Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns.

OBJECTIVES: This study aimed to investigate the incidence rate, clinical phenotype, gene variation spectrum, and prognosis of neonatal hyperhomocysteinemia (HHcy) and explore its diagnosis, individualised treatment, and prevention strategies. METHODS: We screened 84722 neonates for HHcy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with biochemical detection, urine gas chromatography-mass spectrometry (GC-MS), and next-generation sequencing (NGS) for gene analysis to comprehensively differentiate and diagnose diseases. RESULTS: 18 children (P1-P18) were diagnosed with methylmalonic acidemia (MMA) and HHcy, and fourteen known and one new variant of the MMACHC gene were found. Five children showed poor mental reactions, brain dysplasia, lethargy, hyperbilirubinemia, and jaundice, whereas the other 13 children had no evident abnormalities. These children were all cobalamin- and folic acid-reactive types, and they were mainly supplemented with cobalamin, L-carnitine, betaine, and folic acid. The mother of P12 had a prenatal diagnosis at the next pregnancy; the results showed that MMACHC gene was not pathogenic and she gave birth to a healthy baby. One child (P19) was diagnosed with methylenetetrahydrofolate reductase (MTHFR) deficiency, and one new mutation was detected in the MTHFR gene. Patient P19 showed congenital brain dysplasia, neonatal anaemia, and hyperbilirubinemia, and treatment consisted mainly of betaine and cobalamin supplementation. One child (P20) was confirmed to have methionine adenosyltransferase I (MAT I) deficiency but had no clinical manifestations. After treatment, all the children had a good prognosis. CONCLUSION: The incidence of neonatal HHcy in the Zibo area was 1/4236, and the common pathogenic variants were c.609G>A, c.80A>G, and c.482G>A in the MMACHC gene. Patients with HHcy can achieve a good prognosis if pathogenic factors and targeted treatment are identified. Gene analysis and prenatal diagnosis contribute to the early prevention of HHcy.

Comparison of video-stylet and conventional laryngoscope for endotracheal intubation in adults with cervical spine immobilization: A PRISMA-compliant meta-analysis.

BACKGROUND: Although minimization of cervical spine motion by using a neck collar or manual in-line stabilization is recommended for urgent tracheal intubation (TI) in patients with known or suspected cervical spine injury (CSI), it may worsen glottic visualization. The overall performance of video-stylets during TI in patients with neck immobilization remains unclear. The current meta-analysis aimed at comparing the intubation outcomes of different video-stylets with those of conventional laryngoscopes in patients with cervical immobilization. METHOD: The databases of Embase, Medline, and the Cochrane Central Register of Controlled Trials were searched from inception to June 2021 to identify trials comparing intubation outcomes between video-stylets and conventional laryngoscopes. The primary outcome was first-pass success rate, while secondary outcomes included overall success rate, time to intubation, the risk of intubation-associated sore throat, or tissue damage. RESULTS: Five randomized controlled trials published between 2007 and 2013 involving 487 participants, all in an operating room setting, were analyzed. The video-stylets investigated included Bonfils intubation fiberscope, Levitan FPS Scope, and Shikani optical stylet. There was no difference in first-pass success rate (risk ratio [RR] =1.08, 95% confidence interval [CI]: 0.89-1.31, P = .46], overall success rate (RR = 1.06, 95% CI: 0.93-1.22, P = .4), intubation time [mean difference = 4.53 seconds, 95% CI: -8.45 to 17.51, P = .49), and risk of tissue damage (RR = 0.46, 95% CI: 0.16-1.3, P = .14) between the 2 groups. The risk of sore throat was lower with video-stylets compared to that with laryngoscopes (RR = 0.45, 95% CI: 0.23-0.9, P = .02). CONCLUSION: Our results did not support the use of video-stylets as the first choice for patients with neck immobilization. Further studies are required to verify the efficacy of video-stylets in the nonoperating room setting.

Implementation of a machine learning application in preoperative risk assessment for hip repair surgery.

BACKGROUND: This study aims to develop a machine learning-based application in a real-world medical domain to assist anesthesiologists in assessing the risk of complications in patients after a hip surgery. METHODS: Data from adult patients who underwent hip repair surgery at Chi-Mei Medical Center and its 2 branch hospitals from January 1, 2013, to March 31, 2020, were analyzed. Patients with incomplete data were excluded. A total of 22 features were included in the algorithms, including demographics, comorbidities, and major preoperative laboratory data from the database. The primary outcome was a composite of adverse events (in-hospital mortality, acute myocardial infarction, stroke, respiratory, hepatic and renal failure, and sepsis). Secondary outcomes were intensive care unit (ICU) admission and prolonged length of stay (PLOS). The data obtained were imported into 7 machine learning algorithms to predict the risk of adverse outcomes. Seventy percent of the data were randomly selected for training, leaving 30% for testing. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUROC). The optimal algorithm with the highest AUROC was used to build a web-based application, then integrated into the hospital information system (HIS) for clinical use. RESULTS: Data from 4,448 patients were analyzed; 102 (2.3%), 160 (3.6%), and 401 (9.0%) patients had primary composite adverse outcomes, ICU admission, and PLOS, respectively. Our optimal model had a superior performance (AUROC by DeLong test) than that of ASA-PS in predicting the primary composite outcomes (0.810 vs. 0.629, p < 0.01), ICU admission (0.835 vs. 0.692, p < 0.01), and PLOS (0.832 vs. 0.618, p < 0.01). CONCLUSIONS: The hospital-specific machine learning model outperformed the ASA-PS in risk assessment. This web-based application gained high satisfaction from anesthesiologists after online use.

Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1ß in Rats.

BACKGROUND: Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1ß administration-induced behavioral changes and the possible involved mechanisms. METHODS: Rats received intracerebroventricular injection of IL-1ß and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied. RESULTS: Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1ß. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1ß, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1ß-induced above changes, except for the expressions of neurotrophin receptors. CONCLUSION: IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.

[The Effect of Novel Phosphodiesterase 4 Inhibitor ZL-n-91 to the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC50 were calculated. The effects of ZL-n-91 to the cycle of L1210 and K562 cells was detected by PE single staining, and the effects of ZL-n-91 to the apoptosis of L1210 and K562 cells was detected by PE/7AA-D double staining. Western blot was used to detect the effect of ZL-n-91 to the expression levels of apoptosis related proteins. Subcutaneous tumor transplantation model of acute lymphoblastic leukemia L1210 was established in the nude mice, and the inhibitory effect of oral administration of ZL-n-91 to the xenograft was observed. RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION: The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.

Association between perioperative intravenous lidocaine and subjective quality of recovery: A meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To evaluate the impact of perioperative intravenous lidocaine on the quality of recovery (QoR) following surgery. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Postoperative care. INTERVENTION: Intravenous lidocaine during perioperative period. PATIENTS: Adults undergoing surgery under general anesthesia. MEASUREMENTS: The primary outcome was postoperative QoR measured with QoR-40 questionnaire, while the secondary outcomes included five individual dimensions (i.e., emotional, state, physical comfort, psychological support, physical independence, and pain) of QoR-40, intraoperative opioid consumption, and risk of chronic postsurgical pain (CPSP). MAIN RESULTS: Medline, Cochrane Library, Google scholar, and EMBASE databases were searched from inception to June 2021. Fourteen RCTs involving 1148 patients in total undergoing elective surgery published from 2012 to 2021 were included. QoR-40 scores were evaluated at postoperative 24 h (12 trials), 72 h (one trial), and Day 5 (one trial), respectively. Pooled results revealed significantly higher global [mean difference (MD) = 9.65, 95% confidence interval (CI): 6.33 to 12.97; I2 = 97%; 13 RCTs; n = 1085] and individual dimension QoR-40 scores in the lidocaine group than those in placebo group. Subgroup analysis demonstrated no significant impact of the type of surgery, age, gender, surgical time, anesthetic technique, lidocaine dosage, and time of assessment on global QoR-40 scores. The use of intravenous lidocaine was associated with a significant reduction in intraoperative remifentanil consumption compared with that in the placebo group (standardized MD = -0.91, 95%CI: -1.32 to -0.51; I2 = 86%; 10 RCTs; n = 799). There was no difference in risk of CPSP between the two groups [relative risk (RR) = 0.65, 95%CI: 0.33 to 1.25; I2 = 58%; 4 RCTs; n = 309]. CONCLUSION: Our results verified the efficacy of intravenous lidocaine for enhancing postoperative quality of recovery by using a validated subjective tool and reducing intraoperative remifentanil consumption in patients receiving elective surgery under general anesthesia. Further studies are warranted to verify its efficacy in the acute care setting.

Re-expression of DIRAS3 and p53 induces apoptosis and impaired autophagy in head and neck squamous cell carcinoma.

BACKGROUND: p53 and DIRAS3 are tumor suppressors that are frequently silenced in tumors. In this study, we sought to determine whether the concurrent re-expression of p53 and DIRAS3 could effectively induce head and neck squamous cell carcinoma (HNSCC) cell death. METHODS: CAL-27 and SCC-25 cells were treated with Ad-DIRAS3 and rAd-p53 to induce re-expression of DIRAS3 and p53 respectively. The effects of DIRAS3 and p53 re-expression on the growth and apoptosis of HNSCC cells were examined by TUNEL assay, flow cytometric analysis and MTT. The effects of DIRAS3 and p53 re-expression on Akt phosphorylation, oncogene expression, and the interaction of 4E-BP1 with eIF4E were determined by real-time PCR, Western blotting and immunoprecipitation analysis. The ability of DIRAS3 and p53 re-expression to induce autophagy was evaluated by transmission electron microscopy, LC3 fluorescence microscopy and Western blotting. The effects of DIRAS3 and p53 re-expression on HNSCC growth were evaluated by using an orthotopic xenograft mouse model. RESULTS: TUNEL assay and flow cytometric analysis showed that the concurrent re-expression of DIRAS3 and p53 significantly induced apoptosis (P < 0.001). MTT and flow cytometric analysis revealed that DIRAS3 and p53 re-expression significantly inhibited proliferation and induced cell cycle arrest (P < 0.001). Mechanistically, the concurrent re-expression of DIRAS3 and p53 down-regulated signal transducer and activation of transcription 3 (STAT3) and up-regulated p21WAF1/CIP1 and Bax (P < 0.001). DIRAS3 and p53 re-expression also inhibited Akt phosphorylation, increased the interaction of eIF4E with 4E-BP1, and reduced the expression of c-Myc, cyclin D1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGFR) and Bcl-2 (P < 0.001). Moreover, the concurrent re-expression of DIRAS3 and p53 increased the percentage of cells with GFP-LC3 puncta compared with that in cells treated with control adenovirus (50.00% ± 4.55% vs. 4.67% ± 1.25%, P < 0.001). LC3 fluorescence microscopy and Western blotting further showed that DIRAS3 and p53 re-expression significantly promoted autophagic activity but also inhibited autophagic flux, resulting in overall impaired autophagy. Finally, the concurrent re-expression of DIRAS3 and p53 significantly decreased the tumor volume compared with the control group in a HNSCC xenograft mouse model [(3.12 ± 0.75) mm3 vs. (189.02 ± 17.54) mm3, P < 0.001]. CONCLUSIONS: The concurrent re-expression of DIRAS3 and p53 is a more effective approach to HNSCC treatment than current treatment strategies.

Prophylactic diphenhydramine attenuates postoperative catheter-related bladder discomfort in patients undergoing gynecologic laparoscopic surgery: a randomized double-blind clinical study.

BACKGROUND: To evaluate the effectiveness of diphenhydramine, an antihistamine with anti-muscarinic properties, for prevention of postoperative catheter-related bladder discomfort (CRBD). METHODS: Ninety-six ASA physical status I and II adult female patients (20-60 years) scheduled for elective gynecologic laparoscopic surgery were included. Patients were randomized into two groups of 48 patients each. All patients received a detailed preoperative explanation of the possible consequences of CRBD. The control group received normal saline 2 ml, whereas the diphenhydramine group received diphenhydramine 30 mg intravenously after induction of general anesthesia. Then, all patients were catheterized with a 14F Foley catheter and the balloon was inflated with 10 ml of distilled water. All patients who complained of CRBD in the postoperative room were appeased with nursing. Ketorolac 30 mg was used as the rescue drug on patients' request or when the patient was evaluated as having moderate or severe CRBD. Bladder discomfort and its severity were assessed at 1, 2 and 6 h postoperatively. The severity of CRBD was graded as none, mild, moderate and severe. Adverse effects of diphenhydramine such as sedation, dry mouth or GI upset were recorded. RESULTS: The incidence of CRBD was lower in the diphenhydramine group compared with the control group at 2 h (34.8 vs. 58.7%, p = 0.02) and 6 h (23.9 vs. 56.5%, p < 0.01) postoperatively. Diphenhydramine treatment also reduced the severity of CRBD at 6 h postoperatively (p = 0.01). Moreover, the request for rescue for CRBD was lower in diphenhydramine group at 2 h (8.7 vs. 26.1%, p = 0.03). There were no significant differences in side effects, such as sedation, dry mouth or gastrointestinal upset between the two groups (p > 0.05). CONCLUSION: Prophylactic diphenhydramine 30 mg at induction of general anesthesia reduced the incidence and severity of postoperative bladder discomfort without significant side effects in patients receiving gynecologic laparoscopic surgery.

Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat.

Activated microglia-induced neuroinflammation can stimulate the hypothalamic- pituitary-adrenal (HPA) axis to release glucocorticoids and suppress astrocyte functions, such as reducing neurotrophin production, which occur in depression. However, the balance between M1 (pro-inflammation) and M2 (anti-inflammation) microglial phenotypes and the interaction between these two glial cells are unclear in the depression. Hence, the chronic unpredictable mild stress (CUMS)-induced depression model was chosen to study depression- and anxiety-like behaviors, the concentration of corticosterone and relevant hippocampal cytokines, mRNA and protein expressions of microglial and astrocyte markers. To demonstrate the role of M1 phenotype activation in depression, the effect of microglial inhibitor minocycline on these aspects was also evaluated. Six weeks after CUMS exposure, behaviors were tested. Compared to the control group, CUMS increased serum corticosterone concentration and depression-like behaviors, like anhedonia, helplessness and anxiety. Moreover, CUMS increased microglia M1 marker CD11b expression and tumor necrosis factor (TNF)-α, interferon (INF)-γ, interleukin (IL)-1ß and IL-17 concentrations, but decreased the concentration of M2 cytokines, IL-4, IL-10 and IL-13. Meanwhile, CUMS inhibited the expressions of astrocyte marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrKB. Minocycline (40 mg/kg, 45 days) treatment significantly attenuated CUMS-induced behavioral abnormalities, which were associated with the suppressed M1 response, restored GFAP, BDNF and its receptor expression. In conclusion, CUMS-induced depression- and anxiety-like behavior may result from an imbalance between M1 and M2 and suppressed astrocyte function. Minocycline treatment reversed M1 response, which was associated with behavioral normalization.

Bilateral visual loss and cerebral infarction after spleen embolization in a trauma patient with idiopathic thrombocytopenic purpura: A case report.

RATIONALE: Splenic artery embolization (SAE) is a common procedure in trauma patients with blunt splenic injuries. We report a case of acute ischemic stroke following orthopedic surgery in a patient with post-SAE reactive thrombocytosis. PATIENT CONCERNS: A 37-year-old woman with idiopathic thrombocytopenic purpura (ITP) suffered from multiple trauma scheduled for open reduction and internal fixation for right tibial and left radius fracture five days after SAE. The patient did not have any thromboembolic complications, although the platelet counts increased from 43 × 10/L to 568 × 10/L within two days after SAE. Surgery was completed under general anesthesia with tracheal intubation without complications. The patient complained of visual loss followed by limb weakness on the fourth and eighth hour postoperatively. DIAGNOSES: Magnetic resonance imaging (MRI) of head demonstrated ischemic change over bilateral basal ganglia, and occipital areas, suggesting the diagnosis of cortical blindness. INTERVENTIONS: To suppress platelet count and avoid platelet hyper-aggregation, anti-platelet drug (i.e., oral aspirin 100 mg daily), hydration, and hydroxyurea (i.e., 20 mg/kg daily) were used for the treatment of reactive thrombocytosis. OUTCOMES: Although right-sided hemiparesis persisted, the patient reported mild visual recovery. She was discharged four months after SAE with active rehabilitation. LESSONS: Our report highlights an increased risk of acute arterial thromboembolic events in patients with reactive thrombocytosis, especially those undergoing surgery.