Objective To comprehensively understand the dynamic transcriptional landscape during infection through investigating the temporal molecular changes in macrophages RAW 264.7 upon infection with Salmonella typhimurium SL1344.Methods Macrophages RAW 264.7 were infected with Salmonella typhimurium SL1344,and cell samples were collected at 0 h,8 h,and 16 h for RNA-sequencing(RNA-seq).Upstream and downstream analyses of the transcriptome data including differential gene expression,clustering,functional annotation,and mo-lecular network studies were conducted to elucidate the signaling pathways changes in macrophages.Results Infec-ted macrophages exhibited significant morphological and transcriptional changes.Differential gene analysis identified significant upregulation and downregulation patterns.Clustering revealed six gene clusters involving various signaling pathways,such as immune response,membrane transport,and lipid catabolic process.Conclusions Macrophages dynamically respond to Salmonella typhimurium infection,displaying distinct temporal gene expression patterns.The coordinated activation of immune response,membrane transport,and lipid catabolic process pathways implies a multifaceted cellular adaptation to external infections,providing essential insights into the molecular mechanisms of macrophage response to Salmonella typhimurium infection.

Objective To analyze the interaction between voriconazole(VRC)and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR)based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring,so as to provide a basis for the development of individualized VRC combined with immunosuppressants.Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene pol-ymorphism,respectively.And the concentration of immunosuppressants was detected at the same time.The rela-tionship among CYP2C19 gene polymorphism,the concentration of VRC and immunosuppressant and ADR was an-alyzed.Results A total of 61 patients were enrolled in this study,and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1％(33/61)and 9.84％(6/61),respectively.The concentrations of VRC in patients with extensive metabolism(EMs),intermediate metabolism(IMs)and poor metabolism(PMs)were(4.44±3.46),(3.62±3.02)and(10.05±1.46)μg/ml(P＜0.05),respectively.The concentration of tacrolimus af-ter combined with VRC significantly increased compared to tacrolimus alone[(13.4±9.2)ng/ml vs(6.5±3.6)ng/ml;P=0.002],and the concentration of tacrolimus increased along with an increasing of VRC concentration.The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosup-pressants[(3.81±3.48)μg/ml vs(5.84±3.71)μg/ml;P=0.032].The concentration of VRC inpatients with cyclosporine significantly decreased(P＜0.01),while tacrolimus and mycophenolate mofetil had no signifi-cant effect on the concentration of VRC.45.90％(28/61)of the patients had adverse reactions,the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR[(7.07±3.43)μg/ml vs(3.06±2.90)μg/ml;P＜0.001].And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype.Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC,and VRC has significant interaction with immunosuppressants such as tacrolimus.CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individual-ized treatment of tacrolimus and voriconazole,and is expected to minimize toxicity and improve treatment effects.

Objective:To investigate the current situation of community nursing needs of patients with middle and advanced Parkinson ′s disease, analyze the factors affecting the demand, and further explore the possible pathways of action between the factors, so as to provide the basis for formulating targeted community intervention measures in a more comprehensive way. Methods:A cross-sectional survey of 242 patients with middle and advanced Parkinson ′s disease from the Second Hospital Affiliated to the Army Medical University from November 2022 to January 2023 were selected by convenience sampling method, and the Community Care Need Scale, General Data Questionnaire, Readiness for Hospital Discharge Scale, Medical Coping Modes Questionnaire and the Self-management Effectiveness Questionnaire of Parkinson ′s disease patients were used. SPSS 26.0 was used to analyze the data, and investigated the relationship between readiness for hospital discharge, self-management efficacy, active coping styles, and community nursing needs. Results:A total of 234 valid questionnaires were collected, including 108 males and 126 females, aged 39-93 (67.25±8.93) years. The average score of all dimensions from high to low was: disease treatment dimension (4.16±0.42), daily care dimension (4.05±0.97), fall prevention dimension (4.04±0.80), extended care dimension (3.95±0.65), emotional support dimension (3.77±0.65) and self function (3.75±0.72). Univariate analysis indicated that there were statistically significant differences in community nursing needs scores among middle and advanced Parkinson ′s disease patients with different educational level and different family income ( F=5.11, 3.05, both P<0.05). Readiness for hospital discharge, self-management efficacy and positive coping style were negatively correlated with community nursing needs of patients with middle and advanced Parkinson′s disease ( r=-0.567, -0.412, -0.398, all P<0.01), and self-management efficacy and positive coping style played a partial mediating role between readiness for hospital discharge and community nursing needs. Conclusions:There is a wide range of community nursing needs that patients with middle and advanced Parkinson ′s disease, and patients with primary school and below, high school and above, and low family income are higher. It is suggested that the community disease management process should focus on this group of people. Medical institutions should help patients with middle and advanced Parkinson ′s disease improve their ability to manage the disease by improving discharge preparation services, so that they can smoothly transition from hospital to home, thereby reducing the needs for community nursing.

Objective:To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. Methods:The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. Results:The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×10 9/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO 2/FiO 2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO 2/FiO 2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. Conclusion:The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Objective:To evaluate percutaneous mechanical thrombectomy (PMT) using Aspirex device for treating acute iliofemoral deep vein thrombosis (IFDVT).Methods:The clinical and follow-up data of 68 patients with IFDVT at our institution from Jan 2019 to Jun 2021 was retrospectively analyzed.Results:Twenty-six patients who had received PMT combined with auxiliary catheter directed thrombolysis (CDT) were included into group A, and 42 patients received CDT alone were into group B.The final thrombus clearance rates were more than 50%, and the clinical efficacy of thrombolysis was achieved. Group A associated a significant reduction in lysis duration and UK dosage and hospital days and degree of detumescence after 24 h compared with group B,and all aforementioned differences were statistically significant. Hospitalization costs in group A were more than group B. At one year follow-up, there were no significant differences between the two groups in the cumulative prevalence post-thrombotic syndrome (PTS) and the Villalta score and primary patency (92.0% vs. 90.0% , χ2=0.059, P=0.807). Conclusions:The application of PMT using the Aspirex device for acute IFDVT was safe and effective, which could accelerate the clearance of thrombus, and reduce UK dosage, lysis duration, hospital days. However, it increased the hospitalization costs.

BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR 1900023646.
Humans ; Bismuth/therapeutic use* ; Metronidazole/therapeutic use* ; Esomeprazole/pharmacology* ; Minocycline/pharmacology* ; Helicobacter pylori ; Potassium Citrate/therapeutic use* ; Anti-Bacterial Agents ; Tetracycline/adverse effects* ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Amoxicillin

OBJECTIVE To study the toxicity of the extract from Mi ao medicine Wikstroemia indica to zebrafish . METHODS Zebrafish embryo model was used as the object ，after exposure to W. indica extract （10，20，40 μg/mL），the number of spontaneous twitching within 1 min，heart rate within 10 s，the occurrence of malformation and death were detected and recorded . Zebrafish was used as the object ，after exposure to W. indica extract（10-100 μg/mL）for 24，48 and 72 h，and the median lethal concentration（LC50）of W. indica extract to zebrafish at different time points were calculated . After exposure to low ，medium and high concentration （27，37，51 μg/mL）of W. indica extract，the liver phenotype ，hepatocyte apoptosis and lipid deposition of zebrafish were observed ，and the activities of alanine aminotransferase （ALT），aspartate aminotransferase （AST）and lactate dehydrogenase（LDH）in liver tissue were detected . RESULTS Compared with blank group ，the number of spontaneous twitching ， malformation rate （except for 10 μg/mL group ）and mortality of embryos increased significantly in 10，20，40 μg/mL groups of W. indica extract，and the heart rate （except for 10，20 μg/mL group ）of embryos decreased significantly （P＜0.05）. LC50 of W. indica extract to zebrafish at 24，48 and 72 h were 39.850，28.300 and 21.490 μg/mL，respectively. After drug treatment ，the transparency of liver area of zebrafish in low ，medium and high concentration groups of W. indica extract reduced and their shape were enlarged；apoptosis and lipid deposition increased ；the activities of ALT ，AST and LDH in liver tissue were significantly increased （P＜0.05）. CONCLUSIONS Miao medicine W. indica extract had develop mental toxicity to zebrafish embryos and he patotoxicity to zebrafish .

Objective:To explore the real experience and feelings of the medical and nursing staff in the Emergency Department of general hospitals in receiving patients with mental disorders, so as to provide reference for formulating corresponding interventions.Methods:From October to November 2021, a semi-structured in-depth interview was conducted with 16 Emergency Department medical and nursing staff from two Class Ⅲ general hospitals in Nanjing by objective sampling. Colaizzi method was used to analyze the data.Results:After analyzing the interview data, three themes were extracted, namely, the emotional experience in treating and nursing patients with mental disorders, the barriers to providing the best management for patients with mental disorders (barriers at the environment/resource level, barriers at the emergency medical and nursing staff level, and barriers at the patient level) , and the educational needs of receiving patients with mental disorders (improving disease awareness and mental health service ability, and changing the way of thinking) .Conclusions:The medical and nursing staff in the Emergency Department of general hospitals have different degrees of negative emotions when receiving patients with mental disorders. There are insufficient knowledge and ability and a series of barriers when providing mental health services for patients. Managers should take various measures to improve the physical and mental health of patients with mental disorders in Emergency Department.

Objective To establish a method for Emodin assay in Ampelopsis radix, and to improve the quality control of Ampelopsis radix. Methods Reversed phase high performance liquid chromatography was used. The column: Apollo-C₁₈ (4.6 mm×250 mm, 5 μm); mobile phase: methanol:0.2% phosphoric acid (85:15); flow rate: 1.0 ml/min; column temperature: room temperature; detection wavelength: 220 nm. Results With the specified chromatographic conditions, there was a good linear relationship for Emodin in Ampelopsis radix in the range of 0.124-3.968 μg/ml. The linear regression equation was Y= 53 962X–966.46, r=0.999 7. The average recovery was 99.7%. RSD=2.5% (n=9). Conclusion This method is accurate, sensitive and repeatable. It is suitable for the determination of emodin in Ampelopsis radix.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.