Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

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.

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.

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with caffeine citrate in the treatment of respiratory distress syndrome (RDS) in preterm infants receiving continuous positive airway pressure (NCPAP) ventilation.Methods:From August 2019 to April 2021, a total of 112 preterm infants with RDS (26 weeks≤gestational age ≤32 weeks) who were hospitalized in the Neonatal Intensive Care Unit of Xuzhou Central Hospital, were chosen as research subjects. The patients were randomly divided into the LISA combined treatment group ( n=58) and the INSURE group ( n=54). In the LISA combined treatment group, a LISA tube was inserted through the vocal cords under direct vision with a direct laryngoscope and then infused with pulmonary surfactant (PS) into the lung when NCPAP ventilation was applied, and caffeine citrate was given intravenously. In the INSURE group, the patients were endotracheally intubated and infused with PS into the lung through an endotracheal tube, and then extubated and put on NCPAP again. The following indicators were examined: the general clinical data, results of blood gas analysis at 1 h and 6 h after infusion of PS into the lung, clinical efficacy and related complications. Results:①No significant differences were found between the two groups in the general clinical data (all P>0.05).Intra-group comparison within LISA combined treatment group or INSURE group showed that partial pressure of arterial carbon dioxide (PaCO 2), partial pressure of arterial oxygen (PaO 2) of blood gas analysis and PaO 2/fraction of inspired oxygen (P/F) at 1 h and 6 h after infused PS into the lung were all improved compared to those of before treatment, and the differences were statistically significant (all P<0.05). The PaO 2 and P/F in the LISA combined treatment group at 1 h and 6 h after breath support therapy were higher than those in the INSURE group, while PaCO 2 was lower than that in the INSURE group, and the differences were statistically significant (all P<0.05). The duration of noninvasive ventilation, total oxygen inhalation, re-administration of PS, failure rate of machine withdrawal, the rate of tracheal intubation within 72 h and the times of apnea in the LISA combined treatment group were significantly shorter, or lower, or less than those in the INSURE group [3.0 (1.0, 18.0) d vs. 7.5 (2.0, 22.0) d, 5.5 (3.0, 21.0) d vs. 10.5 (4.0, 28.0) d, 9 (15.5%) vs. 17 (31.5%), 6 (10.3%) vs. 14 (25.9%), 5 (8.6%) vs. 12 (22.2%), 5.0 (3.0, 21.0) times vs. 15.0 (4.0, 28.0) times], and the differences were all statistically significant (all P<0.05). The incidence of bronchopulmonary dysplasia in the LISA combined treatment group was less than that in the INSURE group [(5 (8.6%) vs. 13 (24.1%)], and the difference was statistically significant ( P<0.05). There was no significant difference between the two groups in other complications( P>0.05). Conclusions:Compared with INSURE, the LISA technique combined with caffeine citrate can effectively improve oxygenation, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26-32 weeks.

Objective:To study the efficacy and safety of less invasive surfactant administration (LISA) combined with bi-level positive airway pressure (BiPAP) ventilation in premature infants with respiratory distress syndrome (RDS).Methods:Premature infants with RDS at gestational age of 26~32 weeks in the NICU of our hospital from January 2020 to October 2021 were enrolled in this randomized controlled trial. They were randomly assigned to the LISA+BiPAP group or the intubation-surfactant-extubation (INSURE) + nasal continuous positive airway pressure (NCPAP) group, and given the corresponding treatment according to the group. The blood gas analysis at 1 h and 6 h after intratracheal instillation of pulmonary surfactant (PS), medication, noninvasive respiratory support time, total oxygen use time, weaning failure rate and endotracheal intubation rate within 72 h after PS administration were compared between the two groups, as well as the incidence of bronchopulmonary dysplasia (BPD).Results:A total of 86 preterm infants with RDS were enrolled in the study, including 44 in the LISA+BiPAP group and 42 in the INSURE+NCPAP group. Arterial partial pressure of oxygen in the LISA+BiPAP group at 1 h and 6 h after intratracheal instillation of PS were higher than those in the INSURE+NCPAP group, while PaCO 2 and oxygenation index (OI) were lower than those in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The duration of noninvasive respiratory support time [(12.2±8.7) d vs. (16.0 ±7.6) d], total oxygen use time [(16.6 ±8.3) d vs. (20.3±7.4) d], length of hospitalization[(22.6±10.3) d vs. (27.1±12.6) d], weaning failure rate [(11.4% (5/44) vs. 31.0% (13/42)], endotracheal intubation rate within 72 h after PS administration [11.4% (5/44) vs. 28.6% (12/42)], and re-administration of PS [18.2% (8/44) vs. 38.1% (16/42)] in the LISA+BiPAP group were lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The time needed for intubation and the incidence of regurgitation in the LISA+BiPAP group were lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of BPD in the LISA+BiPAP group was lower than those in the INSURE+NCPAP group [11.4% (5/44) vs. 31.0% (13/42)] ( P<0.05), the difference was also statistically significant ( P<0.05). There was no significant difference in the incidence of other complications between the two groups ( P>0.05). Conclusions:LISA combined with BiPAP can effectively improve oxygenation, reduce the mechanical ventilation rate, shorten the duration of non-invasive respiratory support, and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26~32 weeks.

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.

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).

Objective:To evaluate the correlation, consistency and safety of an smartphone application (APP) in screening neonatal jaundice using the smartphone based on the image-based bilirubin (IBB) and transcutaneous bilirubin (TcB).Methods:From July to October 2018, neonates with the age ≤28 d and gestational age ≥35 weeks who were admitted to Department of Neonatal and Obstetrics, Xuzhou Central Hospital without blue light phototherapy were recruited.They were randomly divided into two groups to measure the jaundice value of skin in front of sternum by a cross-control analysis.Jaundice level in group Ⅰ was first measured using the Nezhabaobei? APP in iPhone 6, and then measured using the JM-103 transcutaneous jaundice instrument as the control device.In group Ⅱ, jaundice level was sequencially measured by the control device and the Nezhabaobei? APP.Sex, age, gestational age, birth weight and the mean value of three consecutive tests were recorded.The Pearson′s correlation analysis, Bland-Altman plots consistency analysis, t test and receiver operating characteristic (ROC) curve were used for statistical analysis. Results:A total of 185 eligible neonates were enrolled, including 99 males and 86 females, with the median age of 5 d (3-8 d), gestational age of (37.6 ± 1.7) weeks, and birth weight of (2 950 ± 645) g. There were good correlation ( r=0.860, P<0.05) and consistency (95.1% of the samples fall within the 95% consistency interval) between IBB and TcB.Good correlation and consistency were also yielded in subgroup analyses based on the sex, age, gestational age and birth weight.The consistency was better in subgroups of ≤7 d, >37 weeks and>2 500 g. The ability of IBB to predict TcB>256.5 μmol/L was better than that of TcB>171.0 μmol/L.The area under the ROC curve was 0.93, the cut-off value was 232.6 μmol/L, the sensitivity was 96.7%, and the specificity was 82.6%.The difference of the mean values of IBB and TcB detected for 3 times was significantly lower than that obtained in the first measurement of IBB and TcB [(12.0 ± 34.4) μmol/L vs.(14.4 ± 38.6) μmol/L, P=0.038]. There were no adverse events and no defects in the device itself. Conclusions:There are good correlation and consistency between IBB and TcB.The ability of IBB to predict TcB>256.5 μmol/L is better than that of TcB>171.0 μmol/L, which is safe in clinical use.

Objective To study the influence factors on the accuracy of a smartphone software application (APP) , which is an automated image-based bilirubin (AIB) testing technique for neonatal bilirubin. Methods This was a prospective study involving 179 jaundiced neonates admitted to the Department of Neonatology of the Affiliated Xuzhou Hospital of Southeast University from August to December, 2017. If blood sampling was required to determine total serum bilirubin (TSB), the transcutaneous bilirubin (TcB) and AIB on the sternum (glabella or the visible darkest yellow area were tested in 36 cases at the same time) were also tested. The concentrations of AIB were measured using a mobile phone-based neonatal jaundice monitoring APP with images taken by OPPO R11 smartphone (55 cases were also taken by Huawei Mate 8 and iPhone 6). The accuracy and non-inferiority of AIB comparing with TcB, the correlation and consistency between AIB and TSB and the value of AIB in predicting TSB were analyzed. Non-inferiority trial, student's t test, variance analysis, Pearson's correlation analysis, Bland-Altman plots and receiver operating characteristic (ROC) curve were used as statistical methods. ResuLts A total of 179 neonates were enrolled in this study with the mean gestational age of (36.2±2.1) weeks and the mean birth weight of (2 871±735) g. Based on all data, the mean difference between the absolute value of AIB minus TSB (|AIB － TSB|) and the absolute value of TcB minus TSB (|TcB － TSB|) was 0.77 mg/dl (1 mg/dl=17.1 μmol/L) with the 95%CI of (0.60-0.95) mg/dl, suggesting that the accuracy of AIB was not inferior to that of the TcB. Furthermore, AIB was not inferior to TcB in its accuracy in different subgroups based upon the time after birth ( ≤ 48 h and >48 h), gestational age (≤35 weeks and >35 weeks) and in the daytime subgroup. In the nighttime subgroup, the mean difference between ∣ AIB － TSB ∣ and ∣ TcB － TSB ∣ was 1.47 mg/dl [95%CI: (1.08-1.87) mg/dl], which indicated that the accuracy of AIB was inferior to that of the TcB. There were good correlation (r=0.788) and highly consistency between AIB and TSB based on all data [96.4% (238/247) of the samples were within the 95% limits of agreement of (－4.75 to 5.71) mg/dl]. Such results were also found in different subgroups, such as smartphone brands, detection areas, the time after birth and gestational age. The correlation and consistency between AIB and TSB in daytime subgroup (r=0.924, 98.4%) were obviously stronger than those of the nighttime subgroup (r=0.727, 87.5%). The mean difference between the absolute value of ocular value minus TSB (|ocular value－TSB|)and|AIB－TSB|was 2.13 mg/dl [95%CI: (1.68-2.58) mg/dl], implying a superior accuracy of AIB than ocular estimation. The areas under the ROC curves, the sensitivity and the specificity of AIB for the prediction of TSB >10, >15 and >20 mg/dl were 0.94, 93% and 85%; 0.89, 75% and 87%; and 0.84, 50% and 88%, respectively. ConcLusions AIB is not inferior to TcB in accuracy, and is significantly superior to ocular estimation. There are good correlation and strong consistency between AIB and TSB. The accuracy of AIB, and the correlation and consistency between AIB and TSB are less likely to be affected by the time after birth, gestational age, smartphone brands and areas being examined, but are largely affected when examining during nighttime. Therefore, it is recommended to detect AIB at daytime with bright natural light.