Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Objective To assess the impact of statins combined with sorafenib(SRF)therapy on survival outcomes in patients with metastatic renal cell carcinoma(mRCC).Methods Clinical data of mRCC patients treated in the 908th Hospital of the Joint Security Force from November 2019 to November 2023 were retrospectively analyzed.They were categorized into statin group and non-statin group according to whether they used statins or not,and the differences in the primary endpoint of overall survival(OS),secondary endpoints of progression-free survival(PFS),objective response rate(ORR),and disease control rate(DCR)were compared between the two groups.Results A total of 80 patients were included in the study,with 27 in the statin group and 53 in the non-statin group.There were no statistically significant differences in partial remission,stable disease,disease progression,and DCR between the two groups(P＞0.05);complete remission and ORR were significantly higher in the statin group than in the non-statin group(P＜0.05).Kaplan-Meier analysis showed that,compared with the non-statin group,the median PFS and OS of the statin group were prolonged,and the difference in median PFS between the two groups was statistically significant(P＜0.05).In terms of safety,the incidence of other adverse events was similar in both groups(P＞0.05).Conclusion Statins combined with SRF treatment regimen can improve ORR and DCR and prolong median PFS and OS in patients with mRCC.

Objective: To construct the full-length prokaryotic expression plasmid of the wild type of androgen receptor (AR) and the truncated body of four functional domains，and to identify the fusion protein by Western blot and electrophoretic mobility shift assay ( EMSA) ． Methods: Based on the pGEX-4T-1 vector ，the recombinant plasmids were constructed to express the full-length and functional domains of AR. IPTG was used to induce the expression of the recombinant proteins，which were isolated and purified by glutathione sepharose 4B beads under the optimized condition．The specific protein expression in the bacterial lysate and the purified protein isolated with glutathione sepharose 4B beads was identified by Western blot with AR antibody and GST labeled antibody．The purified protein was incubated with a fluorescent probe of the virus，and the complex was detected by electrophoresis in a non-denaturing gel. Results : The prokaryotic recombinant plasmids of full length and three functional domain truncated AR were successfully constructed．The recombinant clones were identified by using bacterial culture as a template，and further verified by double enzyme digestion．It showed that there were identical bands in the same sizes as the inserted fragments．The nucleotide and the amino acid sequences were aligned to the reference sequence in NCBI GenBank．The GST fusion protein，GST-AR-NTD + DBD (96 ku) and GST-AR-NTD (86 ku) were successfully induced and verified． The purified protein could be directly combined with the viral genome DNA． Conclusion The prokaryotic expression conditions of truncated AR plasmid from the same gene sequence are different．The purified AR protein can be used to understand the direct interaction mechanism between functional domains of AR and other molecules.

Objective To investigate the predictive value of preoperative frailty for pulmonary com-plications(PPCs)after cardiac surgery in elderly patients.Methods A total of 162 elderly patients,109 males and 53 females,aged 65-83 years,BMI 18-36 kg/m2,ASA physical status Ⅱ-Ⅳ,underwent elec-tive open heart surgery from July 2022 to January 2023 were collected.The patients were divided into two groups according to the occurrence of PPCs:the PPCs group(n=57)and the non-PPCs group(n=105).General information,smoking history,alcohol consumption history,EuroSCORE Ⅱ,frailty,chronic comorbidities(hypertension,diabetes mellitus,myocardial infarction,pulmonary hypertension,chronic ob-structive pulmonary disease,sleep apnea syndrome,etc.),Hb,creatinine,albumin,pulmonary function indices,left ventricular ejection fraction,type of surgery,duration of surgery,aortic clamping time,and cardiopulmonary bypass time were collected.Factors with P＜0.2 and clinically significant in the univariate regression analysis were included in the multivariate logistic regression analysis,and the predictive efficacy of the Fried frailty scale and EuroSCORE Ⅱ for PPCs were compared by the area under the ROC curve(AUC).Results PPCs occurred in 57 patients(35.2％).Multifactorial Logistic regression analysis showed that frailty(OR=3.14,95％CI 1.05-9.37,P＜0.05)and EuroSCORE Ⅱ(OR=2.16,95％CI 1.01-4.60,P＜0.05)were risk factors for the development of PPCs.The predictive power of Fried frailty scale(AUC=0.76,95％CI 0.68-0.82)was significantly higher than that of EuroSCORE Ⅱ(AUC=0.65,95％CI 0.57-0.72)(P＜0.05).Conclusion Preoperative frailty is the independent risk factors for pulmonary complications after cardiac surgery in elderly patients,and the Fried frailty scale has a better predictive efficacy compared to EuroSCORE Ⅱ,a traditional risk predictor.

Objective:To evaluate the relationship between preoperative sarcopenia and severe pulmonary complications after cardiac surgery in elderly patients.Methods:Elderly patients undergoing elective open heart surgery in our hospital were collected and divided into non-sarcopenia group and sarcopenia group, according to the diagnostic criteria updated and revised by the Asian Sarcopenia Working Group in 2019. The outcome measure was the development of severe postoperative pulmonary complications (PPCs). The general information of patients and various indexes of surgical conditions were recorded. Risk factors for severe PPCs were identified by multivariate logistic regression analysis. The accuracy of sarcopenia score, American Society of Anesthesiologists (ASA) Physical Status classification, and combination of ASA Physical Status classification and sarcopenia score in predicting severe PPCs was assessed using the receiver operating characteristic curve.Results:A total of 158 patients were finally enrolled, including 36 patients with sarcopenia (22.7%), and the incidence of severe PPCs was 22.2%. Multivariate logistic regression analysis showed that ASA classification, sarcopenia, and duration of surgery were independent risk factors for severe PPCs after cardiac surgery in elderly patients ( P<0.05), and the risk of severe PPCs was approximately 3.21 times higher in sarcopenic patients than in non-sarcopenic patients. The area under the receiver operating characteristic curve of sarcopenia score, ASA Physical Status classification, and ASA Physical Status classification combined with sarcopenia score in predicting severe PPCs were 0.686 (95% confidence interval [ CI] 0.607-0.757), 0.603 (95% CI 0.522-0.680), and 0.714 (95% CI 0.637-0.783), respectively. Conclusions:Preoperative sarcopenia is an independent risk factor for severe PPCs after cardiac surgery in elderly patients, and the preoperative sarcopenia in combination with ASA Physical Status classification in predicting severe PPCs has a certain accuracy.

OBJECTIVE To conduct a c omprehensive clinical evaluation method of Chinese patent medicine ，and to provide reference for rational clinical drug use. METHODS Taking the top 10 Chinese patent medicine injections for promoting blood circulation and removing stasis in Shandong province from 2016 to 2020 collected by the National Rational Drug Use Monitoring Network as an example ，the method combining health technology assessment with objective judgement analysis is used to construct the comprehensive evaluation index system ；based on evidence-based medical evidence and pharmacoeconomic model ，the safety ， effectiveness and economy of the drug were evaluated comprehensively ，and the scores were quantified. RESULTS & CONCLUSIONS The final scores of the 10 kinds of Chinese patent medicine injections were between 26 and 37 scores. Safflower yellow for injection scored the highest score in the treatment of cerebral infarction and angina pectoris of coronary heart disease ， while Ginkgo diterpene lactone meglumine injection and Shuxuening injection had the highest scores in the treatment of coronary heart disease. The clinical comprehensive evaluation method of Chinese patent medicine based on evidence-based medical evidence and pharmacoeconomic model can clarify the comprehensive value of Chinese patent medicine in clinic ，promote rational drug use in clinic ，and provide basis for the next adjustment of medical insurance catalogue and essential medicine catalogue ，decision-making of centralized procurement of related drugs.

Objective:To determine the 50% effective dose (ED 50) of sugammadex for rapid recovery of the signal of intraoperative neuromonitoring of recurrent laryngeal nerve in radical thyroidectomy. Methods:American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, weighing 40-90 kg, scheduled for elective radical thyroidectomy under intraoperative neuromonitoring of recurrent laryngeal nerve, were enrolled in this study.Sufentanil and propofol were intravenously injected, and muscle relaxation monitoring was performed after the patients lost consciousness.Rocuronium 0.6 mg/kg was intravenously injected, and tracheal intubation was performed when the twitch ratio was 0.The infusion rate of rocuronium was adjusted to maintain twitch ratio 0-10%.When the signal needed to be detected, rocuronium infusion was stopped, sugammadex was injected intravenously using up-and-down sequential method, with the initial dose of 2 mg/kg.If a stable signal was detected within 3 min, the concentration decreased by 0.2 mg in the next patient, otherwise the concentration increased by 0.2 mg in the next patient.The Dixon and Massey formula was used to calculate the ED 50 and 95% confidence interval of sugammadex. Results:The ED 50 of sugammadex for the rapid recovery of the signal of intraoperative neuromonitoring of recurrent laryngeal nerve was 0.98 mg/kg, and the 95% confidence interval was 0.94-1.02 mg/kg during radical thyroidectomy. Conclusion:The ED 50 of sugammadex for rapid recovery of the signal of intraoperative neuromonitoring of recurrent laryngeal nerve is 0.98 mg/kg in radical thyroidectomy.

Objective:To evaluate the accuracy of ultrasound-measured pulsatility index (PI) of central retinal arteries in diagnosing low cerebral perfusion pressure (CPP) in the patients with traumatic brain injury.Methods:Fifty-five patients who were admitted to the surgical intensive care unit due to traumatic brain injury with continuous intracranial pressure monitoring were selected.At 72 h after surgery, continuous incracranial pressure and mean arterial pressure were recorded, and peak systolic velocity and end diastolic velocity of central retinal arteries were measured by ultrasound.The invasive CPP and PI were calculated.The correlation between PI and CPP was analyzed.The accuracy of central retinal pulse index in diagnosing low CPP was evaluated by the receiver operating characteristic curve.Results:PI was negatively correlated with CPP ( r=-0.655, P<0.01). The area under the receiver operating characteristic curve of PI in diagnosing low CPP was 0.863 (95% confidence interval 0.761-0.965), and the threshold value was 0.97, sensitivity 92.3%, and specificity 66.7%. Conclusion:Ultrasound-measured PI is more accurate in diagnosing low CPP in the patients with traumatic brain injury.

Objective To evaluate the treatment of posterior malleolar two-part fractures complicated with medial and lateral malleolar fractures via a combination of posterolateral and posteromedial approaches.Methods From January 2014 to January 2017,26 patients were operatively treated at Department of Orthopaedics,Tongji Hospital for posterior malleolar two-part fractures complicated with medial and lateral malleolar fractures via a combination of posterolateral and posteromedial approaches.They were 10 men and 16 women,aged from 53 to 67 years(average,61.5 years).The surgery was conducted in prone position via the posterolateral and posteromedial approaches to expose simultaneously the fractures ends at medial,lateral and posterior malleoli for open reduction.The lateral malleolar fractures were fixated with plate,the medial malleolar fractures with screws and posterior malleolar fractures with plate or cannulated screws depending on the size of the fracture blocks.The outcomes were assessed using the ankle-hindfoot scores of American Orthopaedic Foot and Ankle Society(AOFAS) and the visual analogue scale(VAS).Results Of this cohort,22 were followed up for 30 months on average(range,from 18 to 48 months).All the cases healed by the first intension without any infection.Their postoperative X-ray showed bone union after an average of 12.5 weeks(range,from 10 to 15 weeks).No nonunion,loosening or breakage of implants was found.The mean time for walking with full weight-bearing was 13 weeks(range,from 11 to 16 weeks).Their AOFAS ankle-hindfoot scores at the final follow-ups were 85.4(range,from 80 to 92),yielding 13 excellent and 9 good cases with a good to excellent rate of 100%.Their mean VAS scores were decreased significantly from preoperative 8.6±0.6 to postoperative 1.7±0.3(f=153.000,P=0.000).Conclusion In treatment of posterior malleolar two-part fractures complicated with medial and lateral malleolar fractures,a combination of posterolateral and posteromedial approaches in prone position can expose and reduce simultaneously the fractures ends at medial,lateral and posterior malleoli,leading to satisfactory clinical outcomes.

Objective To determine the minimum alveolar concentration (MAC)of sevoflurane for blunting the responses to surgical incision in 50% adult patients diagnosed as gastric carcinoma and treated with neoadjuvant chemotherapy.Methods Twenty-five ASA physical statusⅠor Ⅱ,and aged 30-50 years patients (14 males and 11 females)diagnosed with gastric carcinoma were enrolled.At least 1 month before the operation,all these patients received 2 cycles (1 chemotherapy cycle was 14 days)of chemotherapy including oxaliplatin and tegafur.At first,the anesthesia induc-tion was started by inhaling 6% sevoflurane.After the patient lost consciousness,the endotracheal in-tubation was performed.And then,the end tidal sevoflurane concentration was adjusted to the target concentration and maintained stable for 15 min.After that,the surgical incision was executed.The Dixon's up-and-down method was used to calculate the MAC.The initial end tidal sevoflurane con-centration was 2.2% and it was increased or decreased by 0.2% in the next patient according to the surgical incision response.If the surgical incision response was positive,the end tidal sevoflurane con-centration was increased;if the surgical incision response was negative,the end tidal sevoflurane con-centration was decreased.The midpoint from negative response to positive response was set as the balance point and the mean value of the concentrations of sevoflurane at all the balance points were calculated as MAC.Results Minor physical activity occurred when the surgical incision started.No body twisting,eye opening or intraoperative awareness occurred.Body moving occurred in 11 patients (44%)when the surgical incision started.The end tidal sevoflurane concentration for blunting the re-sponses to surgical incision in 50% adult patients diagnosed as gastric carcinoma and treated with neo-adjuvant chemotherapy was 1.52%,and the 95% CI was 1.37%-1.65%.Conclusion The MAC of sevoflurane for blunting the responses to surgical incision in 50% adult patients diagnosed as gastric carcinoma and treated with neoadjuvant chemotherapy is 1.52%.