Enhancing Drug Management, Cost Savings, and Staff Satisfaction in Anesthesiology: A Quality Improvement Project in a Chinese Tertiary Hospital.

INTRODUCTION: In alignment with China's national directive for improved drug management in anesthesiology, the Affiliated Hospital of Qingdao University initiated a quality improvement project, aiming to tackle the prevailing challenges of inefficiencies in drug administration, escalating drug costs, and the notable communication gap between pharmacists and anesthesiologists. METHODS: We employed a Plan-Do-Study-Act methodology to establish a pharmacy team and execute a multidimensional pharmaceutical intervention. The interventions included the formulation of standard procedures, guidelines and regulations, assistance from an information system (including automatic dispensing cabinets and prospective prescription review system), communication feedback (via WeChat groups), and education for anesthesiology staff. The intervention spanned from April to September 2023, focusing on optimizing medication management, achieving cost savings, and enhancing the satisfaction of anesthesia team members, with an additional observation from October to December 2023. RESULTS: Following the interventions, improvements were observed in drug management practices. These enhancements included increased compliance with accounting procedures, more rigorous registration of controlled substances, and more effective disposal of liquid residues. There was no adverse events related to high-alert medications or look-alike drug usage errors. The introduction of automatic dispensing cabinets and a prospective prescription review system markedly improved work efficiency. The utilization of a WeChat group facilitated effective communication about unreasonable prescriptions and drug-related issues. Among the 29,061 patients who underwent surgery both before and after the interventions, significant reductions were observed both in the drug proportion and the per capita drug costs (P = 0.03, P = 0.014, respectively). The per capita drug cost decreased by 20.82%, from ¥723.43 to ¥572.78, consistently remaining below ¥600 throughout the 9-month observation period. The per capita cost of monitoring drugs including dezocine, butorphanol, haemocoagulase agkistrodon, penehyclidine, and ulinastatin experienced a significant reduction (P < 0.05). Additionally, in the satisfaction questionnaires returned, a remarkable 94.44% of anesthesiology staff expressed high satisfaction with the comprehensive pharmaceutical interventions. CONCLUSION: The quality improvement project has yielded remarkable positive outcomes, serving as a model worthy of reference and replication in similar healthcare settings.

Diverse immune responses in vaccinated individuals with and without symptoms after omicron exposure during the recent outbreak in Guangzhou, China.

Objectives: During the recent wave of coronavirus disease 2019 (COVID-19) infections in China, most individuals have been vaccinated and exposed to the omicron variant. In the present study, two cohorts were observed in the vaccinated population: vaccinated individuals with symptoms (VIWS) and those without symptoms (VIWOS). Our study aimed to characterize the antibody response in two cohorts: VIWS and VIWOS. Methods: A questionnaire survey was conducted in the community. Blood and saliva samples were collected from 124 individuals in the VIWS and VIWOS cohorts. Capture enzyme-linked immunosorbent assay (ELISA) was performed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies. Results: The questionnaire survey revealed that 30.0 % (302/1005) of individuals in the older adult group (≥65 years) experienced no symptoms, whereas the rate of individuals without symptoms in the younger group (<65 years) was 17.8 % (166/932). Nucleocapsid (N)-specific IgM (N-IgM) was detected in the blood samples at a rate of 69.2 % (54/78) in the VIWS cohort. The positivity rate for N-specific IgA (N-IgA) was 93.6 % (73/78). In addition, the positivity rates of spike (S)-specific IgA (S-IgA) and N-IgA detected in saliva samples were 42 % (21/50) and 54 % (27/50), respectively. Both N-IgA positivity and negativity were observed in the VIWOS cohort. The detection rate of N-IgM positivity was 57.1 % (12/21) in the N-IgA-positive group. In addition, 54.3 % (25/46) of the vaccinated individuals without symptoms were IgA-negative. Conclusions: Our study indicates that substantial N-specific antibodies were induced during omicron infection and that testing for N-IgA in both blood and saliva may aid in the diagnosis of SARS-CoV-2 infection in vaccinated populations.

Patient-derived monoclonal antibodies to SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal domains cross-react with their counterparts of SARS-CoV, but not other human betacoronaviruses.

Introduction: SARS-CoV-2 nucleocapsid (N) protein plays a key role in multiple stages of the viral life cycle such as viral replication and assembly. This protein is more conserved than the Spike protein of the virus and can induce both humoral and cell-mediated immune responses, thereby becoming a target for clinical diagnosis and vaccine development. However, the immunogenic characteristics of this protein during natural infection are still not completely understood. Methods: Patient-derived monoclonal antibodies (mAbs) against SARS-CoV-2 N protein were generated from memory B cells in the PBMCs using the antigen-specific B cell approach. For epitope mapping of the isolated hmAbs, a panel of series-truncated N proteins were used , which covered the N-terminal domain (NTD, aa 46-174 ) and C-terminal domain (CTD, aa 245-364 ), as well as the flanking regions of NTD and CTD. NTD- or CTD-specific Abs in the plasma from COVID-19 patients were also tested by ELISA method. Cross-binding of hmAbs or plasma Abs in COVID-19 patients to other human ß-CoV N proteins was determined using the capture ELISA. Results: We isolated five N-specific monoclonal antibodies (mAbs) from memory B cells in the peripheral blood of two convalescent COVID-19 patients. Epitope mapping revealed that three of the patient-derived mAbs (N3, N5 and N31) targeted the C-terminal domain (CTD), whereas two of the mAbs (N83 and 3B7) targeted the N-terminal domain (NTD) of SARS-CoV-2 N protein. All five patient-derived mAbs were cross-reactive to the N protein of SARS-CoV but showed little to no cross-reactivity to the N proteins of other human beta coronaviruses (ß-CoVs). We also tested 52 plasma samples collected from convalescent COVID-19 patients for Abs against the N proteins of human ß-CoVs and found that 78.8% of plasma samples showed detectable Abs against the N proteins of SARS-CoV-2 and SARS-CoV. No plasma sample had cross-reactive Abs to the N protein of MERS-CoV. Cross-reactive Abs to the N proteins of OC43 and HKU1 were detected in 36.5% (19/52) and 19.2% (10/52) of plasma samples, respectively. Discussion: These results suggest that natural SARS-CoV-2 infection elicits cross-reactive Abs to the N protein of SARS-CoV and that the five patient-derived mAbs to SARS-CoV-2 N protein NTD and CTD cross-react with their counterparts of SARS-CoV, but not other human ß-CoVs. Thus, these five patient-derived mAbs can potentially be used for developing the next generation of COVID-19 At-Home Test kits for rapid and specific screening of SARS-CoV-2 infection.

Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study.

Acute myocardial infarction (AMI) is the most severe form of coronary heart disease caused by ischemia and hypoxia. The study is aimed at investigating the role of neuropeptides and the mechanism of electroacupuncture (EA) in acute myocardial infarction (AMI) treatment. Compared with the normal population, a significant increase in substance P (SP) was observed in the serum of patients with AMI. PGI2 expression was increased in the SP-treated AMI mouse model, and TXA2 expression was decreased. And PI3K pathway-related genes, including Pik3ca, Akt, and Mtor, were upregulated in myocardial tissue of SP-treated AMI patients. Human cardiomyocyte cell lines (HCM) treated with SP increased mRNA and protein expression of PI3K pathway-related genes (Pik3ca, Pik3cb, Akt, and Mtor). Compared to MI control and EA-treated MI rat models, Myd88, MTOR, Akt1, Sp, and Irak1 were differentially expressed, consistent with in vivo and in vitro studies. EA treatment significantly enriched PI3K/AKT signaling pathway genes within MI-associated differentially expressed genes (DEGs) according to Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, it was confirmed by molecular docking analysis that PIK3CA, AKT1, and mTOR form stable dockings with neuropeptide SP. PI3K/AKT pathway activity may be affected directly or indirectly by EA via SP, which corrects the PGI2/TXA2 metabolic imbalance in AMI. MI treatment is now better understood as a result of this finding.

Risk Factors and Incidence of Malignancy After Kidney Transplant in Mainland China: A Single-Center Analysis.

OBJECTIVES: Malignancy is a common cause of death in renal transplant patients. The aim of this study was to investigate incidence, risk factors, and survival rates associated with posttransplant malignancy in kidney transplant recipients. MATERIALS AND METHODS: Between January 2015 and December 2020, 1154 patients underwent kidney transplant at the Affiliated Hospital of Qingdao University. Patients with a history of malignancy or other organ transplant(liver, pancreas, heart, orlungs) were excluded from this study. Patients with incomplete follow-up records were also excluded. Ultimately, our study comprised 811 kidney transplant recipients. The patient characteristics and incidence, type, and risk factors associated with posttransplant malignancy were examined. We also analyzed the overall survival of recipients with posttransplant malignancy. RESULTS: A total of 811 renal transplant recipients were followed up, with a median follow-up period of 3.0 years. Fourteen kidney recipients developed posttransplant malignancy (1.7%), with a mean time to malignancy diagnosis of 2.7 years. The 3-year and 5-year overall survival rates were 91.7% and 91.7%, respectively, in recipients with malignancy and 99.2% and 98.8%, respectively, in recipients without malignancy. The overall survival rate was significantly higher in recipients without malignancy than in those with malignancy (P = .03). Female sex, older recipient age, and history of prior kidney transplant were significant predictors of malignancy development. CONCLUSIONS: Postoperative malignancy in kidney transplantrecipients was associated with lower overall survival rates. Malignancy screening is important for kidney transplant patients, especially for older women and patients with a history of prior kidney transplant.

Abnormal larval neuromuscular junction morphology and physiology in Drosophila prickle isoform mutants with known axonal transport defects and adult seizure behavior.

Previous studies have demonstrated the striking mutational effects of the Drosophila planar cell polarity gene prickle (pk) on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the prickle-prickle (pkpk) and prickle-spiny-legs (pksple) isoforms (hereafter referred to as pk and sple alleles, respectively) exhibit differential phenotypes. While both pk and sple affect larval motor axon transport, only sple confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic pkpk/pksple flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both pk and sple alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in pk/pk larvae, i.e. increased excitatory junctional potential (EJP) amplitude in pk/pk but not in pk/+ or sple/sple. Interestingly, for motor terminal excitability sustained by presynaptic Ca2+ channels, both pk and sple exerted strong effects to produce prolonged depolarization. Notably, only sple acted dominantly whereas pk/+ appeared normal, but was able to suppress the sple phenotypes, i.e. pk/sple appeared normal. Our observations contrast the differential roles of the pk and sple isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.

Effects of Early Acupuncture Combined with Rehabilitation Training on Limb Function and Nerve Injury Rehabilitation in Elderly Patients with Stroke: Based on a Retrospective Cohort Study.

Objective: A case-control study was conducted to explore the effect of acupuncture combined with rehabilitation training on limb function and nerve injury rehabilitation in elderly patients with stroke. Methods: A total of 72 elderly patients with stroke treated from March 2019 to June 2021 in our hospital were enrolled as the object of study. The clinical data were collected and divided into two groups according to their different treatment methods. The patients cured with routine treatment combined with rehabilitation training were taken as the control group and the patients cured with acupuncture combined with rehabilitation training as the study group. The clinical efficacy was recorded, and the cognition and activities of daily living were evaluated by Terrell Cognitive Assessment scale, limb motor function score, and activities of daily living scale. The National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) were employed to compare the neurological function before and after treatment. Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) were adopted to evaluate the functional prognosis. The simplified Fugl-Meyer assessment of motor recovery score was employed to evaluate the limb function of the patients. The Wolf Motor Function Test (WMFT) score was adopted to evaluate the functional rehabilitation effect of the patients. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the serum neurological function indexes such as nerve growth factor, Smur100B protein, and glial fibrillary acidic protein. The cerebral blood flow (CBF), peak time, average transit time, and cerebral blood volume were measured by CT perfusion imaging, and the incidence of side effects during treatment was recorded. Results: Regarding the recovery of cognitive function and daily function after treatment, after treatment, the MoCA and ADL scores were increased, and the comparison indicated that the MoCA and ADL scores of the study group were remarkably higher compared to the control group (P < 0.05). With regard to the FMA-UE scores after treatment, the Fugl-Meyer scores were gradually increased, and the Fugl-Meyer scores in the study group were remarkably higher compared to the control group (P < 0.05) in the next two months. After 2 weeks, 4 weeks, 6 weeks, and 6 weeks of treatment, the WMFT scores gradually increased, and the WMFT score of the study group was remarkably higher compared to the control group. After treatment, the levels of nerve growth factor and S-100B protein were decreased, and the level of glial fibrillary acidic protein was increased. Comparison between the two groups, it indicated the improvement degree of each neurological function index in the study group was remarkably better (P < 0.05). With regard to cerebral hemodynamic indexes after treatment, 1 week after treatment, the CBF and average transit time of the observation group were remarkably higher compared to the control group, and the levels of cerebral blood volume and peak time were remarkably lower compared to the control group (P < 0.05). After 4 weeks of treatment, the cerebral hemodynamic indexes of the observation group did not change remarkably, and they were all lower than 1 week after the treatment. In the terms of side effects, 1 case of limb dysfunction, 1 case of swallowing dysfunction, 1 case of electrolyte disturbance, and none of infection in the study group, the incidence of adverse reactions was 8.33%. In the control group, there were 3 cases of limb dysfunction, 2 cases of swallowing dysfunction, 2 cases of electrolyte disturbance, and 3 cases of infection, and the incidence of adverse reactions was 27.78%. Compared between groups, the incidence of adverse reactions in the study group was lower (P < 0.05). Conclusion: Early use of acupuncture combined with rehabilitation training has a remarkable therapeutic effect on elderly stroke patients. It can remarkably promote the recovery of the patient's condition, remarkably enhance their neurological function, cognitive function, motor function, and daily life function, and effectively strengthen the patient's prognosis score. It has important clinical application value to reduce the incidence of adverse reactions.

STAT1: a novel candidate biomarker and potential therapeutic target of the recurrent aphthous stomatitis.

BACKGROUND: The recurrent aphthous stomatitis (RAS) frequently affects patient quality of life as a result of long lasting and recurrent episodes of burning pain. However, there were temporarily few available effective medical therapies currently. Drug target identification was the first step in drug discovery, was usually finding the best interaction mode between the potential target candidates and probe small molecules. Therefore, elucidating the molecular mechanism of RAS pathogenesis and exploring the potential molecular targets of medical therapies for RAS was of vital importance. METHODS: Bioinformatics data mining techniques were applied to explore potential novel targets, weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of the gene chip data from GSE37265, and the hub genes were identified by the Molecular Complex Detection (MCODE) plugin. RESULTS: A total of 16 co-expression modules were identified, and 30 hub genes in the turquoise module were identified. In addition, functional analysis of Hub genes in modules of interest was performed, which indicated that such hub genes were mainly involved in pathways related to immune response, virus infection, epithelial cell, signal transduction. Two clusters (highly interconnected regions) were determined in the network, with score = 17.647 and 10, respectively, cluster 1 and cluster 2 are linked by STAT1 and ICAM1, it is speculated that STAT1 may be a primary gene of RAS. Finally, genistein, daidzein, kaempferol, resveratrol, rosmarinic acid, triptolide, quercetin and (-)-epigallocatechin-3-gallate were selected from the TCMSP database, and both of them is the STAT-1 inhibitor. The results of reverse molecular docking suggest that in addition to triptolide, (-)-Epigallocatechin-3-gallate and resveratrol, the other 5 compounds (flavonoids) with similar structures may bind to the same position of STAT1 protein with different docking score. CONCLUSIONS: Our study identified STAT1 as the potential biomarkers that might contribute to the diagnosis and potential therapeutic target of RAS, and we can also screen RAS therapeutic drugs from STAT-1 inhibitors.

Benzoylaconine Modulates LPS-Induced Responses Through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells.

Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1ß, ROS, NO, and PGE2. BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. The protein expression of Toll-like receptor 4 (TLR4) and LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of TLR-induced MAPK and NF-κB signaling, were inhibited by BAC in activated RAW264.7 macrophages. Moreover, BAC decreased the levels of TAK1 phosphorylation and pro-inflammatory cytokines and mediators associated with MAPK and NF-κB activation, similar to TLR4 inhibitor TAK-242. These findings demonstrated that BAC exhibited an anti-inflammatory effect by the inhibition of TLR-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.

Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins.

Gastric cancer (GC) is one of the most malignant tumors, accounting for 10% of deaths caused by all cancers. Chemotherapy is often necessary for treatment of GC; the FOLFOX regimen is extensively applied. However, multidrug resistance (MDR) of GC cells prevents wider application of this treatment. Ubenimex, an inhibitor of CD13, is used as an immune adjuvant to treat hematological malignancies. Here, we demonstrate that CD13 expression positively correlates with MDR development in GC cells. Moreover, Ubenimex reverses the MDR of SGC7901/X and MKN45/X cells and enhances their sensitivity to FOLFOX, in part by decreasing CD13 expression, which is accompanied by downregulation of Bcl-xl, Bcl-2, and survivin expression; increased expression of Bax; and activation of the caspase-3-mediated apoptotic cascade. In addition, Ubenimex downregulates expression of membrane transport proteins, such as P-gp and MRP1, by inhibiting phosphorylation in the PI3K/AKT/mTOR pathway to increase intracellular accumulations of 5-fluorouracil and oxaliplatin, a process for which downregulation of CD13 expression is essential. Therefore, the present results reveal a previously uncharacterized function of CD13 in promoting MDR development in GC cells and suggest that Ubenimex is a candidate for reversing the MDR of GC cells.

Ubenimex induces autophagy inhibition and EMT suppression to overcome cisplatin resistance in GC cells by perturbing the CD13/EMP3/PI3K/AKT/NF-κB axis.

Cisplatin (CDDP)-based chemotherapy is a standard treatment for gastric cancer (GC). However, chemoresistance is a major obstacle for CDDP application. Exploring underlying mechanisms of CDDP resistance development in GC and selecting an effective strategy to overcome CDDP resistance remain a challenge. Here, we demonstrate that a transmembrane ectoenzyme, CD13, endows GC patients with insensitivity to CDDP and predicts an undesirable prognosis in GC patients with CDDP treatment. Similarly, CD13 expression is positively related with CDDP resistance in GC cells. A CD13 inhibitor, Ubenimex, reverses CDDP resistance and renders GC cells sensitivity to CDDP, for which CD13 reduction is essential, and epithelial membrane protein 3 (EMP3) is a putative target downstream of CD13. Furthermore, Ubenimex decreases EMP3 expression by boosting its CpG island hypermethylation for which CD13 down-regulation is required. In addition, EMP3 is a presumptive modifier by which CD13 exerts functions in the phosphoinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. Ubenimex inhibits the activation of the CD13/EMP3/PI3K/AKT/NF-κB pathway to overcome CDDP resistance in GC cells by suppressing autophagy and epithelial-mesenchymal transition (EMT). Therefore, CD13 is a potential indicator of CDDP resistance formation, and Ubenimex may serve as a potent candidate for reversing CDDP resistance in GC.

Inter-relationships among physical dimensions, distal-proximal rank orders, and basal GCaMP fluorescence levels in Ca2+ imaging of functionally distinct synaptic boutons at Drosophila neuromuscular junctions.

GCaMP imaging is widely employed for investigating neuronal Ca2+ dynamics. The Drosophila larval neuromuscular junction (NMJ) consists of three distinct types of motor terminals (type Ib, Is and II). We investigated whether variability in synaptic bouton sizes and GCaMP expression levels confound interpretations of GCaMP readouts, in inferring the intrinsic Ca2+ handling properties among these functionally distinct synapses. Analysis of large data sets accumulated over years established the wide ranges of bouton sizes and GCaMP baseline fluorescence, with large overlaps among synaptic categories. We showed that bouton size and GCaMP baseline fluorescence were not confounding factors in determining the characteristic frequency responses among type Ib, Is and II synapses. More importantly, the drastic phenotypes that hyperexcitability mutations manifest preferentially in particular synaptic categories, were not obscured by bouton heterogeneity in physical size and GCaMP expression level. Our data enabled an extensive analysis of the distal-proximal gradient of GCaMP responses upon genetic and pharmacological manipulations. The results illustrate the conditions that disrupt or enhance the distal-proximal gradients. For example, stimulus frequencies just above the threshold level produced the steepest gradient in low Ca2+ (0.1 mM) saline, while supra-threshold stimulation flattened the gradient. Moreover, membrane hyperexcitability mutations (eag1 Sh120 and parabss1) and mitochondrial inhibition by dinitrophenol (DNP) disrupted the gradient. However, a novel distal-proximal gradient of decay kinetics appeared after long-term DNP incubation. We performed focal recording to assess the failure rates in transmission at low Ca2+ levels, which yielded indications of a mild distal-proximal gradient in release probability.

Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and Aminergic Modulatory Motor Terminals in Drosophila.

GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications. Different GCaMP variants were applied in genetic and pharmacological perturbation experiments to examine the Ca2+ influx and clearance processes underlying the GCaMP signal. Distinct mutational and drug effects on GCaMP signals indicate differential roles of Na+ and K+ channels, encoded by genes including paralytic (para), Shaker (Sh), Shab, and ether-a-go-go (eag), in excitability control of different motor terminals. Moreover, the Ca2+ handling properties reflected by the characteristic frequency dependence of the synaptic GCaMP signals were determined to a large extent by differential capacity of mitochondria-powered Ca2+ clearance mechanisms. Simultaneous focal recordings of synaptic activities further revealed that GCaMPs were ineffective in tracking the rapid dynamics of Ca2+ influx that triggers transmitter release, especially during low-frequency activities, but more adequately reflected cytosolic residual Ca2+ accumulation, a major factor governing activity-dependent synaptic plasticity. These results highlight the vast range of GCaMP response patterns in functionally distinct synaptic types and provide relevant information for establishing basic guidelines for the physiological interpretations of presynaptic GCaMP signals from in situ imaging studies.

Generation and characterization of new alleles of quiver (qvr) that encodes an extracellular modulator of the Shaker potassium channel.

Our earlier genetic screen uncovered a paraquat-sensitive leg-shaking mutant quiver1 (qvr1), whose gene product interacts with the Shaker (Sh) K+ channel. We also mapped the qvr locus to EY04063 and noticed altered day-night activity patterns in these mutants. Such circadian behavioral defects were independently reported by another group, who employed the qvr1 allele we supplied them, and attributed the extreme restless phenotype of EY04063 to the qvr gene. However, their report adopted a new noncanonical gene name sleepless (sss) for qvr. In addition to qvr1 and qvrEY, our continuous effort since the early 2000s generated a number of novel recessive qvr alleles, including ethyl methanesulfonate (EMS)-induced mutations qvr2 and qvr3, and P-element excision lines qvrip6 (imprecise jumpout), qvrrv7, and qvrrv9 (revertants) derived from qvrEY. Distinct from the original intron-located qvr1 allele that generates abnormal-sized mRNAs, qvr2, and qvr3 had their lesion sites in exons 6 and 7, respectively, producing nearly normal-sized mRNA products. A set of RNA-editing sites are nearby the lesion sites of qvr3 and qvrEY on exon 7. Except for the revertants, all qvr alleles display a clear ether-induced leg-shaking phenotype just like Sh, and weakened climbing abilities to varying degrees. Unlike Sh, all shaking qvr alleles (except for qvrf01257) displayed a unique activity-dependent enhancement in excitatory junction potentials (EJPs) at larval neuromuscular junctions (NMJs) at very low stimulus frequencies, with qvrEY displaying the largest EJP and more significant NMJ overgrowth than other alleles. Our detailed characterization of a collection of qvr alleles helps to establish links between novel molecular lesions and different behavioral and physiological consequences, revealing how modifications of the qvr gene lead to a wide spectrum of phenotypes, including neuromuscular hyperexcitability, defective motor ability and activity-rest cycles.

Association between DPP4 gene polymorphism and serum lipid levels in Chinese type 2 diabetes individuals.

OBJECTIVE: The goal of the genetic investigation was to identify the associations of serum lipid levels and DPP-4 variants in Chinese type 2 diabetes patients. METHODS: We detected four variants of the DPP4 gene in 190 Chinese individuals with type 2 diabetes and tested for an association with dyslipidemia in 82 selected samples. Data including basic information, HbA1c, FPG, serum lipid parameters were collected. Statistical analysis was performed by SPSS 13.0 through ANOVA and χ2 test. RESULTS: The genetic polymorphism of rs4664443, rs3788979, rs7608798 and rs1558957 in Chinese type 2 diabetes were consistent with Hardy-Weinberg equilibrium. The CT genotype of rs4664443 suffered from higher serum TG (P=0.013), LDL (P=0.044) and ApoB (P=0.006) levels, whereas the TT genotype of rs7608798 exhibited a lower serum TG level (P=0.037). For rs3788979, the serum TG level (P=0.034) and BMI (P=0.04) were significantly different among genotypes. Moreover, serum TG and TC levels and BMI showed a positive correlation with the number unfavorable alleles, and individuals with more than two unfavorable alleles had higher TG (P=0.004), TC (P=0.011), and BMI (P=0.044) values. CONCLUSIONS: This is the first study to investigate DPP4 allelic distributions and their association with dyslipidemia in Chinese type 2 diabetes patients, which may have clinical significance.

[Effect on blood pressure and microcirculation of nail fold in primary hypertension patients treated with acupuncture according to syndrome differentiation].

OBJECTIVE: To verify the efficacy of primary hypertension treated with acupuncture at acupoints selected according to syndrome differentiation and probe into the mechanism of acupuncture for primary hypertension. METHODS: One hundred and thirty-five cases of primary hypertension were randomized into an observation group (108 cases) and a control group (27 cases). In either group, Fengchi (GB 20), Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6) were selected conventionally. In observation group, on the basis of the acupoints selected above, the supplementary points were selected according to syndrome differentiation in Chinese medicine and the control group was selected main points only, once per day. After 15 days acupuncture, the efficacy and changes in microcirculation of nail fold were observed. RESULTS: The remarkable effective rate and the total effective rate were 29.6% (32/108) and 84.2% (91/108) in observation group respectively, which were superior to 18. 5% (5/27) and 70.4% (19/27) as compared with control group separately (both P < 0.05). After treatment, the microcirculation of nail fold was all improved in two groups, of which blood flow state integral, peripheral capillary loop state integral and the total integral were all improved obviously (all P < 0.05). The improvements in observation group were much more significant than those in control group (all P < 0.05). CONCLUSION: Acupuncture is effective significantly on primary hypertension and the point selection according to syndrome differentiation can improve the efficacy, which is probably relevant with the reduction in the peripheral vascular resistance due to the improvements of microcirculatory state in mechanism.

[Observation on therapeutic effect of Yongquan (KI 1) acupoint sticking therapy on infantile nasal obstruction].

OBJECTIVE: To search for an effective therapy for infantile nasal obstruction. METHODS: One hundred and twenty-five cases were randomly divided into an observation group of 62 cases and a control group of 63 cases. The observation group were treated with bilateral Yongquan (KI 1) application with Biyankang Tablet, once each night and the control group with dropping of 0.5% Ephedrine naristillae into the nose, one drop each nose each time, tid. The score for nasal obstruction were recorded before treatment and the third and the fifth days after treatment, and their therapeutic effects were assessed. RESULTS: After treatment, the symptom of nasal obstruction was significantly improved in the two groups (P < 0.01), with no significant difference between the two groups (P > 0.05). After treatment for 5 days, the effective rate was 76.8% in the observation group and 79.7% in the control group, their therapeutic effect being similar (P > 0.05). CONCLUSION: Yongquan (KI 1) acupoint sticking therapy is a safe and effective method for infantile nasal obstruction.