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.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Viral myocarditis(VMC)is the leading cause of dilated cardiomyopathy,which can lead to heart failure and sudden cardiac death.With the development of high-throughput sequencing technology,non-coding RNA(ncRNA)plays an important role in the occurrence and development of VMC.ncRNA promotes the occurrence and development of VMC by regulating viral replication,immune cell function,myocardial cell death,myocardial interstitial fibrosis,and other pathological processes.This article reviews the research progress of ncRNA in VMC and provides new ideas for the pathogenesis,diagnosis,and treatment of VMC.

Objective To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children.Methods A retrospective analysis was performed on 23 chil-dren with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation(arthrography with elastic nail group)from January 2019 to December 2022,including 12 males and 11 fe-males,aged from 2 to 12 years old with an average of(7.36±1.89)years old;According to Judet fracture types,14 children were type Ⅲ and 9 children were type Ⅳ.In addition,23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation(elastic nail group),including 11 males and 12 females,aged from 2 to 14 years old with an average of(7.50±1.91)years old;Judet classi-fication included 15 children were type Ⅲ and 8 children were type Ⅳ.Operative time and intraoperative fluoroscopy times were compared between two groups.Metaizeau evaluation criteria was used to evaluate fracture reduction,and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups.Results Both groups were followed up for 12 to 24 months with an average of(16.56±6.34)months.Operative time and intraoperative fluoroscopy times of elastic nail group were(56.64±19.27)min and(21.13±7.87)times,while those of joint angiography with elastic nail group were(40.33±1 1.50)min and(12.10±3.52)times;there were difference between two groups(P＜0.05).According to Metaizeau evaluation,11 patients got excellent result,9 good and 3 fair in joint angiography with elastic nail group,while in elastic nail group,5 ex-cellent,13 good,4 acceptable,and 1 poor;the difference between two groups was statistically significant(P＜0.05).According to Tibone-Stoltz criteria,14 patients got excellent result,8 good,and 1 fair in joint arthrography with elastic nail group;while in elastic nail group,12 patients got excellent result,9 good,1 fair and 1 poor;there was no significant difference between two groups(P＞0.05).Conclusion Compared to percutaneous elastic intramedullary nail fixation,closed reduction assisted by arthrography has advantages of reduced operation time,decreased intraoperative fluoroscopy frequency,and improved fracture reduction.Arthrography enables clear visualization of the anatomical structures of radius,head,neck,bone,and cartilage in children,facilitating comprehensive display of fracture reduction and brachioradial joint alignment.This technique more pre-cisely guides the depth of elastic intramedullary nail implantation in radius neck,thereby enhancing surgical efficiency and success rate.

The biological characteristics and pathogenicity of Klebsiella oxytoca isolated from sick carrier pigeons in Gansu province were explored by morphological observations,biochemical testing,16S rRNA PCR analysis,and RNA sequencing.The drug resistance and pathogenicity of the isolated strains were studied by histopathological observation,drug susceptibility testing,and pathogenicity analysis.The livers,lungs,hearts,and other organs of the sick pigeons were bleeding.In addition,the livers were yellow and brittle,and the lungs were purulent.A Gram-negative,short,rod-shaped bacterium was successfully isolated from the sick pigeon.Pink,smooth,moist,and round colonies grew on MacConkey's agar.The result of the indigo matrix test was positive.The homology between the amplified 16S rRNA sequence and MN330093.1 was 100.00％,indicating that the sick pigeon was infected with K.oxytoca.The strain was named GS-BY-GG.K.Oxytoca GS-BY-GG was resistant to 10 drugs,including penicillin,ampicillin,and furazolidone,and sensitive to 5 others,which included florfenicol,meropenem,and gentamicin.Histopathological observation showed bleeding in multiple organs.The liver cells were irregu-larly arranged with brown-yellow pigmentation.Extensive cell necrosis and exfoliation were observed in the trachea and mucosal epithelium,with inflammatory cell infiltration in the mucosal layer.The isolates were highly pathogenic in specific pathogen-free chickens.These findings provide support for the clinical diagnosis and control of K.oxytoca GS-BY-GG.

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Heel/surgery* ; Heel Spur/surgery* ; Retrospective Studies ; Calcaneus/surgery* ; Foot Diseases ; Pain ; Endoscopes ; Treatment Outcome

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:To evaluate the clinical status, and analyz obstacles and facilitators for perioperative deep vein thrombosis prevention of brain neoplasms based on the Ottawa model of research use (OMRU).Methods:A total of 93 patients with brain tumors who were admitted to the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from April to May 2021 and 33 nurses in the neurosurgery ward and operating room neurosurgery special group were selected as the baseline review subjects by convenience sampling. Based on the framework of evidence-based continued quality improvement of Fudan University, we searched BMJ Best Practice, UpToDate, The Joanna Briggs Institute Library, International Guideline Library, American Guideline Network, Scottish Intercollegiate Guideline Network, National Institutes for Health and Clinical Technology Optimization, Medline, Medlive, China National Knowledge Infrastructure, VIP, Wanfang and SinoMed according to the '6S' evidence pyramid from inception to January 1, 2021 for all clinical decisions, recommended practices, best practice information, evidence summary, guidelines and expert consensus on venous thrombosis assessment, prevention, screening, nursing and health education. The best evidence was summarized, and the final review indicators were formulated through two rounds of expert correspondence. According to the results of baseline review, barriers and facilitators were analyzed, and countermeasures were developed guided by OMRU.Results:A total of 19 best evidences were included, and 34 review indicators were developed in this study. Among them, only 4 indicators had a compliance rate of 100%, 18 ones had a compliance rate of 0, and the other 12 ones had a compliance rate of 6.5%-97.8%. A multi-factor analysis of the review results showed that the main obstacles of evidence implementation were the feasibility and comprehensibility at evidence level, the lack of knowledge and heavy workloads at the potential practitioner level, insufficient education materials, trainings and preventive equipment at system level. Furthermore, the reliable sources of evidence at evidence level, supports from practitioners at the potential practitioner level and system resources (such as training, national and hospital policies, etc.) at system level may contribute to the clinical application of evidence.Conclusions:There was still a huge gap between the best evidence and clinical practice. The obstacles and facilitating factors in evidence transformation should be evaluated scientifically and comprehensively, and corresponding countermeasures should be given to promote the application of evidence in clinical practice.

Objective:To investigate the influencing factors of anastomotic leakage after laparoscopic intersphincter resection (ISR) for extremely low rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 812 patients who underwent laparoscopic ISR for extremely low rectal cancer in the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from February 2012 to February 2022 were collected. There were 459 males and 353 females, aged (51±11)years. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors of postoperative anastomotic leakage; (4) construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. The COX proportional hazard model was used for univariate and multivariate analyses. The R software(3.5.1 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of the nomogram prediction model. The Bootstrap method was used for internal verification and to calculate the average consistency index (C-index). Results:(1) Surgical situations. All 812 patients underwent laparoscopic ISR for extremely low rectal cancer, including 388 cases undergoing partial ISR, 218 cases undergoing subtotal ISR and 206 cases undergoing complete ISR. All 812 patients underwent ileal protective ostomy, and there were 306 cases with double anastomosis and 203 cases with left colic artery preserved, respectively. The operation time and volume of intraoperative blood loss of 812 patients was (179±33)minutes and (33±13)mL, respectively. (2) Follow-up. All 812 patients were followed up for (13.5±0.9)months. Of the 812 patients, there were 62 cases with postoperative anastomotic leakage and the healing time of these cases was (33±6)days. (3) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that male, neoadjuvant chemoradiotherapy, failure of reser-ving left colic artery were independent risk factors of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer ( hazard ratio=5.98, 4.00, 16.26, 95% confidence interval as 1.66-24.12, 1.30-12.42, 3.00-90.89, P<0.05). (4) Construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. According to the results of multivariate analysis, male, neoadju-vant chemoradiotherapy and failure of reserving left colic artery were used to construct the nomogram prediction model for anastomotic leakage after laparoscopic ISR for extremely low rectal cancer, and the score of these indexes in the nomogram prediction model was 50, 49, 93, respectively. The total score of these index corresponded to the incidence rate of anastomotic leakage. Results of ROC curve showed that the AUC of nomogram prediction model of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer was 0.87 (95% confidence interval as 0.80-0.93, P<0.05), with sensi-tivity and specificity 0.96 and 0.60, respectively. Results of internal verification showed that the C-index of nomogram prediction model was 0.87. Conclusion:Male, neoadjuvant chemoradiotherapy, failure of reserving left colic artery are independent risk factors of anastomotic leakage after laparo-scopic ISR for extremely low rectal cancer, and the nomogram prediction model based on these indexes can predict the incidence rate of postoperative anastomotic leakage.