OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

Objective To analyze the short-term survival and prognostic quality of life of patients with liver cirrhosis complicated by bacterial infection. Methods This study collected and analyzed 300 patients with liver cirrhosis complicated with infection who were hospitalized in the First Affiliated Hospital of Hebei North University, and followed up to discuss their survival and quality of life. Results In this study, the top two causes of infection were spontaneous bacterial peritonitis (60.67% of patients) and pneumonia (50.67% of patients). The second causes were urinary tract infections (15.33%), gastrointestinal infections (12.33%), and other causes. There was no statistically significant difference between male and female patients (P>0.05). In addition, the proportion of hospital infections was 71.00%, and there was no statistically significant difference between male and female patients (P>0.05). A total of 353 strains of pathogenic bacteria were isolated in this study (73.37% of patients with hospital infections). The distribution analysis of pathogenic bacteria showed that the highest proportion of ECO was 35.98%, followed by Klebsiella pneumoniae (18.98%). The distribution trend of 259 strains of pathogenic bacteria among hospital patients was consistent with that of all strains, and the difference was not statistically significant (P>0.05). Gram negative bacteria accounted for 79.60% (281/353) of all detected strains, of which Escherichia coli was mostly detected in patients with spontaneous bacterial peritonitis, Klebsiella Pneumoniae (KPN) and Pseudomonas aeruginosa (PAE) were mostly detected in patients with pneumonia, and Enterococcus (ENF) was mostly detected in patients with urinary tract infection; Among gram-negative bacteria, Staphylococcus epidermidis (SEP) and Staphylococcus aureus (SAU) are mostly found in patients with other infectious causes (blood flow infection, etc.) , and Streptococcus (STR) accounts for a high proportion in patients with Spontaneous bacterial peritonitis. In this study, 9 cases of death prognosis were detected during follow-up, and there was no statistically significant difference in the detection of death prognosis between different bacterial strains in both genders, as well as the difference in detection of death prognosis between hospital infections and out of hospital infections in both genders (P>0.05). There was no statistically significant difference in the detection of death prognosis between males and females due to different causes of infection, P>0.05. The quality of life scores of 291 surviving patients were compared between baseline and follow-up, indicating an increase in follow-up scores, especially in the dimensions of physiological function and physical pain. There was no statistically significant difference between different bacterial strains, infection causes, and hospital/non hospital infections (P>0.05) . Conclusion Spontaneous bacterial peritonitis and pneumonia are the main causes of infection that deserve special attention, and the main pathogens of infection are Gram negative bacteria. Targeted treatment and rehabilitation should be provided for patients with liver cirrhosis complicated by infection. At the same time, the proportion of hospital infections is relatively high, and attention should be paid to, prevention and control measures should be implemented as well.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Scalp arteriovenous fistula (SAVF) is a rare complication of thread-lift sutures for facial rejuvenation.This article reports a 23-year-old female patient who suffered from entotic sounds in left ear after thread lifting. Then, the entotic sounds was gradually aggravated with palpitations. The cerebral angiography showed a high flow scalp arteriovenous fistula in the left temporal region, which got satisfactory result by endovascular embolization with coil and medical glue. There was no recurrence of the fistulas after one year of follow-up.

Scalp arteriovenous fistula (SAVF) is a rare complication of thread-lift sutures for facial rejuvenation.This article reports a 23-year-old female patient who suffered from entotic sounds in left ear after thread lifting. Then, the entotic sounds was gradually aggravated with palpitations. The cerebral angiography showed a high flow scalp arteriovenous fistula in the left temporal region, which got satisfactory result by endovascular embolization with coil and medical glue. There was no recurrence of the fistulas after one year of follow-up.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.

Objective:To translate the health literate healthcare organization 10 item questionnaire(HLHO-10) into Chinese and examine its reliability and validity.Methods:The Chinese version of HLHO-10 questionnaire(HLHO-10-C) was developed by following the Brislin translation model of translation, back translation, cultural adaptation and questionnaire epistemological survey.Five experts and 1 071 medical staff from 24 healthcare organizations in Zhejiang province were selected to conduct the validity and reliability test of the HLHO-10-C.Results:The content validity indices at the item level and total questionnaire level of HLHO-10-C were from 0.8 to 1.0 and 0.96 respectively, and the results of the exploratory factor analysis showed good structural validity.Conclusions:HLHO-10-C proves adequate reliability and validity to serve as a tool for healthcare organizations in evaluating and becoming HLHO. It can also help the implementation of the Healthy China Initiative(2019—2030), which is a performance assessment mechanism for health education and promotion of healthcare providers and health care organizations.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Objective: To investigate the effects of micronutrient supplementation for the elderly on plasma homocysteine level and cognitive function in institutional older adults. Methods: A total of 98 older adults with the score≤11 by mini nutritional assessment short-form aged 65-100 years were enrolled and assigned to either intervention group or control group (n=49 each), with either a package of micronutrient pack or placebo daily, for three months. Fasting blood samples were collected both at baseline and the end of study to detect serum vitamin B₁₂, folate and plasma homocysteine (Hcy) concentrations. Global cognitive function was assessed using the mini-mental state examination (MMSE). The paired t test was used to compare the continuous variables between the two groups after intervention. The relationship between changes in MMSE score and changes in plasma Hcy concentrations was examined by least-squares linear regression. Results: Eighty-two patients completed the study, and 17 patients withdrew from the study due to diarrhea and hospital discharge with the drop rate of 17.3%. Compared to the control group, concentrations of serum vitamin B₁₂ (128.8±34.8 vs 13.3±16.0 pmol/L, P=0.003) and folate (21.1±1.6 vs 0.6±0.5 nmol/L, P<0.01) significantly increased in the intervention group over 3-month supplementation, while plasma Hcy levels were remarkably reduced (-5.3±0.7 vs 1.7±0.3 μmol/L, P<0.01). The incidences of deficiency of folate, deficiency of serum vitamin B₁₂and high Hcy all decreased in intervention group. Although individual item scores in MMSE were not changed markedly, change of total MMSE score in intervention group were higher than that in the control group (1.2±3.0 vs -0.2±2.5, P<0.05). Conclusions The supplementation of the micronutrient pack in long-term care facilities can reduce the incidence of hyperhomocysteinemia, and improve the total MMSE score.