Emergence agitation （EA） is a common complication after general anesthesia， especially in children and adolescents. Remifentanil， as a short-acting μ-receptor agonist， has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network， including regulation of microglial inflammatory pathways， and the modulation of cytokines and chemokines，etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time， reduce the incidence of EA， and further optimize the analgesic effect and recovery quality by combining with other drugs （such as local anesthetics， sedatives， and opioid drugs）. Future research should further explore the mechanism of action of remifentanil， optimize clinical treatment strategies， and conduct large- scale clinical trials to standardize the drug use plan， while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Objective: To examine the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression among healthcare workers, so as to provide the reference for developing effective psychological intervention. Methods: The clinical doctors, nurses and public health professionals were selected using the stratified random cluster sampling method from hospitals, disease prevention and control centers, and health departments in five cities in Shandong Province, including Qingdao, Jinan, Rizhao, Jining and Liaocheng in January 2023. Basic information, mindfulness level, resilience and symptoms of anxiety and depression among healthcare workers were collected using general demographic questionnaires, the 5-item Mindful Attention Awareness Scale, 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder Scale and Patient Health Questionnaire, respectively. The Process program was used to analyze the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression. Results: A total of 1 836 healthcare workers were investigated, including 472 males (25.71%) and 1 364 females (74.29%), and the median age was 39 (interquartile range, 12) years. There were 629 clinical doctors (34.26%), 963 nurses (52.45%) and 244 public health professionals (13.29%). The median scores of mindfulness level and resilience were 22 (interquartile range, 7) and 20 (interquartile range, 4) points, respectively. The detection rates of anxiety and depression symptoms were 49.78% and 72.28%, respectively. The mediation analysis showed that mindfulness level exerted a partial mediating effect between resilience and anxiety symptoms (β=-0.510, P<0.001), with a direct effect value of -0.130 and a mediating effect value of -0.046, and the mediating effect accounted for 26.14% of the total effect; mindfulness level also exerted a partial mediating effect between resilience and depression symptoms (β=-0.575, P<0.001), with a direct effect value of -0.120 and a mediating effect value of -0.052, and the mediating effect accounted for 30.23% of the total effect. Conclusion Mindfulness level plays a mediating effect between resilience and symptoms of anxiety and depression among healthcare workers.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Objective:To compare the efficacy and safety of azacitidine combined with venetoclax or CAG regimen in the treatment of newly treated elderly patients with acute myeloid leukemia (AML).Methods:A retrospective cohort study was conducted. The clinical data of 34 newly treated elderly patients with AML treated in the Fifth People's Hospital of Datong from May 2018 to August 2023 were retrospectively analyzed. According to the treatment regimen, all patients were divided into venetoclax group (azacitidine + venetoclax, 17 cases) and CAG group (azacitidine + CAG regimen, 17 cases). The clinicopathological characteristics, efficacy, adverse reactions and survival of the both groups were compared.Results:There were no statistically significant differences in the clinical data of both groups (all P > 0.05). The complete remission (CR) rate and the objective response rate (ORR) in venetoclax group were higher than those in CAG group [CR: 70.6%(12/17) vs. 47.1% (8/17); ORR: 82.4% (14/17) vs. 64.7% (11/17)],while the differences in CR and ORR were not statistically significant (χ 2 = 2.00, P = 0.163; χ 2 = 2.00, P = 0.244). The follow-up time[ M ( Q1, Q3)] was 25.4 months (7.2 months, 60.3 months). At the end of follow-up, 19 of 34 patients survived (13 cases in venetoclax group and 6 cases in CAG group); 15 died (4 cases in venetoclax group and 11 cases in CAG group). The median overall survival (OS) time was 14.22 months (95% CI: 8.2-60.3 months) and 10.56 months (95% CI: 7.2-50.2 months), respectively in venetoclax group and CAG group;the median progression-free survival (PFS) time was 9.97 months (95% CI: 5.4-40.5 months) and 6.82 months (95% CI: 5.0-36.2 months), respectively, and there were no statistically significant differences in OS and PFS between the two groups (all P > 0.05). Grade 3-4 hematological adverse reactions occurred in 16 and 14 patients in venetoclax group and CAG group, respectively. There were no significant differences in granulocyte deficiency time, platelet deficiency time, infection and bleeding incidence between the two groups (all P > 0.05). Conclusions:Azacitidine combined with venetoclax or CAG regimen have better clinical efficacy and safety for newly treated elderly patients with AML.

Objective:Investigate the prognostic value of high density lipoprotein (HDL) level in patients with streptococcal bloodstream infection.Methods:A total of 698 patients with streptococcal bloodstream infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019 were enrolled. Serum lipid and other clinical data of patients with positive blood culture within 48 h were recorded. The patients were followed up by telephone from January to March in 2020, and the end-point events were recorded, which were all-cause death 60 days after the diagnosis of streptococcal bloodstream infection. The patients were divided into two groups according to the levels of HDL: low HDL group (HDL ≤0.84 mmol/L) and high HDL group (HDL > 0.84 mmol/L). Univariate and multivariate Cox regression analysis were used to analyze the 60-day prognostic factors of patients with streptococcus bloodstream infection. The receiver operating characteristic (ROC) curve was used to explore predictive value of HDL level for 60-day prognosis of patients. Kaplan-Meier survival curve was used to compare the cumulative survival of patients with different HDL levels.Results:(1) A total of 491 patients were enrolled according to the inclusion criteria, and 461 patients were followed up successfully, with a follow-up rate of 93.89%. There were 373 survival patients and 88 death patients at 60 days, with a 60-day mortality rate of 19.09% (88/461). (2) There were significant differences in age, total cholesterol (TC), HDL, low density lipoprotein (LDL), platelets, albumin, fibrinogen, triglyceride (TG), creatinine, alanine aminotransferase, aspartate aminotransferase, white blood cell, PCT, total bilirubin, direct bilirubin, and respiratory failure and shock between the survival group and death group. (3) Multivariate Cox regression analysis showed that HDL ( RR=1.922, 95% CI: 1.186-3.117, P=0.008), aspartate aminotransferase ( RR=1.953, 95% CI: 1.233-3.094, P=0.004), shock ( RR=15.196, 95% CI: 6.953-33.211, P< 0.001), and respiratory failure ( RR=9.509, 95% CI: 4.232-21.367, P < 0.001) were independent risk factors for 60-day mortality of patients with streptococcal bloodstream infection. (4) The ROC curve analysis showed that HDL alone had a certain value in predicting the 60-day prognosis of patients with streptococcal bloodstream infection. The area under ROC curve (AUC) was 0.602, and the AUC of the combined predictive value of HDL, aspartate aminotransferase, shock and respiratory failure was 0.960, with a sensitivity of 92% and a specificity of 92%. (5) Kaplan-Meier survival curve analysis showed that the cumulative survival rate of patients without endpoint event in the HDL > 0.84 mmol/L group was higher than that in the HDL ≤ 0.84 mmol/L group, but without statistically significant difference (Log-Rank test: χ20.843, P<0.358). Conclusions:Patients with low HDL level of streptococcal bloodstream infection have an increased risk of 60-day death. HDL is an independent risk factor for 60-day death in patients with streptococcal bloodstream infection, and can be used as an indicator to evaluate the prognosis of patients with streptococcal bloodstream infection.

BACKGROUND/OBJECTIVES: Hyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear.We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats.MATERIALS/METHODS: A rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzymelinked immunosorbent assays were performed to evaluate the immune and oxidative responses. RESULTS: The expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group.The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment. CONCLUSIONS Resveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.

A fluorescent microsphere-based immunochromatographic strip test (FICT) was developed for the rapid, sensitive, and quantitative detection of porcine reproductive and respiratory syndrome virus (PRRSV) antibodies at the pen-side. The assay was based on the formation of a sandwich immune-complex (anti-pig IgG-PRRSV antibodies-NSP7/N), which was validated by a comparison with IDEXX-ELISA using 3325 clinical specimens. The diagnostic specificity, sensitivity, and accuracy of FICT were 97.28, 93.41, and 94.95%, respectively. FICT showed a good correlation with the virus neutralization assay. Overall, a promising pen-side diagnostic tool was developed for the rapid and quantitative detection of PRRSV antibodies within 15 min.

Objective:To systematically evaluate the clinical effects of microskin grafting and Meek microskin grafting in repairing extensively deep burn wounds using meta-analysis.Methods:Foreign language databases including PubMed and Cochrane Library were searched with the terms of " Meek micrografting, burn" , and Chinese databases including Chinese Journal Full- Text Database, Chinese Biomedical Database, VIP database, and Wanfang Data were searched with the terms in Chinese version of "微粒皮, Meek植皮,烧伤" to retrieve the publicly published randomized controlled trials on the microskin grafting and Meek microskin grafting in repairing extensively deep burn wounds from the establishment of each database to March 20, 2019. The outcome indexes included the survival rate of skin graft, primary healing rate, operation time, and surgical treatment cost after the first operation, as well as the wound healing time and length of hospital stay. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results:A total of 821 patients with extensively deep burns were included in 15 studies, including 410 patients in microskin group who received microskin grafting and 411 patients in Meek microskin group who received Meek microskin grafting. The bias risks of the 15 studies included were uncertain. Compared with those of microskin group, the survival rate of skin graft and primary healing rate of patients in Meek microskin group were significantly increased, with relative risks of 0.76 and 0.66 (95% confidence interval=0.66-0.88, 0.50-0.88, P<0.01), the surgical treatment cost was significantly reduced, with a standardized mean difference of 3.19 (95% confidence interval=1.36-5.01, P<0.01), and the operation time, wound healing time, and length of hospital stay were significantly shortened, with standardized mean differences of 6.05, 2.39, and 2.35 (95% confidence interval=3.66-8.44, 1.43-3.35, 2.03-2.68, P<0.01). Subgroup analysis showed that microskin grafting combined with allogenic skin graft might be a heterogeneous source of operation time. Sensitivity analysis showed that the combined effect size was stable in the operation time, surgical treatment cost, and wound healing time. There was no publication bias in the survival rate of skin graft, operation time, wound healing time, and length of hospital stay ( P>0.05), while the primary healing rate and surgical treatment cost had publication bias ( P<0.01). Conclusions:Compared with microskin grafting, Meek microskin grafting improves the rates of skin graft survival and primary healing, shortens operation time, wound healing time, and length of hospital stay, and reduces the treatment cost in treating extensively deep burn wounds.

OBJECTIVE: To investigate the role of exosome in mediating bortezomib (Btz) resistance in multiple myeloma cells and explore the underlying mechanisms. METHODS: Peripheral blood samples were collected from 15 patients with multiple myeloma with Btz tolerance, and serum exosomes were isolated by ultracentrifugation and identified with electron microscopy, NTA and Western blotting. cultured multiple myeloma cells were treated with gradient concentrations of Btz to determine the optimal drug concentration for subsequent experiment. The cells were pretreated with different concentrations of exosomes, and their sensitivity to BTZ was assessed using MTS assay. We searched the exosome database Exocarta and used STRING to generate the network map and the protein interaction graph. RESULTS: The diameters of the vesicles isolated from the peripheral blood of the patients were mostly below 200 nm with a mean particle size of 153 nm and a mode of 140.1 nm. The results of Western blotting showed that the isolated exosomes expressed the marker proteins CD63, Tsg101 and Alix. In cultured multiple myeloma cells, pretreatment with exosomes resulted in a decreased sensitivity of the cells to bortezomib, and longer treatment durations and higher exosome concentrations consistently enhanced the resistance of the cells to the same Btz concentration. Analysis of the Exocarta database identified human serum exosomal proteins ABCB1, ABCB4, PDCD6IP, and EGFR, among which EGFR served as a network node. CONCLUSIONS Exosome within a specific concentration range may serve as a signal carrier to mediate the resistance of multiple myeloma cells to Btz. EGFR likely plays a key role to promote exosome-mediated Btz resistance in myeloma cells.
Bortezomib ; Drug Resistance, Neoplasm ; Exosomes ; Humans ; Multiple Myeloma ; Ultracentrifugation

Objective: To investigate the clinical value of the serum new molecular markers, soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and soluble hemoglobin scavenger receptor(sCD163), in the diagnosis of sepsis in elderly patients with burns. Methods: A total of 58 inpatients with burns from Jun 2017 to June 2018 were enrolled in the study.Patients were divided into three groups: the sepsis group(n=12), the localized infection group(n=21)and the non-infection group(n=29). The levels of sTREM-1 and sCD163 were determined by enzyme-linked immunosorbent assays(ELISAs). The clinical diagnostic value of sTREM-1 and sCD163 was assessed by receiver operating characteristic(ROC)curve analysis. Results: There was a statistically significant difference in the levels of sTREM-1 and sCD163 at day 1 between the three groups(F=20.994 and 38.363, P<0.01). Serum levels of sTREM-1 and sCD163 were higher in the sepsis group than in the localized infection group and the non-infection group.Serum levels of sTREM-1 and sCD163 were higher in the localized infection group than in the non-infection group.Serum levels of sTREM-1 and sCD163 were lower at day 7 than those at day 1 in all groups(F=21.242 and 41.035, P<0.01). Serum sTREM-1 levels were positively correlated with serum sCD163 levels(r=0.609, P=0.000). The AUC of sTREM-1 and sCD163 for the diagnosis of sepsis was 0.880(95%CI: 0.816~0.926). Conclusions Serum levels of sTREM-1 and sCD163 are elevated with increasing degrees of infection.Monitoring serum sTREM-1 and sCD163 levels is helpful for the diagnosis of sepsis in elderly patients with burns.