OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics （PK）/pharmacodynamics （PD） theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration （MIC） data of colistin sulfate against Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumoniae， Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC （fAUC0－24 h/MIC） ≥15 as the target value， the probabilities of target attainment （PTA） of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC； and the expected population PTA， specifically the cumulative fraction of response （CFR）， for each regimen within a specific bacterial population was further calculated， to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL， PTA of all colistin sulfate regimens （500 000 IU， q12 h； 500 000 IU， q8 h； 750 000 IU， q12 h； 750 000 IU， q8 h； 1 000 000 IU， q12 h） were all more than 90%. When bacterial MIC＝1 µg/mL， PTA for regimen （750 000 IU， q8 h） against A. baumannii， K. pneumoniae， P. aeruginosa， E. coli and E. cloacae， and for regimen （1 000 000 IU， q12 h） against the other four bacterial species （excluding P. aeruginosa） remained above 90%. When bacterial MIC≥2 µg/mL， PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli， the CFR of only colistin sulfate regimen （500 000 IU， q12 h） was less than 90%； for K. pneumoniae， the CFR of only colistin sulfate regimen （750 000 IU， q8 h and 1 000 000 IU， q12 h） was greater than 90%； for the other three bacteria， CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL， colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL， an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Objective:To explore the diagnostic value of serum cystatin C (CysC) and C1q tumor necrosis factor-related protein 9 (CTRP9) levels for diabetic retinopathy (DR) and diabetic macular edema (DME) in patients with type 2 diabetes.Methods:A cross-sectional study was conducted.A total of 135 patients with type 2 diabetes, aged 45-75 years, who were treated in Gansu Provincial Hospital from April 2021 to April 2022 were included.According to DR grading standard, patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group and proliferative DR (PDR) group, with 45 patients in each group.The DR patients were subdivided into DME group (51 cases) and non-DME group (39 cases).A total of 45 healthy subjects were selected as the normal control group.Fasting peripheral venous blood was collected to detect serum glycosylated hemoglobin, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, CysC and CTRP9 levels.The expression of CysC and CTRP9 levels among different groups were compared.The independent influencing factors of DR and DME were evaluated by multivariate logistic regression analysis model.The diagnostic value of serum CysC and CTRP9 in DR and DME were evaluated by receiver operating characteristic (ROC) curve.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Gansu Provincial Hospital (No.2021-301).All patients were informed about the purpose and methods of the study and signed an informed consent form.Results:Serum CysC levels in normal control group, NDR group, NPDR group and PDR group were 0.74(0.67, 0.83), 1.03(0.85, 1.22), 1.40(0.98, 1.63) and 1.66(1.31, 1.85)mg/L, respectively, showing a gradually increasing trend, and the serum CTRP9 levels were (136.90±14.95), (120.23±16.31), (109.50±14.71) and (90.99±13.88)pg/ml, respectively, showing a gradually decreasing trend, with statistically significant overall comparison differences among groups ( Z=89.430, P<0.001; F=74.242, P<0.001), the comparison within groups was statistically significant (all at P<0.05).Compared with non-DME group, the serum CysC level was significantly increased and serum CTRP9 level was significantly decreased in DME group (both P<0.05).Multivariate logistic regression analysis showed that serum CysC (odds ratio [ OR]=19.742, 95% confidence interval [ CI]: 4.515-86.316, P<0.001) was the independent risk influencing factors for the occurrence of DR, and CTRP9 ( OR=0.937, 95% CI: 0.908-0.966, P<0.001) was a protective factor for the occurrence of DR.Serum CTRP9 level ( OR=0.838, 95% CI: 0.778-0.903, P<0.001) was a protective factor for DME.The ROC curve showed that the area under ROC curve (AUC) for serum CysC and CTRP9 levels alone and in combination for the diagnosis of DR in patients with type 2 diabetes mellitus complicated by DR were 0.798, 0.802 and 0.870, respectively.The cutoff values of serum CysC and CTRP9 levels to obtain the best diagnostic efficacy were 1.34 mg/L and 110.12 pg/ml, respectively.The AUC for serum CysC and CTRP9 level alone and in combination for the diagnosis of DME in DR patients were 0.682, 0.923 and 0.923, respectively.The cutoff value of serum CTRP9 level to obtain optimal diagnostic efficacy was 104.68 pg/ml. Conclusions:The enhanced expression of serum CysC level and reduced expression of serum CTRP9 level are the risk factors for the development of DR in type 2 diabetes patients.The decrease of serum CTRP9 level is one of the risk factors for the development of DME in DR patients.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

OBJECTIVE To investigate the protective effect proanthocyanidin B2(PC-B2) on oxidative damage and apoptosis of mouse astrocytes(AS) induced by hydrogen peroxide(H2O2) and its mechanism. METHODS AS were isolated and cultured from neonatal C57BL/6 mice(1−3 d). The optimal concentration of H2O2 and PC-B2 was divided into four groups: normal group, normal+PC-B2 group(100 μg·mL‒1 PC-B2 treated for 24 h), H2O2 model group(200 μmol·L‒1 H2O2 treated for 24 h), PC-B2 group(200 μmol·L‒1 H2O2 and 100 μg·mL‒1 PC-B2 treated for 24 h). The cell viability of each group was detected by CCK-8 method. Cytotoxicity was detected by LDH method. The antioxidant capacity was detected by ABTS and DPPH. The content of MDA and the activity of SOD, CAT and GSH-Px were detected by ELISA kit. Detection of apoptosis in each group was done by TUNEL staining. The mRNA and protein expression levels of Bax, Bcl-2, Caspase-3, Akt/Stat3, p-Akt, p-Stat3 and Nrf2/HO-1 in AS were detected by RT-PCR and Western blotting, respectively. RESULTS PC-B2 could significantly enhance cell viability and inhibit AS apoptosis. Compared with the H2O2 model group, PC-B2 intervention could significantly reduce the content of LDH and MDA in AS, and increase the activity of SOD, CAT and GSH-Px. PC-B2 intervention could inhibit the mRNA and protein expression of Bax and Caspase-3, and up-regulate the mRNA and protein expression of Akt/Stat3, Bcl-2, Nrf2/HO-1. CONCLUSION PC-B2 can enhance the antioxidant capacity of AS through Akt/Stat3 and Nrf2/HO-1 pathways, therefore reduce H2O2-induced AS oxidative damage and apoptosis.

Objective To detect the serum levels of CC chemokine receptor 2(CCR2)and C-reactive pro-tein(CRP)in stroke patients,and analyze their relationship with the severity of stroke associated pneumonia and their clinical significance.Methods A total of 78 patients with stroke associated pneumonia who were di-agnosed and treated in the hospital from October 2022 to February 2023 were collected as the study group,ac-cording to the severity of pneumonia,the study group was divided into mild group(31 cases),moderate group(29 cases),and severe group(18 cases),78 stroke patients who did not develop pneumonia were included into control group.Pearson method was applied to analyze the correlation between serum CCR2 and CRP levels in stroke associated pneumonia patients.Multivariate Logistic regression was applied to analyze the factors influ-encing the occurrence of stroke associated pneumonia.Receiver operating characteristic(ROC)curve was ap-plied to analyze the diagnostic value of serum CCR2 and CRP for stroke associated pneumonia.Results The National Institute of Health stroke scale(NIHSS)score,serum CCR2,and CRP levels in the study group were obviously higher than those in the control group(P<0.05).The levels of serum CCR2 and CRP increased with the aggravation of pneumonia(P<0.05).The levels of serum CCR2 and CRP in the study group were positively correlated(r=0.799,P<0.05).NIHSS score,CCR2,and CRP levels were risk factors for stroke associated pneumonia in stroke patients(P<0.05).The area under the curve(AUC)for the diagnosis of stroke associated pneumonia using serum CCR2 and CRP alone was 0.873 and 0.888,respectively,and the AUC for the combined detection of the two was 0.936,the combined detection of the two was superior to the individual detection of serum CCR2 and CRP(Zcombination-CCR2=1.987,Zcombination-CRP=1.832,P=0.041,0.047).Conclusion Serum CCR2 and CRP are closely related to the severity of stroke associated pneumonia,and their combined detection has high diagnostic value for stroke associated pneumonia.

Medical social work, as a bridge between social welfare policies and healthcare services, is an important force in meeting the diverse and multi-level needs of the people in medical and health care. Due to the particularity of the pediatric population, pediatric medical social work is becoming one of the key areas in the development of medical social work. Beijing Children′s Hospital, Capital Medical University has established a service mode of " collaborative medical and social worker team". The medical social workers acted as supporters to assist healthcare professionals to meet the psychological and social service needs of patients and their families as much as possible, and empowered medical staff′s career development as supporters. At the same time, the medical social workers assisted in the construction of a " child friendly" medical environment, and built a social support network for patients and families. The appropriateness and future prospects of pediatric medical social work were explored, in order to provide reference for its development.

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,with a global prevalence of approximately 30.05% to 32.4% .It is closely associated with various other diseases.In recent years,microRNAs(miRNAs)have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD.miRNAs play significant roles in both lipid metabolism and insulin resistance,exerting specific regulatory functions in the development and progression of NAFLD.miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes.This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism,insulin resistance,and the occurrence and development of NAFLD.