Risk factors, diagnosis and treatment of transient hyperinsulinemic hypoglycemia in newborns / 中国新生儿科杂志

Objective:To study the risk factors, diagnosis and treatment of transient hyperinsulinemic hypoglycemia (HH) in newborns.Methods:From January 2016 to December 2020, newborns with transient HH (HH group) admitted to our hospital were enrolled in this retrospective nested case-control study. Newborns with similar gestational age (GA) (differences of GA<2 w) without HH were matched with 1∶2 ratio as the non-HH group. Clinical characteristics of the two groups were compared and the risk factors and therapeutic results of HH in newborns were analyzed using SPSS 20.0 statistical software.Results:A total of 39 cases were included in the HH group and 75 cases were matched in the non-HH group. The proportion of small for gestational age (SGA) [51.3%(20/39) vs. 32.0%(24/75)], the amount of amino acids (AA) in intravenous infusion[1.0(0.0,1.0) g/(kg·d) vs. 0.0(0.0,1.0) g/(kg·d)], the incidence of hypoglycemia [(4.3±1.9) times vs. (3.6±1.3) times] and the maximum glucose infusion rate (GIR)[(8.3±2.5) mg/(kg·min) vs. (7.4±1.1) mg/(kg·min)] in the HH group were higher than the non-HH group (all P<0.05). The platelet count in the HH group were lower than the non-HH group [(186.9±60.9)×10 9/L vs. (215.3±61.7)×10 9/L, P<0.05]. SGA ( OR=2.535, 95% CI 1.077~5.971), the amount of intravenous AA ( OR=2.180, 95% CI 1.029~4.619) and the maximum GIR ( OR=1.405, 95% CI 1.088~1.815) were independent risk factors for transient HH. In the HH group, 28/39 cases were treated with Diazoxide or Octreotide and the therapeutic effects were good with few adverse drug reactions (ADR). 37/39 cases were recovered within 28 d of birth and the other 2 cases were recovered at 2.5 m and 3.5 m, respectively. Conclusions:SGA, the amount of intravenous AA and higher GIR are risk factors for transient HH in newborns. Diazoxide or Octreotide are effective with few ADR in the treatment of transient HH. Most patients will recover from transient HH in 2 w to 3 m.

Comparation on the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old / 中华危重病急救医学

OBJECTIVE@#To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old.@*METHODS@#A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa.@*RESULTS@#A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%).@*CONCLUSIONS@#The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks / 神经科学通报·英文版

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Research Progress in Pathogenesis of Hypertension in Acute Intermittent Porphyria / 中国医学科学院学报

Acute intermittent porphyria (AIP) has complicated clinical manifestations and is often accompanied by hypertension.AIP may cause hypertension through adrenergic effect,heme deficiency,inflammation,inappropriate secretion of antidiuretic hormone,toxicity of delta-aminolevulinic acid(ALA,aporphyrin precursor),and elevated serum glucose level.The prevention and treatment strategies for AIP accompanied with hypertension mainly include the controlling of porphyria attacks,application of antihypertensive drugs,lifestyle intervention,and management of latent AIP patients.

Efficacy of transcatheter pulmonary valve perforation in neonates with pulmonary atresia with intact ventricular septum / 中华儿科杂志

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO2) were compared before and after operation. In addition, the SpO2 and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO2 was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.

Efficacy and safety of low-dose hydrocortisone for the prevention and treatment of bronchopulmonary dysplasia in very premature infants：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of prophylactic use of low-dose hydrocortisone （HC） for the prevention and treatment of bronchopulmonary dysplasia （BPD）， and to provide evidence-based reference for clinical treatment. METHODS PubMed， Embase， Web of Science， Cochrane Library， CJFD， VIP and Wanfang databases were searched by computer； randomized controlled trials （RCT） about prophylactic use of low-dose HC （trial group） versus placebo or dopamine （control group） in very premature infants were collected from the establishment of the database to Jun. 2022. The quality of the included literature was evaluated by using bias risk assessment tool recommended by Cochrane system evaluator’s manual （version 6.2） after screening the literature and extracting the data. Meta-analysis， sensitivity analysis and publication bias analysis were carried out with RevMan 5.3 statistical software. RESULTS A total of 1 437 very premature infants were included in 9 RCTs. Meta- analysis showed that the incidence of BPD [OR＝0.75， 95%CI（0.58，0.95）， P＝0.02] and fatality [OR＝0.72， 95%CI （0.54， 0.97）， P＝0.03] in trial group were significantly lower than control group； the survival rate without BPD [OR＝1.36， 95%CI （1.06，1.74）， P＝0.02]， the incidences of gastrointestinal perforation [OR＝2.23， 95%CI （1.31，3.78）， P＝0.003] and sepsis [OR＝ 1.27， 95%CI （1.01，1.60）， P＝0.04] in trial group were all significantly higher than control group. There was no significant difference in the incidence of necrotizing enterocolitis， paraventricular leukomalacia， intraventricular hemorrhage， patent ductus arteriosus， hyperglycemia， pneumothorax， retinopathy of premature infants between the two groups （P＞0.05）. Results of sensitivity analysis showed that study results were robust. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS The early prophylactic use of low-dose HC can reduce BPD in very premature infants， reduce fatality， and improve the survival rate without BPD， but we should pay attention to gastrointestinal perforation and sepsis.

Effect of proprioceptive neuromuscular facilitation combined with neuromuscular electrical stimulation on chronic ankle instability / 中国康复理论与实践

ObjectiveTo observe the effect of proprioceptive neuromuscular facilitation combined with neuromuscular electrical stimulation on chronic ankle instability (CAI). MethodsFrom April, 2016 to December, 2021, 48 patients with CAI were randomly divided into control group (n = 24) and observation group (n = 24). Both groups accepted routine rehabilitation, and the observation group accepted proprioceptive neuromuscular facilitation combined with neuromuscular electrical stimulation additionally, for eight weeks. They were assessed with Visual Analogue Scale (VAS), peak torque to body weight of ankle dorsiflexors and plantarflexors (AD/W, AP/W), Y Balance Test (YBT) and Foot and Ankle Disability Index (FADI) before and after treatment. ResultsAfter treatment, VAS score, AD/W, AP/W, YBT and FADI improved in the observation group (|t| > 2.208, P < 0.05), while VAS score and AP/W improved in the control group (|t| > 2.156, P < 0.05); and all the VAS score, AD/W, AP/W, YBT and FADI were better in the observation group than in the control group (|t| > 2.067, P < 0.05). ConclusionProprioceptive neuromuscular facilitation combined with neuromuscular electrical stimulation can effectively relieve the pain of patients with CAI, and increase the muscle strength around the ankle, to improve the stability and balance.

A study on the present situation of depression of residents in Chongqing and its relationship with the administration satisfaction of standardized residency training / 中华医学教育探索杂志

Objective:To understand the current situation and influencing factors of depression among residents in Chongqing, and to explore the relationship between depression and administration satisfaction of the standardized residency training.Methods:Stratified random cluster sampling was used to select 372 residents currently participating the standardized residency training in Chongqing. The patient health questionnaire (PHQ-9) and administration satisfaction of residency training questionnaire were used to conduct a cross-sectional survey on the depression status and satisfaction of residents in Chongqing. SPSS 21.0 software package was used for partial correlation analysis and binary logistic regression analysis to explore the relationship between depression and administration satisfaction of the standardized residency training.Results:Among the 372 residents, 218 had mild depression and above (58.60%). There was a significant difference in the incidence of depression among residents of different ages, educational background, marital status, working hours and administration satisfaction of residency training ( χ2 = 23.02, 17.35, 12.24, 21.70, 95.20; P = 0.028, 0.027, 0.016, 0.041, <0.001 respectively). Partial correlation analysis showed that there was a negative correlation between the total score of depression and the five aspects of the administration satisfaction (total score, instructors, training base, managers and training income) ( r=-0.52, -0.45, -0.47, -0.45, -0.40, all P<0.01). In the binary logistic regression analysis of depression and satisfaction,the satisfaction had a negative impact on depression, and its B value was -1.71, and OR value was 0.18, P<0.001. Conclusion:The incidence of depression among residents in Chongqing is high. Age, educational background, marital status, working hours and administration satisfaction are related to the degree of depression. And the higher the degree of depression, the lower the administration satisfaction of residents. Relevant departments should pay attention to the mental health of residents and improve the quality of standardized residency training.

Construction of assessment index system on the capacity of clinical medical postgraduate tutor and analysis of its reliability and validity / 中华医学教育探索杂志

Objective:To establish an assessment index system on the capacity of clinical medical postgraduate tutor.Methods:On the basis of "literature optimization method", the index system was initially constructed by 14 experts with "Delphi method". Then, through the survey of 109 people, the reliability and validity were tested by Cronbach's α coefficient and exploratory factor analysis. And analytic hierarchy process was used to calculate the weight coefficient of each index. SPSS 26.0 and AMOS 26.0 were applied for statistical analysis. Results:The assessment index system consisted of 2 first-level indexes, 5 second-level indexes and 27 third-level indexes. The Cronbach's α coefficient of the total index system, first-level indexes and second-level indexes ranged from 0.833 to 0.931. Five common factors were extracted by exploratory factor analysis, and the connotation of factors were basically consistent with the theoretical structure. A confirmatory factor model was established with 5 second-level indexes as the first-order factors, what's more, the theoretical model fitted well with the actual data. The combined weight values of "teaching attitude of the tutor", "medical ethics of the tutor", "scientific research projects of the tutor", "dissertation quality of the graduate students", "the quality of the scientific research and training of the graduate students", "the quality of the clinical training of the graduate students", and "disposable scientific research funds of the tutor" ranked in the top 7 weights of third-level indexes. Conclusion:This assessment index system has good reliability and validity with reasonable connotation, which could be used as a reference for tutor evaluation.

Comparison of left and right ventricular Tei indexes in newborns of different gestational age and birth weight / 中国新生儿科杂志

Objective:To compare left and right ventricular Tei indexes and to determine the reference range in newborns of different gestational age (GA) and birth weight (BW).Methods:From February 2019 to June 2021, newborns admitted to the Neonatal Intensive Care Unit of our hospital were enrolled. Tei indexes were measured and calculated during 24 h~7 d after birth and reexamined 1~2 weeks later in some of the newborns. The newborns were assigned into <32 w group, 32~36 w group and ≥ 37 w group according to their GA, < 1 500 g group, 1 500~2 499 g group and ≥2 500 g group according to their BW, and early newborn group (1~7 d) and late newborn group (>7 d) according to their age of evaluation. The data were analyzed using t test, one-way analysis of variance (ANOVA) and correlation analysis with SPSS 20.0 statistical software. Results:A total of 128 cases were included. 42 cases in <32 w group, 43 in 32~36 w group and 43 in ≥37 w group. 42 cases in <1 500 g group, 42 in 1 500 ~ 2 499 g group and 44 in ≥2 500 g group. Tei indexes were reexamined after 7 d of age in 63 preterm infants and in 31 full-term infants. The left and right ventricular Tei indexes of the ≥37 w group were less than the 32~36 w group and the <32 w group in early newborns (left ventricular: 0.382±0.069 vs. 0.431±0.069 and 0.439±0.060, right ventricular: 0.373±0.038 vs. 0.431±0.035 and 0.452±0.064); the right ventricular Tei index of the 32~36 w group was significantly less than the <32 w group ( P<0.05). No significant differences existed in the left ventricular Tei index between the 32 ~ 36 w group and the < 32 w group ( P>0.05). The left and right ventricular Tei indexes of the ≥2 500 g group were significantly less than the 1 500~2 499 g group and the <1 500 g group (left ventricular: 0.385±0.069 vs. 0.434±0.067 and 0.434±0.064, right ventricular: 0.376±0.039 vs. 0.431±0.043 and 0.450±0.061) ( P<0.05).No significant differences existed between the 1 500~2 499 g group and the <1 500 g group ( P>0.05). No significant differences existed in the left and right ventricular Tei indexes between the late newborn group and early newborn group ( P>0.05). For early newborns (1~7 d of age), the reference range of Tei index gradually decreased along with the increase of GA and BW. Conclusions:The left and right ventricular Tei indexes of full-term infants and infants with BW ≥2 500 g are less than preterm and low birth weight infants. The reference range of Tei index in early newborns shows negative correlation with GA and BW.

Etiological identification and phylogenetic analysis of a clustered epidemic caused by norovirus on a patrol boat / 上海预防医学

ObjectiveTo determine the pathogen and phylogenetic characteristics of an uncommon outbreak of recombinant norovirus infection in Daishan County in February 2022. MethodsFluorescence quantitative PCR was used to detect the norovirus in the eight anal swabs collected in the outbreak. In the positive samples， reverse transcription PCR were used to amplify the norovirus. Norovirus sequences were characterized by MEGA7 and Simplot. ResultsNorovirus GⅠ was identified in all eight anal samples. It was further determined to be recombinant norovirus GⅠ.6 ［P11］， with the recombination site at the ORF1-ORF2 junction. The sequence had the highest nucleotide identity （98.75%） to a GⅠ.6［P11］ strain collected in 2018 （GenBank accession number MT357995）. ConclusionAccording to the etiological identification and phylogenetic analysis， this outbreak is confirmed to be caused by the uncommon recombinant norovirus GⅠ.6 ［P11］ in China.

Efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with patent ductus arteriosus / 中华全科医师杂志

Objective:To investigate the efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with haemodynamically significant patent ductus arteriosus (hsPDA).Methods:The preterm infants (gestational age ≤ 32 weeks) with hsPDA who were admitted to neonatal intensive care unit (NICU) of Xuzhou Central Hospital from October 2016 to November 2019 were enrolled in the study. A total of 110 eligible cases were included and randomly divided into three groups for initial treatment: 38 cases received oral ibuprofen 10 mg/kg, and 5 mg/kg after 24 h and 48 h (ibuprofen group), 37 cases received oral paracetamol 15 mg/kg, q.8.h for 3 d (paracetamol group) and 35 cases received oral injection water 1 ml/kg, and 0.5 ml/kg after 24 h and 48 h (conservative management group). The preterm infants who failed in the initial treatment were given high-dose ibuprofen for rescue treatment (oral ibuprofen 20mg/kg, and 10 mg/kg after 24 h and 48 h). Serum creatinine, cystatin C, glutamic-pyruvic transaminase (GPT), total bilirubin, fecal occult blood and urinary prostaglandin E 2 were measured; echocardiography and brain color Doppler ultrasonography examinations were performed before and after treatment. Urine output and complications were recorded. The data were analyzed by ANOVA, t-test, non-parametric test, chi-square test and Pearson correlation coefficient with SPSS 20.0 statistical software. Results:During initial treatment, the success rates of ibuprofen group and paracetamol group were higher than that of conservative management group [71.1% (27/38) and 70.3%(26/37) vs. 40.0% (14/35), P=0.008 and 0.010]. Thirty one patients, who failed in initial treatment, received rescue treatment (8, 7, 16 cases from ibuprofen, paracetamol and conservative groups, respectively). The success rate of rescue treatment with high-dose ibuprofen was 58.1% (18/31). During initial treatment, there were no significant differences in the incidence of oliguria, upper gastrointestinal bleeding, positive fecal occult blood tests, Ⅲ-Ⅳ grade intraventricular hemorrhage, and ≥Ⅱ stage necrotizing enterocolitis among the three groups (all P>0.05). There were no significant differences in the incidence of above complications between rescue treatment and initial treatment [6.5% (2/31) vs. 6.4%(7/110), 3.2%(1/31) vs. 4.5%(5/110), 12.9%(4/31) vs. 6.4%(7/110), 0 vs. 4.5%(5/110), 3.2%(1/31) vs. 1.8%(2/110), all P>0.05]. The changes of serum creatinine and GPT before and after treatment were not significant in all groups ( P>0.05). Serum cystatin C were increased in both ibuprofen group[(0.44±0.17)μmol/L] and paracetamol group [(0.18±0.09)μmol/L] after treatment ( t=-15.70, -14.64; P<0.001), and the increase in ibuprofen group was greater than that in paracetamol group ( P<0.001). Urinary prostaglandin E 2 were decreased in both ibuprofen group [(-11.63±3.70)ng/L] and paracetamol group[(-4.89±1.91)ng/L] after treatment ( t=15.57, 7.03; P<0.001), and the decrease in ibuprofen group was greater than that in paracetamol group ( P<0.001). Serum cystatin C was not significantly increased after high dose ibuprofen rescue treatment [(1.67±0.17)mg/L vs.(1.71±0.21)mg/L; t=-1.12, P=0.273]. Conclusion:Both initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen can effectively promote hsPDA closure in preterm infants without increase of complications. However, renal function indexes such as urine output and serum cystatin C should be monitored. The high-dose ibuprofen is relatively safe, and can be used as one of rescue treatment.

Relationship between central line-associated bloodstream infection and catheter dwell time in neonates / 中华危重病急救医学

The central line-associated bloodstream infection (CLABSI) is a common and serious complication of central venous catheterization, which can lead to various short-term and long-term adverse outcomes. Neonatal CLABSI did not increase linearly with the prolongation of peripherally inserted central catheter (PICC). When the umbilical venous catheter (UVC) is retained for more than 1-2 weeks, the incidence of neonatal CLABSI may increase significantly; PICC replacement at 7-10 days after UVC indwelling may reduce the incidence of CLABSI, but it has not been supported by evidence-based medicine. This article reviews the related studies between neonatal CLABSI and catheter dwell time, in order to plan the indwelling time more reasonably and prevent CLABSI better.

The effects of hyperbilirubinemia on the myocardium of newborn rats / 中国新生儿科杂志

Objective:To study the influences of different levels of hyperbilirubinemia on the myocardium of newborn rats.Methods:Ninety-six 7-day-old newborn SD rats were selected and randomly assigned into control group (n=32, intraperitoneal injection of normal saline 0.5 ml), test group 1 (n=32, intraperitoneal injection of bilirubin solution 100 mg/kg) and test group 2 (n=32, intraperitoneal injection of bilirubin solution 200 mg/kg). Four time points were set at 0 h, 8 h, 24 h and 48 h. The general conditions of 8 rats from every group at each time point were recorded. The total serum bilirubin (TSB), cardiac troponin I (cTnI),heart fatty acid-binding protein (H-FABP) and B-type natriuretic peptide (BNP) were examined. The heart was removed and the pathological changes of the myocardium were observed under microscope. The caspase-3, B-cell lymphoma-2 protein (bcl-2) and bcl-2-associated X protein (bax) were tested. Using SPSS 20.0 statistical software, two-way ANOVA analysis of variance was conducted.Results:The TSB in test group 1 and 2 at 8~48 h were 2.5~4.4 times and 3.5~7.4 times higher than at 0 h [(20.8±3.0~36.5±10.4) μmol/L and (31.9±12.3~67.4±19.0) μmol/L vs. (8.4±2.1) μmol/L and (9.1±2.9) μmol/L]. No significant changes existed in cardiac histopathology at each time point among the three groups. At 48 h, as TSB level increased, the expression of apoptosis-related proteins caspase-3 and bax increased and the expression of bcl-2 decreased. Significant differences existed in the protein levels between any two groups (all P<0.05), except that bcl-2 in test group 1 was similar to control group ( P=0.255). With the prolonged duration of hyperbilirubinemia in test group 2, the expression of caspase-3 and bax increased, while the expression of bcl-2 decreased. Statistically significant differences existed in the protein levels between any two time points (all P<0.05), except that bax in 8 h subgroup was similar to 12 h subgroup ( P=0.820), and bcl-2 in 8 h subgroup was similar to 0 h subgroup ( P=0.064). The cTnI at 8 h, 24 h and 48 h in test group 1 and 2 were all significantly higher than the control group (all P<0.05),however, no significant differences existed between test group 1 and 2 (all P>0.05). H-FABP and BNP showed no significant differences among the three groups at any time point (all P>0.05). Conclusions:Hyperbilirubinemia can induce apoptosis of myocardial cells in newborn rats in a concentration- and time-dependent manner. Hyperbilirubinemia shows no significant effects on cardiac tissue pathology. Hyperbilirubinemia may cause mild injury to myocardium of newborn rats. The injury shows no correlation with TSB level and BNP level was not influenced.

Blockade of Wnt/β-catenin signaling pathway by DKK1 inhibits paraquat-induced transition of lung fibroblasts / 中华急诊医学杂志

Objective:To investigate the effects of inhibition of Wnt/ β-catenin signaling pathway on paraquat (PQ)-induced transition of human lung fibroblast cell line MRC-5 and related molecular mechanisms.Methods:The MRC-5 cells were divided into three groups. Control group: without drug treatment; PQ group: the cells were treated by PQ (50 μmol/L) for 72 hours to establish cell transition model; PQ+DKK1 group: the cells were treated with PQ (50 μmol/L) and DKK1 (10 ng/mL) for 72 hours. Then, the cells were collected, and the transition related signatures including α-SMA, Vimentin and Collagen I were detected by immunofluorescence and Western blot (WB); Meanwhile, the expression levels of Wnt pathway-related molecules including β-catenin, Cyclin D1 and WISP1 were determined by WB, immunofluorescence and real-time fluorescence quantitative PCR (RT-PCR) during the transition; In addition, the inhibitor of Wnt/β-catenin pathway Dickkopf-1 (DKK1) was applied to block the signaling. Then the expression changes of β-catenin, cyclin D1 and WISP1 were detected by WB to verify the inhibitory effect, and the transition marker molecules including α-SMA, Vimentin and Collagen I were also determined by WB.Results:After 72 hours, compared with the Control group, the expression levels of α-SMA, Vimentin and Collagen I of MRC-5 cells in PQ group were increased significantly ( P<0.05); The expression levels of β-catenin, Cyclin D1 and WISP1 of MRC-5 cells in PQ group were significantly up-regulated ( P<0.05); DKK1 could inhibit the high expression of α-SMA, Vimentin and Collagen I of MRC-5 cells during PQ-induced transition ( P<0.05). Conclusions:DKK1 could inhibit PQ-induced transition of lung fibroblasts by interference with Wnt/β-catenin signaling, which was expected to further inhibit pulmonary fibrosis caused by PQ.

Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome / 中国中药杂志

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1β and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

Role of platelets aggregation in the process of ductus arteriosus closure of newborn pups / 中华危重病急救医学

Objective:To investigate the role of platelets aggregation in the developing process of ductus arteriosus closure of newborn pups, and the effect of platelet membrane glycoprotein Ⅱb-Ⅲa (GPⅡb-Ⅲa) receptor antagonist (tirofiban).Methods:Four 24-month-old Beagle bitches were selected and numbered 1, 2, 3, and 4 respectively, and their pups were removed by cesarean section in two batches 1-2 days before the expected date of delivery. Bitches 1 and 2 were the first batch. Eighteen newborn pups were removed after cesarean section as the control group. They were divided into three subgroups: 1-hour subgroup, 4-hour subgroup, and 12-hour subgroup according to postnatal time point, with 6 pups in each subgroup. The newborn pups were injected with normal saline 10 mL/kg via jugular vein immediately after birth. Bitches 3 and 4 were the second batch. Nineteen newborn pups were removed by cesarean section as tirofiban group. They were also divided into three subgroups: 1-hour subgroup ( n = 6), 4-hour subgroup ( n = 6), and 12-hour subgroup ( n = 7) according to the postnatal time point. The newborn pups were injected with tirofiban hydrochloride injection 10 mL/kg (10 mL injection including 2.5 mg of tirofiban) via jugular vein immediately after birth. The diameter of ductus arteriosus was measured by echocardiography. Ductus arteriosus was removed by surgical dissection and divided into two parts. Western blotting and immunohistochemistry were used to detect the expression of platelet membrane GPⅡb-Ⅲa, respectively. Results:In the control group, 1 newborn pup died at 0.5 hour after birth in the 1-hour subgroup. The experiment was completed by 19 in the tirofiban group. Ductus arteriosus of all pups were not closed in 1-hour subgroups of the two groups, and there was no significant difference in the diameter of ductus arteriosus between the control group and the tirofiban group (mm: 1.72±0.08 vs. 1.70±0.11, P > 0.05). Ductus arteriosus of 1 newborn pup in 4-hour subgroup of the control group was closed, but the ductus arteriosus of all the newborn pups in 4-hour subgroup of the tirofiban group were not closed. The diameter of ductus arteriosus of the tirofiban group was significantly larger than that of the control group (mm: 1.52±0.15 vs. 0.95±0.48, P < 0.05). Ductus arteriosus of all pups were closed in 12-hour subgroup of the control group, but the ductus arteriosus of 2 pups of the tirofiban group were still not closed, with the diameter of ductus arteriosus of 1.0 mm and 1.1 mm, respectively. Western blotting showed that at 1-hour, 4-hour and 12-hour after birth, the expression of platelet membrane GPⅡb-Ⅲa was gradually increased in ductus arteriosus of newborn pups of the two groups. The expression of GPⅡb-Ⅲa in 1-hour subgroup of the tirofiban group was significantly lower than that in the control group (GPⅡb-Ⅲa/β-actin: 0.67±0.07 vs. 0.84±0.16, P < 0.05). The expression of GPⅡb-Ⅲa in 4-hour and 12-hour subgroups of the tirofiban group were slightly lower than those in the control group (GPⅡb-Ⅲa/β-action: 0.85±0.12 vs. 0.95±0.11 in 4-hour subgroup, 1.04±0.16 vs. 1.09±0.17 in 12-hour subgroup, both P > 0.05). Immunohistochemistry showed that the change trend of platelet membrane GPⅡb-Ⅲa in ductus arteriosus of newborn pups in both groups was similar to the results of Western blotting. Conclusions:The ductus arteriosus of newborn pups begin to close 1-4 hours after birth, and all closed at 12 hours after birth. The expression of platelet membrane GPⅡb-Ⅲa in ductus arteriosus increase gradually after birth, and the platelet aggregation may participate in and promote ductus arteriosus closure to some extent. Tirofiban, a platelet membrane GPⅡb-Ⅲa receptor antagonist, may delay ductus arteriosus closure of newborn pups to some extent by inhibiting platelet aggregation.

Effects of noninvasive positive pressure ventilation on cardiac function in premature infants using Tei index combined with correction of QT dispersion and B-type natriuretic peptide: a prospective study / 中华围产医学杂志

Objective:To assess the effects of noninvasive positive pressure ventilation on premature infants' cardiac function using Tei index combined with corrected QT dispersion (QTcd) and B- type natriuretic peptide (BNP).Methods:This prospective study involved premature infants from 28 to 32 weeks of gestational age diagnosed with respiratory distress syndrome (RDS) and treated with noninvasive positive pressure ventilation in the Neonatal Intensive Care Unit of Xuzhou Central Hospital from December 2017 to December 2020. According to the mean airway pressure (MAP) during noninvasive positive pressure ventilation, the patients were divided into the low-pressure group (≤6 cmH 2O, 1 cmH 2O=0.098 kPa), medium-pressure group (>6-<9 cmH 2O), and high-pressure group (≥9 cmH 2O). The right ventricular Tei index, QTcd, and blood BNP were monitored during the first 2 h of noninvasive positive pressure ventilation and 12 h after continuous ventilation with stable MAP. Chi-square test, one-way analysis of variance, paired t-test, and Pearson product-moment correlation coefficient were adopted for statistical analysis. Results:Totally 178 premature infants were enrolled, including 75 in the low-pressure, 62 in the medium-pressure, and 41 in the high-pressure group. After continuous ventilation with stable MAP for 12 h, the right ventricle Tei index and QTcd in the high-pressure group were higher than those in the medium- and low-pressure group [Tei index: (0.38±0.05) vs (0.33±0.04) and (0.33±0.04), F=29.18; QTcd: (27.6±4.2) vs (22.8±4.4) and (22.2±4.2) ms, F=23.26, all P<0.001], and the comparison between the medium- and the low-pressure group did not differ significantly. No significant difference was observed in blood BNP levels among the three groups ( F=1.33, P=0.267). The right ventricle Tei index and QTcd increased in the high-pressure group after continuous ventilation with stable MAP for 12 h as compared with those within the first 2 h of noninvasive positive pressure ventilation [Tei index: (0.38±0.05) vs (0.34±0.04), t=－6.61; QTcd: (27.6±4.2) vs (23.4±4.4) ms, t=－5.06, all P<0.001]. However, the figures did not change significantly in the medium- or the low-pressure group (all P>0.05). There were no significant changes in blood BNP in the three groups (all P>0.05). The right ventricle Tei index and QTcd were moderately positively correlated with MAP ( r=0.56 and 0.50, both P<0.001). Conclusions:For the premature infants with RDS, noninvasive positive pressure ventilation has no significant effect on the cardiac function when MAP is less than 9 cmH 2O, but would have a certain effect on the right ventricular function when used at higher pressure (MAP≥9 cmH 2O) and for longer time (>12 h).

The step-up training model for general practice residents based on entrustable professional activities / 中华全科医师杂志

The top-level design and training system of standardized training for residents has been basically completed in China, and now is gradually transiting to connotation construction and quality improvement, with the emphasis on post competency and quality as the core. There are discrepancies in clinical ability among general practice residents of different categories, so the step-up training mode should be adapted for set up and implement of phased training objectives to achieve the overall goal of training qualified general practitioners. The step-up training based on the framework of entrustable professional activities(EPAs)can quantitatively and qualitatively evaluate the competency of general practice residents and continuously track it, so that to ensure the competency of residents. This study has developed assessment item pools of EPAs-based step-up training for general practice residents through literature review and focus group discussion, and proposed implementation plans, and explored the application of EPAs in the step-up training of general practice residents.

Effects of non-invasive positive pressure ventilation on plasma B-type natriuretic peptide level and Tei index of right ventricle in preterm infants / 中华全科医师杂志

Objective:To investigate the effects of non-invasive positive pressure ventilation (NPPV) on plasma B-type natriuretic peptide (BNP) level and Tei index of right ventricle in preterm infants.Methods:Premature infants of gestational age<34 weeks with respiratory distress syndrome who were admitted in Neonatal Intensive Care Unit of Xuzhou Central Hospital and requiring for NPPV from December 2018 to October 2020, were enrolled in the study. Patients were randomly divided into two groups 46 patients received nasal continuous positive airway pressure ventilation (NCPAP group) and 49 patients received bi-level positive airway pressure ventilation (BiPAP group); 42 preterm infants of gestational age<34 weeks and without NPPV were selected as the control group. The plasma BNP, Tei index of right ventricle, mean airway pressure and oxygen index at 0-12 h and 48-60 h after NPPV were monitored in NCPAP group and BiPAP group. The plasma BNP and Tei index of right ventricle at 0-12 h and 48-60 h after admission were monitored in the control group. SPSS 20.0 statistical software was used for data analysis.Results:(1)The plasma BNP and Tei index of right ventricle at 48-60 h after NPPV were significantly higher than those at 0-12 h after NPPV in NCPAP group and BiPAP group [NCPAP group: (287.5±155.5) vs. (179.9±102.3) ng/L, (0.43±0.08) vs. (0.38±0.06); BiPAP group: (303.1±135.4) vs. (186.5±95.6) ng/L, (0.45±0.08) vs. (0.39±0.06); t=6.00, 3.34, 7.47, 4.48; all P<0.05]. There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h and 0-12 h after admission in the control group [(181.9±86.8) vs. (169.5±78.9) ng/L, (0.34±0.05) vs. (0.36±0.05); t=0.83, -1.59; all P>0.05].(2) There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h after NPPV between NCPAP group-and BiPAP group (all P>0.05), but they were significantly higher than those in control group at 48-60 h after admission(all P<0.05). (3)The mean airway pressure and oxygen index at 48-60 h after NPPV in NCPAP group and BiPAP group showed a decrease trend compared to those at 0-12 h after NPPV, but the differences were not significant [NCPAP group: (6.8±1.2) vs. (7.0±1.3) cmH 2O(1 cmH 2O=0.098 kPa), (5.7±2.1) vs. (6.1±2.3); BiPAP group: (7.0±1.3) vs. (7.2±1.2) cmH 2O, (5.5±2.0) vs. (5.8±2.1); t=-1.05, -0.80, -1.88, -0.67; all P>0.05]; while there were no significant differences between the two groups (all P>0.05). (4)There was a positive correlation between the plasma BNP and mean airway pressure ( r=0.48, P<0.001), but no correlation between Tei index of right ventricle and mean airway pressure ( r=0.17, P=0.119) at 48-60 h after NPPV. Conclusion:The cardiac function indexes such as plasma BNP and Tei index of right ventricle in preterm infants are increased at 48-60 h after NPPV. When mean airway pressure is the same, the effects of NCPAP and BiPAP on plasma BNP and Tei index of right ventricle in preterm infants are similar.