OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

To investigate the association between sleep-related phenotypes and the risk of malignancy in pulmonary nodules, and to provide complementary evidence from a general population cohort and genetic analyses.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

BACKGROUND:Buqi Huoxue Compounds have shown significant clinical effects on the treatment of ischemic stroke due to qi deficiency and phlegm stasis,but its specific mechanism of action needs to be further clarified.OBJECTIVE:To observe the effects of Buqi Huoxue Compounds on the neurological function,p-Akt and serum exosome expression in a rat model of cerebral ischemia-reperfusion injury.METHODS:Forty adult male SPF Sprague-Dawley rats,6 weeks old,were randomly divided into sham operation group,model group,Buqi Huoxue Compounds group,Buqi Huoxue Compounds+GW4869 group,with 10 rats in each group.In the latter three groups,a rat model of cerebral ischemia-reperfusion injury was established using thread technique.The sham operation group was given incision and separation without inserting a suture.The Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion;the GW4869+Buqi Huoxue Compounds group was intragastrically given Buqi Huoxue Compounds(6.49 g/kg,administered three times a day)2 hours after reperfusion and intraperitoneally given GW4869[2.5 mg/(kg·d)]2 hours before gavage with 3 days after modeling.Both the sham operation group and model group received equal amounts of saline via gavage,three times a day,for 7 consecutive days.Neurological function,cerebral infarct volume,brain tissue morphology,characterization of serum exosome,p-Akt in the cortical area and CD63 and TSG101 in serum exosome were detected after 7 days of administration.RESULTS AND CONCLUSION:(1)After modeling,compared with the sham operation group,the neurological function scores of the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group were significantly increased(P＜0.01 or P＜0.05).After 7 days of intervention,the neurological function scores of the Buqi Huoxue Compounds group were significantly lower than those of the model group and Buqi Huoxue Compounds+GW4869 group(all P＜0.01).(2)The results of 2,3,5-triphenyltetrazolium chloride staining showed that cerebral infarct foci were observed in the model group,Buqi Huoxue Compounds group,and Buqi Huoxue Compounds+GW4869 group,and the cerebral infarct volume in the Buqi Huoxue Compounds group was smaller than that in the model group and the Buqi Huoxue Compounds+GW4869 group(P＜0.01).(3)The results of hematoxylin-eosin staining showed that the morphological and structural abnormalities of nerve cells in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group were less severe than those in the model group,but some cells still exhibited cytoplasmic agglutination and pyknosis in the Buqi Huoxue Compounds group and Buqi Huoxue Compounds+GW4869 group.(4)NanoSight analysis showed that the diameters of the isolated particles ranged from 60 nm to 300 nm,consistent with the characteristic size of exosomes.(5)Western blot results showed that the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly lower in the model group compared with the sham operation group(P＜0.05 or P＜0.01).Compared with the model group,the expression of p-Akt in the infarct zone and expression of CD63 and TSG101 in serum exosomes were significantly higher in the Buqi Huoxue Compounds group than in the model group(P＜0.05 or P＜0.01).However,the p-Akt expression in the infarct zone and CD63 expression in serum exosomes decreased significantly in the Buqi Huoxue Compounds+GW4869 group(P＜0.05),while TSG101 expression decreased without significant difference after the addition of GW4869.(6)To conclude,Buqi Huoxue Compounds attenuate cerebral ischemia-reperfusion injury and increase the expression of p-Akt in rats by promoting exosome secretion.

Objective To explore the efficacy and safety of flexible ureteroscopic lithotripsy(FURL)combined with flexible negative-pressure sheath in treating patients with 3-4 cm renal calculi with CT value＜1100 Hu,and to identify a safe and effective treatment option for patients with such calculi.Methods A retrospective analysis was conducted on the clinical data of 95 patients undergoing surgical treatment at the Department of Urology,the Second People's Hospital of Anhui Province during Jun.2022 and May 2024.The patients were divided into two groups,including 42 in the FURL with flexible negative-pressure sheath group(FURL group),and 53 in the percutaneous nephrolithotomy(PCNL)group.General data,perioperative indicators,and complication rates were compared between the two groups.Results There were no statistically significant differences between the FURL group and PCNL group in stone-free rate(SFR)3 days postoperatively(83.3％vs.88.7％),1 month postoperatively(95.2％vs.92.5％),and 3 months postoperatively(97.6％vs.94.3％),as well as operation time[(77.65±9.05)min vs.(79.10±8.14)min](P＞0.05).The FURL group had shorter hospital stay[(5.98±1.12)days vs.(9.38±1.57)days],lower decrease in hemoglobin level[(3.17±0.85)g/L vs.(4.98±1.72)g/L],lower visual analog scale(V AS)score on postoperative day 1[(2.60±0.63)vs.(3.77±1.09)]and day 3[(2.29±0.99)vs.(2.70±0.89)],lower postoperative white blood cell count[(7.05±1.66)× 109 cells/L vs.(11.24±2.90)× 109 cells/L],lower C-reactive protein level[(25.73±7.57)ng/L vs.(31.14±5.53)ng/L],lower blood urea nitrogen level[(6.12±1.43)mmol/L vs.(9.85±3.07)mmol/L],and lower serum creatinine level[(84.48±11.57)μmol/L vs.(114.43±21.48)μmol/L](all P＜0.001).The total incidence of complications was also lower in the FURL group(4.8％vs.18.9％,P＜0.05).Conclusion FURL combined with flexible negative-pressure sheath can achieve comparable SFR as PCNL without extending operation time,and it can shorten hospital stay,reduce intraoperative blood loss,have little impact on renal function,reduce inflammatory response and decrease the incidence of complications.

Purpose To investigate the clinicopathological features and diagnosis of breast epithelial-myoepithelial tumors.Methods Collect 10 cases of breast epithelial-myoepithelial tumors.Clinical features,histopathologic fea-tures,immunophenotype,and molecular characteristics were analyzed.Results All patients were female,aged 27-49 years,and the maximum diameter of the mass was 1.5 to 6.0 cm.Among them,8 cases were diagnosed as adeno-myoepithelioma(AME)of the breast,1 case as atypical AME,and 1 case as malignant adenomyoepithelioma(AME-M).All ten patients were alive with no evidence of disease or metastasis,with follow-up periods ranging from 4 to 64 months.All epithelial-myoepithelial tumors consisted of proliferative epithelial and myoepithelial cells,with myoepithe-lial hyperplasia being the predominant component.In the atypical AME case,myoepithelial cells exhibited mild to moderate atypia,with mitotic figures observed occasionally(3/10 HPF).AME-M was composed of solid and cystic ar-eas.In the solid area,myoepithelial cells exhibited moderate to severe atypia with a high mitotic rate(6-8/10 HPF).Additionally,necrosis and areas of squamous cell carcinoma were present,leading to a diagnosis of epithelial-myoepithelial carcinoma.Papillary squamous cell carcinoma was found in cystic area and it involved the adjacent lob-ules.The peripheral breast tissue contained focal ductal carcinoma in situ.The luminal epithelial cells showed expres-sion of CK8/18 and CK7.The myoepithelial cells showed expression of p63,CD10,and SMA.The Ki67 index was less than 10％in AME,40％in atypical AME.In the AME-M,it was 80％in the epithelial-myoepithelial carcinoma component,and 70％in the papillary squamous cell carcinoma component.Sanger sequencing of 6 cases AME and 1 case atypical AME revealed no hotspot mutations in HRAS or PIK3CA.In one case of AME-M,pyrosequencing indica-ted no hotspot mutations of AKT1,KRAS,HRAS,and PIK3 CA in the components of epithelial-myoepithelial carcino-ma and papillary squamous cell carcinoma while one KRAS(c.183A＞C/T,p.Q61H)mutation was present in the peripheral ductal carcinoma in situ.Molecular genetic analysis on 22 short tandem repeat loci showed an identical pat-tern including LOH at D19S433 in both components of AME-M and squamous cell carcinoma.Conclusion AME is an rare tumor with a heterogeneous morphology.The biphasic proliferation of epithelial and myoepithelial components is the key to correct diagnosis.Molecular genetic analysis suggested AME-M and squamous cell carcinoma were clonally independent from the peripheral ductal carcinoma in situ.

Objective:To explore the current status and influencing factors of fatigue in patients with Cushing syndrome in China, so as to provide a basis for clinical interventions.Methods:Convenience sampling was used to select 260 inpatients with Cushing syndrome who met the inclusion and exclusion criteria in 9 ClassⅢ Grade A hospitals within the 7 geographic subregions of China from February to April 2023 for the study. General Information Questionnaire, the Chinese version of the Multidimensional Fatigue Inventory-20, Barthel Index, and Self-Rating Depression Scale were used for the survey.Results:A total of 260 questionnaires were distributed and 241 valid questionnaires were recovered, with an effective recovery rate of 92.7% (241/260). The MFI-20 score of 241 patients with Cushing syndrome was 58.00 (46.00, 64.00). 65.1% (157/241) of patients with Cushing syndrome suffered from fatigue, and 73.2% (115/157) of patients with fatigue exhibited multidimensional fatigue. Univariate analysis showed that there were statistically significant differences in fatigue scores among patients with Cushing syndrome with different cultural levels, recurrence frequency, activity of daily living, hypertension, and depression ( P<0.05). Multiple linear regression analysis showed that depression was a risk factor for fatigue in patients with Cushing syndrome, and the difference was statistically significant ( P<0.05) . Conclusions:Fatigue in patients with Cushing syndrome needs attention. Medical and nursing staff should pay close attention to the psychological status of patients with Cushing syndrome, encourage them to actively cope, alleviate their depression, in order to improve their fatigue.

Objective To explore the efficacy and safety of flexible ureteroscopic lithotripsy(FURL)combined with flexible negative-pressure sheath in treating patients with 3-4 cm renal calculi with CT value＜1100 Hu,and to identify a safe and effective treatment option for patients with such calculi.Methods A retrospective analysis was conducted on the clinical data of 95 patients undergoing surgical treatment at the Department of Urology,the Second People's Hospital of Anhui Province during Jun.2022 and May 2024.The patients were divided into two groups,including 42 in the FURL with flexible negative-pressure sheath group(FURL group),and 53 in the percutaneous nephrolithotomy(PCNL)group.General data,perioperative indicators,and complication rates were compared between the two groups.Results There were no statistically significant differences between the FURL group and PCNL group in stone-free rate(SFR)3 days postoperatively(83.3％vs.88.7％),1 month postoperatively(95.2％vs.92.5％),and 3 months postoperatively(97.6％vs.94.3％),as well as operation time[(77.65±9.05)min vs.(79.10±8.14)min](P＞0.05).The FURL group had shorter hospital stay[(5.98±1.12)days vs.(9.38±1.57)days],lower decrease in hemoglobin level[(3.17±0.85)g/L vs.(4.98±1.72)g/L],lower visual analog scale(V AS)score on postoperative day 1[(2.60±0.63)vs.(3.77±1.09)]and day 3[(2.29±0.99)vs.(2.70±0.89)],lower postoperative white blood cell count[(7.05±1.66)× 109 cells/L vs.(11.24±2.90)× 109 cells/L],lower C-reactive protein level[(25.73±7.57)ng/L vs.(31.14±5.53)ng/L],lower blood urea nitrogen level[(6.12±1.43)mmol/L vs.(9.85±3.07)mmol/L],and lower serum creatinine level[(84.48±11.57)μmol/L vs.(114.43±21.48)μmol/L](all P＜0.001).The total incidence of complications was also lower in the FURL group(4.8％vs.18.9％,P＜0.05).Conclusion FURL combined with flexible negative-pressure sheath can achieve comparable SFR as PCNL without extending operation time,and it can shorten hospital stay,reduce intraoperative blood loss,have little impact on renal function,reduce inflammatory response and decrease the incidence of complications.

Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.

Objective:To retrieve, evaluate, and integrate evidence on output and input record in patients with heart failure.Methods:Literature related to output and input record for patients with heart failure was systematically searched in national and international guideline networks, professional association websites, and databases. The search period was from database establishment to October 31, 2024. Evidence was extracted, integrated, and graded after two researchers independently conducted a literature quality assessment.Results:A total of 15 papers were included, including six guidelines, two expert consensus, two evidence summaries, one recommended practice, two systematic reviews, and two expert opinions. Twenty-five pieces of best evidence were summarized in five areas of objects and content, fluid measurement, recording and aggregation, evaluation and monitoring, and training and guidance.Conclusions:This study summarizes the best evidence for output and input record in patients with heart failure, which may inform nursing staff in their clinical practice. Nursing staff should judiciously select and apply evidence in a clinical context so as to improve the accuracy of output and input record.