ObjectiveTo investigate the independent risk factors for decompensation in patients with liver cirrhosis， to construct a nomogram-based risk assessment model， and to assess its risk assessment performance and clinical value by comparing it with Model for End-Stage Liver Disease （MELD）， MELD combined with serum sodium concentration （MELD-Na）， and MELD 3.0 scoring system. MethodsA retrospective analysis was performed for 514 patients with liver cirrhosis who attended The First Hospital of Shanxi Medical University from January 2020 to May 2025， and related data were collected， including demographic data and laboratory markers. According to the presence or absence of decompensation， the patients were divided into compensation group with 275 patients and decompensation group with 239 patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator regression analysis was used for screening of variables， and the multivariate logistic regression analysis was used to identify independent risk factors for decompensated liver cirrhosis and construct a nomogram model. The receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis were used to assess the discriminatory ability， calibration， and net clinical benefit of the model. ResultsThe multivariate logistic regression analysis showed that low hemoglobin （odds ratio ［OR］=0.984， 95% confidence interval ［CI］： 0.969　—　0.999， P<0.05）， low lymphocytes （OR=0.564， 95%CI： 0.383　—　0.830， P<0.05）， high international normalized ratio （OR=3.131， 95%CI： 1.242　—　7.891， P<0.05）， and low serum sodium （OR=0.922， 95%CI： 0.872　—　0.975， P<0.05） were independent risk factors for decompensation events in patients with liver cirrhosis. Construct the prediction model equation： Logit（P）=intercept value－0.016×hemoglobin－0.573×lymphocytes+1.141×INR－0.081×serum sodium. The nomogram constructed based on these factors had a good discriminatory ability， with an area under the ROC curve （AUC） of 0.787， a specificity of 77.8%， and a sensitivity of 67.4%， and it had significantly better predictive performance than MELD score （AUC=0.718）， MELD-Na score （AUC=0.719）， and MELD 3.0 score （AUC=0.725）. The calibration curve showed good consistency between the probability of risk assessed by the model and the observed probability. The decision curve analysis showed that compared with the MELD-based scores， this model provided higher net clinical benefit across a wide range of risk thresholds. ConclusionThis study successfully constructed and validated a nomogram risk assessment model incorporating hemoglobin， international normalized ratio， lymphocytes， and serum sodium. This model has good clinical practicability and can help to achieve early identification of high-risk patients with decompensated liver cirrhosis and optimize intervention strategies in clinical practice.

Objective To evaluate the clinical utility of combining magnetic resonance imaging (MRI) findings with serum levels of cysteine-rich protein 61 (CYR61) and C-X-C motif chemokine ligand 1 (CXCL1) for early identification of acute stroke. Methods The study was conducted 205 patients with suspected acute stroke admitted to the neurology department of our hospital between April 2021 and April 2024. Based on brain CT imaging and clinical diagnosis, 119 patients were acute stroke group and 86 to non-acute stroke group. All patients underwent MRI examination. Serum levels of CYR61 and CXCL1 were measured. Receiver operating characteristic (ROC) curves were generated to assess diagnostic value, and Kappa tests were used to performed to evaluate the consistency. Results Serum level of CYR61 and CXCL1were significantly higher in the acute stroke group than in the non-acute stroke group (P<0.05). The area under the ROC curve (AUC) for serum CYR61 in diagnosing acute stroke was 0.867 (95%CI: 0.819-0.915), with diagnostic threshold of 6.02 μg/L; for CXCL1, the AUC was 0.818 (95%CI: 0.762-0.875), with a threshold of 1.28 ng/mL. The Kappa values for agreement between MRI, serum CYR61, and CXCL1 clinical diagnosis results were 0.766, 0.586, and 0.528, respectively, the Kappa value for the consistency between the combination of the three with clinical diagnosis results was 0.920 (P<0.05). The sensitivity, negative predictive value, and accuracy of the combination of MRI, serum CYR61, and CXCL1 were obviously higher than that of the individual diagnosis, and the specificity and positive predictive value were obviously higher than that of the individual diagnosis of serum CYR61 and CXCL1 (P<0.05). Conclusion The clinical diagnostic accuracy of MRI combined with serum CYR61 and CXCL1 in the diagnosis of acute stroke is high, the combined diagnosis is obviously better than the individual diagnosis of each indicator.

Glycosylation modification is an important post-translational modification of proteins, which participates in regulating protein half-life, biological activity, and immunogenicity, thereby affecting their functions. Glycoproteins expressed in Pichia pastoris predominantly carry high-mannose type glycans, primarily composed of mannose residues, which starkly contrasts with the complex-type glycans synthesized by mammalian cells. This study aims to transform the high mannose glycosylation modification of P. pastoris into a hybrid glycosylation modification similar to that of mammalian cells through genetic engineering technology. We introduced the mannosidase Ⅰ gene (MDSⅠ) from Trichoderma viride and the human β-1,2-N-acetylglucosaminyltransferase I gene (GnTⅠ) into a previously constructed P. pastoris strain (∆och1) capable of producing Man₈GlcNAc₂ glycans. To precisely regulate the expression of MDSⅠ and GnTⅠ, we designed various promoter combinations, including the strong inducible AOX promoter and the constitutive GAP promoter. The receptor-binding domain (RBD, residues 377-588) of the spike protein from the Middle East respiratory syndrome coronavirus (MERS-CoV) was selected as the reporter protein for this investigation (MERS-RBD). The N-glycosylation profile of MERS-RBD was systematically analyzed using PNGase F digestion coupled with mass spectrometry. The results showed that after the knockout of och1 and the introduction of MDSⅠ and GnTⅠ genes with different promoter combinations, P. pastoris strains capable of producing GlcNAcMan₅GlcNAc₂ glycans were successfully generated. When the AOX promoter was used to control the MDSⅠ gene and the GAP promoter was used to control the GnTⅠ gene, the engineered strain exhibited the highest proportion of hybrid-type GlcNAcMan₅GlcNAc₂ glycans, which accounted for 68.38% of the total N-glycosylation. In conclusion, we successfully engineered a P. pastoris strain capable of synthesizing hybrid-type GlcNAcMan₅GlcNAc₂ glycans, establishing a foundation for subsequent research on the biosynthesis of complex-type N-glycans in P. pastoris.
Glycosylation ; Glycoproteins/genetics* ; Polysaccharides/metabolism* ; N-Acetylglucosaminyltransferases/metabolism* ; Pichia/metabolism* ; Humans ; Mannosidases/metabolism* ; Genetic Engineering ; Trichoderma/genetics* ; Recombinant Proteins/genetics* ; Saccharomycetales

Objective To investigate the expression of serum microRNA(miR)-340-5p,miR-155-5p and their relationship with Th1/Th2 cytokines in patients with chronic hepatitis B.Methods A total of 128 pa-tients with chronic hepatitis B in this hospital from October 2021 to October 2023 were selected as the study group,and 96 healthy subjects from the hospital during the same period were selected as the control group.The expression levels of serum miR-340-5p and miR-155-5p were detected by fluorescence quantitative PCR(qPCR),and the expression levels of serum Th1/Th2 cytokines were detected by enzyme-linked immunosor-bent assay(ELISA).The relationship between miR-340-5p,miR-155-5p and Th1/Th2 cytokines was analyzed by Pearson method,and the influence of serum miR-340-5p and miR-155-5p on the occurrence of chronic HPV infection was analyzed by Logistic regression.Results Compared with the reference group,the serum levels of miR-340-5p,miR-155-5p,IL-4,and IL-13 in the study group decreased(P＜0.05),while the levels of IFN-γand IL-12 increased(P＜0.05).Serum miR-340-5p was negatively correlated with IFN-γ and IL-12(r=-0.315,-0.293,both P＜0.05),and positively correlated with IL-4 and IL-13(r=0.413,0.412,both P＜0.05).Serum miR-155-5p was negatively correlated with IFN-γ and IL-12(r=-0.406,-0.375,both P＜0.05),and positively correlated with IL-4 and IL-13(r=0.343,0.407,both P＜0.05).Serum miR-340-5p(OR=0.735,95％CI:Increased expression levels of 0.590-0.915)and miR-155-5p(OR=0.612,95％CI:0.416-0.900)were protective factors for the occurrence of chronic hepatitis B.IFN-γ(OR=1.652,95％CI:1.170-2.333)and IL-12(OR=1.063,95％CI:1.012-1.116)were risk factors for chronic hepatitis B(P＜0.05).Conclusion Serum miR-340-5p and miR-155-5p are usually low expressed in chronic hepatitis B patients,and they are negatively correlated with Th1 cytokine level and positively correlated with Th2 cytokine level.

Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

This study aims to investigate the characteristics of chitosan-loaded miR-146a nanoparti-cles and explore their protective effect against acute liver cell injury induced by LPS in vitro.Galac-tosylated arginine chitosan(GCA)nanoparticles were successfully synthesized,prepared and used to further prepare GCA-miR-146a nanoparticles with different mass ratios by ion cross-linking method.The binding efficiency of miR-146a by GCA nanoparticles was detected by gel retardation experiment.Particle size,morphology and potential were observed and detected by transmission e-lectron microscopy and Zetasizer NanoZS90 respectively.The cytotoxicity of GCA nanoparticles on HepG2 cells was detected by CCK-8 kit.Cellular uptake was assayed by fluorescence microscopy to select the optimum ratio for the further study.The LPS induced acute liver cell injury were evalua-ted by real-time fluorescence quantitative PCR.The results showed that the mass ratio of GCA-miR-146a was 5∶1.Encapsulation efficiency and drug loading efficiency of the nanoparticles reached 97.11％and 20.08％,respectively.The 100 nm nanoparticles with 1.15 mV surface charge showed uniform morphology.The GCA-miR-146a nanoparticles had no cytotoxicity and had high transfection efficiency on HepG2 cells.The study demonstrated that GCA-miR-146 ananoparticles could significantly increase the expression of miR-146a in HepG2 cells and reduce the mRNA ex-pression levels of IL-6 and TNF-α in vitro.The prepared GCA nanoparticles loaded with miR-146a had high loading efficiency and could protect LPS-induced acute liver cell injury in vitro.

Purpose To analyze the expression of SNAP23 in esophageal squamous cell carcinoma(ESCC)and its influence on invasion of ESCC cells.Methods A total of 41 cases of ESCC and paired normal adjacent tissue(NAT)were collected.The expression and localization of SNAP23 were detected by immunohistochemical EnVision method.The differences of SNAP23 expression levels between ESCC tissues and NAT tissues were compared to analyze the relationship between SNAP23 expression and clinicopathological characteristics.The expression level of SNAP23 in human immortalized esophageal epithelial cells SHEE and ESCC cell lines TE-1,TE-13 and KYSE150 were detected by Western blot.Lentiviral vector transfection technique was used to construct stable transfection cell lines with knock-down and overexpression of SNAP23 gene.The effect of SNAP23 on invasion of ESCC cell line TE-13 was evaluated by cell invasion experiment.Results The expression of SNAP23 in ESCC was significantly higher(53.7％,22/41)than that in the NAT group(19.5％,8/41),the difference was statistically significant(x2=10.303,P＜0.01).The expression level of SNAP23 in ESCC tissues was significantly correlated with maximum tumor diameter(x2=4.193,P＜0.05)and invasion depth(x2=7.264,P＜0.05),but was not correlated with patient gender,age,tumor site,tumor type,pathologic grade,vascular embolus,nerve invasion and lymph node metastasis(P＞0.05).Compared with human immortalized esophageal epithelial cells SHEE,SNAP23 was highly expressed in ESCC cell lines(P＜0.000 1).Compared with the sh-NT group,the invasion of ESCC cell line TE-13 was inhibited when SNAP23 expression was knocked down(P＜0.000 1);compared with the Vector group,the invasion of ESCC cell line TE-13 was enhanced after overexpression of SNAP23(P＜0.000 1).Conclusion SNAP23 is highly expressed in ESCC tis-sue and cell lines,and its expression level in ESCC tissues is positively correlated with tumor maximum diameter and invasion depth;SNAP23 promotes the invasion of ESCC cells.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

OBJECTIVE: To investigate the transfusion and infusion warmer manufacturers, combine the use failures to analyze adverse events, and provide support for enterprise risk management and clinical safe use. METHODS: The sentinels from 7 manufacturing enterprises and 11 medical institutions that participated in Shandong Province's key monitoring program during the "14th Five-Year Plan" period were targeted. This was done by understanding the equipment's principles, structures, and quality control. Additionally, real-world data from January 2019 to December 2023 were collected to count adverse events. RESULTS: During production, there are risks in switching power supply stability and solder joint firmness. Fifteen kinds of faults occurred during use, and common faults such as inability to heat, unable to turn on the machine, and bubbles in the infusion tube accounted for more than 80%. CONCLUSION There are many risk points and failures for transfusion and infusion warmers, so enterprises should improve processes and quality control to address risks, and medical institutions should formulate specifications and maintenance plans to provide targeted theoretical basis for supervision.
Blood Transfusion/instrumentation* ; Risk Factors ; Quality Control ; Humans ; Risk Management ; Equipment Failure

Objective:To explore relevant factors to accurately diagnose BPPV in vertigo children. Methods:A retrospective study was conducted on the proportion of BPPV in children（<18 years） with vertigo who visited the Hearing and Vertigo Diagnosis and Treatment Center of Tianjin Medical University General Hospital from September 2017 to August 2023. The clinical characteristics of BPPV children, including general demographics, medical history, first visit department, comorbidities, canal involvement, response to treatment, and incidence of recurrence, were analyzed. Data analysis was conducted using SPSS 25.0 software. Results:BPPV was diagnosed in 22.8% of patients seen for vertigo during the study period. There are differences in the proportion of BPPV diagnosis among children with dizziness in different age groups（P<0.05）, and the diagnosis of BPPV in the 7-12-year-old group has a longer disease course than in the 13-17-year-old group（P<0.05）. 72.3%（47/65） of patients or their families were able to provide a typical history of positional vertigo. 49.2%（32/65） of BPPV patients had comorbidities, and there were differences in the proportion of comorbidities among different age groups of BPPV patients（P<0.05）. With the progress of study, the proportion of BPPV in children with vertigo has shown an upward trend, and the proportion of children with otolaryngology as the first diagnosis department has also increased（P<0.05）. The proportion of horizontal semicircular canals in children with BPPV has increased. All BPPV patients underwent canalith repositioning maneuvers, with good treatment outcomes and a recurrence rate of 12.3%（8/65）. The recurrence rate in the group of BPPV patients with comorbidities was 21.9%, which was higher than that in the group without comorbidities（P<0.05）. Conclusion:Childhood BPPV has clinical characteristics such as unclear medical history, high proportion of comorbidities, easy recurrence in BPPV children with comorbidities and high proportion of horizontal semicircular canal involvement. For children diagnosed with other vertigo diseases, do not ignore the BPPV diagnostic test. It is recommended to perform routine position tests on children with vertigo if conditions permit to reduce missed diagnosis of BPPV in children.
Humans ; Benign Paroxysmal Positional Vertigo/diagnosis* ; Child ; Retrospective Studies ; Adolescent ; Female ; Male ; Recurrence ; Vertigo/diagnosis* ; Comorbidity ; Child, Preschool