Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms / 生物化学与生物物理进展

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Allergy Associated With N-glycans on Glycoprotein Allergens / 生物化学与生物物理进展

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Association of pregnancy factors with cow's milk protein allergy in infants / 北京大学学报(医学版)

Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2％)was higher than that in the control group(47.3％),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P＞0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P＜0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P＞0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P＞0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

Early prediction of severe acute pancreatitis based on improved machine learning models / 陆军军医大学学报

Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models,and to analyze its clinical value.Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease,the patients were divided into the severe group(n=88)and the non-severe group(n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features.Results In the training set,the area under curve(AUC)of the improved machine learning model was 0.922.In the testing set,the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein,blood chlorine,blood magnesium and fibrinogen level,which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis.Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.

Relationship between serum TSG-6 and col-16 levels and severity of the illness and clinical outcome in patients with active ulcerative colitis / 国际检验医学杂志

Objective To investigate the relationship between serum tumor necrosis factor α stimulated gene 6(TSG-6)and collagen ⅩⅥ(col-16)levels and severity of the illness and clinical outcome in patients with active ulcerative colitis(UC).Methods A total of 79 patients with active UC admitted to the department of gastroenterology in the hospital from January 2020 to January 2023 were selected as the active UC group,56 patients with UC in remission who were similar in gender and age to the active UC group were selected as the remission UC group,and 60 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.Patients with active UC were divided into mild group(n=25),moderate group(n=34)and severe group(n=20)according to the modified Mayo score.Patients with active UC were divided into good prognosis group(n=58)and poor prognosis group(n=21)according to colonoscopy results after 2 months of treatment.Serum TSG-6 and col-16 levels in each group were detected by enzyme-linked immunosorbent assay,Spearman rank correlation analysis was used to analyze the relation-ship between serum TSG-6 and col-16 levels and severity of the illness,and the influence of serum TSG-6 and col-16 levels on clinical outcome was analyzed by multivariate Logistic regression.Receiver operating charac-teristic(ROC)curve was used to evaluate the predictive value of serum TSG-6 and col-16 for poor prognosis in patients with active UC.Results The serum TSG-6 and col-16 levels in active UC group and remission UC group were higher than those in control group,and the serum TSG-6 and col-16 levels in active UC group were higher than those in remission UC group,the difference was statistically significant(P＜0.05).Serum TSG-6 and col-16 levels in severe group and moderate group were higher than those in mild group,and serum TSG-6 and col-16 levels in severe group were higher than those in moderate group,with statistical significance(P＜0.05).By Spearman rank correlation analysis,serum TSG-6 and col-16 in active UC patients were positively correlated with modified Mayo scores(rs=0.695、0.627,P＜0.05).Multivariate Logistic regression analysis showed that compared with＜159.32 ng/mL,patients with serum TSG-6 interquartile interval of 289.15-413.55 ng/mL and＞413.55 ng/mL had a higher risk of poor prognosis.ROC curve analysis results showed that the area under the curve of TG-6 and col-16 in predicting poor prognosis was 0.776 and 0.764,respective-ly.The predictive value of serum TG-6 and col-16 combined detection was better than that of single index(Z=3.392,4.218,P＜0.05).Conclusion The serum TSG-6 and col-16 levels in active UC patients are ab-normally elevated,which is closely related to severity of the illness and clinical outcome.The levels of serum TSG-6 and col-16 can be used as potential biochemical indicators to judge the disease and predict the clinical outcome.

Discussion on the Pathogenesis of Osteonecrosis of the Femoral Head Under the System of Non-uniform Settlement During Bone Resorption and Multidimensional Composite Bowstring Working in Coordination with the Theory of Liver-Kidney and Muscle-Bone Based on the Concept of Liver and Kidney Sharing the Common Source / 广州中医药大学学报

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Accuracy of sacroiliac screw placement in robot-assisted navigation / 中国组织工程研究

BACKGROUND:Orthopedic robots have been widely used in clinical practice,and relevant reports have shown that they have many advantages such as minimal trauma and short surgical time.However,there is currently no clear report on how accurate they are. OBJECTIVE:To evaluate the accuracy of robot-assisted sacroiliac screw insertion. METHODS:A total of 131 patients with sacroiliac joint fracture and dislocation and sacral fracture admitted to the Department of Trauma Surgery,Gansu Provincial Hospital from January 2020 to April 2023 were retrospectively collected,including 131 S1 screws and 46 S2 screws,totaling 177 screws.They were divided into two groups based on whether robot-assisted navigation was performed.There were 63 cases of sacroiliac screws inserted under robot-assisted navigation(observation group),with 36 males and 27 females,aged 19-72 years,with a mean age of(45.3±17.6)years.Among them,39 cases were fixed with only S1 screws,while 24 cases were fixed with S1S2 screws,resulting in a total of 87 sacroiliac screws.Under C-arm fluoroscopy,68 cases of sacroiliac screws were inserted with bare hands(control group),including 41 males and 27 females,aged 23-67 years,with a mean age of(42.6±21.3)years.Among them,46 cases were fixed with simple S1 screws,while 22 cases were fixed with S1S2 screws,resulting in a total of 90 sacroiliac screws.A postoperative CT scan was performed to evaluate the number of S1 screws,S2 screws,total screw level,and calculate accuracy based on the method introduced by SMITH et al. RESULTS AND CONCLUSION:(1)In the observation group,62 S1 screws were accurately placed(62/63),with an accuracy rate of 98%.24 S2 screws were accurately placed(24/24),with an accuracy rate of 100%.The total number of screws accurately placed was 86(86/87),with an accuracy rate of 99%.(2)In the control group,58 S1 screws were accurately inserted(58/68),with an accuracy rate of 85%.19 S2 screws were accurately inserted(19/22),with an accuracy rate of 86%.The total number of screws accurately inserted was 77(77/90),with an accuracy rate of 86%.(3)There was a statistically significant difference in the accuracy of the S1 screw,S2 screw,and total screw between the two groups(P<0.05).It is suggested that the placement of sacroiliac screws under robot navigation has higher accuracy compared to manual placement under C-arm fluoroscopy,but still has a lower error rate in placement.

Mechanical Performance of Porous Titanium Alloy Scaffolds with Different Cell Structures / 医用生物力学

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Application and challenges of NHP laboratory animals in neuroscience / 中国比较医学杂志

Non-human primates(NHP)are becoming increasingly important laboratory animals,especially in the field of neuroscience,where many significant breakthroughs have been made,including research on brain development,neurodegenerative diseases,and psychiatric disorders.However,as their breeding and use grows,biosafety and animal ethics issues should be considered.This review summarizes the application and challenges of NHP laboratory animals in the neuroscience field from the aspects of an NHP overview,feeding and operation,biosafety,and animal ethics.

Discussion on the relationship between the disposal time of hypobaric oxygen chamber and the establishment of rat cardiac arrest model at high altitude / 中华危重病急救医学

Objective:To establish the rat cardiac arrest model in high-altitude hypobaric hypoxia environment, and to explore the effect of the treatment time in the hypobaric oxygen chamber on the reproduction of high-altitude rat cardiac arrest model.Methods:SPF grade healthy male Sprague-Dawley (SD) rats were used as observation subjects. The experiment was conducted in two different altitude areas. The rats from the Plateau Branch of Institute of Cardiopulmonary and Cerebral Resuscitation of Sun Yat-sen University (Xining, Qinghai) were weighed and numbered, and they were placed in a hypobaric oxygen chamber (simulated altitude of 3 000 meters, speed of ascent and descent of 15 m/min, temperature of 20 ℃, cabin pressure of 69.5 kPa, cabin oxygen pressure of 14.5 kPa). After 30 days of feeding, the rats were obtained according to random number table method, and the cardiac arrest model was established by asphyxia method as the 30-day hypobaric hypoxia group. After 60 days of feeding, rats were randomly selected again, and the cardiac arrest model was established as the 60-day hypobaric hypoxia group. Thirty rats were randomly selected from the Institute of Cardiopulmonary Cerebral Resuscitation at Sun Yat-sen University (Guangzhou, Guangdong) by the same method, and the cardiac arrest model was established as the plain control group. The differences in the body weight of rat modeling precursors and the induction time of asphyxia during the modeling process among different groups were compared.Results:Finally, cardiac arrest model was established in 16 rats in the 30-day hypobaric hypoxia group and in 22 rats in the 60-day hypobaric hypoxia group. There was no significant difference in the body weight of rats before modeling among the plain control group, 30-day hypobaric hypoxia group and 60-day hypobaric hypoxia group [g: 429.00 (389.25, 440.75), 440.00 (415.50, 486.25), 440.00 (400.00, 452.50), all P > 0.05]. The asphyxia induction time of rats in the 60-day hypobaric hypoxia group was significantly longer than that in the 30-day hypobaric hypoxia group (s: 294.59±75.39 vs. 234.31±93.86, P < 0.01), even about 1.4 times of the plain control group (s: 294.59±75.39 vs. 208.73±30.88, P < 0.01). There was no significant difference in the asphyxia induction time between the 30-day hypobaric hypoxia group and the plain control group ( P > 0.05). Conclusion:Rats treated in a hypobaric oxygen chamber for 60 days are more suitable for the preparation of high-altitude cardiac arrest model, and are also consistent with the oxygen reserve and hypoxia tolerance of high-altitude rats.

Impact of ambient ozone exposure on death from cardiovascular and cerebrovascular diseases in Minhang District, Shanghai / 环境与职业医学

Background Ozone (O3) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O3 concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O3 risk assessment and related policy making. Objective To quantitatively evaluate the effects of O3 exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. Methods Data of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O3 concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P25) and the 75th percentile (P75) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m−3 increase in daily maximum 8 h concentration of O3 (O3-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O3. Results The associations between O3 and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P<0.05), with the greatest effect size observed at lag03. The ER values of death from cardiovascular and cerebrovascular diseases in general population, male residents, and people aged 65 years and older, from coronary heart disease in male residents, and from stroke in general population increased by 1.02% (95%CI: 0.36%, 1.69%), 1.40% (95%CI: 0.47%, 2.34%), 0.87% (95%CI: 0.19%, 1.55%), 1.96% (95%CI: 0.49%, 3.44%), and 1.02% (95%CI: 0.07%, 1.98%) for a 10 µg·m−3 increase in O3-8 h concentration at lag03, respectively. During the warm season (from April 1 to September 30), the ER values of death from cardiovascular and cerebrovascular diseases and coronary heart disease per 10 µg·m−3 increase in O3 were 1.18% (95%CI: 0.33%, 3.33%) and 2.69% (95%CI: 0.39%, 5.03%), while the O3 effect was only statistically significant on cardiovascular and cerebrovascular diseases during the cold season (from October 1 to March 31 next year). At the middle and high temperature levels, the ER values of death from cardiovascular and cerebrovascular diseases increased by 1.63% (95%CI: 0.32%, 2.96%) and 1.14% (95%CI: 0.17%, 2.12%) respectively. The two-pollutant models showed similar results after including other pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, fine particulate matter, or inhalable particulate matter). Conclusion Ambient O3 pollution may increase the mortality risks of cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke in Minhang District of Shanghai.

Preparation and quality evaluation of Eriodictyol chewable tablet / 中国药房

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

Analysis of the Relationship between Serum miR-873 and miR-138-5p Expression and Immune Microenvironment and Prognosis in Patients with Non-small Cell Lung Cancer / 现代检验医学杂志

Objective To investigate the relationship between serum micro RNA(miRNAs)-873 and micro RNA-138-5p expression and tumor immune microenvironment(TIME)and prognosis in patients with non-small cell lung cancer(NSCLC).Methods A total of 108 NSCLC patients(NSCLC group)and 65 healthy volunteers(control group)who were admitted to Ba'nan Hospital Affiliated to Chongqing Medical University from February 2019 to February 2021 were selected.Real-time quantitative fluorescence polymeric chain reaction(qRT-PCR)was used to detect the expression of miR-873 and miR-138-5p in serum,and multiple immunofluorescence staining was used to detect tumor immune microenvironment indicators.Regular follow-up was conducted after discharge.Pearson analyzed the correlation between the expression of miR-873 and miR-138-5p in serum and the TIME index,and Kaplan-Meier and COX proportional risk regression analyzed the relationship between miR-873 and miR-138-5p and the prognosis of NSCLC patients.Results Comparison with control group,the expressions of miR-873(1.02±0.23 vs 3.15±0.82)and miR-138-5p(1.21±0.26 vs 3.54±0.92)in serum of NSCLC group were decreased,and the differences were statistically significant(t=-25.426,-24.769,all P＜0.05).The expressions of serum miR-873 and miR-138-5p of patients with low-to-moderate differentiation in TNM stages Ⅲ to Ⅳ were lower than those with highly differentiated patients in TNM stages Ⅰ to Ⅱ(t=9.615,10.253;6.889,3.361,all P＜0.05).The expressions of miR-873 and miR-138-5p in serum were negatively correlated with the values of PD-1,PD-L1,CD4 and CD8 H(r=-0.418～-0.673,all P＜0.05).The OS survival rate of NSCLC patients with low expression of miR-873 and miR-138-5p was lower than that of those with high expression of miR-873 and miR-138-5p(Log-Rankχ2=4.724,5.607,P＜0.05).TNM stage Ⅲ～Ⅳ was a risk factor for poor prognosis in patients with NSCLC(P＜0.05),and miR-873 and miR-138-5p were protective factors(P＜0.05).Conclusion The expressions of miR-873 and miR-138-5p in serum of NSCLC patients are down-regulated,which is related to TIME and low survival rate.

Correlation Analysis between Serum miR-133a-3p and PTPN22 Levels Expression and Disease Severity in Patients with Psoriasis Vulgaris / 现代检验医学杂志

Objective To explore the correlation between the serum levels expression of microRNA(miR)-133a-3p,protein tyrosine phosphatase nonreceptor type 22(PTPN22)and the severity of psoriasis vulgaris.Methods A total of 86 patients with psoriasis vulgaris who were admitted to Cangzhou People's Hospital from January 2022 to June 2022 were collected as the observation group.They were separated into a progressive group(n=41)and a quiescent group(n=45)based on the area and severity of the skin lesions.Meantime,86 healthy individuals undergoing plastic surgery examinations were regarded as the control group.Real time fluorescent quantitative PCR(qRT-PCR)method was applied to detect the relative expression levels of miR-133a-3p and PTPN22 in serum.Target Scan Human website was applied to predict the targeting relationship between PTPN22 and miR-133a-3p.Spearman method was applied to analyze the correlation between the expression levels of miR-133a-3p and PTPN22 in serum of patients with psoriasis vulgaris,the psoriasis area and the psoriasis area and severity index score(PASI).Logistic regression was applied to analyze the influencing factors of severity in patients with psoriasis vulgaris.Results Compared with the control group,the serum miR-133a-3p(1.85±0.46 vs 1.05±0.21)expression level in the observation group was increased,while the PTPN22 mRNA(0.76±0.13 vs 1.02±0.18)expression level was reduced,and the difference were statistically significant(t=14.671,10.859,all P<0.05).Compared with the quiescent group,the serum miR-133a-3p(2.05±0.52 vs 1.67±0.41)expression level in the progressive group was increased,while the PTPN22 mRNA(0.66±0.11 vs 0.85±0.15)expression level was reduced and the differences were statistically significant(t=3.780,6.643,all P<0.05).Target Scan Human website predicted that there may be a targeting relationship between miR-133a-3p and PTPN22.Spearman analysis showed that there was a positive correlation between serum miR-133a-3p and PASI score in patients with psoriasis vulgaris(r=0.469,P<0.05),while serum TPN22 mRNA level was negatively correlated with PASI score(r=0.469,P<0.05).Serum miR-133a-3p[OR(95%CI)=2.884(1.261～6.595)]was an independent risk factor for the severity of psoriasis vulgaris,while PTPN22[OR(95%CI)=0.562(0.367～0.860)]was an independent protective factor(all P<0.05).Conclusion The expression level of miR-133a-3p in serum of patients with psoriasis vulgaris was increased,while the expression level of PTPN22 was reduced.The two were closely related to the PASI score and may to some extent reflect the severity of psoriasis patients.

The current situation and influencing factors of breast cancer patients′ anxiety about the upbringing of minor children / 中国实用护理杂志

Objective:To study and analyze the status quo and influencing factors of breast cancer patients′ concern about the upbringing of their minor children, and to provide a reference for clinical improvement of the level of breast cancer patients′ concern about parenting.Methods:A total of 247 breast cancer patients in the daytime ward of Tianjin Medical University Cancer Hospital from March to May 2023 were selected by convenience sampling. The General Information Questionnaire, Parenting Concerns Questionnaire, Parenting Sense of Competence Scale were selected for cross-sectional investigation. The multiple linear regression model was used to analyze the influencing factors of breast cancer patients′ worries about the upbringing of their minor children.Results:Finally, 240 valid questionnaires were ultimately collected. There were 12 patients with breast cancer aged 20-29 years old, 76 patients aged 30-39 years old, 117 patients aged 40-49 years old, and 35 patients aged ≥50 years old. The total score of breast cancer patients′anxiety about minor children′s rearing was (37.34 ± 2.56) points. The scores of each dimension were in order of (15.14 ± 1.02) worry about the actual impact on children, (11.15 ± 0.83) worry about the emotional impact on children, and (11.05 ± 0.71) worry about the parents of children. The total score of parenting competence (66.54 ± 11.68) points. Multiple linear regression analysis showed that parenting competence, educational level, number of underage children, per capita monthly income of families, and TNM stage (T: tumor primary lesion; N: regional lymphnode involvement; M: remote metastasis situation) affected parenting anxiety ( t values were -15.24-8.56, all P<0.05), which could explain 81.2% of the total variation in parenting anxiety level. Conclusions:Breast cancer patients′ concern about the upbringing of minor children is at a medium level, so medical staff should give relevant intervention measures to breast cancer patients with different characteristics, in order to provide reference for reducing the level of concern about the upbringing of minor children.

Fracture accuracy on cortical bone structure under bending load using different numerical methods / 中国组织工程研究

BACKGROUND:Current fracture simulation for cortical bone structure is mainly based on three numerical methods:the element instantaneous failure,continuum damage mechanics,and extended finite element methods.Although many studies focus on cortical bone fracture simulation,few have compared the differences in prediction accuracy using the three numerical methods. OBJECTIVE:To probe the accuracy and applicability of the three numerical methods in simulating cortical bone fracture under bending load. METHODS:The rat femur samples were primarily used to perform the three-point bending experiment.The rat femoral finite element models were established based on the micro-CT images of the femur samples and the three numerical methods were used to conduct the fracture simulations under three-point bending loads.The predicted fracture loads and fracture patterns were compared with the experimental data to determine the accuracy of various numerical methods in simulating cortical bone fracture. RESULTS AND CONCLUSION:(1)The discernible differences in the failure processes could be observed in the same finite element model under the three numerical simulations due to different element failure strategies.(2)The simulation results showed that the fracture simulation using the continuum damage mechanics method was in better agreement with the experimental results.(3)The numerical method that was suitable for simulating cortical bone fracture under bending load could be determined by comparing it with experimental results.The variations in the fracture parameters were observed,and the reason for the differences in the predicted results using different numerical methods was also discussed,which aided in determining the range of applicability of structural fracture simulation for each numerical method and then improving the simulation accuracy.

Low-frequency pulsed magnetic field induces classical transient receptor potential channels 1 to relieve lower limb muscle weakness in patients recovering from COVID-19 / 中国组织工程研究

BACKGROUND:Muscle weakness is a common symptom after coronavirus disease 2019(COVID-19)infection and affects the ability to perform daily activities in humans during recovery.Low-frequency pulsed magnetic field stimulation at a strength of 1.5 mT and a frequency of 3 300 Hz can enhance the maximal voluntary contraction and strength endurance of human skeletal muscle by inducing and activating classical transient receptor potential channel 1(TRPC1),which produces a series of pathological support effects on muscle tissue.It has not been studied whether this means will improve muscle weakness in patients recovering from COVID-19. OBJECTIVE:To select the low-frequency pulsed magnetic field for magnetic stimulation of lower limb muscle groups in patients with COVID-19,in order to observe the effect of this stimulation on the improvement of muscle weakness of lower limb muscle groups in patients with COVID-19 during the recovery period. METHODS:Fourteen patients infected with COVID-19(Omicron strain)positive for Innovita COVID-19 Ab Test(Colloidal Gold)and accompanied by muscle weakness were recruited and randomly divided into two groups:a test group receiving magnetic field stimulation and a control group receiving sham treatment,respectively.The total duration of the trial was 3 weeks.The test group was given low-frequency pulsed magnetic stimulation of the lower limbs every 48 hours and the control group was given the same intervention procedure as the test group but with sham stimulation.Patients in both groups were not informed whether the magnetic stimulation apparatus was running or not.Nine sessions were performed in both groups and the changes in the maximum voluntary contraction,explosive leg force and strength endurance of the local muscle groups of the lower limbs were subsequently observed in both groups. RESULTS AND CONCLUSION:Among the eight local muscle groups collected,seven local muscle groups in the test group showed an increase in the maximum voluntary contraction value after 3 weeks of low-frequency pulsed magnetic field stimulation.In the control group,there were only three muscle groups with improvement in the maximum voluntary contraction.The rate of improvement in the anterior and posterior muscle groups of the left leg in the test group was significantly higher than that in the control group.The longitudinal jump height and peak angular velocity of the knee joint in both groups were improved compared with the pre-test measurement,and the elevation rate of jumping height in the test group was higher than that in the control group.Under the fatigue condition,the decline rates of peak angular velocity of the knee joint and jumping height in the test group decreased significantly,while those in the control group did not change significantly.The above data confirmed that the low-frequency pulsed magnetic field stimulation with the intensity of 1.5 mT and frequency of 3 300 Hz could improve the muscle strength of more local muscle groups in the lower limbs of patients with COVID-19 during the recovery period compared with the human self-healing process,and the whole-body coordination ability and functional status based on explosive leg force of the legs could be significantly improved.Therefore,low-frequency pulsed magnetic field stimulation can be used as an effective,non-exercise rehabilitation tool to improve muscle weakness in the lower limbs of patients with COVID-19.

Analysis of clinical characteristics and the related factors to flare in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To summarize the clinical characteristics and factors that may affect the flare of patients with systemic lupus erythematosus (SLE).Methods:A total of 300 patients with SLE who were treated with standard treatment in the outpatient clinic of the department of rheumatology and immunology of the Second Affiliated Hospital of Air Force Military Medical University of PLA, were enrolled, and the patients were divided into 24 patients in the complete response group, 40 cases in the no response group, 192 cases in the treatment response group, and 44 cases in the low disease activity group according to the response to treatment. The differences in clinical characteristics and survival rates between the groups were compared and analyzed. Comparisons of count data were made using analysis of variance (ANOVA), comparisons of measurement data were made using the chi-square test or the Fisher′s ecact test, and survival rates were expressed as Kaplan-Meier curves. Cox regression analysis was adapted to explore risk factors for flare in these patients.Results:A total of 300 patients were followed. With a median follow-up time of 18 (1, 36) months, a total of 42 patients experienced flare. The clinical characteristics of the four groups were compared, and there were significant differences in age ( F=4.39, P=0.005), the presence of lupus nephritis ( χ2=12.66, P=0.005), hemoglobin level ( F=2.73, P=0.044), NLR level( F=3.88, P=0.010), cystatin C level( F=3.11, P=0.027), anti-RNP antibody ( χ2=12.04, P=0.007), anti-Sm antibody ( χ2=8.33, P=0.040), anti-SSB antibody ( P=0.014), anti-nucleosome antibody ( P=0.014), and anti-ribosomal P protein antibody ( χ2=11.83, P=0.008). There was no significant difference in survival between the four groups. Cox analysis showed that the combination of other autoimmune diseases [ HR(95%CI)=3.23(1.58, 6.57), P=0.001], anti-Sm antibody [ HR(95%CI)=2.15(1.04, 4.43), P=0.038], and anti-RNP antibody [ HR(95%CI)=2.54(1.13, 5.68), P=0.023] were risk factors for flare in patients with SLE who could reach the treatment target. Conclusion:Patients with SLE with different treatment responses have different clinical features, and all treatment can significantly improve the recurrence rate no matter what level of response to treatment. Patients concurrent with other autoimmune diseases, positive anti-Sm antibodies, and positive anti-RNP antibodies are at highrisk of flare.

Propensity score matching study of the feasibility of no-prophylactic abdominal drainage strategy for the minimally invasive minor hepatectomy / 中华肝胆外科杂志

Objective:To evaluate the feasibility of abandoning prophylactic abdominal drainage in patients undergoing minimally invasive minor hepatectomy based on a propensity score matching (PSM) study.Methods:Retrospective review of a prospectively collected database of patients undergoing minimally invasive minor hepatectomy from July 2022 to May 2023 at the Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital. A total of 108 patients were enrolled, including 48 males and 60 females, aged (60.8±13.7) years old. According to whether the abdominal drainage tube was prophylactically placed intraoperatively, patients were divided into two groups: the drainage group (with prophylactic placement of abdominal drainage tubes, n=76); the no-drainage group (without prophylactic placement of abdominal drainage tubes, n=32). PSM was used to compare the perioperative data between the groups, including extent of liver resection, intraoperative blood loss, operative time, and postoperative complications. Postoperative survival status within 90 days was followed up through telephone review. Results:Before PSM, the two groups differed significantly on age and the history of hypertension (both P<0.05). After PSM, there were 23 patients in each group. Patients in the two groups showed comparable results regarding the intraoperative parameters including the surgical method, pathological types, the number and maxium diameter of hepatic lesions, the extent and complexity of liver resection, and the duration of hepatic inflow occlusion (all P>0.05). No postoperative intra-abdominal bleeding occurred in either group. The incidences of postoperative complications were comparable between the groups, including fever, bile leakage, incision infection, and abdominal acupuncture for drainage (all P>0.05). After PSM, compared to patients wothout prophylactic abdominal drainage, prophylactic abdominal drainage group showed a decreased white blood cell counts on postoperative day 1 [9.39(6.30, 10.58)×10 12/L vs. 13.19(10.15, 14.90)×10 12 /L, P=0.006] and a shorter length of postoperative hospital stay [4(3, 5) d vs. 5(4, 5) d, P=0.033]. No postoperative death within 90 days occurred in either group. Conclusion:In minimally invasive minor hepatectomy, abandoning prophylactic abdominal drainage could be feasible, which facilitates fast recovery without increasing the incidence of postoperative fever, perihepatic fluid accumulation and postoperative abdominal acupuncture for drainage.

Correlation of nerve function and prognosis with common serum biochemical indicators in patients with ACI after alteplase intravenous thrombolysis / 中华老年心脑血管病杂志

Objective To explore the correlation of nerve function and prognosis with serum uric acid(UA),homocysteine(Hcy)and low-density lipoprotein cholesterol(LDL-C)in patients with acute cerebral infarction(ACI)after alteplase intravenous thrombolysis.Methods A total of 220 ACI patients undergoing thrombolysis in Changsha First Hospital ICU between January 2020 and December 2022 were enrolled,and according to mRS score at 3 months after thrombolysis,they were divided into poor prognosis group(mRS score＞2,91 cases)and good prognosis group(mRS score ≤2,129 cases).The serum levels of UA,Hcy and LDL-C were compared between the two groups.The correlation between the three indexes and score of National Institutes of Health Stroke Scale(NIHSS),and their predictive value for poor prognosis were analyzed.Results At 1 and 3 d after thrombolysis,the serum levels of UA,Hcy and LDL-C and NIHSS score were sig-nificantly decreased in both groups,and the serum levels of UA and Hcy and NIHSS score at 3 d after thrombolysis were significantly lower than those at 1 d(P＜0.05).The poor prognosis group had obviously higher serum levels of UA,Hcy and LDL-C and NIHSS score at 1 and 3 d after thrombolysis than the good prognosis group(P＜0.05,P＜0.01).Pearson correlation analysis showed that the serum levels of UA,Hcy and LDL-C were positively correlated with NIHSS score at 1 and 3 d after thrombolysis(P＜0.01).ROC curve analysis indicated that the AUC values of UA,Hcy and LDL-C at 1 d after thrombolysis for predicting poor prognosis were 0.707(95％CI:0.639-0.776),0.800(95％CI:0.739-0.860)and 0.624(95％CI:0.550-0.698),respectively,while the values of them at 3 d after thrombolysis were 0.655(95％CI:0.583-0.726),0.730(95％CI:0.664-0.795)and 0.573(95％CI:0.497-0.649),respectively.Conclusion In ACI patients after thrombolysis,the serum levels of UA,Hcy and LDL-C are increased in those with poor prognosis,and are associated with the severity of nerve injury.The levels at 1 d after throm-bolysis have good predictive value for poor prognosis.