Objective To determine whether four-and-a-half LIM-only protein 2(FHL2)can affect macrophage foa-ming by regulating nuclear factor kappa-B(NF-κB)signaling pathway.Methods FHL2 over-expression plasmids and siRNA of FHL2 were constructed and transfected into human monocyte/macrophages cell line THP-1.Western blot was used to detect the expression of FHL2.The cells were stimulated with oxidized low density lipoprotein(ox-LDL)and the expression of IL-6,IL-1β,TNF-α and other cytokines were detected by ELISA.Oil red O staining was used to detect the degree of cell foaming.The protein expression of NF-κB signaling pathway was detected by Western blot.Results The expression of FHL2 increased after transfected with FHL2 over-expression plasmids while decreased in si-FLH2 transfected cells.FHL2 down-regulated secretion of inflammatory cytokines.Down-regulation of FHL2 allevi-ated THP-1 macrophage foaming.The down-regulation of FHL2 inhibited activation of NF-κB signaling pathway,while the over-expression FHL2 showed an opposite trend.Conclusions FHL2 down-regulation inhibits the activation of NF-κB signaling pathway,reduces the secretion of inflammatory cytokines and alleviates foaming of macrophages.

Objective To investigate the correlation between serum interleukin-2 receptor(IL-2R),CD4+/CD8+ and disease activity in patients with lupus nephritis(LN).Methods A total of 38 patients with LN who were treated in Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from March 2021 to December 2022 were enrolled in LN group,and 40 healthy persons who underwent physical examination in the hospital during the same period were included in healthy control group.General clinical data,systemic lupus erythematosus disease activity index(SLEDAI)and pathological classification were collected.LN patients were divided into active group and inactive group according to SLEDAI score,and the difference of clinical indicators between two groups was compared.Results The hemoglobin(Hb),platelet count,albumin(ALB),complement C3 and C4 in LN group were significantly lower than those in healthy control group,the positive rates of antinuclear antibody and anti-double strand DNA antibody(anti-ds-DNA antibody),serum creatinine(SCr)and C-reactive protein were significantly higher than those in healthy control group(P<0.05).The ALB of active group was significantly lower than that of inactive group,and IL-2R,erythrocyte sedimentation rate,24h urinary protein quantity and anti-ds-DNA antibody positive rate were significantly higher than those of inactive group(P<0.05).Serum IL-2R levels in LN patients were positively correlated with SLEDAI,SCr,blood urea nitrogen and 24h urinary protein quantity,and negatively correlated with Hb and complement C3(P<0.05).Conclusion Serum IL-2R can be used as an indicator to judge the degree of LN activity and provide a basis for the judgment of clinical disease activity.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95％CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95％CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P＜0.1).Multivariate analysis showed that the risk of death in patients with onset age＞65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0％CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0％CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P＜0.001,95.0％CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.

Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.

Objective To evaluate the acceptability and effectiveness of different doses of midazolam oral solution in sedating infants during echocardiographic studies.Methods Two hundred and fourty patients aged 1 to 3 years who underwent echocardiographic study in sedation in our hospital were enrolled in this study.After recording the baseline data of all infants,they were randomly divided into four groups:0.3 mg·kg-1 midazolam oral solution group(M1 group),0.5 mg·kg-1 midazolam oral solution group(M2 group),0.7 mg·kg-1 midazolam oral solution group(M3 group)and 0.5 mL·kg-1 10%chloral hydrate administrated rectally group(C group),60 case per group,and the sedation was performed in the corresponding method of each group.The 5-point facial hedonic and Ramsay scales were used to evaluate acceptability and effectiveness in sedation.The onset time and duration time of sedation were recorded.Results Compared with the C group,the 5-point facial hedonic scale scores in M1,M2,and M3 groups increased during sedation(F=17.50,P<0.017).The onset time of sedation in the M1 and M2 groups was longer than that in the C group(P<0.017),and the duration time of sedation in the M1 and M2 groups was shorter than that in the C group(P<0.017).There was no significant difference in the onset time(P=0.85)and duration time(P=0.50)of sedation between the M3 and C groups.The onset time of sedation in the M1and M2groups was longer than that in the M3 group(P<0.017),and the duration time of sedation in the M1 and M2 groups were shorter than that in the M3 group(P<0.017).Conclusions The acceptability of infants with midazolam oral solution sedation under echocardiographic study was better than that of 10%chloral hydrate administrated rectally.There were fewer adverse reactions with the midazolam oral solution.The 0.7 mg·kg-1 midazolam oral solution had a rapid onset of sedation and definite effect.

Objective:To explore the effect of progressive case teaching based on Omaha system in standardized training for new nurses.Methods:Using convenience sampling method, 58 new nurses from Yantai Affiliated Hospital of Binzhou Medical University from January to December 2021 were selected as control group, and 58 new nurses from January to December 2022 were selected as experimental group. Experimental group received progressive case teaching based on Omaha system, while control group received routine standardized training. Both groups received training for six months. After six months of training, the academic performance, clinical thinking ability, and satisfaction of the two groups were compared.Results:After intervention, experimental group scored higher in various dimensions of academic performance and clinical thinking ability, as well as satisfaction scores with the teacher, teaching methods, and teaching effectiveness, compared to the control group, with statistical differences ( P<0.05) . Conclusions:The progressive case teaching based on Omaha system in standardized training for new nurses can improve academic performance, enhance clinical thinking abilities, and gain recognition from new nurses.

Objective:To explore the application effect of multidisciplinary integrated fracture liaison services in preventing postoperative refracture after osteoporotic vertebral compression fractures (OVCF) .Methods:Using the convenient sampling method, a total of 230 OVCF patients who were admitted to Orthopedics Department of Beijing Friendship Hospital Affiliated to Capital Medical University from March 2022 to August 2023 were selected and they were randomly divided into the control group and the observation group by the random number table method, with 115 patients in each group. The control group received routine follow-up management after surgery, while the observation group received multidisciplinary integrated fracture liaison services on the basis of the control group, with an intervention period of 1 year for both groups. Before and after intervention, Osteoporosis Knowledge Tests (OKT), Oswestry disability index (ODI), and lumbar quantitative computed tomography (QCT) were used to evaluate the osteoporosis knowledge level, lumbar spine function and bone density of the two groups. After a one-year follow-up, the incidence of recurrent fractures was compared between the two groups.Results:A total of 7 cases fell off during the intervention period, and 110 cases were collected in the control group and 113 cases in the observation group. After intervention, the total score of OKT and the scores of all dimensions in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05). After intervention, the ODI score of the observation group was lower than that of the control group, and the bone density value was higher than that of the control group, and the differences were statistically significant ( P<0.05). The incidence of recurrent fractures in the control group and observation group was respectively 20.91% (23/110) and 7.96% (9/113), and the difference was statistically significant ( P<0.05) . Conclusions:Multidisciplinary integrated fracture liaison services can effectively improve the knowledge level and bone density of postoperative patients with OVCF, improve lower back function and reduce the occurrence of recurrent fractures.

Objective:To explore the value of conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI) sequence and pathological examination in predicting the efficacy of neoadjuvant chemotherapy (NAC) in advanced breast cancer.Methods:The clinical data of 65 cases of advanced breast cancer with NAC confirmed by pathology in the Affiliated Hospital of Jining Medical University from March 2022 to May 2023 were retrospectively analyzed, including 20 cases in the pathological complete remission (pCR) group and 45 cases in the non pCR group; All patients underwent routine MRI, DWI, DKI examinations and pathological analysis. The clinical pathological data, routine MRI features, apparent diffusion coefficient (ADC) values, mean kurtosis coefficient (MK), and mean diffusion coefficient (MD) between the two groups were analyzed; We compared the differences in various parameters between two groups and plotted receiver operating characteristic (ROC) curves to compare their diagnostic efficacy of NAC in breast cancer.Results:There were significant differences in molecular typing, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and Ki-67 between pCR group and non pCR group (all P<0.05). In pCR group, Her-2 overexpression type and triple negative breast cancer (TNBC) type breast cancer were more common. ER and PR were mostly negative, Her-2 was mostly positive, and Ki 67 was mainly positive. The difference in tumor T2WI signal between the pCR group and the non pCR group was statistically significant ( P<0.05), with the pCR group showing mostly moderate/low T2WI signal. The ADC and MD values of the pCR group were lower than those of the non pCR group, while the MK value of the pCR group was higher than that of the non pCR group, and the differences were statistically significant (all P<0.001). The area under the ROC curve (AUC) for predicting the efficacy of NAC using a clinical pathological model was 0.829, which was higher than the AUC of molecular subtypes, ER, PR, Her-2, and Ki-67 ( Z=3.008, 2.697, 2.815, 2.131, 2.376, all P<0.05); The AUC of the DKI+ DWI predicting the efficacy of NAC was 0.934, which was higher than that of the DWI single sequence model, and the difference in type was statistically significant ( Z=2.396, P=0.017). The diagnostic efficacy of the DKI+ DWI model was higher than that of the single parameter ADC, MD, and MK, and the differences were statistically significant ( Z=2.396, 2.219, 2.161, all P<0.05); The AUC of the combined imaging and pathology model was 0.983, and its diagnostic efficacy was higher than that of the conventional MRI feature model, pathology model, DWI model, and DKI model, with statistically significant differences ( Z=5.877, 2.961, 3.240, 2.264, all P<0.05). Conclusions:The results of pathology, conventional MRI, DWI and DKI parameters of pCR and non pCR breast cancer patients are significantly different, and the combined model is better than the single model in predicting the efficacy of NAC.