[Safety of modified T-piece resuscitator versus nasal cannula oxygen in electronic bronchoscopy for infants: a prospective randomized controlled study]. / 改良Tç»„åˆå¤è‹å™¨ä¸Žé¼»å¯¼ç®¡å¸æ°§ç”¨äºŽå©´å„¿ç”µå­æ”¯æ°”ç®¡é•œæ£€æŸ¥çš„å®‰å ¨æ€§æ¯”è¾ƒï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy. METHODS: A prospective randomized, controlled, and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021. These infants were divided into a nasal cannula (NC) group and a modified T-piece resuscitator (TPR) group using a random number table. The lowest intraoperative blood oxygen saturation was recorded as the primary outcome, and intraoperative heart rate and respiratory results were recorded as the secondary outcomes. RESULTS: Compared with the NC group, the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia (P<0.05). In the modified TPR group, there were 6 infants with mild hypoxemia, 2 with moderate hypoxemia, and 1 with severe hypoxemia, while in the NC group, there were 3 infants with mild hypoxemia, 5 with moderate hypoxemia, and 9 with severe hypoxemia (P<0.05). The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group (P<0.05), but there was no significant difference in the incidence rate of arrhythmias between the two groups (P>0.05). CONCLUSIONS: Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy, and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.

[Clinical characteristics of children with Omicron variant infection in Chengdu area, China]. / 成都地区Omicronå˜å¼‚æ ªæ„ŸæŸ“å„¿ç«¥çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Chengdu of China. METHODS: A retrospective analysis was conducted for the clinical data of 226 children who were infected with the Omicron variant of SARS-Cov-2 and were isolated and treated in Chengdu Shelter Hospital from August 28 to September 21, 2022. According to the presence or absence of clinical symptoms, they were divided into two groups: asymptomatic group and mild symptomatic group. The two groups were compared in terms of clinical characteristics, diagnosis and treatment, and prognosis. RESULTS: Among the 226 children infected with the Omicron variant, 71 (31.4%) were asymptomatic and 155 (68.6%) had mild symptoms. Fever and cough were the most common clinical symptoms, with fever in 95 children (61.3%) and cough in 92 children (59.4%). Of all 226 children, 188 (83.2%) received coronavirus disease 2019 (COVID-19) vaccination. The time to nucleic acid clearance ranged from 6 to 26 days, with a nucleic acid clearance rate of 58.0% (131/226). There were no significant differences among different age groups in sex, early symptoms, clinical typing, nucleic acid re-positive rate, nucleic acid clearance rate, and length of hospital stay (P>0.05). There were no significant differences between the asymptomatic and mild symptomatic groups in age, sex, underlying diseases, COVID-19 vaccination, use of Lianhua Qingwen granules, nucleic acid clearance rate, nucleic acid re-positive rate, and length of hospital stay (P>0.05). CONCLUSIONS: Children infected with the Omicron variant of SARS-Cov-2 in Chengdu generally have mild clinical symptoms, mainly upper respiratory tract infection, which has little threat to the health of children of different ages, and children tend to have a good overall prognosis.

[Clinical Study on Early Extubation and Sequential Non-Invasive Respiratory Support for Children with Acute Respiratory Failure Receiving Invasive Mechanical Ventilation].

Objective: To explore the treatment outcome of the strategy of early extubation and then switching to non-invasive mechanical ventilation in children with acute respiratory failure, and the safety and feasibility of using the strategy to replace traditional methods. Methods: A total of 102 children, aged between 1 month to 14 years old, who had acute respiratory failure and were admitted to the pediatric ICU of West China Second University Hospital, Sichuan University between January 2019 and December 2020 were enrolled and randomly assigned to treatment group 1 (n=55) and treatment group 2 (n=47). In addition, 53 children who had the same condition in the 12 month prior to the beginning of the study were included in the control group. In the two treatment groups, the patients were extubated first, and then weaned off the ventilator. In group 1, when the patient met the invasive-non-invasive switching criteria, the tracheal tube was pulled out and non-invasive bi-level positive airway pressure (BiPAP) ventilation was used for respiratory support. In group 2, high-flow nasal cannula (HFNC) oxygen therapy was used for respiratory support. The traditional progressive weaning method was adopted for the control group (extubing and weaning were performed at the same time). The incidence of ventilator-associated pneumonia (VAP) during the period of tracheal intubation was compared and the mortality of the two groups was evaluated from the point when the patients were recruited. At the time of extubation in the treatment groups and extubation plus weaning in the control group, the pressure support levels, or PC above PEEP, intubation time, sequential time (between 2 treatment groups only), weaning failure rate, and the incidence of laryngeal edema and nasal pressure ulcer were compared. Results: The subjects of the study were predominantly infants (93 cases, 60%) and young children (31 cases, 20%). Among the 155 cases, 82 (53%) were male. There was no statistical difference in age distribution or gender among the groups. There was no significant difference in the clinical indicators among the three groups before tracheal intubation. At the time of extubation, the PC above PEEP in the two treatment groups was higher than that in the control group, and higher in group 1 than that of group 2, the difference being statistically significant (P<0.05). The intubation time of the two treatment groups was shorter than that of the control group, and shorter in group 1 than that of group 2 (P<0.05). The sequential time of group 2 was shorter than that of group 1 (P<0.05). The extubation failure rate and the incidence of VAP in the two treatment groups were lower than those in the control group, and there was no statistically significant difference between the two treatment groups. The incidence of nasal pressure ulcers in group 1 was higher than that in the other two groups (P<0.05). There was 1 death in treatment group 1, and no deaths in treatment group 2 or the control group. There was no significant difference in mortality or the incidence of laryngeal edema after extubation in the three groups. Conclusion: Early extubation and then switching to non-invasive mechanical ventilation can be well tolerated by the patients, and can be used in clinical practice as an effective weaning method for children with acute respiratory failure.

[Analysis of the Characteristics of the Outcomes of Job-Transfer Subspecialty Training Program in Pediatrics in Sichuan].

Objective: To discuss the characteristics of physician trainee outcomes after completion of the job-transfer subspecialty training in pediatrics, a program designed to increase the number of pediatricians, in Sichuan Province and to provide countermeasures for alleviating the shortage of pediatricians. Methods: We collected with questionnaire surveys information on changes in the workload and salaries experienced by physicians who completed the job-transfer subspecialty training program in pediatrics between February 2017 and May 2020 in Sichuan Province. Then, we compared the characteristics of physicians who successful became pediatricians and those who did no. Results: A total of 208 physicians completed the job-transfer subspecialty training program in pediatrics. Among them, 178, accounting for 85.6%, completed the questionnaire survey, and 120, accounting for 67.4%, had a background in other subspecialties than pediatrics. The majority (>90%) of physicians who participated in the training program came from secondary or lower levels of hospitals from the cities and prefectures all over Sichuan Province. In this study, we found that the rate of successful job transfer from being a physician to being a pediatrician in Sichuan Province in the past four years was 85.0% (102/120), with the year-by-year results being 88.2% (15/17) in 2017, 72.7% (16/22) in 2018, 86.7% (39/45) in 2019, and 94.% (32/34) in 2020. There was no significant difference between physicians who had successful job transfer and became pediatricians and those who failed to do so in terms of gender, age, hospital level, specialization prior to the job transfer, whether or not the hospital had a pediatrics department, amount of support for the pediatrics department, whether or not the physician was working at a new hospital after the job transfer, salaries, and changes of responsibilities during COVID-19 (all P>0.05). There was significant difference in the change of workload after completion of the training program between physicians who had successful job transfer and became pediatricians and those who failed to do so ( χ 2=9.037, P=0.003), and 78.4% of the trainees stated that their workload had increased after the job transfer. There was a moderate correlation between successful job transfer and changes in workload after the transfer (|Phi[ψ] |=0.729). Conclusions: The policy of government-supported job-transfer subspecialty training in pediatrics has played an active and important role in the swift resolution of the shortage of pediatricians. However, finding the root cause of and addressing the problem of the overwhelming workload of pediatricians remain challenging issues to be resolved.

Value of heparin-binding protein in the diagnosis of severe infection in children: a prospective study. / è‚ç´ ç»“åˆè›‹ç™½å¯¹å„¿ç«¥é‡ç—‡æ„ŸæŸ“è¯Šæ–­ä»·å€¼çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the value of heparin-binding protein (HBP) in the diagnosis of severe infection in children. METHODS: This study was a prospective observational study. The medical data of children who were admitted to the pediatric intensive care unit due to infection from January 2019 to January 2020 were collected. According to the diagnostic criteria for severe sepsis and sepsis, the children were divided into a severe sepsis group with 49 children, a sepsis group with 82 children, and a non-severe infection group with 33 children. The three groups were compared in terms of related biomarkers such as plasma HBP, serum C-reactive protein, serum procalcitonin, and platelet count. The receiver operating characteristic (ROC) curve was plotted to investigate the value of plasma HBP level in the diagnosis of severe infection (including severe sepsis and sepsis). RESULTS: The severe sepsis and sepsis groups had a significantly higher plasma HBP level on admission than the non-severe infection group (P<0.05). Compared with the sepsis and non-severe groups, the severe sepsis group had significantly higher serum levels of C-reactive protein and procalcitonin and a significantly lower platelet count (P<0.05). Plasma HBP level had an area under the ROC curve of 0.590 in determining severe infection, with a sensitivity of 38.0% and a specificity of 82.4% (P<0.05). CONCLUSIONS: There is an increase in plasma HBP level in children with severe infection, and plasma HBP level has a lower sensitivity but a higher specificity in the diagnosis of severe infection and can thus be used as one of the markers for the judgment of severe infection in children.

[Value of metagenomic next-generation sequencing in children with hemophagocytic syndrome with central nervous system involvement]. / å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨ä¼´æœ‰ä¸­æž¢ç¥žç»ç³»ç»Ÿå—ç´¯å„¿ç«¥å™¬è¡€ç»†èƒžç»¼åˆå¾ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the value of metagenomic next-generation sequencing (mNGS) in detecting intracranial Epstein-Barr virus (EBV) infection in children with hemophagocytic syndrome (HPS) with central nervous system involvement. METHODS: A retrospective analysis was performed for the cerebrospinal fluid mNGS results of 30 HPS children with central nervous system involvement, which were compared with the results of cerebrospinal fluid EBV-DNA detection and serum EBV antibody profile. The change in serum EBV-DNA copy number after treatment was used to evaluate the efficacy of targeted therapy. RESULTS: The positive rate of EBV in cerebrospinal fluid determined by mNGS was significantly higher than that of EBV-DNA in cerebrospinal fluid (100% vs 10%, P<0.001) and had no significant difference from the positive rate of serum EBV antibody profile (100% vs 93%, P>0.05). The median number of sequences determined by mNGS was 2 400, and serum EBV-DNA copy number before treatment was moderately positively correlated with the number of EBV sequences (rs=0.693, P<0.001). The multiple linear regression analysis showed that the number of sequences determined by mNGS in cerebrospinal fluid increased with the increase in serum EBV-DNA copy number before treatment (P<0.05). CONCLUSIONS: EBV-associated HPS often results in EBV-infected viral encephalitis, and mNGS can significantly increase the detection rate of EBV in cerebrospinal fluid, which may help with clinical diagnosis.

[Clinical features and antibiotic sensitivity of invasive pneumococcal disease versus noninvasive pneumococcal disease in children].

OBJECTIVE: To analyze the clinical data of children with invasive pneumococcal disease (IPD) or noninvasive pneumococcal disease (NIPD), and to provide a reference for clinical diagnosis and treatment. METHODS: A retrospective analysis was performed on the medical data and the drug susceptibility test results of isolated strains of 518 children who were hospitalized due to Streptococcus pneumoniae (SP) infection from January 2013 to December 2017. According to the location of the isolated strains, the children were divided into an IPD group with 35 children and an NIPD group with 483 children. RESULTS: The children with IPD had a median age of 2.2 years, and the children aged ≤5 years accounted for 80.0%. For the children with IPD, the main type of infection was meningitis which was observed in 19 children (54.3%), and the most common underlying disease was hematological malignancy in 8 children (22.9%); 14 children (40.0%) were admitted to the pediatric intensive care unit (PICU), 18 children (51.4%) experienced complications, and 8 children (22.9%) died. For the children with NIPD, the median age was 1.2 years; the main type of infection was pneumonia in 429 children (88.8%), and the most common underlying disease was congenital heart disease in 60 children (12.4%); 60 children (12.4%) were admitted to the PICU, 102 children (21.1%) experienced complications, and 11 children (2.3%) died. The IPD group had significantly higher incidence rate of complications, PICU admission rate, and mortality rate than the NIPD group (P < 0.01). The invasive SP strains had a significantly lower susceptibility rate to penicillin than noninvasive SP strains (68.6% vs 94.2%, P < 0.01). CONCLUSIONS: SP infection is common in children under 5 years of age, and the children with underlying diseases including hematological malignancy are at high risk for IPD. Although the complication rate, PICU admission rate, and mortality rate of NIPD children are lower than those of IPD children, they still cannot be ignored. Penicillin may be used as an empirical treatment for children with NIPD, but not for those with IPD.

[High-risk factors for early failure of high-flow nasal cannula oxygen therapy in children].

OBJECTIVE: To determine the high-risk factors for early failure of high-flow nasal cannula (HFNC) oxygen therapy in children with acute respiratory insufficiency (ARI). METHODS: The clinical data of 123 children with ARI were reviewed who received HFNC oxygen therapy in the pediatric intensive care unit from January to June, 2018. The children who did not require an upgrade of respiratory support during hospitalization and were successfully weaned from HFNC were classified as HFNC success group (69 cases). Of the remaining children (54 cases) who required an upgrade of their respiratory support during hospitalization, those that needed to upgrade their respiratory support within 48 hours of receiving HFNC were classified as early HFNC failure group (46 cases). Risk factors for early failure of HFNC were determined using multivariate logistic regression analysis. RESULTS: The incidence rates of shock, sepsis, intracranial hypertension syndrome, and multiple organ dysfunction syndrome were significantly higher in the early HFNC failure group than in the HFNC success group (P<0.05). Before implementation of respiratory support, the early HFNC failure group had significantly lower Glasgow coma score, pH value, and oxygenation index and significantly higher Pediatric Risk of Mortality (PRISM) score and PaCO2/PaO2 ratio than the HFNC success group (P<0.05). Multivariate logistic regression analysis showed that PRISM score >4.5 and PaCO2/PaO2 ratio >0.64 were independent risk factors for early HFNC failure (OR=5.535 and 9.089 respectively; P<0.05). CONCLUSIONS: Pediatric ARI patients with PRISM score >4.5 or PaCO2/PaO2 ratio >0.64 have relatively high risk of early HFNC failure.

Carbon-Dots-Based Lab-On-a-Nanoparticle Approach for the Detection and Differentiation of Antibiotics.

Fluorescent carbon dots (CDs) have received considerable attention in recent years due to their superior optical properties. To take further advantages of these unique features, herein, a CDs-based "lab-on-a-nanoparticle" approach for the detection and discrimination of antibiotics is developed. The sensing platform was designed based on the different channel's fluorescence recoveries or further quenching of the full-color emissive CDs (F-CDs) and metal ion ensembles upon the addition of antibiotics. The F-CDs exhibited unusually comparable emission intensity nearly across the entire visible spectrum even as the excitation wavelength is shifted, making it very suitable for the construction of multi-channel sensing systems. The sensing platform was fabricated on the basis of the competing interaction of metal ions with the F-CDs and antibiotics. Three metal ions (i.e., Cu2+ , Ce3+ and Eu3+ ) can efficiently quench the fluorescence of the F-CDs. Upon the addition of antibiotics, the fluorescent intensities either recovered at different emission wavelengths or were further quenched to various degrees. The fluorescence response patterns at different emission wavelength were characteristic for each antibiotic and can be quantitatively differentiated by standard statistical methods (e.g., hierarchical clustering analysis and principal component analysis). Moreover, as an example, the proposed method was applied for quantitative detection of oxytetracycline with a limit of detection to be 0.06 µm. Finally, the sensing system was successfully employed for residual antibiotics detection and identification in real food samples.

Repeated electroacupuncture treatment attenuated hyperalgesia through suppression of spinal glial activation in chronic neuropathic pain rats.

BACKGROUND: Cumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are also complicated in the analgesic effect of EA intervention. But the roles of microgliacytes and astrocytes of spinal cord in the process of EA analgesia remain unknown. METHODS: A total of 120 male Wistar rats were used in the present study. The neuropathic pain model was established by chronic constrictive injury (CCI) of the sciatic nerve. The rats were randomly divided into sham group, CCI group, and sham CCI + EA group, and CCI + EA group. EA was applied to bilateral Zusanli (ST36)-Yanlingquan (GB34). The mechanical (both time and force responses) and thermal pain thresholds (PTs) of the bilateral hind-paws were measured. The number of microgliacytes and activity of astrocytes in the dorsal horns (DHs) of lumbar spinal cord (L4-5) were examined by immunofluorescence staining, and the expression of glial fibrillary acidic protein (GFAP) protein was detected by western blot. RESULTS: Following CCI, both mechanical and thermal PTs of the ipsilateral hind-paw were significantly decreased beginning from the 3rd day after surgery (P < 0.05), and the mechanical PT of the contralateral hind-paw was considerably decreased from the 6th day on after surgery (P < 0.05). CCI also significantly upregulated the number of Iba-1 labeled microgliacytes and the fluorescence intensity of glial fibrillary acidic protein (GFAP) -labeled astrocyte in the superficial laminae of DHs on bilateral sides (P < 0.05). After repeated EA, the mechanical and thermal PTs at bilateral hind-paws were significantly relieved (P < 0.05). The increased of number of microgliacytes was markedly suppressed by 2 days' EA intervention, and the average fluorescence intensity was suppressed by 2 weeks' EA. The expression of GFAP protein were down-regulated by 1 and 2 weeks' EA treatment, respectively (P < 0.05). CONCLUSIONS: Repeated EA can relieve neuropathic pain and mirror-image pain in chronic neuropathic pain rats, which is probably associated with its effect in downregulating glial cell activation of the lumbar spinal cord, the microgliacyte first and astrocyte later.

Decabrominated Diphenyl Ethers (BDE-209) in Chinese and Global Air: Levels, Gas/Particle Partitioning, and Long-Range Transport: Is Long-Range Transport of BDE-209 Really Governed by the Movement of Particles?

In this paper, we report air concentrations of BDE-209 in both gas- and particle-phases across China. The annual mean concentrations of BDE-209 were from below detection limit (BDL) to 77.0 pg·m-3 in the gas-phase and 1.06-728 pg·m-3 in the particle-phase. Among the nine PBDEs measured, BDE-209 is the dominant congener in Chinese atmosphere in both gas and particle phases. We predicted the partitioning behavior of BDE-209 in air using our newly developed steady state equation, and the results matched the monitoring data worldwide very well. It was found that the logarithm of the partition quotient of BDE-209 is a constant, and equal to -1.53 under the global ambient temperature range (from -50 to +50 °C). The gaseous fractions of BDE-209 in air depends on the concentration of total suspended particle (TSP). The most important conclusion derived from this study is that, BDE-209, like other semivolatile organic compounds (SVOCs), cannot be sorbed entirely to atmospheric particles; and there is a significant amount of gaseous BDE-209 in global atmosphere, which is subject to long-range atmospheric transport (LRAT). Therefore, it is not surprising that BDE-209 can enter the Arctic through LRAT mainly by air transport rather than by particle movement. This is a significant advancement in understanding the global transport process and the pathways entering the Arctic for chemicals with low volatility and high octanol-air partition coefficients, such as BDE-209.

[Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To explore the mechanisms of neuroprotective effects of c-Jun N-terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: Sixty-four 7-day-old Sprague-Dawley rats were divided into four groups: hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24 hours after HI. Western blot was used to detect the protein expression of JNK, p-JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was used to detect the apoptotic cells. RESULTS: Compared with the sham-operated group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased (P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3 proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI. TUNEL positive cells were reduced in the AS601245-treated rats compared with the HI and DMSO vehicle groups 24 hours after HI (P<0.01). CONCLUSIONS: JNK activity increases in the neonatal rat brain with HI damage. JNK activity inhibition can inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of neuronal apoptosis.

Involvement of hippocampal acetylcholinergic receptors in electroacupuncture analgesia in neuropathic pain rats.

BACKGROUND: Cumulating evidence has shown a close correlation between electroacupuncture stimulation (EAS) frequency-specific analgesic effect and central opioid peptides. However, the actions of hippocampal acetylcholinergic receptors have not been determined. This study aims to observe the effect of different frequencies of EAS on the expression of hippocampal muscarinic and nicotinic acetylcholinergic receptors (mAChRs, nAChRs) in neuropathic pain rats for revealing their relationship. METHODS: Forty male Wistar rats were randomly and equally divided into sham, CCI model, 2, 2/15 and 100 HzEA groups. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EAS was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 30 min, once daily for 14 days except weekends. The mechanical pain thresholds (withdrawal latencies, PWLs) of bilateral hindpaws were measured. The expression levels of hippocampal M1 and M2 mAChR, and α4 and ß2 nAChR genes and proteins were detected by quantitative RT-PCR and Western blot, separately. The involvement of mAChR and nAChR in the analgesic effect of EAS was confirmed by intra-hippocampal microinjection of M1mAChR antagonist (Pirenzepine) and α4ß2 nAChR antagonist (dihydro-beta-erythroidine) respectively. RESULTS: Following EAS, the CCI-induced increase of difference values of bilateral PWLs on day 6 and 14 was significantly reduced (P < 0.05), with 2/15 Hz being greater than 100 Hz EAS on day 14 (P < 0.05). After 2 weeks' EAS, the decreased expression levels of M1 mAChR mRNA of both 2 and 2/15 Hz groups and M1 mAChR protein of the three EAS groups, α4 AChR mRNA of the 2/15 Hz group and ß2 nAChR protein of the three EAS groups were considerably increased (P < 0.05), suggesting an involvement of M1 mAChR and ß2 nAChR proteins in EAS-induced pain relief. No significant changes were found in the expression of M2 mAChR mRNA and protein, α4 nAChR protein and ß2 nAChR mRNA after CCI and EAS (P > 0.05). The analgesic effect of EAS was abolished by intra-hippocampal microinjection of M1mAChR and α4ß2 nAChR antagonists respectively. CONCLUSIONS: EAS of ST36-GB34 produces a cumulative analgesic effect in neuropathic pain rats, which is frequency-dependent and probably mediated by hippocampal M1 mAChR and ß2 nAChR proteins.

NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain.

BACKGROUND: Cumulating evidence has revealed the effectiveness of acupuncture therapy in relieving pain via immunoregulation. However, its underlying mechanism remains unknown. The present study was designed to determine the changes of immunogenic responses at different time-points of electroacupuncture (EA) interventions in neuropathic pain rats. METHODS: The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EA was applied at Zusanli (ST36) and Yanglingquan (GB34) for the EA groups. The thermal pain threshold was detected with an algesia-detector. The subgroups of plasma and splenic lymphocytes were determined via fluorescence-activated cell sorting. Specific inflammatory cytokines were assayed using an ELISA-based bead multiplex assay. The activities of splenic natural killer (NK) cells and cytotoxic T lymphocytes were detected by methyl thiazolyl tetrazolium colorimetric method. For confirming the involvement of NK cell in EA-analgesia, anti-asialo-ganglio-N-tetraosylceramide (anti-asialo-GM1) antibody was given to CCI rats before EA. RESULTS: Following CCI, the thermal pain threshold of the affected hind footpad was significantly decreased, and increased from the 3rd day to the 12th day after EA interventions, presenting a time-dependent tendency from the 5th day on. From day 3 to 5 of EA interventions, the percentages and activity of splenic NK cells, concentrations of splenic interleukin-2 (IL-2) and beta-endorphin (ß-EP) were significantly increased. Meanwhile, the concentrations of plasma IL-2, IL-1ß and gamma-interferon (IFN-γ) were significantly decreased and returned to the normal level on day 12 following EA. Plasma transforming growth factor-ß (TGF-ß) levels were considerably upregulated on day 5 and 12 following EA. The CD4+/CD8+ T cell ratio was markedly downregulated compared with the control and CCI groups on day 5 and returned to the normal level on day 12 following EA. After depleting NK cells by anti-asialo-GM1 antibody, the increased thermal pain threshold following EA intervention was obviously reduced. CONCLUSIONS: Repeated EA interventions have a time-dependent cumulative analgesic effect in neuropathic pain rats, which is closely associated with its regulatory effects on NK cells, splenic IL-2, ß-EP, and plasma IL-2, IL-1ß, IFN-γ and TGF-ß levels.

[Risk factors for accelerated junctional escape rhythm in children early after percutaneous ventricular septal defect closure].

OBJECTIVE: To identify the risk factors for accelerated junctional escape rhythm (AJER) in children early after percutaneous ventricular septal defect (VSD) closure. METHODS: A retrospective controlled study was conducted on 42 children who had AJER within one week after percutaneous VSD closure between January 2008 and October 2012. These subjects were compared with controls without AJER after VSD closure in terms of age, sex, diameter of VSD, occluder size, difference between occluder size and diameter of VSD, and distance between VSD and aortic valve ring. Risk factors for AJER were identified by logistic regression analysis. RESULTS: Compared with the control group, the AJER group had a longer distance betweenVSD and aortic valve ring, a larger diameter of VSD (basal diameter), a larger occluder size (waist diameter) , and a bigger difference between the waist diameter of occluder and diameter of VSD (P<0.05). Logistic regression analysis showed that distance between VSD and aortic valve ring (OR=1.813, P<0.05) and occluder size (OR=1.671, P<0.05) are primary risk factors for AJER. CONCLUSIONS: AJER early after percutaneous VSD closure is related to diameter of VSD, occluder size, difference between the waist diameter of occluder and diameter of VSD, and distance between VSD and aortic valve ring. The distance between VSD and aortic valve ring and occluder size are primary risk factors for AJER.

[Significance of Tp-Te interval for risk stratification of ventricular premature contractions in children].

OBJECTIVE: To investigate the significance of Tp-Te interval for risk stratification of ventricular premature contractions (VPC) in children. METHODS: A total of 120 children with VPC were divided into benign VPC (n=40), organic disease (n=40) and ventricular parasystole groups (n=40) according to the etiology of VPC; another 40 children who underwent physical examination were selected as the normal control group. The four groups were compared in terms of Tp-Te intervals and Tp-Te/QT ratios in leads V3, V4 and V5. RESULTS: The Tp-Te interval in lead V3 was significantly longer in the organic disease group than in the other groups (P<0.05), the benign VPC group had a significantly shorter Tp-Te interval in lead V4 than the normal control and organic disease groups (P<0.05), and the organic disease group had a significantly longer Tp-Te interval in lead V5 than the benign VPC group (P<0.05). The Tp-Te/QT ratios in leads V3-V5 were significantly higher in the organic disease group than in the other groups (P<0.05). The Tp-Te/QT ratios in leads V4 and V5 showed significant differences between the ventricular parasystole and benign VPC groups (P<0.05). CONCLUSIONS: Tp-Te interval is susceptible to changes in heart rate, and it is of little value for the risk stratification of VPC in children. Tp-Te/QT ratio, however, may be used as an important non-invasive index for clinical risk stratification of VPC in children and is worthy of further study.

Electroacupuncture Alleviates Pain Responses and Inflammation in Collagen-Induced Arthritis Rats via Suppressing the TLR2/4-MyD88-NF-κB Signaling Pathway.

Results: EA intervention and OxPAPC injection could relieve mechanical allodynia and thermal hyperalgesia caused by CIA. Paw edema and pathological damage of synovium were significantly ameliorated after EA intervention and OxPAPC injection. Furthermore, EA intervention and OxPAPC injection markedly reduced the contents of serum TNF-α, IL-1ß, and IL-6, as well as the protein expression levels of synovial TLR2, TLR4, MyD88, and NF-κB p-p65. In particular, the expression of TLR2 and TLR4 on synovial fibroblasts and macrophages in synovium was significantly reduced by EA intervention. Conclusions: Repeated EA stimulation at ST36 and SP6 can effectively relieve joint pain and synovial inflammation caused by RA in CIA rats. The analgesic and anti-inflammatory effect of EA may be closely related to the inhibition of innate immune responses driven by the TLR2/4-MyD88-NF-κB signaling pathway in the synovium.

Differential proteomics analysis of the analgesic effect of electroacupuncture intervention in the hippocampus following neuropathic pain in rats.

BACKGROUND: Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. METHODS: The chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI with electroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. RESULTS: After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were "cysteine metabolism", "valine, leucine, and isoleucine degradation" and "mitogen-activated protein kinase (MAPK) signaling". CONCLUSIONS: These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.

[Effects of transcutaneous auricular vagus nerve stimulation on bone and cartilage destruction in rats with rheumatoid arthritis].

OBJECTIVE: To observe the alleviating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on articular cartilage and bone destruction in rats with collagen-induced arthritis (CIA), and explore the cellular and molecular mechanisms of taVNS against rheumatoid arthritis (RA). METHODS: The male SD rats were randomly divided into normal control group (n=12), model group (n=12), and taVNS group (n=12). The CIA rat model was established by multi-point injection of emulsion prepared from type Ⅱ bovine collagen and Freund's incomplete adjuvant into the root of rat tail. The rats in the taVNS group were treated with taVNS at bilateral auricular conchae, 30 min per time, once a day, for consecutive 28 d. The cartilage destruction of the ankle joint was observed by safranin O-fast green staining, the production of osteoclasts in the joint tissue by tartrate-resistant acid phosphatase (TRAP) staining, and the bone erosion by X-ray and Micro-CT imaging. The protein expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) in the synovial tissues were detected by Western blot. RESULTS: Compared with the normal control group, the CIA rats presented with typical RA symptoms and elevated arthritis index (AI,P<0.05). After intervention with taVNS, the AI remarkably declined in comparison with that in the model group (P<0.05). Compared with the control group, the model group displayed loss of cartilage matrix in the ankle joint, thinned cartilage layer, obvious cartilage damage, and increased number of osteo-clasts in the joint (P<0.01); the imaging results showed bone loss and three-dimensional structural destruction of ankle joint and aggravated bone erosion (P<0.01); the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio were significantly elevated in the synovial tissue of ankle joint (P<0.01, P<0.05), while the expression level of OPG was decreased (P<0.05). Compared with the model group, taVNS resulted in relatively intact cartilage layer of ankle joint, alleviated cartilage destruction, decreased number of osteoclasts (P<0.01), improved bone erosion, loss, and three-dimensional structural destruction (P<0.01), and diminished MMP-1, MMP-3, and MMP-13 expression and RANKL/OPG ratio in the synovial tissue of ankle joint (P<0.05, P<0.01), while the expression level of OPG was increased (P<0.05). CONCLUSION: taVNS effectively relieves bone and cartilage destruction in CIA rats, which might be related to its efficacy in reducing the production of osteoclasts in joint tissues and down-regulating the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio.

[The influence of inhibiting notch signal on pulmonary vascular remodeling induced by PDGF].

OBJECTIVE: To explore the influence of inhibiting Notch signal on pulmonary vascular remodeling induced by PDGF. METHODS: Vessel strips taken from healthy Wistar rats were cultured together with extrogenous PDGF, the potent smooth muscle cell proliferation stimulators, for 7 days. Some vessel strips were cultured with PDGF and gamma-secretase inhibitor DAPT, a Notch signaling inhibitor for 7 days. Vascular wall thickness, PCNA and caspase-3 positive cell rate were examined in vessel strips. The alterations of Notch 1 to 4 receptor and HERP1, 2 mRNA were discerned by FQ-PCR to observe the influence of DAPT on Notch signal. At the same time, above indexes, which were related with pulmonary vascular remodeling, were measured too. RESULTS: PDGF stimulation in the cultured normal pulmonary arteries resulted in vascular medial thickness increase for about 50%, accompanied by significant increase in PCNA positive cell rate and decrease of caspase-3 positive cell rate. When DAPT were added to inhibit Notch signaling, the expression of HERP1, 2 mRNA decreased, the degrees of PDGF induced vascular medial thickness and PCNA positive cell rate increase as well as caspase-3 positive cell rate decrease were all attenuated notably. CONCLUSION: Inhibiting Notch signal induced by gamma-secretase inhibitor lead to the suppression of pulmonary vascular remodeling induced by PDGF, suggesting inhibition of Notch signal pathway might be a novel strategy in the intervention of pulmonary hypertension.