OBJECTIVE: To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree. METHODS: A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.483G>T (p.Gln161His) was rated as a pathogenic variant (PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION The homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.
Female ; Humans ; Pedigree ; Muscle Hypotonia ; Hearing Loss, Sensorineural ; Protein Deficiency ; Mutation

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Background::Whether anesthetic depth affects postoperative outcomes remains controversial. This meta-analysis aimed to evaluate the effects of deep vs. light anesthesia on postoperative pain, cognitive function, recovery from anesthesia, complications, and mortality. Methods::PubMed, EMBASE, and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients. The co-primary outcomes were postoperative pain and delirium (assessed using the confusion assessment method). We conducted a meta-analysis using a random-effects model. We assessed publication bias using the Begg’s rank correlation test and Egger’s linear regression. We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery.Results::A total of 26 trials with 10,743 patients were included. Deep anesthesia compared with light anesthesia (a mean difference in bispectral index of -12 to -11) was associated with lower pain scores at rest at 0 to 1 h postoperatively (weighted mean difference = -0.72, 95% confidence interval [CI] = -1.25 to -0.18, P= 0.009; moderate-quality evidence) and an increased incidence of postoperative delirium (24.95% vs. 15.92%; risk ratio = 1.57, 95% CI = 1.28-1.91, P < 0.0001; high-quality evidence). No publication bias was detected. For the exploratory secondary outcomes, deep anesthesia was associated with prolonged postoperative recovery, without affecting neurocognitive outcomes, major complications, or mortality. In the subgroup analyses, the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively, without statistically significant subgroup differences, and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries, without statistically significant subgroup differences. Conclusions::Deep anesthesia reduced early postoperative pain but increased postoperative delirium. The current evidence does not support the use of deep anesthesia in clinical practice.

Objective:To explore the implementation of individualized lung protection ventilation strategy in pediatric acute respiratory distress syndrome(pARDS)guided by transthoracic electrical impedance tomography(EIT)and critical care ultrasound(CCU).Methods:We retrospectively analyzed the therapeutic process of protective ventilation strategy in one case of severe pARDS.EIT and CCU were used to guide the implementation of lung protective ventilation strategy.Results:EIT was used to guide lung recruitment and optimal positive end-expiratory pressure titration.CCU was used to assess hemodynamics and lung status of ARDS patient, and guide the implementation of right ventricular protective ventilation and circulatory protective ventilation.Finally, the patient eventually survived.Conclusion:The idea of ARDS protective ventilation has changed from traditional lung protective ventilation to right heart protective ventilation and circulatory protective ventilation, and finally achieved the protection of pulmonary vascular endothelium.EIT and CCU enrich the understanding of the pathophysiology and protective ventilation strategy in pARDS.

Objective:To study the respiratory morbidity and the risk factors of respiratory complications in late-preterm infants.Methods:The data of 959 late-preterm infants in 21 hospitals in Beijing from October 2015 to April 2016 were collected.These infants were divided into the respiratory morbidity group (237 cases) and the control group (722 cases) according to whether they had short-term respiratory morbidity after birth.Clinical data of the two groups were compared.Results:Among the 959 late-preterm babies, 530 were male and 429 were female.Two hundred and thirty-seven cases (24.7%) developed short-term respiratory morbidity after birth.Infectious pneumonia developed in the most cases (81 cases, 8.4%), followed by transient tachypnea (65 cases, 6.8%), amniotic fluid aspiration (51 cases, 5.3%), and respiratory distress syndrome (24 cases, 2.5%) successively.All the infants recovered and discharged.There were no differences between gender and maternal age between 2 groups (all P>0.05). Compared with the control group, more late-preterm infants were delivered by cesarean section (73.4% vs.59.7%, χ2=14.43, P<0.001) and the 1-minute Apgar score was lower [(9.41±1.66) scores vs.(9.83±0.53) scores, t=5.40, P<0.001] in the respiratory morbidity group.The differences were statistically significant.There were more cases with maternal complications in the respiratory morbidity group that in the control group (66.7% vs.58.6%, χ2=4.877, P=0.027), but no difference in various complications between 2 groups was observed ( P>0.05). In the respiratory morbidity group, the most frequent complications were maternal hypertension and preeclampsia (27.8% vs.22.6%, χ2=2.728, P=0.099). There were no differences between 2 groups in gestational age, birth weight and birth length (all P>0.05). There were more infants small for gestational age and large for gestational age in the respiratory morbidity group than in the control group (18.8% vs.14.1%, 6.3% vs.2.4%, χ2=8.960, P=0.011). The duration of hospitalization of the respiratory morbidity group was significantly longer than that of the control group [(9.00±4.42) d vs.(6.82±4.19) d, t=6.676, P<0.001] since the infants with respiratory morbidity needed to be hospita-lized. Conclusions:Respiratory diseases occur in about 1/4 of late-preterm infants.Infants who are delivered by cesarean section and whose mothers are complicated with the maternal hypertension and preeclampsia should be monitored closely.Respiratory support should be provided for infants not appropriate for gestational age who are more likely to suffer from respiratory diseases, so that they can successfully pass through the transition period.

Objective:To design a checklist for interhospital transfer of patients undergoing extracorporeal membrane oxygenation (ECMO) therapy and apply it in clinical practice to ensure the transfer safety of patients.Methods:Using convenience sampling, 27 cases of critically ill patients who were transported by the ECMO team of the Department of Critical Care Medicine of Henan Provincial People's Hospital from September 2017 to November 2018 were selected as the control group, and the ECMO interhospital transport was implemented from December 2018 to February 2020, 14 cases of critically ill patients were set as the experimental group.The checklist for interhospital transfer of patients undergoing ECMO therapy was compiled based on relevant literature and guidelines, and applied to critically ill patients who were transported between hospitals under the support of ECMO. The incidence of adverse events between two groups was compared.Results:The incidence of adverse events decreased after the application of the checklist, the difference was not statistically significant (χ 2=3.516, P=0.061) . Conclusions:The use of the ECMO interhospital transfer checklist can effectively standardize the transfer process, improve work efficiency and quality, may reduce transfer risks, and ensure patients' safety.

Objective To establish a quality standard of yinqiao xiaozhen mixture. Methods Preparation of Forsyth-ia,Arctium lappa L.,and Honeysuckle were identified by TLC method.The concentration of baicalin in yinqiao xiaozhen mixture was determined by HPLC method. Results The qualitative identification method can detect Forsythia,Arctium lappa L.,and Honeysuckle.TLC spots were clear.TLC method has strong specificity.The linear range of baicalin was 0.122 5-1.531 2 μg,r=0.999 9,the average sample recovery rate was 99.42%,RSD was 2.19%,respectively. Conclusion The method is simple,ac-curate and repeatable,which can be used for quality control of Qinqiao xiaozhen mixture.

Objective To explore the effect of nursing intervention of national free progestation eugenic health examination on service objects planned to pregnancy.Methods A total of 872 couples in Panyu District of Guangzhou were selected from January 2014 to January 2016 based on convenient sampling. All of them complied with family planning policy, planned to pregnancy and received national free progestation eugenic health examination. The participants were divided into control group (n=436) and observation group (n=436) according to the method of lottery. The control group received national free eugenic health examination, and the observation group received additional nursing care and comprehensive guidance based on the control group. The distribution of high-risk factors of the couples was recorded. The knowledge of birth defects and progestational eugenics and the pregnancy outcomes were observed.Results There were no statistically significant differences in the incidence of reproductive tract infection, pre-pregnancy virus screening, abnormal pre-pregnancy laboratory findings, adverse pregnancy outcome, family history of high risk, wife/husband environmental exposure, and other high-risk factors between two groups (P>0.05). There were significant differences in health and nutrition during pregnancy, the optimal reproductive age, the importance of progestation examination, the normal physiological process of pregnancy, the time of folic acid supplementation, and the prevention of birth defects between two groups (P<0.05). The observation group had significantly higher normal pregnancy rate and lower miscarriage and stillbirth rate compared with the control group (95.15% vs. 85.82% for normal pregnancy; 2.99% vs. 13.42% for miscarriage; 0.75% vs. 1.87% for stillbirth;P<0.05).Conclusions Nursing intervention in progestation eugenic health examination can effectively improve the eugenic knowledge, attitude and behavior, and the outcome of pregnancy. It can reduce the risk of birth defects.

Objective To detect the levels of peptidylarginine deiminase 4 (PAD4) mRNA and neutrophil extracellular traps (NETs) of the peripheral blood neutrophils in rheumatoid arthritis (RA) patients and to study the association between PAD4 and NETs in RA.The anti-cyclic citrullinated peptide (anti CCP) antibodies,disease activity score (DAS28) score,erythrocyte sedimentation rate (ESR) were recorded.Its value in the pathogenesis of RA was explored.T test,rank-sum test,Pearson and Spearman correlative analysis were used for statical analysis.Methods The serum double-stranded DNA (dsDNA)/NETs in 43 RA patients and 20 healthy controls were detected by PicoGreen dsDNA Quantitation Kits (Invitrogen).Real-time quantitative polymerase chain reaction (RT-PCR) was used to determine the expression of PAD4 mRNA in neutrophils,and the relationship between dsDNA/NETs and their clinical indexes were analyzed.Results ① The level of peripheral blood neutrophils PAD4 mRNA in RA was significantly higher than healthy controls [1.493(0.831,2.607)] vs [0.631(0.358,1.489)],(Z=-2.07,P=0.039).The levels of serum PAD4 mRNA in RA treated with disease-modifying antirheumatic drugs (DMARDs) were lower than untreated with DMARDs but no significant difference was found (Z=-1.19,P=0.234).② The levels of serum dsDNA/NETs in RA patients were significantly higher than in healthy controls (t=3.4,P=0.001).③ The levels of serum dsDNA/NETs in RA were positively correlated with DAS28 score,ESR,CRP and PAD4 mRNA (r=0.36,P=0.036;r=0.345,P=0.042;r=0.36,P=0.043;r=0.42,P=0.017) but not with anti-CCP antibodies (r=0.277,P=0.154).Conclusion ① PAD4 may play an important role in the pathogenesis of RA.② NETs maybe associated with disease activity and play an important role in RA pathogenesis,inhibit NETs generation or improve the ability to clear NETs,perhaps can treat RA.③ PAD4 probably play an important role in rheumatoid arthritis by influencing the formation of the NETs.

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-alpha after ischemia-reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev-IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-alpha in the lung. Lung permeability was significantly increased after ischemia-reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-alpha. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-alpha, which also contributed to the lung-protective effect of sevoflurane.
Anesthetics, Inhalation/*therapeutic use ; Animals ; Capillary Permeability/drug effects ; Gene Expression Regulation/drug effects ; Lung/*drug effects/metabolism/pathology ; Lung Diseases/*drug therapy/genetics/metabolism/pathology ; Male ; Methyl Ethers/*therapeutic use ; Protein Kinase C-alpha/*metabolism ; Protein Transport/drug effects ; RNA, Messenger/genetics ; Rats, Wistar ; Reperfusion Injury/*drug therapy/genetics/metabolism/pathology ; Zonula Occludens-1 Protein/analysis/*genetics