Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective:To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods:A total of 22 813 newborns (12 065 males and 10 748 females) born at the Women's Hospital of Nanjing Medical University from March 18, 2022, to October 31, 2023, were selected. The Dystrophin gene ( DMD) was detected using chip capture next-generation sequencing technology, followed by bioinformatics analysis. Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Serum creatine kinase levels were also tested in suspected male patients. Descriptive analysis was applied for this study. Results:Among the 10 748 girls, 14 carriers of DMD gene were detected (0.013%), of which, nine cases were validated in the family; one case was a de novo mutation, five were inherited from the mother, and three were inherited from the father. The screening identified nine suspected patients among the boys (0.075%), and eight of them were confirmed by family validation, in which three were de novo mutations, and five were inherited from the mother. Among all identified DMD mutations, deletions were the most common one, accounting for 52.2% (12/23), incluling four cases of deletion at 49-51 exon. Conclusions:Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy. According to the preliminary statistics, the incidence rate of DMD/BMD in this area is 1/1 341 male infants and the hotspot mutation is exon 49 to 51 deletion.

Objective To investigate the risk factors and clinical characteristics of asphyxia-related acute kidney injury (AKI) in neonates. Methods A retrospective analysis was conducted on the clinical data of neonates with asphyxia-related AKI (AKI group, n=100) and asphyxia withont AKI neonates (control group, n=228) admitted to the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2023. Laboratory indicators and clinical data from both groups were collected to analyze the risk factors and clinical characteristics of asphyxia-related AKI in neonates. Results Statistically significant differences were observed in levels of lactate, base excess (BE), serum potassium, serum creatinine, and urea nitrogen between the AKI and control groups (P < 0.05). Multivariate Logistic regression analysis revealed that low 5-minute Apgar score, high lactate level, and hyperglycemia were independent risk factors for asphyxia-related AKI in neonates. The areas under the curve (AUCs) for the 5-minute Apgar score, lactate, and blood glucose in predicting AKI were 0.825(95%CI, 0.767 to 0.882), 0.968(95%CI, 0.942 to 0.993), and 0.845(95%CI, 0.795 to 0.894), respectively. The incidence of maternal hypertension during pregnancy also showed a significant difference between the two groups (P < 0.05). Significant differences were also noted in 1-minute and 5-minute Apgar scores, as well as the incidence of intrauterine distress between the AKI and control groups (P < 0.05). Furthermore, the AKI group exhibited statistically significant differences in respiratory distress syndrome (RDS), respiratory failure, necrotizing enterocolitis (NEC), severe intracranial hemorrhage, pulmonary hemorrhage, use of diuretics, and blood purification etc. compared to the control group (P < 0.05). There were 24 deaths in the AKI group, with 16 cases in AKI stage 3 and 8 cases in AKI stage 2, while only 3 deaths occurred in the control group. The difference in mortality rate between the two groups was statistically significant (P < 0.05). Conclusion Low 5-minute Apgar score, high lactate levels, and hyperglycemia are independent risk factors for AKI in neonates. Neonates with AKI are prone to developing multi-organ dysfunction, and asphyxia-related AKI can increase mortality rates. Therefore, comprehensive prevention and treatment measures are crucial.

Objective:To analyze the results of ATP7B gene screening in neonates and explore the linkage disequilibrium between different mutation loci, providing a basis for the clinical diagnosis and genetic counseling of Wilson′s disease.Methods:A total of 12 619 newborns who were born in Women′s Hospital of Nanjing Medical University during March 18 and December 30, 2022, including 6 605 male neonates and 6 014 female neonates, with birth weight of (3.44±0.56) kg, were retrospectively collected. The results of ATP7B gene screening in all newborns were analyzed.Next-generation sequencing technology was employed to detect the pathogenic loci of ATP7B gene, and the identified loci were verified using Sanger sequencing. PLINK 1.9 software was used to analyze the linkage disequilibrium of different mutation loci.Results:Among 12 619 neonates, 22 cases were diagnosed with 2-3 pathogenic mutations in the ATP7B gene (suspected positive). Among them, 20 cases were recalled for family verification, and 2 cases refused to recall. The verification results showed that 3 newborns had mutations of two loci respectively from their parents and were preliminarily diagnosed with Wilson′s disease, the other 17 neonates were carriers of the c.3316G>A/c.588C>A or c.1708-1G>C/c.1168A>G mutation loci arranged in a cis-acting manner from the father source or maternal source. A total of 249 pathogenic mutation carriers were detected (232 cases carrying 1 pathogenic mutation, and 17 cases carrying 2 pathogenic mutations), with a carrier rate of 1/51. Among them, the mutation c.2333G>T was most frequently detected (1/207), followed by c.2975C>T (1/421), c.2621C>T (1/742), c.2755C>G (1/971) and c.2605G>A (1/971). The results of linkage disequilibrium analysis in both c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G showed that D ′=1, which showed complete linkage disequilibrium. Conclusion:The carrier rate of pathogenic mutations in the ATP7B gene is relatively high.Moreover, the c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G pathogenic mutation loci are likely to be arranged in a cis-acting manner, highlighting the existence of linkage disequilibrium between the two groups of mutations. This finding provides important reference value for the clinical diagnosis and genetic counseling of Wilson disease.

Objective:To investigate the current status of women′s level of birth experience and lactation initiation time and explore the effect of level of birth experience on lactation initiation time.Methods:This was a cross-sectional study. A convenience sampling method was used to select 622 maternal cases attending the Affiliated Hospital of Jining Medical College from November, 2020 to January, 2021, and the distribution of their labor experience level and lactation initiation time was investigated by questionnaire and follow-up assessment.Results:There were 622 women with transvaginal deliveries who had lactation initiation times of more than 72 h in 241 cases (38.75%). The scores for each dimension of the Childbirth Experience Questionnaire (CEQ) were (49.63 ± 8.58)points, and the scores for each dimension of CEQ were perceived safety, professional support, involvement and self-efficacy in descending order. The results of the correlation analysis showed that there was a negative correlation between the scores on each dimension of CEQ and the total score and lactation initiation time ( r values were -0.436 to -0.146, all P<0.01). Stratified regression analysis showed that after controlling for age, number of births, gestational weeks of labour, illness during pregnancy and labour analgesia as the underlying variables affecting lactation initiation time, the scores for self-efficacy, involvement, perceived safety and professional support in the CEQ all affected lactation initiation time after delivery ( t values were -6.76 to -2.02, all P<0.05). Conclusions:The birth experience and lactation of women who deliver via vaginal birth need to be taken into account. The more negative the birth experience, the longer the lactation initiation time. The women′s involvement in the birth process, their own competence, perceived safety and level of professional support are all valid influencing indicators of lactation initiation time.

Objective:To investigate the regional homogeneity (ReHo) among the major depressive disorder patients without mixed features (MDD noMF), major depressive disorder with mixed features (MMF), bipolar disorder with mixed features (BMF) and bipolar disorder patients without mixed features (BD noMF) patients, and to explore the brain activity and functional connectivity patterns of the MMF and BMF patients. Methods:This was a cross-sectional study. The MDD noMF patients (MDD noMF group), MMF patients (MMF group), BMF patients (BMF group), BD noMF patients (BD noMF group), and age-and gender-matched healthy controls (HC group) were recruited from Beijing Anding Hospital, Capital Medical University between April, 2021 and June, 2022. All the participants underwent resting-state functional MRI scanning. The ReHo values was computed with the DPABI software based on the MATLAB. Firstly, the difference in ReHo among the patients with MDD noMF, MMF, BMF, BD noMF and HC group were estimated by the analysis of covariance and the post-hoc method (LSD or Games-Howell). And then, the brain regions with significant different ReHo values were selected as the seeds to calculate the functional connectivity with the whole brain. Results:A total of 29 cases in the MDD noMF group, 24 cases in the MMF group, 26 cases in the BMF group, 29 cases in the BD noMF group, and 42 in the HC group were included. The differences in ReHo values in the left fusiform and the left precuneus of the 5 groups were statistically significant ( P<0.05). Among of them, the ReHo values of the left fusiform were lower in the MMF, BMF and BD noMF groups compared with the HC group ( P<0.05), while the ReHo values of the left precuneus in MDD noMF, MMF, BMF and BD noMF groups were higher than that in the HC group ( P<0.05). The ReHo value of the left fusiform was lower in the MMF group compared with the MDD noMF group ( P=0.001); the ReHo value of the left fusiform was lower in the BMF group compared with the MDD noMF and BD noMF groups ( P<0.05). The functional connectivity between the left fusiform and vermis, left insula, right putamen, and left medial superior frontal gyrus, and functional connectivity between the left precuneus and right superior frontal gyrus (dorsolateral) showed significant difference among the MDD noMF, MMF, BMF, BD noMF and HC groups ( P<0.05). Compared with HC group, MDD noMF, MMF, BD noMF groups showed higher functional connectivity between the left fusiform and the vermis, and MDD noMF, MMF, BMF, BD noMF group showed higher functional connectivityy between the the left fusiform and the left insula, left medial superior frontal gyrus and right putamen ( P<0.05). Compared with the MDD noMF group, the MMF, BMF and BD noMF groups showed higher functional connectivity between the left fusiform and the left insula ( P<0.05). Compared with the MDD noMF group, the BMF and BD noMF groups had higher functional connectivity between the left fusiform and the left medial superior frontal gyrus ( P<0.05). The BMF group showed higher functional connectivity of the left fusiform with the right putamen than the MDD noMF and BD noMF groups. Additonally, the BMF and BD noMF groups showed higher functional connectivity between the left precuneus and the right superior frontal gyrus (dorsolateral) than HC, MDD noMF and MMF groups ( P<0.05). Conclusions:MMF and BMF patients have local abnormalities of functional activity synchronization in the left fusiform and precuneus and abnormal functional connectivity patterns with multiple brain regions. MMF and BMF patients have specific neuroimaging features compared to MDD noMF or BD noMF patients and also share similar neuroimaging pathogenesis.

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

Background: Percutaneous transforaminal endoscopic discectomy (PTED) has been widely used in the treatment of lumbar degenerative diseases. Epidural injection of steroids can reduce the incidence and duration of postoperative pain in a short period of time. Although steroids are widely believed to reduce the effect of surgical trauma, the observation indicators are not uniform, especially the long-term effects, so the problem remains controversial. Therefore, the purpose of this paper was to evaluate the efficacy of epidural steroids following PTED. Methods: We searched PubMed, Embase, and the Cochrane Database from 1980 to June 2021 to identify randomized and non-randomized controlled trials comparing epidural steroids and saline alone following PTED. The primary outcomes included postoperative pain at least 6 months as assessed using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). The secondary outcomes included length of hospital stay and the time of return to work. Results: A total of 451 patients were included in three randomized and two nonrandomized controlled trials. The primary outcomes, including VAS and ODI scores, did not differ significantly between epidural steroids following PTED and saline alone. There were no significant intergroup differences in length of hospital stay. Epidural steroids were shown to be superior in terms of the time to return to work (P < 0.001). Conclusions Intraoperative epidural steroids did not provide significant benefits, leg pain control, improvement in ODI scores, and length of stay in the hospital, but it can enable the patient to return to work faster.