OBJECTIVE: To explore the genotype-phenotype correlation in a Charcot-Marie-Tooth type 2A2A (CMT2A2A) pedigree and to provide genetic counseling for its subsequent pregnancies. METHODS: A Chinese pedigree presenting with "lower limb muscle atrophy and movement disorders" at the Prenatal Diagnosis Center of Xuzhou Central Hospital between January and August 2024 was selected as the study subject. Relevant clinical data were collected from the pedigree members. Peripheral blood samples from affected individuals, and amniotic fluid and/or chorionic villus samples were obtained for DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Pathogenicity assessment and bioinformatic analysis were conducted. This study was approved by the Medical Ethics Committee of Xuzhou Central Hospital (Ethics No. XZXY-LK-20240111-0019). RESULTS: All affected individuals in this pedigree were females, whom included the proband, her mother, and her first daughter. Earlier age of onset was associated with more severe lower limb atrophy. A heterozygous missense variant of the MFN2 gene, namely c.314C>T (p.Thr105Met), was identified in the proband, her mother, daughter, and the third fetus from a re-marriage. The same variant was absent in her elder brother, current husband, and her fourth fetus. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG) and recommendations from Clinical Genome Resources (ClinGen), the variant was classified as pathogenic (PP1_Strong+PM1+PS3+PS4_Moderate+PP3_Moderate+PM2_Supporting). Analyses with PROVEAN and Mutation Taster had categorized the variant as "deleterious" and "disease-causing", respectively. Analysis with Uniprot and Jalview showed that the affected amino acid residue is conserved across multiple species. ChEBI software predicted that the variant may alter the polarity of the 105th amino acid residue. CONCLUSION The c.314C>T (p.Thr105Met) missense variant of the MFN2 gene probably underlie the CMT2A2A in this pedigree. Above finding has enabled prenatal diagnosis and genetic counseling for its subsequent pregnancies.
Adult ; Female ; Humans ; Male ; Charcot-Marie-Tooth Disease/genetics* ; East Asian People/genetics* ; Exome Sequencing ; Genetic Testing/methods* ; GTP Phosphohydrolases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation, Missense ; Pedigree

Objective:To explore the genotype-phenotype correlation in a Charcot-Marie-Tooth type 2A2A (CMT2A2A) pedigree and to provide genetic counseling for its subsequent pregnancies.Methods:A Chinese pedigree presenting with " lower limb muscle atrophy and movement disorders" at the Prenatal Diagnosis Center of Xuzhou Central Hospital between January and August 2024 was selected as the study subject. Relevant clinical data were collected from the pedigree members. Peripheral blood samples from affected individuals, and amniotic fluid and/or chorionic villus samples were obtained for DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Pathogenicity assessment and bioinformatic analysis were conducted. This study was approved by the Medical Ethics Committee of Xuzhou Central Hospital (Ethics No. XZXY-LK-20240111-0019).Results:All affected individuals in this pedigree were females, whom included the proband, her mother, and her first daughter. Earlier age of onset was associated with more severe lower limb atrophy. A heterozygous missense variant of the MFN2 gene, namely c. 314C>T (p.Thr105Met), was identified in the proband, her mother, daughter, and the third fetus from a re-marriage. The same variant was absent in her elder brother, current husband, and her fourth fetus. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG) and recommendations from Clinical Genome Resources (ClinGen), the variant was classified as pathogenic (PP1_Strong+ PM1+ PS3+ PS4_Moderate+ PP3_Moderate+ PM2_Supporting). Analyses with PROVEAN and Mutation Taster had categorized the variant as " deleterious" and " disease-causing" , respectively. Analysis with Uniprot and Jalview showed that the affected amino acid residue is conserved across multiple species. ChEBI software predicted that the variant may alter the polarity of the 105th amino acid residue. Conclusion:The c. 314C>T (p.Thr105Met) missense variant of the MFN2 gene probably underlie the CMT2A2A in this pedigree. Above finding has enabled prenatal diagnosis and genetic counseling for its subsequent pregnancies.

Objective:To explore the genotype-phenotype correlation in a Charcot-Marie-Tooth type 2A2A (CMT2A2A) pedigree and to provide genetic counseling for its subsequent pregnancies.Methods:A Chinese pedigree presenting with " lower limb muscle atrophy and movement disorders" at the Prenatal Diagnosis Center of Xuzhou Central Hospital between January and August 2024 was selected as the study subject. Relevant clinical data were collected from the pedigree members. Peripheral blood samples from affected individuals, and amniotic fluid and/or chorionic villus samples were obtained for DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Pathogenicity assessment and bioinformatic analysis were conducted. This study was approved by the Medical Ethics Committee of Xuzhou Central Hospital (Ethics No. XZXY-LK-20240111-0019).Results:All affected individuals in this pedigree were females, whom included the proband, her mother, and her first daughter. Earlier age of onset was associated with more severe lower limb atrophy. A heterozygous missense variant of the MFN2 gene, namely c. 314C>T (p.Thr105Met), was identified in the proband, her mother, daughter, and the third fetus from a re-marriage. The same variant was absent in her elder brother, current husband, and her fourth fetus. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG) and recommendations from Clinical Genome Resources (ClinGen), the variant was classified as pathogenic (PP1_Strong+ PM1+ PS3+ PS4_Moderate+ PP3_Moderate+ PM2_Supporting). Analyses with PROVEAN and Mutation Taster had categorized the variant as " deleterious" and " disease-causing" , respectively. Analysis with Uniprot and Jalview showed that the affected amino acid residue is conserved across multiple species. ChEBI software predicted that the variant may alter the polarity of the 105th amino acid residue. Conclusion:The c. 314C>T (p.Thr105Met) missense variant of the MFN2 gene probably underlie the CMT2A2A in this pedigree. Above finding has enabled prenatal diagnosis and genetic counseling for its subsequent pregnancies.

Humans ; Aged ; Acute Kidney Injury ; Risk Factors ; Creatinine

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with nasal intermittent positive pressure ventilation (NIPPV) in the treatment of infants with respiratory distress syndrome (RDS).Methods:A prospective study was conducted on preterm infants of gestational age ≤34 weeks with RDS who were admitted to the Neonatal Intensive Care Unit of Xuzhou Central Hospital from October 2019 to November 2021. The infants were randomly assigned into the LISA+NIPPV group and the intubation-surfactant-extubation (INSURE) +nasal continuous positive airway pressure (NCPAP) group. In the LISA+NIPPV group, with the support of NIPPV, a Lisa tube was inserted through the vocal cords under direct vision with direct laryngoscope, and then pulmonary surfactant (PS) was infused into the lung. In the INSURE+NCPAP group, the patients were endotracheally intubated and infused with PS into the lung through endotracheal tube, then extubated and continued to receive NCPAP therapy (INSURE). The blood gas analysis at 1 h and 6 h after PS infusion, the adverse reactions during injection, clinical efficacy, bronchopulmonary dysplasia (BPD) and other related complications were compared between the two groups.Results:A total of 112 preterm infants with RDS were enrolled, including 58 in the LISA+NIPPV group and 54 in the INSURE+NCPAP group. The blood oxygen partial pressure (PaO 2) and PaO 2/FiO 2 (P/F) in the LISA+NIPPV group were significantly higher than those in the INSURE+NCPAP group at 1 h and 6 h after PS infusion, while carbon dioxide partial pressure (PaCO 2) were significantly lower than that in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The rate of tracheal intubation within 72 h (15.5% vs. 33.3%), the duration of non-invasive ventilation [ (7.5 ± 4.3) d vs.(9.9 ± 5.5) d ], total oxygen inhaling [ (10.5 ± 3.5) d vs.(13.3 ± 4.1) d ], failure rate of machine withdrawal (8.6% vs. 31.0% ), the times of apnea [7.0 (3.0-21.0) times vs. 15.0 (4.0-28.0) times ] and re-administration of PS (17.2% vs. 33.3%) in the LISA+NIPPV group were significantly lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of regurgitation in the LISA+NIPPV group was lower than that in the INSURE+NCPAP group (13.8% vs. 35.2%), and the difference was statistically significant ( P<0.05). There was no significant difference in the time needed for intubation between the two groups ( P>0.05). The occurrence of BPD in the LISA+NIPPV group was significantly lower than that in the INSURE+NCPAP group (10.3% vs. 25.9%), and there was no significant difference in other related complication between the two groups (all P>0.05). Conclusions:LISA combined with NIPPV in the treatment of preterm infants with RDS can effectively improve oxygenation, reduce carbon dioxide retention, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD.

Objective:To investigate changes in arterial acid-base and electrolytes after repeated episodes of ventricular fibrillation (VF) and defibrillation in a swine model.Methods:Sixteen Peking white swine, weighting (32±2.5) kg, were placed with temporary pacemaker electrodes via the left femoral vein into the right ventricle after anesthesia. Then VF was electrically induced by using a programmed electrical stimulation instrument. An arterial cannula was inserted into the left femoral artery to measure mean arterial blood pressure and cardiac output using a PiCCO monitor, with blood samples collected. The pigs were randomly divided into two group: the manual defibrillation group (MD, n=8) and the automated external defibrillation group (AED, n=8). The first defibrillation was attempted with the manufacturer’s dose (150 J) for 15 s after the successful induction of VF in the MD group. If spontaneous circulation was not recovered, 2-min chest compression and subsequent defibrillation (200 J) were attempted. For the AED group, the defibrillation was delivered following voice prompts of the AED. After the return of spontaneous circulation, the pig was allowed to stabilize for 30 min, followed by the induction of the next episode of VF. The above process was repeated five times. Arterial blood gas, cardiac biomarkers, and hemodynamic variables were measured at 30 min after the return of spontaneous circulation. Results:All pigs were successfully induced VF five times and defibrillated successfully. There were no significant changes in heart rate and mean arterial blood pressure between the two groups after repeated episodes of VF and defibrillation. Compared with baseline measurements, cardiac output tended to decrease after repeated episodes of VF and defibrillation but was not statistically significant (all P>0.05). There were no significant differences in arterial pH, HCO 3-, sodium, and lactic acid in the two groups between each measurement time point and baseline values after repeated VF (all P>0.05), but potassium levels in the two groups decreased with time, and the difference was statistically significant compared with the baseline measurement (all P<0.05). There were no significant differences in myoglobin, creatine kinase isoenzyme-MB, and cardiac troponin I for the two groups compared with baseline values after repeated episodes of VF and defibrillation or various episodes of VF between the two groups (all P > 0.05). Conclusions:Repeated episodes of VF and defibrillation have no significant effect on pH balance, but significantly decrease blood potassium. Clinical approaches (MD vs. AED) do not affect defibrillation effect, with no significant differences in hemodynamic variables and myocardial injuries.

Objective:To make Excel spreadsheet of arterial blood gas analysis to judge the types of acid-base imbalance quickly and accurately, and guide the clinical treatment of acid-base disorders.Methods:According to the Henderson-Hasselbalch equation, the compensation formula of acid-base imbalance prediction, the theory of acid-base balance and the related research progress, the analysis process of acid-base balance disorder was settled, and the IF function in Microsoft Office Excel 2003 was used to edit the formula to make Excel spreadsheet for arterial blood gas analysis.Once the pH value, artery blood carbon dioxide pressure (PaCO 2), actual bicarbonate (HCO 3-), sodiumion (Na + ), chlorineion (Cl -) and compensatory time-limited parameters were input, the types of acid-base imbalance can be shown.Arterial blood gas analysis of 185 cases from intensive care unit at Xuzhou Central Hospital was determined by Excel spreadsheet group and manual group respectively, the results and time of judging the type of acid-base imbalance were compared between two groups for statistical analysis. Results:The results of acid-base imbalance between two groups were compared, and 42 cases were normal and simple acid-base and the consistent rate was 100%, double acid-base imbalances of 107 cases with the consistent rate of 97.20%, triple acid-base imbalances of 36 cases with the consistent rate of 91.67%.After Kappa consistency test (Kappa value=0.944) and Pair chi-square Test (McNemar-Bowker Test)( P=0.223), the results of two groups were consistent.It took less time to judge the results of normal or simple acid-base imbalance[(32.32±4.26)s vs.(75.88±19.22)s], double acid-base imbalance[(31.28±5.31)s vs.(137.56±37.64)s] and triple acid-base imbalance[(32.98±4.23)s vs.(315.09±89.37)s] by the Excel spreadsheet group compared with the manual group, and the differences were statistically significant ( P<0.01). Conclusion:The automatic judging of Excel spreadsheet for arterial blood gas analysis can quickly and accurately determine the types of acid-base imbalance in arterial blood gas analysis and has more advantages for triple acid and base imbalance especially with simple interface and simple operation.And it can avoid the missing judgment of acid and base imbalance when pH is 7.35 to 7.45.

Objective:To investigate the clinical application of noninvasive high frequency oscillatory ventilation(nHFOV)and heated humidified high flow nasal cannula(HHHFNC)in sequential ventilator evacuation of preterm infants with very low birth weight with respiratory distress syndrome(RDS).Methods:A total of 88 preterm infants of very low birth weight with RDS were enrolled in the study, who had received endotracheal intubation invasive ventilation and were ready to be replaced by non-invasive ventilation at neonatal intensive care unit(NICU)of Xuzhou Central Hospital from May 2017 to January 2020.All premature infants were routinely treated with caffeine citrate.They were divided into two groups through random number table: nHFOV/HHHFNC group(45 cases)and continuous positive airway pressure(nCPAP)/oxygen hood group(43 cases). nHFOV was given after invasive ventilator removal and HHHFNC transition was followed after nHFOV withdrawal in the nHFOV/HHHFNC group, while nCPAP was given after invasive ventilator removal and oxygen hood was followed after nCPAP withdrawal in the nCPAP/oxygen hood group.The main observation consequences were compared with arterial blood gas indexes after invasive ventilator evacuation, weaning effect and the incidence of related complications.Results:(1)There were no statistically differences between the two groups in terms of gender, gestational age, birth weight, Apgar score at 1 min and 5 min after birth, the number of glucocorticoid usage in 24 h before delivery, the number of pulmonary surfactant usage, invasive ventilation time and RDS grading( P>0.05). (2)The PaO 2, PaCO 2and oxygenation index(OI=100×MAP×FiO 2/PaO 2)of the nHFOV/HHHFNC group at 1 h and 24 h after invasive ventilator removal showed significant difference compared with the nCPAP/oxygen hood group( P<0.05). The differences as the following listed were statistically significant( P<0.05)between the two groups, including the failure rate of invasive ventilation weaning during 72 h [9%(4/45)vs.26%(11/43)], the incidence of frequent apnea [7%(3/45)vs.23%(10/43)], the failure rate of nHFOV and nCPAP noninvasive ventilation weaning [4%(2/45)vs.21%(9/43)], the oxygen-used time [12.02(9.08~12.31)d vs.14.44(11.32~13.26)d] and the incidence of nasal injury [4%(2/45)vs.26%(11/43)]. (3)The time of the first noninvasive ventilation of nHFOV and nCPAP, the incidences of lung air leakage, neonatal necrotizing enterocolitis, grade Ⅲ to Ⅳ intraventricular hemorrhage, above stageⅡretinopathy, bronchopulmonary dysplasia and the mortality rate between the two groups showed no statistical significance( P>0.05). Conclusion:nHFOV and HHHFNC used in the sequential ventilator evacuation of RDS in preterm infants with very low birth weight could improve oxygenation, reduce CO 2retention, improve the success rate of machine weaning and reduce the occurrence of apnea and nasal injury.

Objective:To judge the type of acid-base balance disorder automatically according to the results of arterial blood gas analysis by using the IF function editing formula in an Excel spreadsheet.Methods:The four-step analysis was used to carry out programmatically through establishing acid-base balance disorder analysis process: ① the acid and base types were determined according to pH value and the primary or main type of acid-base balance disorder was determined according to the pH value combined with blood carbon dioxide pressure (PaCO 2), HCO 3- and their change rate; ② the expected compensation formula was selected to determine whether there was mixed acid-base imbalance, according to the primary or main acid-base imbalance type; ③ the potential HCO 3- should be calculated to replace the measured HCO 3- when the primary acid-base imbalance was divided into two parts according to the prior two steps: respiratory acidosis or respiratory alkalosis accompanied with anion gap (AG) increased-metabolic acidosis and compared with the compensatory interval calculated by the predicted compensatory formula for acid or alkali to determine whether there were triple acid-base imbalance (TABD); ④while the following two parts were judged: metabolic acidosis accompanied with AG increased-metabolic acidosis according to the prior two steps, ΔAG↑/ΔHCO 3-↓should be calculated to determine whether there was metabolic alkalosis or metabolic acidosis with normal AG. The results of arterial blood gas analysis were judged by using the editing formula of IF function in Excel 2003 spreadsheet. A total of 96 patients admitted to the department of intensive care unit (ICU) of Xuzhou Central Hospital were enrolled. According to the results of arterial blood gas analysis, the type of acid-base imbalance of patients was judged by both artificial judgment (artificial group) and Excel spreadsheet automatic judgment (Excel spreadsheet group). The artificial group was composed by 2 associate chief physicians from neonatal intensive care unit (NICU) and 1 attending respiratory physician. If the results were inconsistent, the decision should be made after discussion. In the Excel spreadsheet group, data were input by one NICU attending physician and checked by another. The differences in the results and the time spent in judging the type of acid-base imbalance between the two groups were compared. Results:Forty-two types of acid-base imbalance were obtained by using the four-step analysis method and inputting relevant parameters such as pH, PaCO 2, actual HCO 3-, Na +, Cl - and compensation time limited into the Excel spreadsheet for blood gas analysis. Data analyses of 96 patients showed that the accuracy of using Excel spreadsheets to automatically determine the type of acid-base imbalance was higher than artificial group, but there was no statistically significant difference between the two groups [normal and simple acid-base imbalance: 100% (26/26) vs. 100% (26/26), mixed acid-base imbalance: 100% (51/51) vs. 96.08% (49/51), TABD: 100% (19/19) vs. 89.47% (17/19), all P > 0.05], and it took less time to judge the results of blood gas analysis by the Excel spreadsheet group compared with the artificial group (s: normal and simple acid-base imbalance: 31.13±4.70 vs. 74.20±16.53, mixed acid-base imbalance: 31.59±5.49 vs. 138.10±22.26, TABD: 30.98±5.40 vs. 308.40±78.12, all P < 0.01). Conclusion:The automatic judging Excel spreadsheet with blood gas analysis can quickly and accurately determine the type of acid-base imbalance in arterial blood gas analysis.

Objective To assess the clinical efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) for prevention of extubation failure in preterm infants with respiratory distress syndrome (RDS).Methods From March 2016 to December 2017,75 preterm infants (≤32 weeks gestation) with RDS who needed noninvasive respiratory support after a period of mechanical ventilation with an endotracheal tube in neonatal intensive care unit were studied.They were randomly assigned into the HHHFNC group (38 cases) and the NCPAP group (37 cases) by using a random number table.The main observation was the success rate of removal of the ventilator,duration of noninvasive ventilation time,the total oxygen inhaling time,feeding conditions and incidence of adverse events.Results The baseline demographic characteristics of the two groups were similar in terms of gestational age,birth weight,gender,incidence of cesarean delivery,premature rupture of membranes,administrations of antenatal glucocorticoid prophylaxis,Apgar scores at 1 and 5 minutes (P ＞ 0.05).No significant difference was found in the success rate of removal of the ventilator between HHHFNC group and NCPAP group(94.7 ％ vs.91.9％,P ＞ 0.05).The time of noninvasive ventilation,the total oxygen inhaling time and hospital stay in the NCPAP group were shorter than those in the HHHFNC group,but there were no significant differences between two groups (P ＞ 0.05).The occurrence of abdominal distention (10.5％ vs.27.05％),nasal trauma(5.2％ vs.21.6％),head shaping(0 vs.32.4％) were lower in HHHFNC group than those in NCPAP group (P ＜0.05).The time needed to achieve total enteral nutrition[(10.1 ± 1.2) d vs.(14.1 ± 1.6)d] and the incidence of feeding intolerance (13.1％ vs.29.7％) were reduced in HHHFNC group than those in NCPAP group (P ＜ 0.05).Conclusion As an respiratory support for the treatment of preterm infants with RDS after extubation,HHHFNC has the similar efficacy with NCPAP.However,HHHFNC has lower incidence of nasal trauma,abdominal distension and feeding intolerance,and further clinical research is needed.