ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

BACKGROUND:Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis,and Hemin can regulate the expression of mitochondria-related proteins. OBJECTIVE:To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS:(1)In vitro cell experiment:Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis.The optimal concentration of Hemin(0,1,10,20,40,80,and 160 μmol/L)for the intervention in mouse chondrocytes was determined by cell counting kit-8 method.Chondrocytes were randomly divided into control group,model group(interleukin-1β)and Hemin group(interleukin-1β+Hemin).Reactive oxygen species,mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected.(2)In vivo experiment:Adult C57BL/6 mice were randomly divided into normal group,model group(osteoarthritis)and Hemin group(osteoarthritis+Hemin),with eight mice in each group.After 4 weeks of Hemin treatment,the behavioral test and histopathological observation of the knee joint were performed in each group.Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION:In vitro experiment:the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L.Compared with the model group,the level of reactive oxygen species was significantly reduced,the mitochondrial membrane potential was significantly improved,and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes.In vivo experiment:After 4 weeks of treatment,compared with the model group,the lower limb function of mice in the Hemin group was significantly improved,the histopathological score was significantly improved,and the apoptosis of knee chondrocytes was significantly reduced.All these findings indicate that Hemin can alleviate oxidative stress,restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β.Hemin can improve extracellular matrix degradation,promote chondrocyte anabolism,reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis.It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment.

AIM: To investigate the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters in patients with hypertensive retinopathy(HRP).METHODS: A total of 50 patients(22 left eyes and 28 right eyes)with HRP admitted to our hospital from June 2021 to June 2023 were retrospectively included as the experimental group, and 50 healthy physical examination subjects(22 left eyes and 28 right eyes)during the same period were included as the healthy group. Pearson correlation was used to analyze the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters.RESULTS: The AUC values of fundus blood flow parameters and carotid artery ultrasound blood flow parameters and their combined diagnosis of HRP were 0.853, 0.844 and 0.935, respectively. Pearson correlation analysis showed that carotid systolic peak blood flow velocity was negatively correlated with foveal avascular zone(FAZ)area, FAZ circumference and non-circularity index, and positively correlated with macular vascular density(all P<0.05). The end-diastolic blood flow velocity was positively correlated with FAZ area and macular vascular density(all P<0.05). The internal carotid artery resistance index was positively correlated with FAZ area(P<0.05).CONCLUSION: The combination of fundus blood flow parameters and carotid artery ultrasound blood flow parameters in the diagnosis of HRP has good application value in the diagnosis of HRP.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To investigate the clinical efficacy of Qingpeng Ointment(composed of Aconiti Penduli Radix,,Benzoinum,Artificial Moschus,Oxytropis Falcatae Herba,Rhei Pumili Radix Et Rhizoma,Fructus Phyllanthi,etc.)combined with Secukinumab Injection in treating patients with plaque psoriasis of blood stasis syndrome type.Methods From October 2022 to March 2024,a total of 86 patients diagnosed as plaque psoriasis of blood stasis syndrome type from the Department of Dermatology,Chuzhou First People's Hospital Affiliated to Anhui Medical University were enrolled.The patients were equally randomized into an observation group and a control group using a simplified randomization method,with 43 cases in each group.The control group received subcutaneous injection of Secukinumab Injection,while the observation group received additional topical application of Qingpeng Ointment based on the regimen for the control group.Both groups were treated for 3 months.The following parameters in both groups were assessed before and after treatment:the severity scores of skin lesion(including erythema,infiltration,and scale),traditional Chinese medicine(TCM)syndrome scores,quality of life scores,serum levels of inflammatory factors[interleukin 17A(IL-17A),interleukin 10(IL-10),vascular endothelial growth factor(VEGF)],and leukocyte p38 mitogen-activated protein kinase(MAPK)expression levels(including staining intensity scores and positive cell percentage scores).After treatment,the clinical efficacy and total incidence of adverse reactions were compared between the two groups.Results(1)After 3 months of treatment,the markedly-effective rate was 81.40%(35/43)in the observation group versus 58.14%(25/43)in the control group.The intergroup comparison showed significantly superior clinical efficacy in the observation group(χ2=8.378,P＜0.05).(2)After treatment,both groups exhibited significant reductions in the severity scores of skin lesion(including erythema,infiltration,and scale),TCM syndrome scores,quality of life scores,serum levels of inflammatory factors(IL-17A,IL-10,and VEGF),and expression levels of p38 MAPK in leukocytes(including staining intensity scores and positive cell percentage scores)(all P＜0.05),and the observation group demonstrated significantly greater reductions in all parameters than the control group(P＜0.05).(3)The total incidence of adverse reactions was 6.98%(3/43)in the observation group versus 13.95%(6/43)in the control group,showing no statistically significant intergroup difference(χ2=1.117,P＞0.05),and all adverse reactions in both groups resolved spontaneously within 1-2 day(s)after treatment.Conclusion Qingpeng Ointment combined with Secukinumab Injection demonstrates significant clinical efficacy in treating plaque psoriasis with blood stasis syndrome,and is effective on alleviating skin lesions and exerting anti-inflammatory effects through the suppression of leukocyte p38 MAPK expression.

Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.

Objective:To acquire the implementation effect of the neonatal Phenylketonuria(PKU)Screening Project in Dong-guan,and evaluate its economic effectiveness,so as to provide references for the prevention and control policies of genetic defects in newborns.Methods:Choosing PKU children born in Dongguan from January 2012 to December 2021(excluding BH4 deficien-cy)as the subjects,conduct the cost-benefit and cost-effectiveness analysis on the prevention and treatment of PKU.The relevant data was gained from questionnaire surveys,statistical data,medical service prices of non-profit medical institutions in Dongguan,and relevant literature materials.Results:In the past 10 years,1 245 243 newboms were screened for PKU in Dongguan,the average screening rate is 93.32％.Among them,29 were diagnosed with PKU,with a positive rate of 1:42939.During continuous follow-up,23 cases were diagnosed.Among the 23 follow-up cases,only 1 had intelligence at the critical value,while the rest were normal.The total cost of screening is 29.728 7 million,and the total benefit is 14.239 9 million.The cost-effectiveness ratio is 102.51:1,the cost-benefit ratio is 1:4.79.Conclusion:Neonatal phenylketonuria(PKU)screening in Dongguan has significant social and economic benefits.It's necessary to continue and improve the screening work,especially the policy which can benefit the PKU's full life.

By analyzing the design principles and treatment modes of Gambro Prismaflex CRRT device,based on the basic structure and treatment process,and the typical failure cases of pressure joints and scale zeroing test failures in continuous renal replacement therapy(CRRT)equipment were analyzed,the targeted solution and maintenance strategies were proposed to ensure the stable and efficient operation of CRRT equipment.

Objective To explore the clinical characteristics and risk factors of death during hospitalization in patients with community-acquired pneumonia(CAP)complicated with diabetes mellitus(DM).Methods A retrospective analysis was performed on 566 patients with CAP hospitalized in the Second Affiliated Hospital of Kunming Medical University from January 2018 to January 2022.The patients were divided into simple CAP group(n=478)and CAP combined with diabetes(CAP+DM)group(n=88)according to whether they had diabetes,and then CAP+DM group(n=88)was divided into survival group(n=69)and death group(n =19)according to whether the patients died during hospitalization.The clinical data and laboratory test indicators of patients in different groups were compared.Cox regression analysis was used to screen the risk factors of death during hospitalization in the CAP+DM group.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of independent risk factors on hospitalization death.Results Compared with the simple CAP group,the CAP+DM group had significant differences in age,concomitant hypertension,coronary heart disease,CURB-65 score,neutrophil to lymphocyte ratio(NLR),C-reactive protein(CRP),procalcitonin(PCT),albumin(ALB),prealbumin(PA),glucose(GLU),serum potassium(K),calcium(Ca),phosphorus(P),magnesium(Mg),lactic acid(Lac),non-invasive ventilation time,ICU occupancy rate and mortality rate(P<0.05);Compared with the survival group,there were statistically significant differences in CURB-65 score,NLR,CRP,PCT,GIU,ALB,PA,serum iron(Fe),Ca,non-invasive ventilation time,and ICU admission rate among the death group patients(P<0.05).Cox regression analysis showed that the increase of NLR level and the decrease in PA level were the risk factors for in-hospital death in patients with CAP complicated with diabetes(P<0.05).When the PA cutoff value was 91 mg/L,the AUC,sensitivity,and specificity for predicting in-hospital death of CAP patients with diabetes were 0.849,84.2%and 81.2%,respectively.Conclusion Patients with CAP combined with diabetes are more serious and have worse prognosis than those with CAP alone.PA has a good predictive value for the prognosis of these patients.Early detection and active intervention should be carried out to reduce the in-hospital mortality of patients.

Objective:To explore the mechanism by which miRNA-4469 (miR-4469) regulates the proliferation and invasion of renal cancer cells in vitro.Methods:The survival differences of patients with different expression levels of miR-4469 were analyzed based on the OncomiR database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the expression of miR-4469 in renal cancer cell lines ACHN, OS-RC-2, SK-RC-20, 769-P, A498 and normal renal tubular epithelial cell line HK-2, and the renal cancer cells with the lowest expression level of miR-4469 were divided into miR-4469 group and control group, and were transfected with miR-4469 mimic and negative control sequence, respectively. The CCK-8 assay was used to detect the cell proliferation ability (expressed as absorbance value) in the two groups, and Transwell assay was used to analyze the number of invasive cells in the two groups. TargetScan Release 8.0 software was used to predict the binding site between miR-4469 and protein disulfide isomerase A4 (PDIA4) mRNA, and dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-4469 and PDIA4 mRNA. qRT-PCR method was used to detect the expression of PDIA4 mRNA in cells of each group, and Western blotting method was used to detect the expression levels of PDIA4 protein and PI3K-AKT-m-TOR pathway proteins in cells of each group.Results:Analysis of relevant data from the OncomiR database showed that compared with patients with low miR-4469 expression, the overall survival of renal cancer patients with high miR-4469 expression was better ( P < 0.001). The relative expression of miR-4469 in each renal cancer cell line was lower than that in HK-2 cells (all P < 0.05), and the expression of miR-4469 in 769-P cells was the lowest, which were selected to perform the subsequent experiments. The proliferation ability of 769-P cells in the miR-4469 group was lower than that in the control group ( P < 0.01). The number of 769-P cell invasions in the miR-4469 group were less than that in the control group [(19±3) cells vs. (64±7) cells, t = 5.44, P = 0.002]. Compared with the co-transfection of wild-type PDIA4 and miR-4469 negative sequence group, the relative luciferase activity of cells in the co-transfection of wild-type PDIA4 and miR-4469 mimic sequence group was lower (0.42±0.07 vs. 1.01±0.08, t = 5.74, P = 0.001); there was no statistical difference in cell luciferase activity between the co-transfected mutant PDIA4 and miR-4469 negative sequence group and the co-transfected mutant PDIA4 and miR-4469 mimic sequence group (0.99±0.11 vs. 1.02±0.11, t = 0.19, P = 0.001). The relative expression levels of PDIA4 mRNA in 769-P cells in the miR-4469 group were lower than that in the control group (0.98±0.23 vs. 7.19±2.23, t = 2.77, P = 0.032). Compared with the control group, the expression of PDIA4 protein and PI3K-AKT-m-TOR pathway-related p-PI3K, p-AKT, p-mTOR, and p-SGK1 proteins in 769-P cells in the miR-4469 group were all lower (all P < 0.05). Conclusions:miR-4469 may be related to the survival of renal cancer patients, and its expression is down-regulated in various renal cancer cell lines. miR-4469 may inhibit the proliferation and invasion of renal cancer 769-P cells by regulating the PI3K-AKT-m-TOR pathway through PDIA4.