OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

ObjectivesTo investigate the ultrasound features and etiological distribution of non-immune hydrops fetalis. MethodsA total of 232 cases of diagnosed non-immune hydrops fetalis were recruited from December 2012 to January 2019 in The First Affiliated Hospital of Sun Yat-sen University. The ultrasound features and the results of prenatal diagnosis of hydrops fetalis were retrospectively analyzed. Results1. Non-immune hydrops fetalis was often associated with TTTS stage Ⅳ （50/232， 21.55%）； skin edema （159/232， 68.53%） was the mostly identified fluid collection； the most frequently combined malformations were anomalies of the cardiovascular system （15/232， 6.47%）. 2. Totally 185 cases accepted further prenatal genetic test and the abnormal detection rate was 40.54% （75/185）， while the abnormal detection rate of chromosome examination （including chromosome karyotype analysis and CMA） was 26.49% （49/185）. The abnormal detection rate of isolated NIHF was lower than that of non-isolated NIHF （32.64% vs 68.29%， p< 0.05）. Chromosome karyotype analysis was only performed in 57 cases， and abnormalities were detected in 14 cases （24.56%）. CMA only was performed in 31 cases and abnormalities were detected in 13 cases （41.94%）. Both Chromosome karyotype analysis and CMA were performed in 88 cases. Variation was detected in 22 cases （25%）， 3 cases （3.41%） showed abnormalities detected only by Chromosome karyotype analysis， while 6 cases （6.82%） had abnormalities detected only by CMA. The extra detection rate of CMA was 3.41% （3 cases） compared with Chromosome karyotype analysis. Variation was both detected by Chromosomal karyotype analysis and CMA in 13 cases （14.77%）. In this study， 30 cases of variation were detected by Chromosomal karyotype analysis （30/145， 20.69%）. The most common was 45， X （19/145， 13.10%）， followed by 47， XX， + 21 / 47， XY， + 21 （3/145， 2.07%）. CMA detected 32 cases of variation， including 12 cases of CNVs （10.08%）， 4 of which were pathogenic CNVs （3.36%）. Genetic analysis detected abnormalities in 26 of 27 cases. The most common abnormality in gene detection cases was αThalassemia --^SEA/--^SEA （21/26， 80.77%）， followed by PTPN11 gene mutation （2/26，7.69%）. 3. The causes of genetically normal NIHF included fetal-maternal blood transfusion， infection and unexplained anemia. ConclusionsThe most common etiology of non-immune hydrops fetalis is TTTS stage Ⅳ and the most frequently associated malformations are cardiovascular system abnormalities in our center. The most common abnormal karyotypes of non-immune hydrops fetalis are 45， X. CMA offers extra detection rate compared with Chromosome karyotype analysis in NIHF. The most common monogenic disease is αThalassemia--^SEA/--^SEA. The genetic abnormality detection rate of non-isolated NIHF is higher.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load

This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia model [MAR_ADP= (41.67±4.55)%, MAR_AA= (53.22±2.83)%, MAR_THR= (73.33±5.04)%] indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregation [MAR_ADP= (26.13±4.60)%, MAR_AA= (35.53±13.73)%, P<0.01], while aspirin played a strong inhibitory effect on AA-induced platelet aggregation [MAR_AA= (8.13±2.99)%]. Salvianolic acid A (10 mg·kg^-1) significantly improved the neurological function, cerebral infarction volume [(10.77±7.80)%] and brain edema [(79.72±0.83)%] compared with the model group [(43.50±12.69)%, (82.25±0.89)%] (P<0.01), while the effect of aspirin (100 mg·kg^-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.

Traditional Chinese herbs are readily contaminated by mold that produced mycotoxins which are closly related to the herbs' external factors and external environments during the storage process. In this study, Citri Reticulatae Pericarpium was used as example, and the characteristics of traits, water content, active components (naringin, hesperidin, sinensetin, naringin, tangeretin) and the accumulation of aflatoxins (AFs) were selected as the evaluation indexes. Citri Reticulatae Pericarpium was stored under different environments and packaging materials for 12 months, and then the quality changes and mildew of Citri Reticulatae Pericarpium were examined. The results showed that the color of Citri Reticulatae Pericarpium was deepened after storage, but without mildew phenomenon. Besides, the sample storage in kraft paper and woven bags had varying degrees of moth phenomenon after 12 months storage, and the water content exceeded the limit of Chinese Pharmacopoeia. In addition, the contents of the five active constituents obviously decreased, especially for hesperidin, which did not meet the pharmacopoeia standard after storage. AFs were not detected in any of the tested samples. According to the results, we conclude that low temperature and humidity environment is more suitable for the storage of Citri Reticulatae Pericarpium, and that packaging materials should be further investigated. This study is of great significance for preventing the mold to contaminate the traditional Chinese medicine and ensuring the quality, effectiveness and safety of TCMs.

BACKGROUNDThe conventional venous access for cardiovascular implantable electronic device (CIED) is the subclavian vein, which is often accompanied by high complication rate. The aim of this study was to assess the efficacy and safety of optimized axillary vein technique.

METHODSA total of 247 patients undergoing CIED implantation were included and assigned to the axillary vein group or the subclavian vein group randomly. Success rate of puncture and complications in the perioperative period and follow-ups were recorded.

RESULTSThe overall success rate (95.7% vs. 96.0%) and one-time success rate (68.4% vs. 66.1%) of punctures were similar between the two groups. In the subclavian vein group, pneumothorax occurred in three patients. The subclavian gaps of three patients were too tight to allow operation of the electrode lead. In contrast, there were no puncture-associated complications in the axillary vein group. In the patient follow-ups, two patients in the subclavian vein group had subclavian crush syndrome and both of them received lead replacement. The incidence of complications during the perioperative period and follow-ups of the axillary vein group and the subclavian vein group was 1.6% (2/125) and 8.2% (10/122), respectively (χ2 = 5.813, P = 0.016).

CONCLUSIONOptimized axillary vein technique may be superior to the conventional subclavian vein technique for CIED lead placement.

TRIAL REGISTRATIONwww.clinicaltrials.gov, NCT02358551; https://clinicaltrials.gov/ct2/show/NCT02358551?term=NCT02358551& rank=1.

Aged ; Axillary Vein ; Defibrillators, Implantable ; adverse effects ; Electrodes, Implanted ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Pacemaker, Artificial ; adverse effects ; Perioperative Care ; Pneumothorax ; diagnosis ; etiology ; Postoperative Complications ; Prosthesis Implantation ; adverse effects ; Subclavian Vein

Objective To investigate the influence of long non-coding RNA HOTAIR in proliferation and apoptosis of human tongue squamous cell carcinoma in vitro and in vivo. Methods siHOTAIR was used to inhibit the HOTAIR expression in Tb3.1 human tongue squamous cell carcinoma cell line. The experiments were divided into siHOTAIR group, nonsense sequence group and blank control group. Real-time PCR was used to detect the HOTAIR expression. MTT assay was employed to determine the cell survival. The expression levels of Bcl2, BAX, caspase-3, cleaved caspase-3 were examined by Western blot assay. Tb3.1 xenograft tumor model was established in BALB/c nude mice, and the tumor model was divided into control group, negative group, and siHOTAIR treated group. The tumor tissues were measured by immunohistochemistry stain (IHC) and TUNEL assay. Results The detection of real-time PCR showed that HOTAIR expression was reduced after treated with siHOTAIR. Western blots assay showed that Bcl-2 protein was suppressed while cleaved caspase-3 and BAX protein were up-regulated after treated with siHOTAIR. MTT assay indicated that the cell survival rate was significantly reduced in siHOTAIR treated group. Flow cytometry detected that apoptosis levels were increased in siHOTAIR group. The level of cell senescence was higher in the siHOTAIR group than that of control group. Results of IHC indicated that Ki-67 and Bcl-2 protein of tumor tissue were inhibited, while BAX and cleaved caspase-3protein expressions were elevated simultaneously in the siHOTAIR group. TUNEL assay suggested that more apoptosis was observed in siHOTAIR group. Conclusion HOTAIR can affect proliferation and apoptosis of tongue squamous cancer cells. HOTAIR may be one of the new candidate targets for human tongue cancer therapy.

OBJECTIVETo evaluate efficacy and safety of second-generation tyrosine kinase inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML).

METHODSThe clinical data and follow-up results of 163 patients with chronic-phase chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the nearly 3 years were analysed retrospectively, among 163 patients 47 received dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease progression and safety were evaluated.

RESULTSAfter treatment for 3 months, the rate of complete hematologic response(CHR) in three treatment groups were 77%, 79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%, 91% and 90%, respectively. By 3 months, the rates of complete cytogenetic response(CCyR) with dasatinib and nilotinib were higher than that with imatinib (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months were significantly higher than that for imatinib (1%) (P<0.05 for both comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%, respectively (P<0.05 for both comparison). Progression to the accelerated or blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%) received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3 second-generation TKI treatments were similar.

CONCLUSIONBoth dasatinib and nilotinib induced strikingly higher and faster rates of complete cytogenetic response and major molecular response, with a statistically significant difference from imatinib.

Antineoplastic Combined Chemotherapy Protocols ; Blast Crisis ; Dasatinib ; Disease Progression ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Protein Kinase Inhibitors ; Pyrimidines ; Retrospective Studies ; Treatment Outcome

Objective To explore the expressions of Cyclin-dependent kinase 5 (CDK5) and Epithelial-Mesenchymal Transition (EMT) related proteins including N-cadherin, Vimentin and E-cadherin in head and neck squamous cell carcino? ma (HNSCC), and to determine the relationship between the expression of CDK5 and prognosis. Methods The expression levels of CDK5 and EMT related proteins were evaluated by immunohistochemistry in 55 patients who were diagnosed as HN?SCC. They were also analyzed in different clinical pathological factors. The correlation of CDK5 and EMT related proteins as well as the relationship between the expression of CDK5 and prognosis were also analyzed. Results The expression level of CDK5 was significantly higher in patients with lymph node metastasis than that in patients with non-lymph node metastasis (91.67%vs 30.23%, P<0.05). It’s also higher in T3-T4 stages than that in T1-T2 stages (85%vs 20%, P<0.05). The ex?pression levels of N-cadherin and Vimentin were significantly higher in patients with lymph node metastasis than those in patients with non-lymph node metastasis (75.00%vs 6.98%;91.67%vs 27.91%, all P<0.05). However, the expression level of E-cadherin was significantly lower in patients with lymph node metastasis (8.33%vs 86.05%, P<0.05) compared to that in patients without. CDK5 was positively correlated with N-cadherin and Vimentin, but negatively correlated with E-cad?herin (rs=0.512, 0.443,-0.363, all P<0.01). The 3-year survival rates were significantly lower in patients with high expres?sion of CDK5 (37.5%) than that in patients with low expression of CDK5 (87%, Log-rankχ2=12.678, P<0.01). Conclusion CDK5 and EMT related proteins were activated abnormally in HNSCC with lymph node metastasis. CDK5 may be a new bio?logical marker for prognosis of HNSCC.