative VAS score at 6,24,and 48 hours than the SMP group[(6.38±0.69)vs.(7.87±0.88);(3.62±0.73)vs.(5.81±0.83)and(3.12±0.33)vs.(3.81±0.60)],with statistical significance(P＜0.05).Conclusion Both surgical methods have a high SFR in the treatment of renal calculi of 2-3 cm.SMP has the advantages of short operation time,low hospitalization costs,and high SFR for lower calyx calculi,while UAS+FURS has the advantages of little bleeding,minimal trauma,and short hospital stay.Surgeons can make reasonable choices based on the patients'condition and willingness,combined with their own surgical experience.

Objective To analyze the anesthetic effect and hemodynamic impact of oxybutynin(OBI)combined with dexmedetomidine(DEX)on patients undergoing endoscopic dacryocystorhinostomy(En-DCR).Methods Patients who underwent En-DCR from February 2024 to May 2024 at Mianyang Wanjiang Eye Hospital were recruited.They were randomly divided into the DEX group(DEX administration only)and the combined group(DEX combined with OLI administration)according to the random number table method.The primary observational index in this study was the 24-h postoperative pain numerical rating scale(NRS)scores.The secondary observation indexes were heart rate(HR),mean arterial pressure(MAP),respiratory recovery time(SRT),extubation time(ET)and awakening time(AT),peak systolic value(PSV),end-diastolic blood flow velocity(EDV),resistance index(RI)and blood flow(BF).The occurrence of adverse events in patients during hospitalization was observed and recorded.Results A total of 80 patients were included in the study,with 40 in each of the DEX group and the combined group.In terms of analgesia,the NRS scores in the combined group were lower than those in the DEX group at T1(within 0.5 h after catheter removal),T2(4 h postoperatively),T3(8 h postoperatively),and T4(24 h postoperatively)(P＜0.05),and the remedial analgesia rate in the combined group was significantly lower than that in the DEX group(P＜0.05).Regarding anesthetic effects,HR and MAP at time points T6(during induction of anesthesia),T7(intraoperatively)and T8(during resuscitation)were lower in the combined group than in the DEX group(P＜0.05);and SRT,ET and AT were shorter in the combined group compared with the DEX group(P＜0.05).In terms of hemodynamics,at 24 h postoperatively,PSV,EDV and BF were significantly higher in both groups compared with those before anesthesia,whereas RI was significantly lower than before anesthesia(P＜0.05);PSV,EDV and BF were higher in the combined group than those in the DEX group,and RI was lower than that in the DEX group(P＜0.05).Regarding adverse reactions,the incidence of adverse reactions in the combined group was significantly lower than that in the DEX group(P＜0.05).Conclusion OLI combined with DEX prophylactic analgesia for patients with En-DCR is effective,not only to reduce postoperative pain,stabilize hemodynamics,shorten the time of extubation and awakening,and reduce the incidence of adverse reactions.

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.

【Objective】 To investigate the risk factors of frailty syndrome in elderly patients with acute coronary syndrome （ACS） and their impact on prognosis. 【Methods】 The elderly patients with ACS aged 65 and over， who were hospitalized in the Department of Cardiology and Geriatric Cardiology of The First Affiliated Hospital of Xi’an Jiaotong University from September 2020 to February 2021， were selected in the cross-sectional survey. The patients were divided into frailty syndrome and non-frailty syndrome groups via the Chinese revised version of Tilburg Frailty Scale. We collected the patients’ activities of daily living， nutrition， depression， sleep quality， total cholesterol， triglycerides， low-density lipoprotein， and adverse events during hospitalization and within 30 days of discharge. We then performed LOG-BINOMIAL regression to analyze the risk factors of frailty syndrome. 【Results】 A total of 250 elderly ACS patients were enrolled， and 118 patients were diagnosed with frailty syndrome with 47.2% prevalence of frailty syndrome. There was a significant difference in the average score between the frailty syndrome group and the non-frailty syndrome group （11.06±2.53 vs. 5.77±1.54， P<0.01）. Multivariate regression analysis revealed that age （PR=2.01 CI： 1.81-2.22， P<0.001）， hypertension （PR=1.20 CI： 1.09-1.30， P<0.001）， chronic kidney disease （PR=1.16 CI：1.04-1.29， P=0.012）， and NT-proBNP （PR=1.20 CI： 1.07-1.35， P=0.004） were risk factors for frailty syndrome in elderly ACS patients. The incidence of arrhythmia and pulmonary infection during hospitalization and the rate of readmission within 30 days after discharge were significantly higher in the frailty syndrome group than those in the non-frailty syndrome group （P<0.05）. 【Conclusion】 There is a higher incidence of frailty syndrome in elderly patients with ACS. Older age， hypertension， chronic kidney disease and high NT-proBNP can increase the risk of frailty syndrome. In clinical practice， attention should be paid to the above factors， and reasonable intervention should be provided in time.

Objective To compare the success rate and complication rate between real-time ultrasound-guided and technique modified methods of right subclavian vein puncture in tumor patients during implantation of totally implanted port, and to evaluate their effectiveness and safety. Methods We randomly divided 260 tumor patients into ultrasound-guided group and technique modified group, and compared the success rate, pneumothorax, arterial injury, ectopic catheter, local hematoma, puncture times, pinch-off syndrome, etc. Results The success rate of primary puncture in the ultrasound-guided group was better than that in the technique modified group (96.92% vs. 86.15%, P=0.002). The overall complication of the ultrasound-guided group was lower than that of the technique modified group (0 vs. 9.23%, P < 0.001). The incidence of pneumothorax (0 vs. 3.85%, P=0.024) and accidental arterial injury (0 vs. 3.08%, P=0.044) in the ultrasound-guided group were lower than those in the technique modified group. There was no arteriovenous fistula and pinch-off syndrome in any group. Conclusion Compared with the technique modified group, the ultrasound-guided group has more advantages in puncture. Patients with vascular variability can be detected in time.

Objective:To systematically evaluate the clinical effect of biliary stent combined with intra-biliary radiofrequency ablation and stent alone in the treatment of malignant obstructive jaundice.Methods:The PubMed, Cochrane library, Embase, HowNet, Wanfang, Weipu were systematically searched, the search time was up to February 2021. To collect and compare the clinical efficacy studies of combined intra-biliary radiofrequency ablation in the treatment of patients with malignant obstructive jaundice before biliary stent placement. After literature screening, data extraction and quality assessment conducted by two independent reviewers. Meta-analysis was performed with the patients' 1-year survival rate, 6-month patency rate after biliary stent operation, and comparative changes in postoperative complications as the main outcome indicators.Results:Finally, 9 studies were included, comprising 2 randomized controlled studies (RCT) and 7 retrospective studies, involving a total of 443 patients, with 211 cases in the biliary stent combined with intra-biliary radiofrequency ablation group and 232 cases in the stent alone group. The results of meta-analysis showed that in two joint groups compared with the stent alone group, in overall analysis, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.24, 95% CI: 0.13-0.42) and 1-year survival rate increased ( OR=3.79, 95% CI: 2.08-6.90), the differences are statistically significant ( P<0.001), there was no statistical difference in the complications ( P=0.13). In ERCP group, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.21, 95% CI: 0.08-0.55), and the 1-year survival rate significant increase ( OR=3.63, 95% CI: 1.76-7.48), the differences are statistically significant ( P<0.01). In PTCD group, the rate of re-obstruction of the biliary tract decreased 6 months after stenting ( OR=0.25, 95% CI: 0.12-0.51), and the 1-year survival rate significant increase ( OR=4.13, 95% CI: 1.42-12.03), the differences are statistically significant ( P<0.01). Conclusion:Compared with the stent-only group, the combined group is safe and effective in treating malignant obstructive jaundice.

ObjectiveTo investigate the effect of kaempferol on the proliferation, migration, invasion, and apoptosis of human hepatoma Bel-7402 cells and related molecular mechanism. MethodsHepatoma Bel-7402 cells cultured in vitro were randomly divided into control group and low-, middle-, and high-concentration experimental groups. The experimental groups were treated with low-, middle-, and high-concentration kaempferol (25, 50, and 100 μmol/L), and the control group was treated with an equal volume of dimethyl sulfoxide. CCK-8 assay was used to observe the effect of kaempferol on the viability of Bel-7402 cells; plate colony formation assay was used to evaluate the effect of kaempferol on cell colony formation ability; wound healing assay and Transwell chamber were used to observe the effect of kaempferol on cell migration and invasion; Western blot was used to measure the expression of apoptosis- and cycle-related proteins. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter 24 hours of treatment, the cell viability was 100.00%±2.72% in the control group and 75.70%±2.42%, 62.79%±2.45%, and 43.41%±2.11%, respectively, in the low-, middle-, and high-concentration experimental groups, and compared with the control group, the experimental groups had a significant reduction in cell viability (all P＜0.05). The number of cell colonies was 923.3±35.2 in the control group and 682.7±24.4, 464.0±22.0, and 327.3±14.0, respectively, in the low-, middle-, and high-concentration experimental groups, and compared with the control group, the experimental groups had a significant reduction in cell colony formation ability (all P＜0.05). After 24 hours of treatment, the relative migration rate was 100.00%±1.11% in the control group and 63.33%±1.16%, 51.72%±3.23%, and 37.18%±2.71%, respectively, in the low-, middle-, and high-concentration experimental groups, and the number of transmembrane cells was 212.0±3.0 in the control group and 134.0±2.0, 71.0±2.0, and 34.0±1.0, respectively, in the low-, middle-, and high-concentration experimental groups; compared with the control group, the experimental groups had significant reductions in relative migration rate and number of transmembrane cells (all P＜0.05). After 48 hours of treatment, compared with the control group, the low-, middle-, and high-concentration experimental groups had a significant reduction in the expression of the anti-apoptotic protein Bcl-2 (all P＜0.05), a significant increase in the expression of the pro-apoptotic protein Bax (all P＜0.05), and a significant reduction in the expression of C＜italic/＞yclinD1 (all P＜005). ConclusionKaempferol can inhibit the proliferation, migration, and invasion of human hepatoma Bel-7402 cells and promote the apoptosis of such cells, possibly by regulating the apoptosis proteins Bax and Bcl-2 and downregulating the expression of CyclinD1.

[Objective]Analyzing clinical experience and academic view of Pro. LIAN Jianwei for the treatment of eructation in order to completely learn and master his experience.[Method] Analyzing 4 belching cases of Pro. LIAN, and combining his therapeutic experience and view. [Result] According to the view of Pro. LIAN Jianwei, there are 4 common types in clinic, the type of accumulation in stomach and intestine, the type of spleen and stomach deficiency, the type of liver qi stagnation, the type of liver and spleen disharmony. Promoting digestion and harmonizing stomach to treat the type of food accumulation in stomach;benefiting qi and strengthening spleen to treat the type pf spleen and stomach qi deficiency;smoothing liver and regulating qi to treat type of liver and stomach disharmony; regulating liver and spleen to treat type of liver and spleen disharmony;eliminating damp to treat type of spleen deficiency with damp;activating blood to treat stasis caused by prolonged diseases. Prescriptions of Pro. LIANbased on methods which changed with syndromes. He insisted that treatments base on differentiation;prescriptions base on methods, which make effect well. [Conclusion] It is worthy for our students to learn and imitate clinical experience and academic view of Pro. LIAN Jianwei for the treatment of eructation.

Objective To evaluate the effects of body position and cuffed endotracheal tube (cETT) position on the intracuff pressure during tonsillectomy in the pediatric patients.Methods Sixty pediatric patients,aged 3-12 yr,scheduled for elective tonsillectomy under general anesthesia,were divided into group A and group B using a random number table,with 30 patients in each group.The cETTs were placed on one side of the blade of Davis retractor in group A.The cETTs were placed between the blade of Davis retractor and the body of tongue in group B.The intracuff pressure was recorded when the head was in the neutral position (T1),after changing to the head back position (T2) and when the retractor was placed for operation (T3).Results The intracuff pressure was significantly higher at T2 than at T1 in the two groups (P＜0.01).The intracuff pressure was significantly higher at T3 in group A and lower at T3 in group B than at T2 (P＜0.01).Compared with group A,the intracuff pressure was significantly decreased at T3 (P＜0.01),and no significant change was found in the intracuff pressure at T1,2 in group B (P＞0.05).Conclusion The intracuff pressure is affected by body position and cETT position during tonsillectomy in the pediatric patients,and routine monitoring of the intracuff pressure is recommended.