Objective: To design HBV DNA proficiency testing and system comparison samples with different concentration gradients, analyze their detection results in PCR detection systems, evaluate the nucleic acid detection capabilities of laboratories and differences between detection systems, and put forward suggestions for continuous quality improvement to participating laboratories. Methods: Three groups of randomly numbered proficiency testing samples (with HBV DNA reference concentrations of <2, 7.5, and 30 IU/mL respectively) were taken as the detection objects. Using nucleic acid test data from 11 provincial blood station laboratories as the source, the samples were grouped by detection system and laboratory successively, and statistical analysis was conducted. Results: Statistical analysis of the detection data of the three groups of samples based on detection systems and laboratories showed that from low to high concentration, the coincidence rate between the detection results of different detection systems and laboratories and the expected results showed an increasing trend: 38.89%, 85.90%, and 100.00%; the same system exhibited certain differences in performance among different laboratories. Conclusion: Through this proficiency testing and system comparison, it is found that there are certain differences in the detection capabilities of different laboratories and different nucleic acid test systems. Blood station laboratories should standardize processes, strengthen quality management and data analysis on the basis of being familiar with the detection performance of their detection systems, and at the same time strengthen the control of laboratory interference factors to continuously improve the nucleic acid detection capabilities of blood station laboratories.

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objectives:To explore the feasibility of using hemodynamic phenotypes to guide antihypertensive treatment medication. Methods:This study prospectively included 100 hypertensive patients who received outpatient treatment at Haidian Hospital in Beijing from January 2021 to December 2021.Evaluation of blood pressure was conducted using laboratory and home blood pressure measurements,impedance cardiogram(ICG)detection was performed.Following hemodynamic phenotypes and therapeutic phenotypes were established:hyperkinetic phenotype(increased heart rate)using β-blockers,large artery phenotype(increased large artery resistance index)using calcium antagonists,peripheral vascular phenotype(increased peripheral vascular resistance index)using renin angiotensin system inhibitors,and high-volume phenotype(increased blood volume saturation)using diuretics.Patients were randomly divided into ICG group(n=50,medication treatment based on hemodynamic characteristics)and control group(n=50,treatment based on hypertension guidelines and clinical experience).Patients were followed up for 8 weeks and the blood pressure reduction amplitude and compliance rate were compare between the two groups. Results:There was no statistically significant difference in baseline data such as sex,age,height,weight,and hemodynamic parameters between the two groups(all P＞0.05).There was no statistically significant difference in the types of baseline medication between the two groups(P＞0.05).After medication adjustment,the types of medication increased,but the difference between the two groups was still not statistically significant(P＞0.05).Clinic blood pressure:After 8 weeks,decreases in systolic([8.38±27.78]mmHg,1 mmHg=0.133 kPa)and diastolic([3.94±18.15]mmHg)blood pressure were greater in the ICG group as compared to the control group(both P＜0.05).The blood pressure compliance rate(＜140/90 mmHg)was higher in the ICG group than that in the control group(66.0%vs.42.0%,P＜0.05).Family blood pressure:after 8 weeks,the reduction in systolic([8.22±21.31]mmHg,P＜0.01)and diastolic([4.76±13.88]mmHg,P＜0.05)blood pressure was greater in the ICG group compared to the control group.The blood pressure compliance rate(＜135/85 mmHg)was higher in the ICG group than that in the control group(70.0%vs.48.0%,P＜0.05).Changes in corresponding hemodynamic parameters before and after two different antihypertensive drugs:the heart rate,arterial resistance index,peripheral vascular resistance index,and blood volume saturation of the ICG group all significantly decreased compared to baseline(all P＜0.05).The control group showed a significant decrease in peripheral vascular resistance index compared to baseline(P＜0.05),while there was no statistically significant difference in heart rate,large artery resistance index,and blood volume saturation compared to baseline(all P＞0.05). Conclusions:By using impedance cardiogram to assess hemodynamic phenotypes and accurately guide the selection of antihypertensive drugs based on hemodynamic phenotypes,it is possible to more effectively lower blood pressure and improve blood pressure compliance.

Objective:To explore the relationship between AluYb8 insertion in the MUTYH gene and the risk of decreased left ventricular diastolic function in the elderly.Methods:In the retrospective analysis, 498 elderly patients with decreased left ventricular diastolic function(the disease group)and 155 people without left ventricular diastolic function(the control group)were recruited.Polymerase chain reaction was employed to analyze the genotype distribution of AluYb8 insertion in MUTYH gene.Cardiac function was measured by high-resolution color Doppler ultrasound.Results:The frequencies of the A/A, A/P and P/P genotypes were 30.1%(150/498), 48.4%(241/498)and 21.5%(107/498)in patients with decreased left ventricular diastolic function, and 27.7%(43/155), 54.8%(85/155)and 17.5%(27/155)in the control group, respectively.There were no significant differences in genotype( χ2=2.162, P=0.339)and allele frequency( χ2=1.342, P=0.794)between the two groups.Further analysis after stratification revealed that there were statistically significant differences in genotype( χ2=7.173, P=0.028)and allele frequency( χ2=8.352, P=0.015). Multivariate Logistic regression analysis showed that, in elderly patients with diabetes, P-allele carriers had a higher risk of decreased left ventricular diastolic function than non-carriers( OR=3.450, 95% CI: 1.148-10.372, P=0.027). Conclusions:AluYb8 insertion in the MUTYH gene may be associated with the risk of decreased left ventricular diastolic function in the elderly with diabetes.

Objective:To search for and summarize the best evidence on non-pharmacological interventions for orthostatic hypotension in patients with Parkinson disease.Methods:Based on the 6S model, the relevant guidelines, clinical decisions, evidence summaries, systematic reviews and expert consensus on non-pharmacological interventions for orthostatic hypotension in Parkinson disease patients were systematically retrieved from domestic and foreign databases. The search time was from the establishment of the database to December 2022. Two researchers independently screened the literature, evaluated the quality of the included literature, and extracted and summarized evidence that met the quality standards.Results:A total of 15 articles were included, including 4 guidelines, 2 clinical decision-making articles, 1 evidence summary article, 3 systematic evaluations and 5 expert consensus articles. A total of 24 pieces of best evidence were summarized from 7 aspects, including purpose, evaluation, capacity intervention, exercise intervention, posture intervention, physical intervention, health education and support.Conclusions:The best evidence on non-pharmacological intervention for orthostatic hypotension in patients with Parkinson disease can provide a reference for the practice of clinical medical staffs. It is suggested to apply the best evidence in combination with the patient's condition, preference and clinical environment, so as to reduce the incidence of orthostatic hypotension in patients with Parkinson disease and to ensure the safety of patients.

Objective:To investigate the efficiency and safety of peritoneal dialysis (PD) in pediatric patients with acute kidney injury (AKI).Method:A retrospective study of children who underwent PD for AKI in the First Affiliated Hospital of Xi’an Jiaotong University from 2003 to 2013 was performed, and the laboratory examinations, the causes, the complication, the prognosis and the risk factors were evaluated.Results:The study included 48 children, with the age of (67.6±51.7) months (ranging from 3 months to 15 years old), including 31 males (64.6%) and 34 co-infections (70.8%). Primary glomerulonephritis (27.1%) was the most common cause of AKI, followed by the hemolytic uremic syndrome (18.7%) and drug induced AKI (18.7%). Peritoneal dialysis was performed manually using percutaneous or adapted catheters. The duration of PD during hospitalization was 11(7,14) days. PD treatment was highly effective in attenuation of toxics retention and correction of electrolyte disturbances (all P<0.05). There were 3 cases of PD-related complications, including 1 case of peritonitis, 1 case of catheter outflow obstruction, 1 case of catheter exit site hematoma, and no child patient died of PD complications. Among the AKI children, 37 cases (77.1%) recovered with the PD treatment and had the catheter successfully removed till discharge, 7 cases (14.6%) needed further peritoneal dialysis and 4 cases (8.3%) died. The serum albumin level was significantly higher in patients who got recovered with PD treatment than other unrecovered cases [(32.6±6.7) g/L vs (23.2±4.3) g/L, t=-3.994, P<0.001]. Conclusions:PD can be safely and efficiently performed for the treatment of pediatric AKI. Low albumin level may be related to poor prognosis of AKI.

Objective To evaluate the relationship between autophagy and diabetes mellitus-caused influence on ischemic preconditioning ( IP )-induced cardioprotection in rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 12 weeks, weighing 290-320 g, were used in this study. Diabe-tes mellitus was induced by high-fat and high-sucrose diet ( lasting for 1 week) and intraperitoneal streptozo-tocin 50 mg∕kg ( for 2 consecutive days) and confirmed by fasting blood glucose level≥16. 65 mmol∕L ( for 1 week) . Thirty rats with diabetes mellitus, weighing 350-450 g, were divided into 3 groups ( n=10 each) using a random number table method: sham operation group ( DM-S group) , myocardial ischemia-reperfusion ( I∕R) group ( DM-IR group) and IP group ( DM-IP group) . Another 30 non-diabetic rats were selected and divided into 3 groups ( n=10 each ) using a random number table method: sham operation group (S group), myocardial I∕R group (IR group) and IP group. Myocardial ischemia was induced by ligation of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. IP was produced by 3 cycles of 5-min ischemia followed by 5-min reperfusion prior to establishment of myo-cardial I∕R injury model in IP and DM-IP groups. Blood samples were collected from the internal jugular vein at the end of reperfusion for measuring serum concentrations of cardiac troponin I ( cTnI) and creatine kinase-MB ( CK-MB) . The rats were then sacrificed and myocardial tissues were obtained for determination of myocardial infarct size and expression of microtubule-associated protein 1 light chain 3 Ⅱ ( LC3 Ⅱ) , Beclin-1, phosphatidyl-inositol 3-kinase (PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt) and mammalian target of rapamycin ( mTOR) ( by Western blot) . p-Akt∕Akt ratio was calculated. Results Compared with S group, the serum cTnI and CK-MB concentrations were significantly increased, the percentage of myocardial infarct size was increased, the expression of LC3Ⅱand Beclin-1 in myocardial tis-sues was up-regulated, the expression of PI3K and mTOR was down-regulated, and p-Akt∕Akt ratio was decreased in IR group (P<0. 05). Compared with IR group, the serum cTnI and CK-MB concentrations were significantly decreased, the percentage of myocardial infarct size was decreased, the expression of LC3Ⅱand Beclin-1 in myocardial tissues was down-regulated, the expression of PI3K and mTOR was up-regulated, and p-Akt∕Akt ratio was increased in IP group ( P<0. 05) . Compared with DM-S group, the se-rum cTnI and CK-MB concentrations were significantly increased, the percentage of myocardial infarct size was increased, the expression of LC3Ⅱ and Beclin-1 in myocardial tissues was up-regulated, the expres-sion of PI3K and mTOR was down-regulated, and p-Akt∕Akt ratio was decreased in DM-IR group ( P<0. 05) . There was no significant difference in the parameters mentioned above between DM-IP group and DM-IR group (P>0. 05). Conclusion The mechanism by which diabetes mellitus abolishes IP-induced cardioprotection may be related to inhibiting activation of PI3K-Akt-mTOR signaling pathway and enhanced autophagy in rats.

Objective To find the efficient modification groups of anti-proteinase hydrolyzation in polypeptide by investigat-ing and comparing the relation between the functional groups and their ability to inhibit proteinase hydrolyzation. Methods Reverse phase-high performance liquid chromatography(RP-HPLC)method was developed to investigate in vitro metabolisms of new drug LXT101 and its structural modified analogs LZN series and LMP series in pancreatin system. All the separations of peptide drugs and their digested fragments were monitored at 225 nm. Results The good linear range was 4.0-400 μg/ml(r>0.9990)for new drug LXT101 and its structural modified analogs,i.e.,LZN series and LMP series. The recoveries of all peptide drugs ranged from 95.0%to 98.7%in pancreatin systems. The relative standard derivations(RSD)of intra-day and inter-day were less than 1.5%and 2.5%,re-spectively. The revealed order of digested half-life of the peptide drugs was LZN series>LMP series>LXT101. Conclusion The study of different sites and different functional groups on the lifetime indicates that the half-lives of peptides are prolonged by introducing the functional groups in the suitable sites of peptide,which feature as proteinase inhibitors,such as carbamoyl(Cbm),acetyl(Ac),para-amino-phenylalanine(Aph)or para-uramido-phenylalanine(Uph),which work as either proton donor or acceptor. Our results can pro-vide some useful and valuable information on structural design of peptide drug with long lifetime and high activity.

Objective To explore the effect of dexmedetomidine on hemodynamics in hypertensive patients undergoing thyroid surgery with local anesthesia.Methods Sixty patients with preoperatively diagnosed class Ⅰ to Ⅱ hypertension undergoing selective thyroidectomy were randomly divided into D (dexmedetomidine) and M (midazolam) groups (30 patients in each group).Doses of dexmedetomidine 0.5 μg/kg were finished in 20 minutes injection in patients of D group before the start of the surgery,then sequentially maintained at the rate of 0.1 ～ 0.5 μg/ (kg · h) with decreasing speed of 0.1 μg/(kg · h) when systolic pressure kept down to 110 mmHg or heart rare down to 60 bpm or Ramsay score of 3 points.The patients in M group were injected with midazolam 0.04 mg/kg 20 minutes before the start of surgery,then maintained at the rate of 0.02 ～ 0.05 mg/(kg · h),decreasing speed of 0.1 mg/(kg · h) to keep Ramsay score of 3 points if necessary.Two groups of patients with Ramsay score of 3 points but a high blood pressure (higher than 30％ of basic level) or heart rate (more than 100 bpm) were treated with drugs during operation.Record the systolic pressure,diastolic pressure,heart rate and Ramsay score at the time of before medication (T0),the injection of local anesthetics (T1),the start of surgery (T2),pain compliments required additional local anesthetics (T3),dealing with gland (T4) and the end of surgery,VAS in 8 h after operation and adverse reaction were recorded.Results In D group,the dosages of urapidil and esmolol [(10 ±5)mg and (0 ±0)mg] were significantly less than those in patients of M group [(60 ± 10) mg and (80 ±5) mg,t =14.82,t =19.78,P ＜ 0.05].Blood pressure and heart rate were all significantly decreased at the time of T1,T2 and T5 when comparing with T0(P ＜0.05 orP ＜0.01),and only heart rate was significantly decreased at the time of T3 and T4 (P ＜ 0.05).While in M group,blood pressure and heart rate were higher than basic levels at the time of T3 and T4 (P ＜ 0.05).Besides,lower blood pressure and heart rate were less than those in M group at all observed time expect T0 (P ＜ 0.05).Conclusions Good sedation effects can be produced by both dexmedetomidine and midazolam in hypertensive patients undergoing thyroid surgery with local anesthesia,but dexmedetomidine was determined more suitable in sedation and anti-hypertension in patients with light to moderate hypertension for better hemodynamic stability effect with local anesthesia.