Objective:To explore the effect of esketamine on inflammatory cytokines and myocardial injury markers in children undergoing living-donor liver transplantation (LT).Methods:Considering the inclusion criteria, 50 children with biliary atresia were selected for living donor LT. They were equally randomized into two groups of control (C) and esketamine (E) (25 cases each). Esketamine 0.5 mg/kg was administered to group E during induction and continued at a dose of 0.5 mg·kg –1·h -1 after an induction of anesthesia. Group C provided the same dose of 0.9% sodium chloride injection during induction and then continued to pumping until the end of the procedure. Basic profiles of two groups were recorded. Hemodynamic parameters, such as heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP), were monitored at 5 min of anesthesia induction (T 0), 30 min of anhepatic phase (T 1), immediately after repercussion (T 2), 30 min of neohepatic phase (T 3) and end of surgery (T 4) in both groups. Central venous blood samples were collected at T 0, T 1, T 3 and T 4. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB) ,tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured. The incidence of adverse cardiac events, postoperative mechanical ventilation time, ICU stay and hospitalization length were compared. Results:As compared with T 0, mean arterial pressure (MAP) at T 2 declined markedly in group E [(48.6±12.7) mmHg (1 mmHg=0.133 kPa) vs (55.6±10.7) mmHg, P<0.001] and C [(39.3±8.0) mmHg vs (53.2±9.4) mmHg, P<0.001 ] ;As compared with T 0, the TNF-α and IL-6 spiked at T 3 in group C [169.0 (207.1) ng/L vs 43.8 (26.4) ng/L, (132.63±51.75) ng/L vs (51.79±17.83) ng/L, P<0.001] and E [78.5 (138.8) ng/L vs 43.8 (26.4) ng/L, (87.44±32.17) ng/L vs (51.79±17.83) ng/L, P<0.001 ] ; In group C, the concentration of myocardial injury markers CK-MB and cTnI rose at T 3/T 4 compared with T 0[T 3 vs T 0: 5.7 (5.4) μg/L vs 4.0 (3.5) μg/L, 0.09 (0.08) μg/L vs 0.02 (0.02) μg/L; T 4 vs T 0: 5.3 (5.0) μg/L vs 4.0 (3.5) μg/L, 0.07 (0.08) μg/L vs 0.02 (0.02) μg/L, P<0.001 ]. In group E, the levels of CK-MB and cTnI were higher at T 3/T 4 than those at T 0[T 3 vs T 0: 7.0 (5.0) μg/L vs 4.6 (2.1) μg/L, 0.06 (0.09) μg/L vs 0.03 (0.04) μg/L; T 4 vs T 0: 5.4 (4.9) μg/L vs 4.6 (2.1) μg/L, 0.03 (0.06) μg/L vs 0.03 (0.04) μg/L; P<0.001]. Compared with group C, the MAP of E rose at T 1/T 2/T 3 [(58.8±10.3) mmHg vs (53.3±8.6) mmHg, P=0.048; (48.6±12.7) mmHg vs (39.3± 8.0) mmHg, P=0.003; (55.8±7.4) mmHg vs (51.5±7.3) mmHg, P=0.044]. Compared with group C, TNF-α and IL-6 decreased in E at T 3/T 4[T 3: 78.5 (138.8) ng/L vs 169.0 (207.1) ng/L, P=0.010; (87.44±32.17) ng/L vs (132.63±51.75) ng/L, P=0.017. T 4: 62.3 (118.3) ng/L vs 141.3 (129.2) ng/L, P=0.001; (74.34±26.38) ng/L vs (100.59±30.40) ng/L, P=0.002]. Compared with group C, cTnI decreased in E at T 3/T 4[0.06 (0.09) μg/L vs 0.09 (0.08) μg/L, P=0.014; 0.03 (0.06) μg/L vs 0.07 (0.08) μg/L, P=0.003]. Compared with group C, the mechanical ventilation time in group E decreased [195 (120) min vs 315 (239) min, P<0.001]. Compared with group C, the incidence of severe hypotension [16%(4/25) vs 48% (12/25), P=0.015 ], bradycardia [12% (3/25) vs 36 % (9/25), P=0.047 ], myocardial ischemia [4 % (1 /25) vs 24 % (6/25), P=0.042 ] and premature ventricular contractions [0 vs 4 %(1/25), P=0.312 ] decreased in group E. Conclusion:Intraoperative dosing of esketamine may suppress inflammatory reactions and alleviate perioperative myocardial injury in children undergoing living-donor LT.

Objective:To identify the risk factors for postreperfusion syndrome (PRS) during living donor liver transplantation in pediatric patients with biliary atresia.Methods:The clinical data from pediatric patients who underwent living donor liver transplantation from January 2020 to December 2021 in our hospital were retrospectively analyzed. The clinical data included: (1) general information of the pediatric patients such as age, gender, height and body weight; (2) preoperative data such as left ventricular ejection fraction, pediatric end-stage liver disease score, serum aminotransferase, aspartate aminotransferase, total bilirubin, International Normalised Ratio and creatinine concentrations, and whole blood Hb concentration; (3) intraoperative data such as vital signs and blood gas analysis parameters immediate before reperfusion, time of anhepatic phase, donor liver cold ischemia time, transplanted liver quality, time of surgery, anesthesia time, volume of urine, blood loss, amount of blood transfused, and amount of fresh frozen plasma transfused. The pediatric patients were divided into PRS group and non-PRS group according to whether intraoperative PRS occurred. Risk factors for PRS were analyzed using binary logistic regression analysis.Results:A total of 304 pediatric patients were finally enrolled, with 132 cases in PRS group and 172 cases in non-PRS group. The incidence of PRS was 43.4%. The results of logistic regression analysis showed that prolonged liver graft cold ischemic time ( OR=1.031, 95% confidence interval 1.021-1.042, P<0.001) and body temperature <36 ℃ immediately before reperfusion ( OR=3.095, 95% confidence interval 1.656-5.785, P<0.001) were risk factors for PRS. Conclusions:Body temperature immediately before reperfusion<36.0 ℃ and prolonged liver graft cold ischemic time are risk factors for PRS during living donor liver transplantation in pediatric patients with biliary atresia.

Objective Although goal-directed fluid therapy (GDFT) has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator. Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications. We conducted mediation analysis using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates. Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI: 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.
Humans ; Blood Pressure ; Goals ; Postoperative Complications/epidemiology* ; Hemodynamics ; Fluid Therapy/methods*

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.
Humans ; Rifampin/therapeutic use* ; Antibiotics, Antitubercular/therapeutic use* ; Mycobacterium tuberculosis ; Ethambutol/pharmacology* ; Isoniazid/pharmacology* ; Paraffin Embedding ; Retrospective Studies ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.
Rats ; Animals ; Myocytes, Cardiac ; Atrial Remodeling ; Rats, Sprague-Dawley ; Heart Failure/metabolism* ; RNA, Messenger/metabolism* ; Potassium

Patients with organophosphate poisoning usually die from respiratory depression and respiratory failure. The incidence of rhabdomyolysis is relatively low, but the mortality rate is extremely high once it occurs. In this paper, the treatment of a patient with acute phoxim poisoning was analyzed. The patient developed severe rhabdomyolysis syndrome on the 3rd day of treatment, the creatine kinase exceeded the normal value by more than 300 times (up to 103510.65 U/L) , and renal failure occurred. Clinical treatment included active detoxification, blood purification, organ support, and internal environment maintenance. The patient's rhabdomyolysis continued, and the condition worsened. Finally, the family gave up the treatment and the patient died. It is suggested that attention should be paid to the occurrence of rhabdomyolysis syndrome during the treatment of organophosphorus poisoning, and timely blood purification technology may be the key to treatment.
Humans ; Rhabdomyolysis/chemically induced* ; Organothiophosphorus Compounds ; Creatine Kinase ; Incidence ; Acute Kidney Injury

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

The Chinese medicine injections prepared by the natural products containing sesquiterpenoids caused various adverse reactions in clinical use, among which skin allergic reactions are the most common. However, whether the reason of allergic reaction was related to the three isoprene units contained in the sesquiterpenoids is not clear, so the evaluation of drug safety has important guiding significance. The sesquiterpenoids are small molecular substances, and they are not antigens or haptens. They may induce anaphylaxis reactions by acting mast cells directly. Current research confirmed that Mas-related G protein-coupled receptor-X2 (MRGPRX2) which is a 7-transmembrane G protein coupled receptor on mast cells was a key target mediated allergic reactions induced by many small molecular drugs. Unlike IgE-mediated allergic reactions, pseudo-allergic reaction is related to dosage and dosing rate, and occurs in the first exposure to the sensitizer. In this paper, a series of experiments in vitro found that not all sesquiterpenoids caused anaphylactoid reactions. Ginsenoside Re, ginsenoside Rb1 and germacrone were selected as representative of sesquiterpenoids for calcium imaging assay. The data confirmed that only germacrone activated calcium mobilization through MRGPRX2, causing an increase in intracellular calcium ion concentration in mast cells. Furthermore, the release rate of β-hexosaminidase and the release amount of histamine analysis confirmed that germacrone induced mast cells degranulation directly. Knockdown of MRGPRX2 expression by siRNA and competitive binding experiments against ciprofloxacin were used to prove the target of germacrone was MRGPRX2. The results indicated that germacrone could activate mast cells directly to induce anaphylactoid reaction via MRGPRX2, which might be the reason of skin allergic reactions caused by injections containing germacrone.

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Design ; Humans ; Organophosphonates ; chemical synthesis ; pharmacology