Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective To investigate the effects of different anesthesia depths on stress states and inflammatory mediators in patients undergoing video-assisted thoracoscopic lobectomy.Methods A total of 89 lung cancer patients who underwent video-assisted thoracoscopic lobectomy were selected as study subjects.Based on intraoperative bispectral index(BIS)range,the patients were divided into deep anesthesia group(BIS of 40 to＜50,n=45)and shallow anesthesia group(BIS of 50 to＜60,n=44).Vital signs(mean arterial pressure,heart rate and blood oxygen saturation),anesthesia re-covery time,extubation time,dosage of vasoactive drugs,postoperative pain intensity[Visual Ana-logue Scale(VAS)],postoperative analgesic dosage,perioperative stress state[prostaglandin E2(PGE2),nerve growth factor(NGF)and substance P(SP)],levels of inflammatory mediators[neuron-specific enolase(NSE),tumor necrosis factor-α(TNF-α)and S100β protein]at different time points(before anesthesia induction,immediately after intubation,before lesion resection and at the end of surgery)and the incidence of anesthesia-related adverse reactions were compared between the two groups.Results Before lesion resection and at the end of surgery,the mean arterial pressure and heart rate in the deep anesthesia group were significantly lower than those in the shallow anesthe-sia group(P＜0.05).The anesthesia recovery time and extubation time in the deep anesthesia group were significantly longer than those in the shallow anesthesia group(P＜0.05).At the end of surgery and on postoperative day one,the levels of PGE2,NGF and SP in the deep anesthesia group were significantly lower than those in the shallow anesthesia group,while the levels f NSE,TNF-α and S100β protein were significantly higher than those in the shallow anesthesia group(P＜0.05).There were no significant differences in the dosage of vasoactive drugs,VAS scores,sufentanil dos-age and the incidence of anesthesia-related adverse reactions between thetwo groups(P＞0.05).Conclusion During one-lung ventilation in patients undergoing video-assisted thoracoscopic surgery lobectomy,deep anesthesia can effectively control surgical stress and maintain stability of intraopera-tive hemodynamics,but it is associated with delayed postoperative awakening and more pronounced inflammatory response.Shallow anesthesia results in faster postoperative awakening and lower levels of inflammatory mediators,but it is associated with more significant intraoperative stress response and unstable hemodynamics.

Objective:To compare the clinical effect of surgical treatment of congenital preauricular fistulas in children during the local infection period and static inflammatory period. Methods:Forty children with congenital preauricular fistula infection treated in our hospital from January 2020 to December 2022 were selected as the experimental group, and 39 children with congenital preauricular fistula inflammation at static period were selected as the control group. The fistula of the two groups of children aged between 1-14 years old was located in front of the foot of the ear wheel or the foot of the ear wheel, and all were unilateral fistulas. The postoperative follow-up was 6 months to 2 years, and the efficacy of the two groups was compared. Results:There was no significant difference in the healing rate of stage Ⅰ and stage Ⅱ between the two groups（P>0.05）. There was no significant difference in fistula recurrence rate and satisfaction with the preauricular scar between the two groups after treatment（P>0.05）. There was no significant difference in postoperative hospital stay between the experimental group and the control group（P>0.05）. Conclusion:The effect of surgical treatment of congenital preauricular fistula in the infected period is similar to that of surgical treatment in the static period of inflammation, and it can reduce the pain of dressing change under local anesthesia in children, avoid the second operation in children, and reduce the economic cost. This treatment method is worthy of clinical promotion. Appropriate incision and resection method were designed according to the fistula and infection sites.
Humans ; Child ; Infant ; Child, Preschool ; Adolescent ; Fistula/surgery* ; Inflammation ; Craniofacial Abnormalities/surgery* ; Cicatrix ; Treatment Outcome

Objective To restrospectively analyze the risk factors for blood transfusion during ce-sarean section and neonate outcomes. Methods A total of 291 parturients ( 60 cases with blood transfusion during surgery and 231 cases without blood transfusion during surgery) who underwent cesarean section from November 2016 to March 2017 in our hospital were selected. The significant covariates in one-way analysis of variance were analyzed by logistic regression analysis. The odds ratio ( OR) and 95％ confidence interval ( CI) were calculated. The risk factors for blood transfusion during cesarean section were identified, and neonate outcomes were analyzed. Results Placenta increta, placenta accrete and pernicious placenta pre-via were the risk factors for blood transfusion during cesarean section, with OR value ( 95％ CI ) 13. 5 (2. 6-56. 8), 6. 1 (2. 1-11. 6) and 3. 3 (1. 6-8. 6), respectively. The prolonged gestational age was a protective factor, and the OR value ( 95％ CI) was 0. 3 ( 0. 2-0. 5) . The duration of operation, anesthesia time and length of hospital stay were significantly prolonged in blood transfusion group as compared with non-blood transfusion group ( P<0. 05) . The body weight and 1-min Apgar score of newborns were signifi-cantly lower in blood transfusion group than in non-blood transfusion group. Conclusion Placenta increta, placenta accrete and pernicious placenta previa are the risk factors for blood transfusion during cesarean sec-tion. Blood transfusion is not helpful for neonate outcomes.