Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

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

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

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
Alternative Splicing ; Carcinogenesis ; Glycolysis ; Heterogeneous-Nuclear Ribonucleoproteins/physiology* ; Humans ; MicroRNAs/physiology* ; Neoplasms/pathology* ; Polypyrimidine Tract-Binding Protein/physiology* ; RNA, Long Noncoding/physiology*

OBJECTIVETo explore the correlation between syndrome types of late-onset acne female patients and constitutions of Chinese medicine (CM).

METHODSA questionnaire was performed in 365 late-onset acne female patients and 135 healthy subjects (as the control) using Professor WANG Qi's. methods and Standards for Chinese Medical Constitutions Classification.

RESULTSTheir CM constitutions were sequenced as damp-heat constitution, yin-deficiency constitution, balanced constitution, yang-deficiency constitution, blood-stasis constitution, qi-stagnation constitution, qi-deficiency constitution, phlegm-damp constitution, inherited special constitution, with statistical difference when compared with those of the control group ( χ2 = 85.206, P < 0.01). In the 365 female late-onset acne patients, 114 (31.23%) were with Chongren imbalance syndrome, 108 (29.59%) were with blood stasis or coagulated phlegm syndrome, 83 (22.74%) were with dampness heat syndrome, and 60 (16.44%) were with wind heat syndrome. There was statistical difference in CM constitution distributions among different CM syndrome types (χ2 = 105.671, P < 0.01). The distribution of CM medical constitutions was different between the two groups. Biased constitutions were often seen in the patient group, while balanced constitution was often seen in the control group. Binary Logistic regression analysis indicated that influencing factors covered sweet food, light diet, roasted food, coffee, stress, work pressure, and family pressure. Of them light diet was one protective factor, while the rest were adverse factors.

CONCLUSIONThe etiology and syndrome types of female late-onset acne female patients were associated with CM constitution.

Acne Vulgaris ; epidemiology ; Body Constitution ; Female ; Humans ; Medicine, Chinese Traditional ; Surveys and Questionnaires ; Syndrome ; Yang Deficiency ; Yin Deficiency

OBJECTIVETo study the role of c-jun N-terminal kinase (JNK) signaling pathway in chondrocyte apoptosis induced by nitric oxide (NO) using NO donor sodium nitroprusside (SNP) and JNK inhibitor SP600125.

METHODSArticular chondrocytes were separated from New Zealand rabbits aged 3 weeks by mechanical digestion and enzyme digestion and identified by toluidine blue staining, and then the chondrocytes were treated with SNP and SP600125 for 24 h. The cell apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of nuclear factor-kappa B (NF-κB) p65 and p53 were measured by western blot.

RESULTSCompared with those in control group, the early apoptotic rate of SNP-treated chondrocytes increased as the concentration of SNProse, exhibiting a concentration dependency (P < 0.05), and the expression levels of NF-κB p65 and p53 also increased (P < 0.05); JNK inhibitor SP600125 inhibited these increases (P < 0.05).

CONCLUSIONJNK signaling pathway plays an important role in NO-induced chondrocyte apoptosis. JNK inhibitor SP600125 can reduce NO-induced apoptosis and expression of NF-κB p65 and p53 in articular chondrocytes of rabbits in a concentration-dependent manner.

Animals ; Anthracenes ; pharmacology ; Apoptosis ; drug effects ; Cells, Cultured ; Chondrocytes ; drug effects ; metabolism ; pathology ; MAP Kinase Signaling System ; drug effects ; NF-kappa B ; metabolism ; Nitric Oxide ; pharmacology ; Rabbits ; Transcription Factor RelA ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo construct the plasmid reference molecules for detection of transgenic tomato line Zeneca B,Da,F using quantitative real-time PCR(qPCR).

METHODSThree plasmid reference molecules pEasy-T3-APX, pEasy-T3-16A and pEasy-T3-16S were cloned based on reverse genetics, which contain the target fragments of tomato endogenous reference gene apx (ERG-apx), gene-specific sequence of pg(GS-pg) and construct-specific sequence of vectors pJR16S/pJR16A (CS-16S/CS-16A) of Zeneca B,Da,F, respectively. Primers and Taqman probes were designed by Beacon Designer 7.5.The specificity, sensitivity, reproducibility and the limit of detection(LOD) of the qualitative and quantitative PCR system based on the plasmid reference molecules were evaluated. PicoGreen was used to measure the DNA concentration of the plasmid reference molecules. Two sets of samples containing 1% or 0.1% (w/w) pEasy-T3-16A or pEasy-T3-16S mixed with pEasy-T3- APX as background DNA were prepared for evaluating the efficacy of the qPCR system.

RESULTSThe target fragments for qPCR detection were anchored, ERG-apx 108 bp, GS-pg 108 bp , CS-16S 109 bp and CS-16A 102 bp. The three plasmid reference molecules were confirmed at the expected sizes by restriction enzyme digestion. The qPCR results showed that the RSD of reproducibility were 0.2% to1.5%, LOD was 25 copies, R2 values for these standard curves were 0.994 ~0.998 and amplification efficiencies were 93.3%~102.4%.The bias between the test and true values of two sets of mixed samples ranged from -9.3% to 14.7% after adjusting by conversion factors(Cf).

CONCLUSIONThe plasmid reference molecules and qPCR system for qualitative and quantitative detection of transgenic tomato line Zeneca B,Da,F have been established successfully.

Base Sequence ; DNA, Plant ; genetics ; Lycopersicon esculentum ; genetics ; Plants, Genetically Modified ; genetics ; Plasmids ; Real-Time Polymerase Chain Reaction ; methods

Objective To investigate the effect of micro RNA-21 (miRNA-21) knocking on the Tb3.1 human tongue squamous cell carcinoma growth. Methods Anti-sense miRNA-21 oligonucleotide was delivered with oligofectamine to suppress Tb 3. 1 tongue cancer cell growth in vitro. Real-time polymerase chain reaction (PCR) was conducted to detect the miRNA-21 expression after transfection. Methyl thiazolyl tetrazolium(MTT) assay was used to determine Tb 3. 1 cell survival rate. Apoptosis were examined by flowcytometry. Matrigel matrix and transwell assay were used to determine Tb 3.1 cell colony formation and migration ability. Antigen KI-67 (Ki67), B cell lymphoma (Bcl-2), phosphatase and tensin homolog (PTEN), matrirx metalloproteinase 2(MMP-2, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) protein expression in Tb 3. 1 cell were measured by Western blotting. Results miRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3. 1 cells with AS-miRNA-21 transfection was significantly suppressed (F=27.02, P = 0.00) and early phase apoptosis(F =26. 641 ,P = 0. 001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein weredown regulated while PTEN and TIMP-1 protein expression was increased. Conclusions Blocking miRNA-21 expression in Tb3.1 cell could suppress cancer cell growth in vitro and miRNA-21 can serve as a novel target candidate for human tongue cancer gene therapy.

Objeclive To assess the effects of rhBNP on left ventrieular(LV)remodeling in rats with acute myocardial infaretion(AMI).Methods AMI was induced by ligating coronary arteryin male Sprague Dawley rats.Two days after surgery,AMI rats received intravenous infusion of rhBNP(15 μg/kg or 5 μg/kg once daily,n=15 each)or saline(placebo control,n=15)through Jugular Vein.Sham-operated mrs(a=15)served as normal control. Four weeks later,hemodynamie measurements were performed,left ventrieular weight (LVW),ratio of left ventfieular weight to body weight(LVW/BW),left ventrieular diameter(LVD)and infaret size were determined.P1asnla angiotensin Ⅱ and myocardial angiotensin Ⅱ levels were also measured.Results Compared with sham-operated rats,LVW,LVW/BW,LVD and myocardial angiotensin Ⅱ level were significantly increased,while the LV systolic pressure(LVSP),±dp/dt were significantly reduced in saline treated AMI rats(all P<0.05).LVW/BW,MI size,LVD and myocardial angiotensin Ⅱ in rhBNP treated AMI rats were significantly lower[LVW:(492.6±34.0)mg,(498.8±47.8)mg,(570.0±24.2)mg,P<0.01;LVW/BW:2.0±0.2,2.0±0.2,2.3±0.1,P<0.01;LVD:(25.3±2.9)%,(31.4±3.0)%,(46.4±3.0)%,P<0.01;myocardial angiotensin Ⅱ:(881.3±62.7)pg/L,(1186.0±94.5)pg/L,(2436.7±280.3)pg/L,P<0.05],while LVSP and ± dp/dt in rhBNP treatment groups were significantly increased than saline treated AMI rats f P<0.05 or P<0.01).Conclusion RhBNP is effective in attenuating left ventficular Itemodeling after AMI in rats.

OBJECTIVETo assess the value of routine intra-aortic balloon pump (IABP) support in patients with high-risk acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).

METHODSThe clinical data of 41 patients with high-risk AMI undergoing emergency PCI with routine IABP support were retrospectively reviewed, and 38 patients paired with the former group receiving emergency PCI for high-risk AMI without IABP support at the same time were included as the control group. Thirty days after the operation, the two groups were compared for myocardial ischemic events, left ventricular function and major adverse cardiac events (MACE).

RESULTSPatients receiving IABP support had a significantly lower incidence of myocardial ischemic events than those without IABP (4.9% vs 15.8%, P<0.05), and showed greater improvement in the left ventricular function. Significant differences were also observed in the mortality rate, incidence of reinfarction and revascularization rate between the two groups, but not in the rate of MACE.

CONCLUSIONPatients undergoing PCI for high-risk acute AMI can benefit from routine IABP support in terms of improvement of left ventricular function and reduce myocardial ischemic events and the rate of MACE. These results, however, still await further confirmation by large-scale clinical trials.

Angioplasty, Balloon, Coronary ; Female ; Humans ; Incidence ; Intra-Aortic Balloon Pumping ; methods ; Male ; Middle Aged ; Myocardial Infarction ; mortality ; therapy ; Myocardial Ischemia ; Retrospective Studies ; Treatment Outcome ; Ventricular Function, Left