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.

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

OBJECTIVE To investigate the effect and mechanism of acute exposure to sodium cyanide(NaCN)on brain nerve damage induced by closed hypoxia in mice.METHODS ① Mice were randomly divided into hypoxia+NaCN 0(hypoxia control group),2.56,3.8,and 5.1 mg·kg-1 groups.After ip adminis-tration of different concentrations of NaCN,the mice were immediately placed into a closed hypoxic tank and the hypoxia survival time was observed.②Mice were divided into normal control,NaCN 3.8 mg·kg-1,hypoxia(30 and 60 min)and NaCN 3.8 mg·kg-1+hypoxia(30 and 60 min)groups.After grouping,the pH,oxygen saturation(sO2),oxygen tension(pO2)and carbon dioxide partial pressure(pCO2)of arterial blood of mice were detected using an arterial blood gas analyzer.The cortical cerebral blood flow of mice was detected using a laser speckle imager.The dry and wet brain tissue were weighed separately,and the brain moisture content was calculated.The kit was used to detect the activity of total superoxide dismutase(T-SOD)and the content of malondialdehyde(MDA)in the hippocampus.TUNEL staining was used to detect the apoptosis rate of cells in the hippocampus.HE staining was used to detect path-ological changes in the hippocampus.RESULTS ①Compared with the hypoxic control group,the sur-vival time of mice in the hypoxic+NaCN groups was significantly prolonged(P<0.01).②Compared with the normal control group,the hypoxia 30 min group showed upregulation of arterial blood p CO2(P<0.05),downregulation of p O2(P<0.05).The hypoxia 60 min group showed upregulation of arterial blood p CO2(P<0.05)and downregulation of cortical cerebral blood flow(P<0.05).In the NaCN 3.8 mg·kg-1 group,arterial blood p O2 and s O2 were significantly downregulated(P<0.05),so was cortical cerebral blood flow(P<0.01),but MDA content and T-SOD activity were significantly upregulated(P<0.01),and the brain moisture content was increased(P<0.01).Compared with the hypoxia 30 min group,s O2 and p O2 of arterial blood in the NaCN+hypoxia 30 min group were significantly upregulated(P<0.05),while p CO2 was significantly downregulated(P<0.05).Compared with the hypoxia group at corresponding time points,the NaCN+hypoxia 30 or 60 min groups showed significant downregulation of cerebral blood flow(P<0.01),significant upregulation of MDA content and T-SOD activity(P<0.01),and signifi-cant upregulation of brain moisture content(P<0.01).HE staining results showed that the NaCN 3.8 mg·kg-1 group and the NaCN+hypoxia group(30 or 60 min)showed significant cell swelling and vacuolization in cells in the hippocampal tissue,a decrease in the number of neurons,nuclear pyknosis and deep staining.TUNEL fluorescence results showed that the NaCN 3.8 mg·kg-1 group significantly increased the apop-tosis rate of the mouse hippocampus compared with the normal control group(P<0.05).The NaCN+ hypoxia 30 and 60 min groups significantly increased the apoptosis rate of the mouse hippocampus compared with the hypoxia group at corresponding time points(P<0.05).CONCLUSION NaCN can exacerbate hypoxia induced decrease in cerebral blood flow,oxidative stress in brain tissue,and neuro-nal apoptosis in mice,thereby reducing oxygen consumption in closed hypoxic tanks and prolonging their survival time.The mechanism is related to reduced utility of cell oxygen,delaying CO2 accumulation and increasing free oxygen in vivo.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective:To evaluate the effectiveness and safety of ultrasound-guided percutaneous polidocanol sclerotherapy of the thyroglossal duct cysts in children.Methods:A retrospective analysis of 26 children who were treated with ultrasound-guided percutaneous puncture sclerosis for thyroglossal duct cysts in Beijing Children′s Hospital, Capital Medical University from October 2019 to April 2022, the size of the cyst before treatment was recorded, and the cyst volume in accordance with V(ml) =1/6 πabc cyst volume was calculated. The follow-up time was the 1st, 3rd, 6th, and 12th months after sclerotherapy. And the cyst volume and volume reduction ratio at different time points was calculated. According to changes in the cystic volume, the treatment was considered effective if the cyst volume reduction rate was≥50%. Cosmetic grading scores (CGS) were performed pre-treatment and at the last follow-up after sclerotherapy using the WHO grading system. Complications were recorded during the follow-up period.Results:The cyst volume before treatment was 2.67 (3.78)ml, and the cyst volume at the 1st, 3rd, 6th and 12th month after treatment were 0.66(1.83), 0.45(0.87), 0.40(0.70), 0.38 (0.63)ml, respectively, there were significant differences between pre-treatment and each time point after-treatment (all P<0.001); the volume reduction rate at the last follow-up was (81.48±14.57)%. The reduction rate of cyst volume was more than 50% at the last follow-up in 22 children, the treatment efficiency was 84.62% (22/26). The cosmetic grading scores at the last follow-up after sclerotherapy was 1.74(1.50), and it decreased significantly compared with the pre-treatment score 3.85(0)( P<0.001). There was no skin pigmentation, pain in the injection area, local urticaria and blistering after sclerotherapy, no adverse reactions such as cyst bleeding and drunkenness-like reaction, and no serious complications occurred. There were 2 cases of cysts that presented infection with fever, and no serious complications occurred. Conclusions:Ultrasound-guided percutaneous sclerotherapy is a safe and effective minimally invasive treatment for thyroglossal duct cysts in children.

Objective:To compare the clinical outcomes and correction effects of kyphosis between Zero-profile device (Zero-p) and plate/cage structures (PCC) in treating cervical spondylotic myelopathy (CSM) patients with cervical kyphosis.Methods:From August 2016 to July 2018, a total of 54 cases of cervical spondylotic myelopathy patients with cervical kyphosis were analyzed retrospectively, including 26 cases treated with Zero-p and 28 cases treated with PCC system. There was no significant difference between the two groups in gender, age, body mass index (BMI) and operative segment. The operation duration and the blood loss were recorded. The clinical outcomes of the patients were measured by visual analogue score (VAS) for neck pain and Japanese Orthopedic Association (JOA) score for neurological function. Moreover, JOA recovery rate was obtained to assess the surgical results. The cervical lordosis (C 2-C 7 Cobb angle), the Cobb angle of the operation segment, the C 2-C 7 vertical axis (C 2 SVA) and the cervical range of motion (ROM) were measured on the lateral and dynamic radiographs of the cervical spine, respectively. Results:In the Zero-p group, the operation duration was 83.0±14.9 (range 60-120) min, intraoperative blood loss was 70.5±27.3 (range 30-150) ml. In PCC group, the operation duration was 100.0±23.9 (range 65-145) min, intraoperative blood loss was 104.2±38.8 (range 30-250) ml. There were significant difference in above parameters between two groups ( t=3.40, 2.06; P=0.00, 0.04). The follow-up duration in Zero-p group was 30.4±5.8 (range 24-36) months and 31.2±4.9 (range 24-36) months in PCC group without significant difference ( t=1.061, P=0.291). The VAS/JOA score of the Zero-p group was improved from (5.9±1.0)/(9.2±1.7) preoperatively to (2.1±0.8)/(14.9±1.0) at 1 month postoperatively, and to (3.4±1.0)/(15.1±0.9) at the last follow-up. The difference between them was statistically significant ( F=130.96, 221.40, P=0.00). The VAS/JOA score of the PCC group was improved from (5.9±1.1)/(8.7±1.6) preoperatively to (2.3±0.9)/(14.9±1.0) at 1 month after surgery, and to (2.6±0.9)/(15.6±1.1) at the last follow-up. The difference between them was statistically significant ( F=303.35, 126.64, P=0.00). However, the VAS score of neck pain in the Zero-p group at the last follow-up was significantly deteriorated, which was significantly higher than that in PCC group ( P<0.05). The cervical lordosis/operative segment Cobb angle in the Zero-p group was improved from preoperative (-6.7°±2.7°)/(-6.5°±3.2°) preoperatively to (14.2°±4.9°)/(12.9°±4.9°) at 1 month postoperatively, and to (5.9°±4.7°)/(5.0°±4.0°) at the last follow-up with statistical significance ( F=196.98, 179.97, P=0.00). The cervical lordosis/operative segment Cobb angle in the PCC group was improved from (-5.7°±3.5°)/(-6.1°±4.0°) preoperatively to (13.9°±6.9°)/(13.0°±6.4°) 1 month after surgery, and to (11.0°±5.5°)/(10.4°±5.6°) at the last follow-up with statistical significance ( F=127.27, 119.98, P=0.00). However, the cervical lordosis and operative segment Cobb angle at the last follow-up in the Zero-p group were significantly lost compared with those at 1 month after surgery, which were significantly smaller than those in the PCC group ( P<0.05). The incidence of dysphagia after operation was 7.7% (2/26) in the Zero-p group and 28.6% (8/28) in the PCC group (χ 2=5.11, P=0.02). Conclusion:For CSM patients with cervical kyphosis, PCC could achieve much better mid-term kyphotic correction and clinical outcomes. However, Zero-p should be avoided as much as possible.

Objective To study the clinical impact of microvascular invasion (MVI) on patients with intrahepatic cholangiocarcinoma (ICC) after R0 resections.Methods The clinicopathological data of 359 patients with ICC who underwent R0 resection in the Zhongshan Hospital,Fudan University between January 2000 and December 2008 were retrospectively studied.Univariate analysis and multivariate analysis were carried out to study factors related to postoperative survival outcomes and recurrence.The impact of MVI on patients with ICC after R0 resection was studied.Results The incidence of MVI was 13.6％ in the study cohort.MVI was correlated with HBV infection (P ＜ 0.05),liver cirrhosis (P ＜ 0.05) and tumor differentiation (P ＜ 0.05).The 1-,3-,5-year overall survival (OS) between the MVI positive and negative groups were 50.0％,20.9％,12.2％ and 63.9％,33.1％,22.0％ respectively (P ＜ 0.05),and the median survival time was 13 months and 18.5 months (P ＜0.05).The 1-,3-,5-year recurrence free survival (RFS) rates between the MVI positive and negative groups were 29.7％,12.7％,8.5％ and 50.6％,26.9％,18.4％,respectively (P ＜0.05),and the median recurrence free survival time was 8 months and 12.5 months (P ＜ 0.05).Multivariate analysis showed that MVI was an independent risk factor affecting recurrence after R0 resection (HR 1.852,95％ CI:1.075 ～ 3.195,P ＜ 0.05).Conclusions The occurrence of MVI in ICC patients was associated with hepatitis B infection.MVI was an independent risk factor affecting recurrence in ICC patients after R0 resection.However,it was not an independent risk factor of overall survival in patients after R0 resection.The clinical impact of MVI on patients with ICC was not as strong as for hepatocellular carcinoma.

Objective To investigate the application of remote monitoring systems for cardiac implantable electronic devices (CIED) and its success rate of data transmission in elderly patients.Methods A total of 97 elderly patients who had previously undergone procedures for pacemaker implantation,implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy (CRT) with remote monitoring capabilities between January 2013 and October 2016 at our hospital were enrolled.We evaluated the effect of the remote monitoring systems for data transmission,compared the outpatient follow-up rates between the groups one year after implantation,and conducted a telephone survey of patients.Results A total of 97 elderly patients,including 70 with pacemakers,20 with ICD and 7 with CRT,were enrolled in this study.Participants had a mean age of (78.2-±-6.4) years and 64 were male (66.0％).The Home Monitoring system was used for 85 cases and the Merlin.net remote monitoring system was used for 12 cases.Overall,95 patients (97.9 ％) completed the remote monitoring procedure,68 patients (70.1％) completed the outpatient follow-up,and 90 patients (92.8％) completed the telephone survey during a one-year follow-up period.The satisfaction rate for the remote monitoring systems was 94.4％ (85 patients),and 80 patients (90.0％％) expressed a willingness to continue to use the remote monitoring system if a replacement was needed.Conclusions For elderly patients with CIED,the remote monitoring systems can improve the follow-up rate with a high degree of satisfaction.

Objective To observe the biocompatibility of rabbit bone marrow mesenchymal stem cells (BMSCs)combined with allogeneic decalcified bone matrix(DBM)after transfecting adenoviral recombinant human bone morphogenetic protein-2(Ad-rhBMP-2).Methods The rabbit allogeneic DBM material was prepared according to the Ursit method.After transfecting Ad-BMP-2 on rabbit bone marrow mesenchymal stem cells,the immunohistochemical was used to detect the expression of BMP-2 in the transfected cells;after 48 h of transfection,the cells were planted on the allograft DBM,then the scanning electron microscopy was used to observe the cell growth and adhesion condition on material,and the proliferation condition of BMSCs was detected by MTT. Results After 48 h of adenoviral transfection,BMSCs could express BMP-2 successfully.The scanning electron microscopy showed that the cells after transfection adhered well and massively proliferated on DBM material.The MTT assay showed that the prolifer-ation condition of the cells after transfection planted on DBM was normal,which showed no statistically significant difference when compared with the control group (P >0.05).Conclusion The Ad-BMP-2 transfection on BMSCs is well biocompatible to allogene-ic DBM.