OBJECTIVE: We propose a novel region- level self-supervised contrastive learning method USRegCon (ultrastructural region contrast) based on the semantic similarity of ultrastructures to improve the performance of the model for glomerular ultrastructure segmentation on electron microscope images. METHODS: USRegCon used a large amount of unlabeled data for pre- training of the model in 3 steps: (1) The model encoded and decoded the ultrastructural information in the image and adaptively divided the image into multiple regions based on the semantic similarity of the ultrastructures; (2) Based on the divided regions, the first-order grayscale region representations and deep semantic region representations of each region were extracted by region pooling operation; (3) For the first-order grayscale region representations, a grayscale loss function was proposed to minimize the grayscale difference within regions and maximize the difference between regions. For deep semantic region representations, a semantic loss function was introduced to maximize the similarity of positive region pairs and the difference of negative region pairs in the representation space. These two loss functions were jointly used for pre-training of the model. RESULTS: In the segmentation task for 3 ultrastructures of the glomerular filtration barrier based on the private dataset GlomEM, USRegCon achieved promising segmentation results for basement membrane, endothelial cells, and podocytes, with Dice coefficients of (85.69 ± 0.13)%, (74.59 ± 0.13)%, and (78.57 ± 0.16)%, respectively, demonstrating a good performance of the model superior to many existing image-level, pixel-level, and region-level self-supervised contrastive learning methods and close to the fully- supervised pre-training method based on the large- scale labeled dataset ImageNet. CONCLUSION USRegCon facilitates the model to learn beneficial region representations from large amounts of unlabeled data to overcome the scarcity of labeled data and improves the deep model performance for glomerular ultrastructure recognition and boundary segmentation.
Humans ; Electrons ; Endothelial Cells ; Learning ; Podocytes ; Kidney Diseases

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

OBJECTIVE To establish the correlation evaluation and quality evaluation method of HPLC fingerprint grade of color sorting Lonicerae Japonicae Flos, and provide technical basis for the grade standard of color sorting Lonicerae Japonicae Flos. METHODS The chromatographic column was SVEA C18(250 mm×4.6 mm, 5 μm); mobile phase was acetonitrile(A)- 0.2% formic acid aqueous solution(B); gradient elution; injection volume was 10 μL; detection wave length was 245 nm; volume flow rate was 0.5 mL·min-1; column temperature was 38 ℃. The common peak determination and similarity evaluation of HPLC chromatogram data were carried out by using the Similarity Evaluation System of Traditional Chinese Medicine Chromatographic Fingerprints(Version 2012); the color sorting grade evaluation was carried out by CA, PCA and PLS-DA. The first part of Chinese Pharmacopoeia 2020 Edition was used to measure the quality control indicators, and the data were analyzed comprehensively. RESULTS A total of 28 common peaks were identified in the fingerprints, and 7 components were identified. The similarity of 24 batches of color sorting grade samples was 0.936-0.968. CA and PCA divided 28 batches of Lonicerae Japonicae Flos samples into 4 categories, which were basically consistent with the classification of color sorting, and PLS-DA achieved a discrimination result that was very consistent with the classification of color sorting. The color sorting grade was negatively correlated with the diameter, flowering rate, damage rate, and luteolin content of Lonicerae Japonicae Flos. The color sorting grade was positively correlated with chlorogenic acid, 3,5-di-O-caffeoyl quinic acid and 4,5-di-O-caffeoyl quinic acid. There was a clear correlation between the color sorting of Lonicerae Japonicae Flos and established fingerprint overall. There were differences in the quality of Lonicerae Japonicae Flos in the color sorting grade. Based on the sensory indicators of diameter, flowering rate, and damage rate, the content, diameter, flowering rate, and damage rate of luteolin showed a trend from high to low, ranging from third grade>second grade>first grade>special grade. The content of three phenolic acids showed a trend from high to low, ranging from special grade>first grade>second grade>third grade. Among the special grade, the content of three phenolic acids was the highest. CONCLUSION Combining the content of luteolin and phenolic acids as evaluation and control indicators for color selection grade is feasible and scientific, which can achieve intelligent color sorting grade production of Lonicerae Japonicae Flos grade.

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

Objective To understand the current status of chronic disease prevention literacy among primary and secondary school students in Dalian and to provide evidence for developing health education regarding chronic diseases and promotion strategies in students. Methods A total of 1 058 students from four districts or counties in Dalian were investigated through a questionnaire survey using stratified cluster sampling in 2015. A multiple linear regression method from Stata 15. 0 was used to identify the influencing factors of chronic disease prevention literacy among primary and junior school students. Results The current status of chronic disease prevention literacy was 6. 62 ％ among primary and junior school students in Dalian,and it was higher in urban students than in those from rural areas (P <0. 001),higher in junior school than in primary school (P < 0. 001),and higher in girls than in boys (P = 0. 034). There also appeared to be a positive regression relationship with parents' higher education degrees (P < 0. 001). Conclusion The current status of chronic disease prevention literacy is low among primary and secondary school students in Dalian. We should strengthen their health literacy level, mobilize the role of their parents,and especially increase chronic disease prevention awareness and the self-care ability of the rural students.

OBJECTIVE:To explore an effective method to formulate management-related strategies for off-lable use of drugs by the evidence-based medicine. METHODS:The process of guideline formulation included seven procedures,i.g. establishment ofguideliesformulation workgroup;investigation and selection of the status quo on off-label drug use;identification of the clinical problems;retrieval and evaluation and comprehensing of evidence;applification of GRADE in evidence quality grading;formation of the recommendations consensus;peer review and result publication. And eventually guidelines were formed based on the steps. This study took off-label use of rheumatoid immunoprotective subjects as a case to explore. RESULTS & CONCLUSIONS:Based on the evidence evaluation system and above 7 steps,the methods and process of guideline formulation on off-label use of rheuma-toid immunoprotective subjects that integrated administration,law,clinical medicine,pharmacy subjects were made .The process of guideline formulation fully reflects multidisciplinary characteristics of the workgroup,the advanced nature of the process,the comprehensiveness of evidence ,the rigor of evidence quality grading,and the normalization of consensus. It provides reference in methodology for establishing a comprehensive evidence-based evaluation and management system of off-label use of drugs for all clinical specialist disease. Therefore,this scientific research results may promote the standardization and legalization of the off-label use of drugs management in China.

Objective:To compare the clinical effects of direct anterior approach (DAA) and posterolateral piriformis-sparing approach (Mis-PLA) for minimally invasive surgery of total hip arthroplasty.Methods: The patients who had total hip arthroplasty from March 2015 to February 2016 were randomly divided into 2 groups: DAA group and Mis-PLA group.In the study,43 patients (45 hips) were performed with total hip replacement via the direct anterior approach (DAA group).As comparison,39 patients (42 hips) were performed with total hip replacement via the posterolateral piriformis-sparing approach (Mis-PLAgroup) at the same period.DAA group:27 male patients (27 hips),and 16 female patients (18 hips),with an average age of (57.4±7.3) years,preoperative Harris score (41.4±8.7),body mass index(BMI)(24.3±2.2) kg/m2;Mis-PLA group: 25 male patients (26 hips),14 female patients (16 hips),with an average age of (59.2±7.3) years,preoperative Harris score (39.6±8.4),BMI (24.7±2.5) kg/m2.The length of incision,operation time,blood loss,postoperative Harris score were observed and specially the hip functional recovery was fully assessed.Results: (1) All the incisions healed by first intention.No complications were found in both groups.The length of incision:DAA group:(9.2±0.7) cm and Mis-PLA group:(9.5±0.6) cm.No statistical significant differences were found (P=0.053).The operation time:DAA group (74.3±10.1) min and Mis-PLA group(37.5±4.3) min,which showed statistically significant differences(P<0.01).Blood loss:DAA group(229.6±79.2) mL and Mis-PLA group (215.7±56.0) mL.Nostatistical significant differences were found (P=0.366).(2) The patients in both groups were followed up for 6-12 months.The Harris hip scores for 6 weeks' follow-up:(85.5±4.1) in DAA group and (79.0±4.4) in Mis-PLA group,which indicated statistically significant differences (P<0.01).The Harris scores for the 6-month follow-up:(94.3±2.7) in DAA group and (95.2±1.9) in Mis-PLA group.No statistically significant differences were found (P=0.125).The basic daily hip function analysis for the 6-week follow-up:walking speed: no statistically significant differences were found between the two groups(P=0.298);Climbing stairs: Mis-PLA group' outcome was better than DAA group's with statistical differences (P=0.047);Circling,sitting and wearing shoes and socks: outcomes in DAA group exceeded Mis-PLA group's with statistically significant differences (P<0.01,P=0.016,P<0.01).Conclusion: Total hip arthroplasty through either DAA or Mis-PLA approaches could result in very satisfactory clinical effect.Comparing with DAA,Mis-PLA requires less operation time,shorter learning curve,which indicates that it is a re-latively safer approach.The advantages of total hip arthroplasty through direct anterior approach lie in less positional limitation in the early stage of postoperative period,as well as a faster recovery of hip function.

Objective To evaluate risk factors for multidrug-resistant Acinetobacter baumannii (MDRAB)infec-tion,so as to provide reference for making preventive and control measures of MDRAB infection.Methods Clinical data of patients with Acinetobacter baumannii (A.baumannii )infection in a hospital between April 2011 and Sep-tember 2012 were surveyed,distribution and specimen sources of A.baumannii and MDRAB were analyzed,and risk factors of MDRAB were assessed.Results Of 236 isolates of A.baumannii,74 (31.36%)were MDRAB .The isolation rate of MDRAB in intensive care unit and neurosurgery department was up to 60.00%(27/45)and 58.06%(18/31)respectively;MDRAB were mainly isolated from wound (45.45%),respiratory tract (34.27%),and urinary tract (17.65%).Univariate analysis revealed that difference in length of hospital stay,use of serum albumin,fiberbronchoscopy, coma days,tracheotomy,use of ventilator,incisional drainage,urinary catheterization,use of carbapenems,and antimicro-bial days in different groups were statistically different (P <0.05).Multivariate logistic regression analysis revealed that tracheotomy(OR95%CI :1.152-7.187),use of ventilator(OR95%CI :1.263 -7.664)were independent risk factors for MDRAB infection.Conclusion Tracheotomy and use of ventilator play an important role in the producing and sprea-ding of MDRAB ,management on drug-resistant bacteria is important in reducing MDRAB infection.