Silencing of activating transcription factor 4 inhibits neuronal necroptosis after intracerebral hemorrhage in vitro / 中国组织工程研究

BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.

Expression and Clinical Significance of KIF11,β-catenin and GSK-3β in Cervical Cancer / 医学研究杂志

Objective To investigate the expression of kinesin family member 11(KIF11),β-catenin and glycogen synthase ki-nase-3β(GSK-3β)in cervical cancer and its clinical significance.Methods The expression of KIF11,β-catenin and GSK-3β in 102 cases of cervical cancer,52 cases of high-grade squamous intraepithelial lesion(HSIL)and 46 cases of low-grade squamous intra-epithelial lesion(LSIL)and 40 cases of chronic cervicitis were detected by immunohistochemistry,to analyze the relationship between the expression of the three indicators and the clinicopathological characteristics of cervical cancer patients,and to analyze the correlation be-tween the three indicators.COX proportional hazards model was used to analyze the prognostic factors of cervical cancer patients.Results With the progression of cervical lesions,the positive rates of KIF1 1 and β-catenin increased gradually,while the positive rates of GSK-3β decreased gradually(P＜0.05).The positive expressions of KIF11,β-catenin and GSK-3β in cervical cancer tissues were significantly different in International Federation of Gynecology and Obstetrics(FIGO)stage,differentiation degree and lymph node metastasis(P＜0.05),but there was no significant difference among different ages and pathological types(P＞0.05).The expression level of KIF11 was positively correlated with β-catenin(r=0.461,P＜0.05),and the expression level of β-catenin was negatively correlated with GSK-3β(r=-0.692,P＜0.05).The expression level of KIF11 was negatively correlated with GSK-3β(r=-0.336,P＜0.05).The average survival time of patients with positive expression of KIF11 and β-catenin was shorter than that of pa-tients with negative expression,and the average survival time of patients with positive expression of GSK-3 β was longer than that of pa-tients with negative expression of GSK-3β.COX regression analysis showed that FIGO stage,lymph node metastasis,KIF11 and β-catenin were independent risk factors for the prognosis of cervical cancer patients,and GSK-3β was an independent protective factor.Conclusion KIF11,β-catenin and GSK-3β are abnormally expressed in the tissues of cervical cancer patients.KIF11 may be in-volved in the regulation of Wnt/β-catenin pathway in the development of cervical cancer.The combined detection of KIF11 may provide a new reference for the diagnosis and prognosis of cervical cancer.

Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy / 中国肺癌杂志

BACKGROUND@#The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.@*METHODS@#We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.@*RESULTS@#All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.@*CONCLUSIONS@#Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Research progress and clinical significance of the correlation between breast cancer heterogeneity and contrast-enhanced ultrasound / 中国医师杂志

Breast cancer is a highly heterogeneous tumor originating from genetic basis, with significant differences in morphology, immunophenotype and therapeutic response, which poses great challenges to the treatment of breast cancer patients. Therefore, it is very important to understand the diversity of different molecular biological states and expressions in tumor cells to obtain good therapeutic effects for breast cancer. Contrast-enhanced ultrasound (CEUS) is widely used as a non-invasive real-time diagnostic technique for breast tumors. At present, many domestic and foreign literatures have reported that there is a certain correlation between molecular biological indicators related to breast cancer and the characteristics of CEUS, which is expected to provide a reference for preoperative treatment through non-invasive and convenient ultrasound examination. The combination of ultrasound contrast agent and ultrasound can mediate the drug therapy of breast cancer, which makes the targeted delivery and targeted regulation of drugs possible, thus improving the efficiency of chemotherapy drugs. In this review, we reviewed the relationship between molecular markers related to breast cancer and CEUS and the application of ultrasound contrast agents in targeted therapy of breast cancer.

Application of contrast-enhanced ultrasonography in differentiating benign and malignant breast BI-RADS 4 nodules / 中国医师杂志

Objective:To explore the application value of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant breast imaging reporting and data system (BI-RADS) type 4 nodules.Methods:The clinical data of 81 patients (82 nodules) with breast tumors admitted to the People′s Hospital of Inner Mongolia from February 2018 to January 2022 were retrospectively analyzed, all of whom were classified as BI-RADS. All patients underwent preoperative CEUS examination and underwent puncture biopsy or surgical treatment. Quantitative analysis software was used to draw a time intensity curve (TIC), quantitatively analyzing peak intensity (PI), area under the curve (AUC), baseline intensity (BI), time to peak (TTP), arrival time of contrast agent (AT), slope up (AS), half peak time (DT/2), and slope down (DS). We analyzed the differences in imaging parameters of the tumor edge zone in patients with benign and malignant breast tumors, and plotted the subject operating characteristic (ROC) curve for predicting benign and malignant breast tumors using statistically significant quantitative parameters. Area under the curve and cutoff values were calculated. The differences in imaging parameters between different regions of the tumor in the malignant breast group were analyzed.Results:PI and AUC at the margin of breast malignant tumor were higher than those of breast benign tumor (all P<0.001); There was no significant difference in PI, AUC in the central and surrounding tissues of breast malignant tumor, and BI, TTP, AT, DT/2, DS, AS in the central, marginal and surrounding tissues of breast malignant tumor compared with benign tumor of breast (all P>0.05). After drawing the receiver operating characteristic of PI and AUC at the edge of breast tumor, it was concluded that the area under the curve of PI in predicting benign and malignant breast tumors was 0.740 ( P<0.001), the sensitivity was 67.6%, the specificity was 77.8%, and the Youden′s J statistic was 0.453; The area under the curve of AUC was 0.743 ( P<0.001), the sensitivity was 67.6%, the specificity was 73.3%, and the Youden′s J statistic was 0.409. There was no statistically significant difference in PI and AUC at the edge of breast malignant tumors compared to the center of the tumor ( P=0.471, P=0.988); The PI and AUC of the center and edge of breast malignant tumors were higher than those of the surrounding breast tissue (all P<0.001). Conclusions:The blood flow perfusion characteristics of the marginal zone of breast tumors have certain diagnostic value in distinguishing between benign and malignant tumors, and can be used as a non-invasive indicator for distinguishing between benign and malignant breast tumors.

Expert consensus on platelet-rich plasma treatment for osteochondral lesion of talus (version 2023) / 中华创伤杂志

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

A Case Report of Blau Syndrome / 罕见病研究

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Clinical effects and mid-term follow-up analysis of para-split laminotomy for lumbar spinal canal tumors / 国际外科学杂志

Objective:To investigate the surgical outcome and prognostic factors of para-split laminotomy for removal of lumbar spinal canal tumors.Methods:Retrospectively review the clinical data of 35 patients suffering lumbar spinal canal tumors, who underwent the para-split laminotomy for tumor resection in Department of Neurosurgery, Clinical Medical College of Yangzhou University from October 2016 to August 2019, including 16 males and 19 females, and the age was(40.1±10.6)years. Intraoperative blood loss, operation time, tumor resection, tumor pathological results, perioperative complications were observed. Follow-up situations, including tumor recurrence, bony fusion of laminae and spinal stability. Follow-up using outpatient examination and telephone interview was performed by the end of August 2022. The JOA back pain scoring system was used to evaluate the neurological function of the spinal cord, and paired t-test were performed to compare the overall preoperative and postoperative spinal cord neurological function scores. Linear regression and multiple linear regression were used to analyze the prognostic factors. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and the comparison before and after operation was performed by paired t-test. Mearsurement data of skewed distribution were expressed as M( Q1, Q3). Count data were expressed as cases. Results:The tumors of 35 patients were resected completely. The median blood loss was 100(75, 140)mL and the average operative duration was (181.1±42.7) min. The postoperative pathological results were as follows: 24 neurilemmomas, 6 meningiomas, 4 ependymomas and 1 neurofibroma. There were no surgery-related complications occurred. The postoperative follow-up ranged from 36 to 69 months, with no tumor recurrence or spinal instability, and bony fusion of laminae seen in some patients on CT imaging. The overall spinal cord neurological function scores of pre and post operation were(19.5±3.4)versus(25.4±2.2), Paired t-test analysis revealed a significant difference between the overall postoperative spinal cord neurological function scores and the preoperative scores, and the postoperative scores were better than the preoperative scores( P<0.05). Multiple linear regression analysis showed a positive correlation between preoperative JOA scores and postoperative JOA scores, and postoperative JOA scores has negative correlation with tumor volume and the age at the time of operation ( P<0.05). Conclusion:Para-split laminotomy with less damage to the posterior spinal structures can effectively improve the neurological function of the spinal cord and protect the stability of the lumbar spine in patients with lumbar spinal canal tumors, and the better the preoperative neurological function of the spinal cord, the better the prognosis of patients, and the smaller the tumor volume, the better the prognosis.

Quality Marker （Q-marker） of Tinosporae Radix Associated with Efficacy of "Relieving Sore Throat" / 中国实验方剂学杂志

ObjectiveTo study the potential quality marker （Q-marker） of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， multivariate statistical analysis （MSA）， and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were employed to screen out the main marker components that caused differences between groups. Moreover， network pharmacology technology was applied to predict the potential "sore throat-relieving" components， and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds， including alkaloids， diterpenoid lactones， and sterols， were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA： Columbamine， jatrorrhizine， palmatine， menisperine， and columbin. Network pharmacology analysis yielded six compounds： tetrahydropalmatine， palmatine， menisperine， fibleucin， neoechinulin A， and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6， epidermal growth factor receptor， prostaglandin G/H synthase 2， matrix metalloproteinase-9， proto-oncogene tyrosine-protein kinase Src and other targets， and regulating Hepatitis B， influenza A， human T-cell virus infection， human cytomegalovirus infection， coronavirus disease-2019， and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine， menisperine， and columbin， which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix， which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

Current Situation and Research Progress of Minimally Invasive Treatment on Central Nervous System Tumors / 肿瘤防治研究

Central nervous system (CNS) tumors pose a substantial risk to human health. Conventional therapeutic modalities, including surgical excision, radiotherapy, and chemotherapy, exhibit inherent limitations and adverse effects. Nonetheless, the emergence of minimally invasive surgical techniques and advanced imaging technology have spurred research interest in the realm of neurology toward developing minimally invasive treatments for neurosurgical tumors. These approaches encompass tumor laser interstitial thermal therapy, tumor treating fields, photodynamic therapy, and other related interventions. Minimally invasive treatments offer notable advantages, such as reduced tissue trauma, expedited recovery, and pronounced therapeutic efficacy, rendering them extensively employed in clinical settings. This comprehensive review aims to elucidate accomplishments in the field of minimally invasive CNS tumor treatments while delineating prospective avenues for future development.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

Clinical anatomy of cast specimens of the pancreatic duct / 解剖学报

Objective To explore the distribution and structure of pancreatic ducts and lobules in human pancreas and explore their clinical application value. Methods Three human pancreatic specimens were dissected, 2 of which were fresh whole pancreas samples which were collected from the donated human bod)' after dead,UW organ preservation solution was immediately perfused, and the pancreatic duct was rinsed at low pressure. The surface and internal structure of 1 case was observed as a fixed specimen. Paraffin sections were taken for HE staining to observe the structure of lobules and the distribution of catheters in the leaves. Results The gross specimen showed that the pancreas was composed of lobules of different sizes, with thin layers of connective tissue between the lobules. The pancreatic duct had a complete cast structure and could be clearly displayed to the main duct and the branches of the interlobular duct. The diameters of the interlobular ducts varied widely, and finally a main trunk flowed into the main duct. Each trunk was distributed independently, and the distal pancreatic duct formed a lobule-like structure with different sizes of lobules and no interlobular communication. HE staining showed that the pancreatic lobules were surrounded by connective tissue, in which vascular and ductal structures were visible. Intralobular duct could also be observed in the pancreatic lobules. Conclusion The cast specimen of the human pancreatic duct can clearly show the branch distribution of the pancreatic duct, and the study of the morphological of the pancreatic duct and lobular structure is of great reference value for understanding the clinical problems.

Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).@*METHODS@#The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.@*RESULTS@#Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001).@*CONCLUSION@#The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

Effect of hepatic ischemia-reperfusion rats-derived exosomes on microglial pyroptosis / 中华麻醉学杂志

Objective:To evaluate the effect of hepatic ischemia-reperfusion (I/R) rats-derived exosomes on microglial pyroptosis.Methods:Twenty clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 20-50 g, were divided into 2 groups ( n=10 each) using a random number table method: sham operation group (group S) and hepatic I/R group (group I/R). The serum of rats in S group and I/R group was collected, and exosomes were isolated from the sera using differential centrifugations.Microglial cells were co-cultured with PKH26-labeled exosomes for 6 h. The intake of exosomes in microglial cells was determined using immunofluorescence staining.Primary microglial cells were seeded onto 6-well culture plates at a density of 5×10 5 cells/ml and were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), 10 7 cells/ml I/R-exosomes treated group (group 10 7), 10 8 cells/ml I/R-exosomes treated group (group 10 8), and 10 9 cells/ml I/R-exosomes treated group (group 10 9). Microglia in each group were co-cultured with the corresponding concentration of I/R-exosomes for 6 h. The expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cleaved-caspase-1 and gasdermin-D (GSDMD) was detected using Western blot.Primary microglial cells were divided into 3 groups ( n=24 each) by a random number table method: control group (group C), sham operation-exosomes treated group (group S-exosome) and I/R-exosomes treated group (group I/R-exosome). In S-exosome group and I/R-exosome group, exosomes 10 8 cells/ml in S group and I/R group were given, respectively, to incubate cells for 6 h. The expression of NLRP3, ASC and GSDMD mRNA was determined by real-time polymerase chain reaction, and the levels of interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) in the cell culture supernatant were measured by enzyme-linked immunosorbent assay. Results:The results from immunofluorescence staining showed that I/R-exosomes colocalized with microglia.The 10 8 cells/ml I/R-exosomes and 10 9 cells/ml I/R-exosomes up-regulated the expression of NLRP3, ASC, GSDMD and cleaved-caspase-1 in microglial cells ( P<0.01). Compared with group C and group S-exosome, the expression of NLRP3, ASC and GSDMD mRNA in microglial cells was up-regulated, and the levels of IL-18, IL-1β and TNF-α in the supernatant were elevated in group I/R-exosome ( P<0.01). Conclusions:Hepatic I/R rats-derived exosomes can promote microglial pyroptosis.

Progress in the application of new ultrasound technology in evaluation the efficacy of neoadjuvant chemotherapy for breast cancer / 中国医师杂志

In recent years, the incidence rate of breast cancer has increased rapidly and is tending to be younger. The application of neoadjuvant chemotherapy (NAC) can reduce the tumor stage, which is conducive to surgical resection or breast conserving surgery. Therefore, it is very important to evaluate the curative effect of NAC in breast cancer by imaging for the choice of operation timing. In recent years, with the rapid development of new ultrasound technologies such as contrast-enhanced ultrasound and elastography, these new technologies can provide more abundant imaging information and basis for individualized treatment of breast cancer, which has become a research hotspot of the curative effect of breast cancer NAC. This article reviews the research progress of new ultrasound technology in evaluating the curative effect of NAC in breast cancer in recent years.

Relationship between serum exosomes and microglial pyroptosis during brain injury in a young rat model of hepatic ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the relationship between serum exosomes and microglial pyroptosis during brain injury in a young rat model of hepatic ischemia-reperfusion (I/R).Methods:Forty-six clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 40-60 g, were allocated into 4 groups using a random number table method: sham operation group (group S, n=10), hepatic I/R group (group I/R, n=13), treatment with serum exosome in sham-operated young rat group (group S-Exosome, n=10), and treatment with serum exosomes in young rats with I/R group (group I/R-Exosome, n=13). The common trunk of the portal vein, left hepatic artery and bile duct was clamped for 60 min resulting in ischemia of 70% of the liver in anesthetized animals.After 6 h of reperfusion, the serum was collected to extract exosomes in S group and I/R group, and the serum exosome suspension 100 μl of S group and I/R group was injected through the tail vein in S-Exosome group and I/R-Exosome group, respectively.The expression of serum exosome marker proteins CD9 and CD81 was determined by Western blot in S group and I/R group.Serum and hippocampi were obtained from each group at 6 h after the corresponding treatment.The expression of NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD), pro-caspase-1, cleaved-caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC) in the hippocampus was detected using Western blot, and the expression of GSDMD in hippocampal tissues was determined by immunohistochemistry.The levels of interleukin-1beta (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in serum and hippocampal tissues and S100β and NSE in serum were determined by enzyme-linked immunosorbent assay.In group I/R-Exosome, 3 rats were selected, and their serum exosomes were extracted, labeled with PKH26 red fluorescence and then injected via the tail vein, and the co-localization between exosomes and microglia was identified by immunofluorescence technique. Results:Compared with group S, the expression of serum CD9 and CD81 was significantly up-regulated in group I/R, the expression of NLRP3, GSDMD, cleaved-caspase-1 and ASC in hippocampal tissues was significantly up-regulated, the levels of IL-18, IL-1β and TNF-α in serum and hippocampal tissues and S100β and NSE in serum were increased in I/R and I/R-Exosome groups ( P<0.05), and no significant change was found in the parameters mentioned above in group S-Exosome ( P>0.05). The positive expression of GSDMD was significantly increased in I/R and I/R-Exosome groups ( P<0.05), no positive expression of GSDMD was found in S and S-Exosome groups ( P>0.05), and the results of immunofluorescence showed the co-localization between exosomes and microglia. Conclusions:The mechanism by which hepatic I/R induces brain injury may be related to serum exosomes-mediated microglial pyroptosis in young rats.

Practice and analysis of empowerment reform of service invention in medical institutions / 中华医学科研管理杂志

Objective:To stimulate innovation vitality, the government promulgated the Pilot Implementation Plan for Granting Scientific and Technological Achievements Ownership or Long- term Use Right to Scientific Research Investigators. As one of the 40 pilot institutions, Beijing JiShuiTan Hospital attached great attention to it and, through the exploration and practice of pilot work, combined with the transformation of medical institutions' achievements Status quo, summarized the experiences of job scientific and technological achievements empowerment. Methods:Explored the mechanism and mode to empower researchers with the ownership or long-term right of service invention according to the policy review and case studies.Results:Developed hospital-level empowerment reform program and related supporting documents, Beijing JiShuiTan Hospital has completed the first empowerment work in Beijing.Conclusions:The reform of empowering scientific and technological achievements gives a new pathway to transform scientific and technological achievements in medical institutions, which will promote the transformation process of service invention-creation.

Effects of ultrasound-guided nerve block combined with dexmedetomidine on postoperative oxidative stress in patients with hip fracture and diabetes / 中国医师进修杂志

Objective:To explore the effect of ultrasound-guided nerve block combined with dexmedetomidine (DEX) on postoperative oxidative stress in patients with hip fracture and diabetes.Methods:From March 2017 to December 2019, 78 patients with diabetes who underwent hip fracture surgery were enrolled and divided into two groups by random number table method, with 39 cases in each group. After the operation, the control group was treated with ultrasound-guided femoral nerve combined with lateral femoral cutaneous nerve block with 0.375% ropivacaine, and the study group was treated with ultrasound-guided femoral nerve combined with lateral femoral cutaneous nerve block with 0.375% ropivacaine and DEX 0.5 μg/kg. Patients in both groups were received patient controlling intravenous analgesia (PCIA) after the operation, and visual analogue scoring (VAS) was used to evaluate the resting pain score of the patients at 4 h (T 1), 8 h (T 2), 16 h (T 3), 24 h (T 4), 36 h (T 5) and 48 h after operation (T 6). The levels of serum superoxide dismutase (SOD), malondialdehyde (MDA), 8-hydroxydeoxyuridine (8-OHdG), at T 1 and T 6 were compared between the two groups. The management system of continuous glucose monitoring system (CGMS) was used to calculate the mean amplitude of glycemic excursions(MAGE), largest amplitude of glycemic excursions (LAGE), absolute means of daily differences (MODD) of the patients during 48 h after operation, and the correlation between the blood glucose fluctuation indicators and the oxidative stress of the study group were compared. Results:The scores of VAS in the study group at T 1-T 6 were lower than those in the control group , the difference were statistically significant ( P<0.05). At T 6, the level of serum SOD in the study group was higher than that in the control group: (79.58 ± 13.55) kU/L vs. (64.16 ± 11.95) kU/L; the level of serum MDA and 8-OhdG in the study group were higher than those in the control group: (4.36 ± 0.81) μmol/L vs. (5.64 ± 0.94) μmol/L, (1.06 ± 0.19) μg/L vs.(1.42 ± 0.22) μg/L, the differences were statistically significant ( P<0.05). The levels of MAGE, LAGE, MODD in the study group were lower than those in the control group: (2.42 ± 0.47) mmol/L vs. (5.19 ± 0.96) mmol/L, (3.47 ± 0.64) mmol/L vs. (7.61 ± 1.32) mmol/L, (1.21 ± 0.27) mmol/L vs. (2.74 ± 0.46) mmol/L, the differences were statistically significant ( P<0.05). The correlation analysis showed that the blood glucose fluctuation indicators MAGE, LAGE and MODD of the study group were negatively correlated with SOD, and were positively correlated with MDA, 8-OHdG ( P<0.05). Conclusions:The use of ultrasound-guided nerve block combined with dexmedetomidine (DEX) for patients with hip fracture and diabetes can improve the analgesic effect, reduce oxidative stress of the patients, and improve the blood glucose fluctuation indicators.

Long non-coding RNA SPATA31D5P promoting proliferation, migration and invasion of breast cancer cells through adsorption of microRNA-320a / 解剖学报

Objective Long non-coding RNA(lncRNA) are aberrantly expressed in breast cancer(BC) and strongly associated with its survival prognosis. The aim of this study is to investigate the expression and effect of IncRNA SPATA31D5P on the invasion and migration capacity of breast cancer cells through adsorption of miR-320a. Methods Totally 30 cases of BC tissues and paraneoplastic tissues were collected, and the expression levels of SPATA31D5P in BC tissues and BC cell lines were detected by Real-time PCR. MDA-MB-231 cells were transfected with SPATA31D5P siRNA interference vector, and cell proliferation, invasion and migration capacity were determined using the cell counting kit-8 assay (CCK-8), 5-ethynyl-2'- deoxyuridine(EdU), Transwell and wound-healing assay respectively. And cell cycle and apoptosis were detected by flow cytometry. Bioinformatics approachs were used to screen for miRNAs that could bind complementarily to SPATA31D5P, and the regulatory effect of SPATA31D5P on miR-320a was detected by Real-time PCR and dual luciferase reporter assay. Results SPATA31D5P levels were significantly higher in BC tissues than in adjacent normal breast tissues, and SPATA31D5P expression was higher in each BC cell line than in normal breast epithelial cells MCF10 A. The level of SPATA31D5P in the interference group was 0. 288±0. 052, which was lower than that of the blank control group 1. 114±0. 096 and negative control (NC) group 1. 079±0. 128 (P< 0. 01). The proliferation activity of MDA- MB-231 cells in the interfered group was significantly reduced and apoptotic rate was obviously increased compared to the NC and control groups (P<0. 01) ;the Gj phase block was observed in the interfered group; the scratch healing rate and number of perforated cells in the interference group were (14. 36 ± 1. 75) % and (26±1.52), which were lower than (52. 25± 1.87)% and ( 67. 33 ± 2. 91 ) of the NC group (PcO.Ol). Dual luciferase experiments confirmed that SPATA31D5P could directly regulate miR-320a expression and luciferase activity. Conclusion SPATA31D5P is highly expressed in BC, interfering with SPATA31D5P expression effectively inhibits the proliferation, migration and invasion of MDA-MB-231 cells, and the mechanism may be related to the targeted regulation of miR-320a.

Neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane in male offspring rats / 中国职业医学

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.