Objective To address the absence of matrix specified for the determination of intrinsic uniformity in the current standard, and to investigate the effect of source distances on intrinsic spatial linearity, the intrinsic uniformity and intrinsic spatial linearity of 16 probes in eight SPECT devices were measured and analyzed with different matrices and source distances, in order to determine the optimal measurement conditions. Methods According to the standard Specification for Testing of Quality Control in Gamma Cameras and Single Photon Emission Computed Tomograph (SPECT) (WS 523—2019), the intrinsic uniformity was measured using 64 × 64 and 256 × 256 matrices and the intrinsic spatial linearity was measured using of 1.7 and 3 m source distances. Results When intrinsic uniformity was measured with the 64 × 64 matrix, more than 50% of the probes showed lower values. When intrinsic spatial linearity was measured with the 3 m source distance, more probes showed lower values. Conclusion The 64 × 64 matrix is recommended for the determination of intrinsic uniformity and a source distance of ＞5 FOV is recommended for the measurement of intrinsic spatial linearity.

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

BACKGROUND: Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. METHODS: Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. RESULTS: There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. CONCLUSIONS At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.
Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mice ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins B-raf/genetics*

Objective:To investigate the emergency surgical effect of ruptured intracranial dural arteriovenous fistula (DAVF).Methods:Patients with ruptured intracranial DAVF underwent microsurgery in the Department of Neurosurgery, Nanping First Hospital Affiliated to Fujian Medical University from May 2013 to July 2022 were retrospectively included. The clinical, imaging and follow-up data were collected, and the clinical characteristics, selection of surgical methods and treatment effects of patients were summarized.Results:A total of 8 patients with DAVF were enrolled. Their age ranged from 11 to 60 years (average, 48 years). There were 7 males and 1 female. All 8 patients suffered from intracranial hemorrhage, manifested as headache and vomiting in 2 cases, simple conscious disturbance in 2 cases, conscious disturbance with cerebral hernia in 3 cases, and conscious disturbance with limb paralysis in 1 case. The fistula was located in the anterior fossa in 4 cases (including 2 cases with aneurysms), the middle fossa in 2 cases (including 1 case with moyamoya disease), the transverse sinus in 1 case, and the anterior 1/3 area of the sagittal sinus in 1 case. Cognard classification: 7 patients were type Ⅲ and 1 was type Ⅳ. After admission, all patients underwent emergency craniotomy and microsurgery to remove hematoma. Among them, 4 patients underwent decompressive craniectomy at the same time, 1 patient with moyamoya disease underwent dural turnover and temporalis muscle application at the same time, and 2 patients with aneurysms at the same location were clipped at the same time. Postoperative re-examination of head CT showed that the hematoma was cleared satisfactorily and the midline was no shift in all 8 patients. CT angiography (CTA) showed that the fistula disappeared within 2 weeks. Seven patients were followed up within 1-12 months after operation. CTA or digital subtraction angiography showed no recurrence of DAVF. Two patients with aneurysms did not have residual or recurrent aneurysms. All patients had no new neurological symptoms, and the Glasgow Outcome Scale score in 2 patients increased by 1 compared with that at discharge.Conclusion:Emergency microsurgery is an effective method for the treatment of ruptured intracranial DAVF, especially for patients with special parts or complicated hematoma, cerebral hernia, and other vascular diseases.

Objective:To understand the oral health and frailty status of the elderly in the community in Beijing and analyze the correlation between the two, so as to provide a reference for the frailty management of the elderly in the community.Methods:This study was a cross-sectional study. Using the multi-stage stratified sampling method, a total of 241 community elderly people in 9 communities in Beijing from July to December 2021 were selected as the research objects. They were investigated using the general information questionnaire, Mini-Nutritional Assessment (MNA) and the Fried Frailty Phenotype. Univariate analysis and ordinal logistic regression analysis were used to explore the influencing factors of frailty among the elderly in the community. A total of 260 questionnaires were distributed in this study and 241 valid questionnaires were recovered, with an effective recovery rate of 92.6%.Results:Among the 241 community elders, 115 (47.7%) were not frail, 92 (38.2%) were pre-frail and 34 (14.1%) were frail. Ordinal Logistic regression analysis showed that the number of teeth of 0-9, 10-19, dry mouth and incomplete or unrepaired restoration of missing teeth were risk factors for frailty among the elderly in the community ( P<0.05) . Conclusions:From the perspective of oral health, this study further analyzes the risk factors of frailty in the elderly in the community. Medical institutions and elderly care institutions at all levels can use oral health status as a screening item for the frailty risk of the elderly in the community, providing new ideas for the prevention and intervention of frailty in the community.

As an important zoonotic pathogen, Staphylococcus aureus has led to serious mastitis and endometritis in infected dairy cows. In this study, a total of 164 strains of S. aureus were isolated from dairy cows in Xinjiang Province, China, and subjected to assays to determine drug susceptibility and biofilm (BF) formation ability. Enterotoxin-related genes were detected, and the transcription levels of genes related to BF formation were determined by using reverse transcription-quantitative polymerase chain reaction. Moreover, the pathogenicity of isolates with different BF formation abilities was determined by measuring their hemolysis activity, half lethal dose (LD₅₀) and organ bacterial load. The results showed that 86.0% of S. aureus isolates could form BF. Among them, 42.1% of the strains had weak BF formation ability, and most strains with a strong BF formation ability were ica gene carriers. The S. aureus isolates displayed multidrug resistance and their drug resistance was positively correlated with their BF formation ability. Moreover, 96.3% of the S. aureus isolates carried enterotoxin genes. Among them, the detection rates of the novel enterotoxin genes were higher than those of conventional enterotoxin genes. Furthermore, isolates with a strong BF formation ability had higher LD50 but lower hemolysis ability and organ bacterial load than those of the isolates with weak or no BF ability. However, isolates without BF ability produced more severe pathological changes than those of isolates with strong BF formation ability. These findings suggest that higher BF ability and presence of novel enterotoxin genes are important characteristics of S. aureus isolates from dairy cows in Xinjiang Province, China, and such isolates may pose potential threats to food safety.
Bacterial Load ; Biofilms ; China ; Drug Resistance ; Drug Resistance, Microbial ; Drug Resistance, Multiple ; Endometritis ; Enterotoxins ; Female ; Food Safety ; Hemolysis ; Lethal Dose 50 ; Mastitis ; Polymerase Chain Reaction ; Staphylococcus aureus ; Staphylococcus ; Virulence

PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
Area Under Curve ; Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Data Mining ; Early Detection of Cancer ; Female ; Genome ; Humans ; Methods ; MicroRNAs* ; Plasma ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity

Objective To compare laparoscopic Keyhole parastomal hernia repair with re-ostomy technique or without re-ostomy in the treatment of stoma hernia,then analyze the advantages of reconstruction ostomy,and summarize the key technical points of the reconstruction operation.Methods From Jan 2010 to Dec 2016,68 stoma hernia patients underwent laparoscopic Keyhole parastomal hernia repair with reostomy technique,52 patients underwent laparoscopic Keyhole parastomal hernia repair without re-ostomy technique.The preoperative,intraoperative and postoperative parameters were analyzed.Results Compared to without re-ostomy group,the re-ostomy reconstruction group had low incidence rate of intestinal fistula (x2 =5.411,P =0.033),patch infection (x2 =6.823,P =0.014),the incidence of postoperative serous swelling and serum swelling (x2 =14.266,P ＜0.001),postoperative recurrence (x2 =8.688,P =0.005) and postoperative appearance dissatisfaction (x2 =9.479,P =0.004).Conclusion Laparoscopic parastomal hernia repair and re-ostomy technique reduces the incidence rate of intestinal fistula,patch infection and serous swelling and serum swelling,decreases the postoperative recurrence rate and appearance dissatisfaction.

Objective To observe the role of intermediate conductance calcium?activated potassium channels (KCa3.1) in alkalinization and β?glycerophosphate induced vascular calcification. Methods Vascular smooth muscle cells (VSMCs) and aortic rings were obtained from rat thoracic aorta, and then randomly divided into control group (pH was provided into 7.4, 8.0), high phosphorus groups (pH was provided into 7.4, 7.7 and 8.0, VSMCs in three groups were treated with 10 mmol/L β?glycerophosphate; HCl and NaHCO3 were used to adjust the pH) and TRAM?34 group (20 nmol/L was added into pH8.0 high phosphorus dulbecco's modified eagle's medium). Calcium deposition and alkaline phosphatase (ALP) activity were measured by Alizarin red staining, calcium content and enzyme linked immunosorbent assay after cells were simulated for 12 days. Intracellular free Ca2 + was measured by ELISA. The expression of KCa3.1, runt?related transcription factor 2 (Runx2) were detected by RT?PCR and Western blotting 4 days after cells were stimulated. Calcium deposition was measured by von Kossa staining and calcium content after aortic rings were cultured for 12 days. The expressions of KCa3.1 and Runx2 were detected by immunohistochemistry after aortic rings were cultured for 4 days. Results Compared with control group, calcification in VSMCs and aortic rings were significantly increased in high phosphorus group (P<0.05) while decreased in TRAM?34 group (P<0.05). Compared with control group, the expressions of KCa3.1, Runx2 and the activity of ALP in high phosphorus groups were increased (P<0.05) while decreased in TRAM?34 group (P<0.05). Besides, expressions of Runx2 and KCa3.1 were augmented as the pH was higher (P<0.05). The expression of Runx2 in aortic rings was the same situation. Besides, the Ca2+ influx was blocked by TRAM?34 (P<0.05). Conclusions Alkalinization contributes to β?glycerophosphate induced VSMCs calcification through increase of Ca2 + influx, up?regulation of KCa3.1 and promotion of osteogenic/chondrogenic differentiation.

Objective To observe the role of TRAM-34 (1-((2-chlorophenyl) diphenylmethyl)-1H-pyrazole),the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1),on β-glycerophosphate induced vascular calcification in vitro.Methods Vascular smooth muscle cells (VSMCs) were obtained from rat thoracic aorta,and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10％ fetal bovine serum),high phosphorus group (cultured in DMEM with 10％ fetal bovine serum and 10％ β-glycerophosphate) and TRAM-34 group (20 nmol/L TRAM-34 was added into high phosphorus DMEM).Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2 (Runx2) was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit.Results (1) Compared with control group,calcification was significantly increased in high phosphorus group ((121.67 ± 6.17) mg/g vs.(84.38 ±8.17) mg/g,P ＜0.05) and this effect could be attenuated by TRAM-34 ((93.31 ± 11.36) mg/g,P ＜0.05 vs.high phosphorus group) after 12 days culture.Similar results were found in aortic rings cultured for 12 days—high phosphorus group:(7.17 ± 0.57) mg/g vs.control:(1.18 ± 0.13) mg/g (P ＜ 0.05) and TRAM-34:(4.71 ±0.42) mg/g,P ＜0.05 vs.high phosphorus group.(2) Compared with control group,the calcium influx was higher in high phosphorus group (349.22 ±40.47 vs.151.67 ± 16.94,P ＜0.05)and reduced in TRAM-34 group (194.67 ± 22.21,P ＜ 0.05 vs.high phosphorus group) in VSMCs simulated for 4 days.(3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630 ±0.033 vs.0.340 ±0.058 and 0.865 ±0.031 vs.0.414 ±0.011,both P ＜ 0.05) and lower in TRAM-34 group (0.399 ± 0.023 and 0.575 ± 0.014,both P ＜ 0.05 vs.high phosphorus group) in VSMCs simulated for 4 days.Besides,compared with high phosphorus group,the expression of Runx2 was decreased in control group (0.113 ± 0.010 vs.0.067 ± 0.008,P ＜ 0.05) and TRAM-34 group (0.069±0.006,P＜0.05) after aortic rings were cultured for 4 days.(4) Compared with control group,the activity of ALP was significantly increased in high phosphorus group (96.56 ± 9.84vs.46.92 ± 4.60,P ＜0.05) and decreased in TRAM-34 group (70.20 ± 8.41,P ＜ 0.05 vs.high phosphorus group) in VSMCs simulated for 12 days.Conclusion KCa3.1 blocker TRAM-34 can inhibit β3-glycerophosphate induced VSMCs and aortic ring calcification through inhibiting calcium influx,downregulating Runx2 expression and attenuating osteogenic differentiation.