1.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
2.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
3.Association of digit ratio with polymorphisms at three loci of matrix metalloproteinase 9 gene in Ningxia Han youths
Meng-Yi YANG ; Jin ZHANG ; Shi-Bo NIU ; Jie DANG ; Zhan-Bing MA ; Hong LU ; Zheng-Hao HUO ; Yu XU ; Dan SHEN
Acta Anatomica Sinica 2025;56(1):74-79
Objective To investigate the association of digit ratio with single nucleotide polymorphism(SNP)at three loci(rs17576,rs3918249,rs9509)of matrix metallopeptidase 9(MMP-9)gene.Methods A total of 804 Ningxia Han youths(399 males and 405 females)were used as the study subjects.A digital camera was used to take frontal photographs of the hands,and image analysis software was used to mark the anatomical points and measure the lengths of each finger of both hands(2D,3D,4D,5D);Multiplexed PCR was used to detect the three polymorphic sites of the MMP-9 gene,SPSS 25.0 and R Studio software were used for data analysis and plotting.Results The 2D/3D(P<0.05)and 2D/4D(left,P<0.01,right,P<0.05)of both hands,2D/5D(P<0.01),3D/5D,4D/5D(P<0.05)of the right hand,and 3D/4D(P<0.05)of the left hand in female youths of Ningxia Han were significantly higher than those in males,Differences in genotypes and allele frequencies at all 3 loci of the MMP-9 gene were not statistically significant between genders(P>0.05).Right hand 2D/4D was significantly associated with genotypes at the rs17576 and rs3918249 loci in male youths(P<0.05).Conclusion MMP-9 gene SNPs(rs17576 and rs3918249)may be associated with the formation of 2D/4D of Ningxia Han male youths.
4.Sterilization efficacy of common disinfection methods and their effects on bioactive components in human milk: a network meta-analysis
Chinese Journal of Perinatal Medicine 2025;28(7):558-568
Objective:To systematically evaluate the impact of common disinfection methods on key human milk bioactive components [lactoferrin, lysozyme, immunoglobulin A (IgA), lipase, milk fat globule structure] and their sterilization efficacy.Methods:We searched eight databases (CNKI, Wanfang, VIP, Yiigle, PubMed, Web of Science, Cochrane Library, CINAHL) from inception to January 22, 2024, including 25 controlled studies. Network meta-analysis was performed using Stata 17.0, with surface under the cumulative ranking curve (SUCRA) values ranking seven methods: holder pasteurization (HoP), high-temperature short-time pasteurization (HTST), freezing, high-pressure processing (HPP), high hydrostatic pressure (HHP), ultraviolet-C (UV-C), and thermal ultrasound (TUS). Primary outcomes included bioactive component retention rates, milk fat globule integrity, and sterilization efficacy against representative pathogens [ Staphylococcus aureus, cytomegalovirus (CMV)]. Results:Bioactive component retention varied significantly: HPP demonstrated optimal lactoferrin preservation (SUCRA=98.2%, retention rate=92.4%±3.1%); HHP showed superior lysozyme retention (SUCRA=91.0%, retention rate=88.6%±2.5%); HTST maximized IgA preservation (SUCRA=75.5%, retention rate=72.3%±4.2%); UV-C achieved highest lipase retention (SUCRA=92.7%, retention rate=90.1%±1.9%). HPP maintained larger milk fat globules versus HoP. All methods achieved≥6-log pathogen reduction. HPP surpassed HoP/HTST in eliminating S. aureus (6-log vs. 4-log at 5-6 log CFU/ml initial load); HHP reduced CMV from 5.0 to 3.7 log PFU/ml (30 min), outperforming HoP (4.1 log). Non-thermal techniques (HPP/HHP/UV-C) better suppressed pathogen versus HoP. Conclusions:Bioactive component preservation is method-specific clinical protocols should therefore be optimized according to target component: HPP is recommended for lactoferrin/milk fat globule integrity; HHP for lysozyme; HTST for IgA; UV-C for lipase. While all methods meet safety standards, non-thermal technologies offer superior long-term pathogen suppression, providing optimized options for milk banks and clinical breastfeeding support.
5.Sterilization efficacy of common disinfection methods and their effects on bioactive components in human milk: a network meta-analysis
Chinese Journal of Perinatal Medicine 2025;28(7):558-568
Objective:To systematically evaluate the impact of common disinfection methods on key human milk bioactive components [lactoferrin, lysozyme, immunoglobulin A (IgA), lipase, milk fat globule structure] and their sterilization efficacy.Methods:We searched eight databases (CNKI, Wanfang, VIP, Yiigle, PubMed, Web of Science, Cochrane Library, CINAHL) from inception to January 22, 2024, including 25 controlled studies. Network meta-analysis was performed using Stata 17.0, with surface under the cumulative ranking curve (SUCRA) values ranking seven methods: holder pasteurization (HoP), high-temperature short-time pasteurization (HTST), freezing, high-pressure processing (HPP), high hydrostatic pressure (HHP), ultraviolet-C (UV-C), and thermal ultrasound (TUS). Primary outcomes included bioactive component retention rates, milk fat globule integrity, and sterilization efficacy against representative pathogens [ Staphylococcus aureus, cytomegalovirus (CMV)]. Results:Bioactive component retention varied significantly: HPP demonstrated optimal lactoferrin preservation (SUCRA=98.2%, retention rate=92.4%±3.1%); HHP showed superior lysozyme retention (SUCRA=91.0%, retention rate=88.6%±2.5%); HTST maximized IgA preservation (SUCRA=75.5%, retention rate=72.3%±4.2%); UV-C achieved highest lipase retention (SUCRA=92.7%, retention rate=90.1%±1.9%). HPP maintained larger milk fat globules versus HoP. All methods achieved≥6-log pathogen reduction. HPP surpassed HoP/HTST in eliminating S. aureus (6-log vs. 4-log at 5-6 log CFU/ml initial load); HHP reduced CMV from 5.0 to 3.7 log PFU/ml (30 min), outperforming HoP (4.1 log). Non-thermal techniques (HPP/HHP/UV-C) better suppressed pathogen versus HoP. Conclusions:Bioactive component preservation is method-specific clinical protocols should therefore be optimized according to target component: HPP is recommended for lactoferrin/milk fat globule integrity; HHP for lysozyme; HTST for IgA; UV-C for lipase. While all methods meet safety standards, non-thermal technologies offer superior long-term pathogen suppression, providing optimized options for milk banks and clinical breastfeeding support.
6.Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway
Shan-Shan LI ; Lu PAN ; Zhen-Ye ZHANG ; Meng-Dan ZHOU ; Xu-Fei CHEN ; Ling-Ling QIAN ; Min DAI ; Juan LU ; Zhi-Ming YU ; Shipeng DANG ; Ru-Xing WANG
Diabetes & Metabolism Journal 2024;48(4):716-729
Background:
Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified.
Methods:
In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed.
Results:
In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation.
Conclusion
Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.
7.Radiological shoulder parameter associated with postoperative satisfaction in Lenke type 1 adolescent idiopathic scoliosis
Fang XIE ; Dan GENG ; Fei WANG ; Jinggang DANG ; Liyu XIA ; Zhuojing LUO ; Xueyu HU
Chinese Journal of Orthopaedics 2024;44(8):525-531
Objective:To analyze the radiographic parameters of shoulder balance that affect the postoperative satisfaction of Lenke type 1 adolescent idiopathic scoliosis (AIS).Methods:A total of 98 patients with AIS who underwent posterior pedicle screw fusion in Xijing Hospital of Air Force Medical University from August 2017 to July 2020 were retrospectively analyzed. There were 26 males and 72 females, aged 15.2±5.3 years (range, 10-24 years). Distribution of upper instrumented vertebrae: T 2 58 cases (59%), T 3 25 cases (26%), T 4 15 cases (15%); Distribution of lower instrumented vertebrae: T 12 63 cases (64%), L 1 28 cases (29%), L 2 4 cases (4%), L 3 3 cases (3%). Clavicle angle (CA), radiographic shoulder height (RSH), and coracoid height difference (CHD), clavicle-rib cage intersection difference (CRID), T 1 tilt angle, first rib tilt angle, clavicle chest angle difference(CCAD) and Scoliosis Research Society-22 (SRS-22) scale were compared before and after operation. Binary logistic regression was used to analyze the radiographic indicators of shoulder balance that affected the postoperative satisfaction of Lenke type 1 AIS. The receiver operating characteristic (ROC) curve was drawn to determine the threshold value of the imaging index. Results:All operations were successfully completed. The operation time was 260±80 min (range, 220-320 min), and the intraoperative blood loss was 360±110 ml (range, 300-700 ml). There was no nerve, dural or vascular injury during operation. RSH, CHD, CRID, T 1 tilt angle, first rib tilt angle, and CCAD at the final follow-up were 4.0 (0, 13.9) mm, 7.0 (0, 12.9) mm, 4.0 (0, 10.0) mm, 4.8° (3.3°, 8.2°), 5.3°±3.9°, and 5.5° (3.0°, 8.9°), respectively, which were less than the preoperative 10.6 (2.0, 20.3) mm, 10.3 (2.5, 15.9) mm, 8.0 (1.0, 15.2) mm, 7.6° (3.5°, 12.2°), 7.5°±6.9°, 8.5° (3.6°, 18.3°), and the difference was statistically significant ( P<0.05). The SRS-22 function, pain, appearance, and psychological scores at the final follow-up were 4.6 (4.0, 4.9), 4.1±0.5, 4.1±0.7, and 4.2 (3.9, 4.8) points, respectively, which were greater than the preoperative scores of 4.2 (3.8, 4.6), 4.0±0.7, 3.5±0.7, and 4.0 (3.5, 4.4) points, the difference was statistically significant ( P<0.05). Binary logistic regression showed that CCAD was an independent radiographic indicator of shoulder balance that affected the satisfaction of AIS patients after orthopaedic surgery ( OR=0.826, P=0.040). ROC curve showed that the area under the curve and 95% CI was 0.726 (0.572, 0.865), and the threshold was 6.6°. Conclusion:CCAD is an independent radiographic parameter of shoulder balance that affects the postoperative satisfaction of AIS. Patients are more likely to achieve a satisfactory outcome when their postoperative CCAD is ≤6.6°, which can be used clinically as a radiographic parameter to assess the efficacy of orthopaedic spine surgery.
8.Status of delivery room continuous positive airway pressure in very preterm infants in China
Chun CHEN ; Dan DANG ; Xinyue GU ; Juan DU ; Lee Shoo K. ; Lizhong DU ; Yun CAO ; Wenhao ZHOU ; Siyuan JIANG ; Chuanzhong YANG ; Jianguo ZHOU
Chinese Journal of Perinatal Medicine 2024;27(12):1007-1014
Objective:To investigate the current status, trends, and differences among institutions in the application of delivery room continuous positive airway pressure (DRCPAP) for very preterm infants treated in the institutions in the Chinese Neonatal Network (CHNN). Also, to explore the impact of DRCPAP on the outcomes of very preterm infants in China.Methods:A retrospective cohort study was conducted. Based on the CHNN very preterm infant cohort, very preterm infants (gestational ages ranging from 25 weeks +0 to 31 weeks +6) born in-hospital and treated in 79 tertiary neonatal intensive care units (NICUs) participating in the CHNN from 2019 to 2021 were included. The usage rates of DRCPAP in different hospitals, as well as gestational ages and years, were described. Data were analyzed using the Chi-square test (or Fisher's exact test) or t-test. A multivariate logistic regression model was established to explore the correlation between DRCPAP and clinical outcomes. Results:(1) A total of 18 048 very preterm infants were included. Among them, 3 666 (20.3%) received DRCPAP, and 14 382 (79.7%) did not. (2) The usage rate of DRCPAP for very preterm infants among different institutions is from 0.0% to 94.5%. Fourteen institutions did not use DRCPAP, and 55 institutions had a usage rate below 30%. The usage rate of DRCPAP in very preterm infants increased annually, from 13.8% (818/5 916) in 2019 to 26.0% (1 583/6 097) in 2021 ( χ2trend=122.00, P<0.001). (3) The DRCPAP group had higher rates of maternal assisted reproductive technology pregnancy, chorioamnionitis, a full course of antenatal corticosteroids, gestational diabetes, fetal distress, antenatal magnesium sulfate use, and cesarean delivery compared to the non-DRCPAP group [20.3% (744/3 665) vs. 17.6% (2 529/14 369), χ2=14.45; 23.0% (695/3 021) vs. 16.4% (1 956/11 926), χ2=72.57; 57.1% (2 090/3 660) vs. 54.3% (7 766/14 302), χ2=9.55; 23.0% (844/3 669) vs. 20.7% (2 969/14 342), χ2=9.77; 8.7% (319/3 666) vs. 7.0% (1 006/14 371), χ2=12.51; 87.1% (3 186/3 657) vs. 82.0% (11 736/14 312), χ2=81.38; 63.5% (2 327/3 664) vs. 60.7% (8 722/14 369), χ2=9.59; all P<0.05]. While the incidence of hypertensive disorders of pregnancy and the proportion of infants not using antenatal corticosteroids were lower in the non-DRCPAP group [17.1% (626/3 660) vs. 22.6% (3 183/14 084), χ2=44.70; 14.2% (520/3 661) vs. 19.7% (2 814/14 284), χ2=57.34; all P<0.05]. The DRCPAP group had lower birth weight and gestational age, higher 1 min and 5 min Apgar scores, and lower neonatal transport stabilization index scores [(1 308±314) g vs. (1 325±315) g, t=2.90; (29.5±1.7) weeks vs. (29.7±1.6) weeks, t=3.96; (7.9±1.8) scores vs. (7.6±1.9) scores, t=-9.80; (9.0±1.1) scores vs. (8.7±1.3) scores, t=-13.01; (11.0±9.4) scores vs. (13.1±9.8) scores, t=11.31; all P<0.05]. The incidence of early-onset sepsis was higher in the DRCPAP group than in the non-DRCPAP group [1.8% (68/3 578) vs. 1.3% (193/14 296), adjusted OR (95% CI): 1.417 (1.028-1.955)], while the rates of tracheal intubation within 72 hours, PS use, invasive mechanical ventilation, mortality, admission hypothermia, grade Ⅲ-Ⅳ intracranial hemorrhage, and stage≥3 ROP were all lower in the DRCPAP group compared to the non-DRCPAP group [22.6% (830/3 666) vs. 36.9% (5 310/14 374), adjusted OR (95% CI): 0.499 (0.448-0.555); 53.1% (1 947/3 666) vs. 58.3% (8 388/14 377), adjusted OR (95% CI): 0.764 (0.697-0.836); 30.1% (1 104/3 662) vs. 43.9% (6 307/14 366), adjusted OR (95% CI): 0.539 (0.487-0.595); 7.4% (274/3 666) vs. 10.6% (1 526/14 342), adjusted OR (95% CI): 0.709 (0.601-0.836); 57.5% (2 103/3 657) vs. 66.5% (9 501/14 287), adjusted OR (95% CI): 0.722 (0.661-0.788); 3.0% (101/3 366) vs. 5.9% (763/12 932)], adjusted OR (95% CI): 0.525 (0.412-0.669); 2.2% (65/2 954) vs. 3.3% (367/11 121), adjusted OR (95% CI): 0.692 (0.505-0.947); all P<0.05]. There were no statistically significant differences between the two groups in the incidence rates of BPD at a corrected gestational age of 36 weeks, patent ductus arteriosus ligation, spontaneous intestinal perforation, and pneumothorax. Conclusions:Domestically, the application of DRCPAP might be related to a decrease in the demand for invasive ventilation, the use of surfactants, and mortality, but it might not reduce the occurrence of bronchopulmonary dysplasia, at a corrected gestational age of 36 weeks. In recent years, the use of DRCPAP in very premature infants in China has increased, but the overall usage rate is still low, and there are significant differences between units, requiring continuous quality improvement.
9.Status of delivery room continuous positive airway pressure in very preterm infants in China
Chun CHEN ; Dan DANG ; Xinyue GU ; Juan DU ; Lee Shoo K. ; Lizhong DU ; Yun CAO ; Wenhao ZHOU ; Siyuan JIANG ; Chuanzhong YANG ; Jianguo ZHOU
Chinese Journal of Perinatal Medicine 2024;27(12):1007-1014
Objective:To investigate the current status, trends, and differences among institutions in the application of delivery room continuous positive airway pressure (DRCPAP) for very preterm infants treated in the institutions in the Chinese Neonatal Network (CHNN). Also, to explore the impact of DRCPAP on the outcomes of very preterm infants in China.Methods:A retrospective cohort study was conducted. Based on the CHNN very preterm infant cohort, very preterm infants (gestational ages ranging from 25 weeks +0 to 31 weeks +6) born in-hospital and treated in 79 tertiary neonatal intensive care units (NICUs) participating in the CHNN from 2019 to 2021 were included. The usage rates of DRCPAP in different hospitals, as well as gestational ages and years, were described. Data were analyzed using the Chi-square test (or Fisher's exact test) or t-test. A multivariate logistic regression model was established to explore the correlation between DRCPAP and clinical outcomes. Results:(1) A total of 18 048 very preterm infants were included. Among them, 3 666 (20.3%) received DRCPAP, and 14 382 (79.7%) did not. (2) The usage rate of DRCPAP for very preterm infants among different institutions is from 0.0% to 94.5%. Fourteen institutions did not use DRCPAP, and 55 institutions had a usage rate below 30%. The usage rate of DRCPAP in very preterm infants increased annually, from 13.8% (818/5 916) in 2019 to 26.0% (1 583/6 097) in 2021 ( χ2trend=122.00, P<0.001). (3) The DRCPAP group had higher rates of maternal assisted reproductive technology pregnancy, chorioamnionitis, a full course of antenatal corticosteroids, gestational diabetes, fetal distress, antenatal magnesium sulfate use, and cesarean delivery compared to the non-DRCPAP group [20.3% (744/3 665) vs. 17.6% (2 529/14 369), χ2=14.45; 23.0% (695/3 021) vs. 16.4% (1 956/11 926), χ2=72.57; 57.1% (2 090/3 660) vs. 54.3% (7 766/14 302), χ2=9.55; 23.0% (844/3 669) vs. 20.7% (2 969/14 342), χ2=9.77; 8.7% (319/3 666) vs. 7.0% (1 006/14 371), χ2=12.51; 87.1% (3 186/3 657) vs. 82.0% (11 736/14 312), χ2=81.38; 63.5% (2 327/3 664) vs. 60.7% (8 722/14 369), χ2=9.59; all P<0.05]. While the incidence of hypertensive disorders of pregnancy and the proportion of infants not using antenatal corticosteroids were lower in the non-DRCPAP group [17.1% (626/3 660) vs. 22.6% (3 183/14 084), χ2=44.70; 14.2% (520/3 661) vs. 19.7% (2 814/14 284), χ2=57.34; all P<0.05]. The DRCPAP group had lower birth weight and gestational age, higher 1 min and 5 min Apgar scores, and lower neonatal transport stabilization index scores [(1 308±314) g vs. (1 325±315) g, t=2.90; (29.5±1.7) weeks vs. (29.7±1.6) weeks, t=3.96; (7.9±1.8) scores vs. (7.6±1.9) scores, t=-9.80; (9.0±1.1) scores vs. (8.7±1.3) scores, t=-13.01; (11.0±9.4) scores vs. (13.1±9.8) scores, t=11.31; all P<0.05]. The incidence of early-onset sepsis was higher in the DRCPAP group than in the non-DRCPAP group [1.8% (68/3 578) vs. 1.3% (193/14 296), adjusted OR (95% CI): 1.417 (1.028-1.955)], while the rates of tracheal intubation within 72 hours, PS use, invasive mechanical ventilation, mortality, admission hypothermia, grade Ⅲ-Ⅳ intracranial hemorrhage, and stage≥3 ROP were all lower in the DRCPAP group compared to the non-DRCPAP group [22.6% (830/3 666) vs. 36.9% (5 310/14 374), adjusted OR (95% CI): 0.499 (0.448-0.555); 53.1% (1 947/3 666) vs. 58.3% (8 388/14 377), adjusted OR (95% CI): 0.764 (0.697-0.836); 30.1% (1 104/3 662) vs. 43.9% (6 307/14 366), adjusted OR (95% CI): 0.539 (0.487-0.595); 7.4% (274/3 666) vs. 10.6% (1 526/14 342), adjusted OR (95% CI): 0.709 (0.601-0.836); 57.5% (2 103/3 657) vs. 66.5% (9 501/14 287), adjusted OR (95% CI): 0.722 (0.661-0.788); 3.0% (101/3 366) vs. 5.9% (763/12 932)], adjusted OR (95% CI): 0.525 (0.412-0.669); 2.2% (65/2 954) vs. 3.3% (367/11 121), adjusted OR (95% CI): 0.692 (0.505-0.947); all P<0.05]. There were no statistically significant differences between the two groups in the incidence rates of BPD at a corrected gestational age of 36 weeks, patent ductus arteriosus ligation, spontaneous intestinal perforation, and pneumothorax. Conclusions:Domestically, the application of DRCPAP might be related to a decrease in the demand for invasive ventilation, the use of surfactants, and mortality, but it might not reduce the occurrence of bronchopulmonary dysplasia, at a corrected gestational age of 36 weeks. In recent years, the use of DRCPAP in very premature infants in China has increased, but the overall usage rate is still low, and there are significant differences between units, requiring continuous quality improvement.
10.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Result Analysis
Print
Save
E-mail