OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

The treatment of glioblastoma, the most prevalent malignant tumor in the central nervous system, poses considerable challenges. Glioblastoma multiforme, classified as a grade Ⅳ highly malignant brain glioma by the World Health Organization, is typically managed through a combination of surgery, postoperative chemotherapy, and radiotherapy. The treatment of glioblastoma is complicated by its infiltrative nature, genetic heterogeneity, and presence of the blood-brain barrier. Almost all cases of glioblastoma experience recurrence despite aggressive therapy, exploring the development of updated molecular treatment strategies that can improve overall efficacy. A crucial aspect in modern neurosurgery is the precise delineation of brain regions in terms of their anatomy and function. It serves as the fundamental basis for investigating variations in the distribution of brain gliomas. Hence, this review will elucidate the origin of glioblastomas and analyze the potential factors contributing to the spatially specific distribution of gliomas on the basis of a theoretical framework of brain connectomics research. Molecular characteristics, information pathways, tumor microenvironment landscape, and immunology will inform the analysis. We aim to identify novel biomolecular targets and therapeutic pathways to gain scientific insights for effective glioblastoma treatment.

Objective To analyze the CT signs of acute blunt or penetrating intestinal injury,and to improve the diagnostic accuracy of multi spiral CT for intestinal injury.Methods The CT and clinical data of 63 patients with intestinal injury confirmed by clinical surgical exploration who underwent emergency CT scan were collected,and the CT findings and surgical findings were comparatively analyzed.Results There were 63 cases of intestinal injury,of which 26 cases were complicated with mesenteric injury.The direct CT signs of intestinal injury included intestinal wall thickening sign and intestinal discontinuity sign,which accounted for 64%(40/63)and 17%(10/63),respectively.The indirect CT signs of intestinal injury included intraperitoneal/retroperitoneal gas sign,intraperitoneal/retroperitoneal effusion sign,intramural air,and portal venous gas,which accounted for 72%(45/63),88%(55/63),7%(5/63)and 5%(3/63),respectively.Conclusion Recognizing the CT signs of intestinal injury,such as intestinal wall thickening sign,intestinal discontinuity sign,intraperitoneal/retroperitoneal gas sign,intraperitoneal/retroperitoneal effusion sign,intramural air,and portal venous gas can help to make the early and correct diagnosis of intestinal injury if combined with clinical practice.

BACKGROUND:Numerous scholars have previously researched certain greater tuberosity fractures and the procedures used to treat them.Few researchers,however,have studied the comminuted split fracture of the greater tuberosity of the humerus(Liu-Gang type IV)with rotator cuff tear in great detail. OBJECTIVE:To compare the clinical therapeutic effect of open repair position modified calcaneal plate combined with suture anchors and proximal humeral internal locking system(PHILOS)plate in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV). METHODS:Case data of 30 patients with comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)from May 2012 to May 2022 were retrospectively analyzed.They were divided into the modified calcaneal plate combined with suture anchor group(group A)and the PHILOS with#2 Johnson group(group B),with 15 cases in each group.Intraoperative blood loss,surgical time,and incision length of all patients were recorded.Pain visual analog scale score,Constant-Murley score,as well as shoulder joint abduction,forward flexion,external rotation,and dorsal expansion activities during the last follow-up(>1 year)were evaluated. RESULTS AND CONCLUSION:(1)The surgical incision length and operation time were shorter,and blood loss was less in group A than those in group B(P<0.05).(2)No significant difference in visual analog scale score and Constant-Murley score was detected between the two groups(P>0.05).(3)During the last follow-up,forward flexion in group A was better than that in group B(P<0.05).No significant difference in abduction,external rotation,and dorsal expansion was determined between group A and group B(P>0.05).(4)In terms of complications,there was 1 case of shoulder joint pain and discomfort in group A(7%),2 cases of subacromial impingement syndrome,2 cases of upward movement of nodules,and 2 cases of shoulder joint pain(40%)in group B.There were significant differences in complication rates between the two groups(P=0.031).(5)In summary,the modified calcaneal plate combined with suture anchors in the treatment of comminuted fracture of split-type greater tuberosity of humerus combined with rotator cuff tears(Liu-Gang type IV)could better restore the forward flexion function of the shoulder joint and has a small incision,less blood loss,shorter operation time and fewer complications.

BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Objective To establish a stable and reliable method for the determination of ethylene oxide residue,and to analyze ethylene oxide residue in multi components made of different materials involved in some medical devices,so as to provide references for sample selection and ethylene oxide residue detection of multi-component medical device kits.Methods A method for the determination of ethylene oxide residue of multi-component medical devices was developed using headspace-gas chromatography and DB-WAX column under the conditions of headspace extraction with equilibration at 80℃ for 20 min,and the weighing mass,linearity,limit of detection,limit of quantification,precision and recovery of the method were determined.Trials of the method were carried out on the items undergoing ethylene oxide sterilization,including disposable perineal care kit,disposable gynecological examination kit,disposable suture dressing kit,disposable debridement kit and the components contacting human body in the disposable dialysis kit,and the abilities of different materials of the components were analyzed in absorbing,retaining and releasing ethylene oxide.Results The method showed high linearity(r=0.999 8)in the range of ethylene oxide mass concentration from 0.4 to 16.0 μg/mL with a weighing mass of 1.00 g,which had the limit of detection being 0.11 μg/mL,the limit of quantification being 0.37 μg/mL and the relative standard deviations(RSDs)for the precision from 0.35％to 1.52％.The average recoveries of different spiked amounts of ethylene oxide in the three blank matrices ranged from 92.68％to 101.42％with the relative standard deviations(RSDs)from 2.46％to 7.59％,which all satisfied the detection requirements.The components made of rubber and acrylonitrile-butadiene-styrene copolymer(ABS)in multi-component medical device kits had the highest ethylene oxide residues,followed by the components made of wood,degreased cotton,polypropylene and polystyrene.Conclusion The method proposed gains advantages in easy operation and high specificity,quantification and reproducibility,which can be used for the determination of ethylene oxide residue in the multi-component medical device kit undergoing ethylene oxide sterilization.References are provided for sample selection of multi-component medical devices.[Chinese Medical Equipment Journal,2024,45(1):56-61]

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objective To explore the effect of barretinib on mice with acute lung injury(ALI)by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The male C57BL/6 mice were randomly divided into control group,model group and experimental-L,-M-H groups.Except for the control group,the other four groups were constructed ALI models by intraperitoneal injection of lipopolysaccharide.The control and model groups were given equal volume 0.9％NaCl by gavage.The experimental-H,-M,-L groups were administered with 1.00,0.50 and 0.25 mg·mL-1 barretinib solution 200 μL by gavage.Five groups were treated for 48 hours with once every 12 hours.The levels of inflammatory cytokine in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay.The expression levels of Occludin,JAK2 and STAT3 in mouse lung tissue were detected by Western blot.Results The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid for experimental-M,-H groups,model group and control group were(228.48±25.41),(198.53±23.11),(317.32±32.85)and(48.93±2.59)ng·L-1;the levels of interleukin-6 were(118.81±14.85),(98.58±13.82),(172.23±25.94)and(49.47±3.06)ng·L-1;the relative expression levels of Occludin were 0.48±0.13,0.49±0.11,0.28±0.09 and 0.69±0.21;the phospho-JAK2/JAK2 ratios were 0.51±0.13,0.32±0.09,0.75±0.21 and 0.16±0.05;the phospho-STAT3/STAT3 ratios were 0.43±0.11,0.27±0.08,0.78±0.21 and 0.17±0.05,respectively.The differences of above indicators were statistically significant between the experimental-M,-H groups,control group and model group(all P＜0.05).Conclusion Barretinib can reduce the lung inflammatory response and improves the level of tight junction protein in lung tissue to protect ALI mice by inhibiting the JAK2/STAT3 signaling pathway.

Objective:To investigate the status of medical care seeking delay and diagnosis delay of pulmonary tuberculosis (PTB) patients in Tongzhou District and Changping District of Beijing, analyze the related factors and put forward suggestions for early detection and scientific management of PTB patients.Methods:A retrospective epidemiological survey was conducted to collect the incidence data of PTB registered in Tongzhou and Changping from January 1 to December 31, 2021 by using the Chinese Tuberculosis Information Management System, and telephone interview were used for information supplement. Multivariate logistic regression model and decision tree model were used to analyze the influencing factors of medical care seeking delay and diagnosis delay of PTB patients.Results:In 2021, the medical care seeking delay time M( Q1, Q3) in the PTB patients in Tongzhou and Changping was 11 (5, 26) days, with a delay rate of 41.71%. Results from multivariate logistic regression model analysis revealed that factors influencing the medical care seeking delay included regular health check-up ( OR=0.033, 95% CI: 0.008-0.147), coughing for less than 2 weeks or showing any symptom of PTB before medical care seeking ( OR=0.378, 95% CI: 0.215-0.665), showing other symptoms before medical care seeking( OR=2.791, 95% CI: 1.710-4.555), no work or school in medical care seeking ( OR=2.990, 95% CI: 1.419-6.298). The diagnosis delay time M( Q1, Q3) in the PTB patients was 8 (0, 18) days, with a delay rate of 35.20%. Multivariate logistic regression model analysis revealed that the factors influencing the diagnosis delay of PTB included being diagnosed at a specialized tuberculosis hospital ( OR=0.426, 95% CI: 0.236-0.767) or a tuberculosis prevention and control institution ( OR=1.843, 95% CI: 1.061-3.202) and being traced as a source of infection ( OR=2.632, 95% CI: 1.062-6.521). The overall performance of the multivariate logistic regression model was comparable to that of the decision tree model, with the decision tree model exhibiting higher sensitivity but lower specificity. Conclusions:The medical care seeking delay rate and diagnosis delay rate of tuberculosis in Tongzhou and Changping were at low levels in 2021. However, it is still necessary to strengthen the health education and active screening, improve the public awareness of PTB prevention and control, and further improve the level of medical services and medical access to reduce the medical care seeking delay and diagnosis delay of PTB patients.