OBJECTIVES: To explore the mechanism of Pingchuanning Formula (PCN) for inhibiting airway inflammation in rats with asthmatic cold syndrome. METHODS: A total of 105 SD rats were randomized equally into 7 groups, including a control group, an asthmatic cold syndrome model group, 3 PCN treatment groups at high, medium and low doses, a Guilong Kechuanning (GLCKN) treatment group, and a dexamethasone (DEX) treatment group. In all but the control rats, asthma cold syndrome models were established and daily gavage of saline, PCN, GLCKN or DEX was administered 29 days after the start of modeling. The changes in general condition, lung function and lung histopathology of the rats were observed, and inflammatory factors in the alveolar lavage fluid (BALF), oxidative stress, lung tissue ultrastructure, cytokine levels, and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed. RESULTS: The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass, food intake, and water intake, reduced FEV_0.3, FVC, and FEV_0.3/FVC, obvious inflammatory cell infiltration in the lung tissue, and increased alveolar inflammation score and counts of neutrophils, eosinophils, lymphocytes, macrophages, and leukocytes in the BALF. The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues, where the expressions of HMGB1, Beclin-1, ATG5, TNF-α, IL-6,IL-1β, and IL-13 and the LC3II/I ratio were increased, while the levels of Bcl-2 and IFN-γ were decreased. PCN treatment significantly improved these pathological changes in the rat models, and its therapeutic effect was better than that of GLKCN and similar to that of DEX. CONCLUSIONS PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy, thereby attenuating airway inflammatory damages.
Animals ; Rats ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Asthma/pathology* ; Beclin-1 ; HMGB1 Protein/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Male ; Lung/pathology* ; Inflammation

To develop a method for determining the antibody-dependent cell-mediated phagocytosis (ADCP) activity of human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) based on the reporter gene assay, we established an ADCP activity assay with Jurkat/NFAT/FcγRIIa cells as the effector cells and BT474 as the target cells. Then, the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were optimized by the method of design of experiment (DOE). The method showed a significant dose-response relationship, which was complied with the four-parameter equation: y=(A-D)/[1+(x/C)^B]+D. The durability ranges of the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were (2.5-4.0)×10⁵ cells/mL, 3-5, 1.0-2.0 h, 0 h, and 5.0-6.0 h, respectively. The results of the methodological validation showed that the linear equation was y=1.106 8x-0.011 6, r=0.969 2. The established method showed the relative accuracy ranging from -6.59% to 2.98% and the geometric coefficient of variation less than 11% in the intermediate precision test. Furthermore, the method was target-specific. The method was then applied to the determination of ADCP activity of HER2-targeted ADC, demonstrating the result of (103.5±5.7)%. We developed a reporter gene assay for determining the ADCP activity of HER2-targeted ADC and the assay demonstrated high accuracy and good reproducibility, which proposes a highly efficient and approache for evaluating ADCP effect of this HER2-targeted ADC, and also provides a referable technique for characterizing the Fc effector functions of ADCs with diverse targets.
Humans ; Receptor, ErbB-2/immunology* ; Phagocytosis/drug effects* ; Immunoconjugates/immunology* ; Genes, Reporter ; Antibody-Dependent Cell Cytotoxicity ; Jurkat Cells

Objective:To evaluate the efficacy of adjusted Narcotrend Index (NI) value guidancecombined with small-dose esketamine for program-controlled closed-loop target-controlled infusion (TCI) system.Methods:Forty-eight American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱpatients, regardless of gender, aged 18-55 yr, with body mass index of 18-25 kg/m 2, scheduled for elective laparoscopic surgery under general anesthesia, were assigned to control group (group C, NI baseline value median 36) and esketamine group(group E, NI baseline value median 46) using a random number table method, with 24 cases in each group. Anesthesia induction and maintenance were carried out using effect-site concentration TCI(Schnider model for propofol infusion and Minto model for remifentanil infusion). After the NI value was maintained at 26-46 during anesthesia maintenance, a small dose of esketamine was given (as an intravenous bolus 0.2 mg/kg, followed by an infusion of 5 μg·kg -1·min -1for 30 min) in group E, and the equal volume of normal saline was given instead in group C. Program-controlled closed-loop TCI was then started, and the target effect-site concentrations of propofol and remifentanil were adjusted every 5 min according to the corresponding preset NI baseline value. The main outcome measures were the percentage of time of NI value maintained in the target range within 1 h after administration of esketamine. Secondary outcome measures were the consumption of propofol and remifentanil, postoperative recovery time, incidence of nausea and vomiting, pain and shivering within 1 h after surgery. Patients were followed for intraoperative awareness on 2nd day after operation. Results:The performance of the program-controlled closed-loop TCI systems was within the safe clinical threshold, with no intraoperative awareness occurred in both groups. The consumption of propofol and remifentanil was significantly reduced in group E as compared to group C( P<0.05). There were no statistically significant differences in the percentage of time of NI value maintained in the target range, postoperative recovery time and incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Adjusted NI value guidance combined with small-dose esketamine provides better efficacy when used for program-controlled closed-loop TCI system.

Objective To summarize the clinical experience of the treatment for complex aortic coarctation with extra anatomic bypass and anatomic correction techniques. Methods The clinical data of patients with complex aortic coarctation treated in the First Affiliated Hospital of Nanjing Medical University and Friendship Hospital of Ili Kazakh Autonomous Prefecture between April 2012 and November 2020 were retrospectively reviewed. Results A total of 12 patients were enrolled, including 5 males and 7 females aged 11-54 (34.3±16.2) years. Extra anatomic bypass grafting was performed in 8 patients and anatomic correction was performed in 4 patients. The operations were successful in all patients. There was no perioperative death. The average cardiopulmonary bypass time was 203.0±46.0 min (7 median incision patients), and the average intraoperative blood loss was 665.0±102.0 mL. The average postoperative ventilator support time was 32.3±7.5 h, and the average postoperative hospital stay time was 10.2±4.3 d. The mean drainage volume of median incision was 1 580.0±360.0 mL, and the mean drainage time was 9.3±2.7 d. The mean drainage volume of left thoracotomy was 890.0±235.0 mL, and the mean drainage time was 4.8±2.5 d. One patient had a transient hoarse after operation and recovered 6 months later. The follow-up period ranged from 2 to 10 years with an average time of 81.0±27.0 months. All patients had a recovery of hypertension, cardiac afterload after 2 years postoperatively. One patient who received an artificial blood vessel replacement in situ was examined stenosis recurrence at the third year after discharge. Others were asymptomatic during the follow-up period. There were no death or other complications. Conclusion The treatment strategy for complex aortic coarctation should be individualized according to the anatomical features and concomitant heart diseases. Extra anatomic bypass technique is a safe and feasible choice.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORT™ dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats’ amygdala were tested, and the expressions of miR-339-5p in each group of rats’ amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3’UTR and take MOR mRNA as a target. Conclusions Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology* ; Brain/physiology* ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods* ; Nerve Net/physiology* ; Transcranial Direct Current Stimulation/methods*

Objective:To investigate the implementation status of protective restraints for psychiatric patients.Methods:The self-developed psychiatric protective restraint questionnaire was used to investigate 2 101 patients who had experienced at least one protective restraint during hospitalization in psychiatric institutions in 15 provinces and cities from March to May 2019 to analyze the current status of protective restraint of psychiatric patients.Results:A total of 2 101 questionnaires were distributed and 1 897 valid questionnaires were returned. The duration of constraint of 1 897 patients was 3 (1, 8) h, with the shortest duration of 1 h and the longest duration of 72 h. There were statistically significant differences in duration of restraint for patients with different genders, hospitals, marital status, first diagnosis on admission and history of self-harm or commit suicide ( P<0.05) . Conclusions:There is an urgent need to establish a set of standardized restraint procedures in clinical practice to prevent unreasonable use of restraints.

Objective:To investigate the value of monitor carotid velocity time integral (VTI) and corrected flow time (FTc) by bedside ultrasound before and after passive leg raising (PLR) in predicting fluid responsiveness in critically ill patients.Methods:A prospective observational study was conducted. Fifty patients with critical illness admitted to the First People's Hospital of Fuyang Hangzhou from January 2020 to March 2021 were enrolled. The clinical data including the gender, age, body mass index (BMI), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, and the duration of mechanical ventilation were recorded. The changes of carotid VTI and FTc were measured by bedside ultrasound, and the values of heart rate, mean arterial pressure (MAP), central venous pressure (CVP), stroke volume index (SVI), and intrathoracic blood volume index (ITBVI) were measured by pulse indicated continuous cardiac output (PiCCO) monitor before and after PLR in all patients. According to the changes of SVI before and after PLR, the patients were divided into fluid responsiveness positive group with the change rate of SVI≥15% and fluid responsiveness negative group with the change rate of SVI < 15%. The differences in the values of VTI, FTc, CVP, and ITBVI obtained before and after PLR (ΔVTI, ΔFTc, ΔCVP and ΔITBVI) were calculated and then compared between the two groups. The predictive values of these indicators on fluid responsiveness in critically ill patients were analyzed by receiver operator characteristic curve (ROC curve), and their relationship with the difference in SVI (ΔSVI) obtained before and after PLR was evaluated by Pearson correlation analysis.Results:Fifty patients were all enrolled in this study, in which 27 patients were fluid response and 23 patients were fluid nonresponse. Basic clinical data were not different between the two groups. The values of ΔVTI, ΔFTc, ΔCVP, and ΔITBVI in fluid response were all significantly higher than those in fluid nonresponse [ΔVTI (cm): 2.07±1.16 vs. 0.67±0.86, ΔFTc (ms): 4.00±6.10 vs. 0.01±2.26, ΔCVP (cmH 2O, 1 cmH 2O = 0.098 kPa): 1.67±1.14 vs. 1.00±1.17, ΔITBVI (mL/m 2): 98±69 vs. 48±70, all P < 0.05]. ROC curve analysis showed that ΔVTI, ΔFTc, ΔCVP and ΔITBVI were all positive for predicting fluid responsiveness, their area under ROC curve (AUC) and 95% confidence interval (95% CI) were 0.870 (0.769-0.972), 0.694 (0.547-0.841), 0.684 (0.535-0.832) and 0.709 (0.564-0.855), respectively. When using ΔVTI 0.92 cm, ΔFTc 1.45 ms, ΔCVP 1.50 cmH 2O and ΔITBVI 44.50 mL/m 2 as the threshold values, the sensitivities were 96.3%, 63.0%, 44.4% and 81.5%, and the specificities were 65.2%, 78.3%, 82.6% and 56.5%, respectively, in which the predictive value of ΔVTI was the largest. Pearson correlation analysis indicated that ΔVTI, ΔFTc, ΔCVP, and ΔITBVI were positively associated with ΔSVI ( r values were 0.971, 0.334, 0.440, 0.650, P values were 0.000, 0.018, 0.001, 0.000, respectively). Conclusion:Carotid ΔVTI and ΔFTc monitored by bedside ultrasound before and after PLR could be as effective as conventional indicators in predicting fluid responsiveness in critically ill patients, and the predictive value of ΔVTI was better than others.

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate remains 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.