Micropeptide PACMP inhibition elicits synthetic lethal effects by decreasing CtIP and poly(ADP-ribosyl)ation.

Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

A rapid and low-cost platform for detection of bacterial based on microchamber PCR microfluidic chip.

Polymerase chain reaction (PCR) has been considered as the gold standard for detecting nucleic acids. The simple PCR system is of great significance for medical applications in remote areas, especially for the developing countries. Herein, we proposed a low-cost self-assembled platform for microchamber PCR. The working principle is rotating the chamber PCR microfluidic chip between two heaters with fixed temperature to solve the problem of low temperature variation rate. The system consists of two temperature controllers, a screw slide rail, a chamber array microfluidic chip and a self-built software. Such a system can be constructed at a cost of about US$60. The micro chamber PCR can be finished by rotating the microfluidic chip between two heaters with fixed temperature. Results demonstrated that the sensitivity of the temperature controller is 0.1℃. The relative error of the duration for the microfluidic chip was 0.02 s. Finally, we successfully finished amplification of the target gene of Porphyromonas gingivalis in the chamber PCR microfluidic chip within 35 min and on-site detection of its PCR products by fluorescence. The chip consisted of 3200 cylindrical chambers. The volume of reagent in each volume is as low as 0.628 nL. This work provides an effective method to reduce the amplification time required for micro chamber PCR.

Application of metagenomic next-generation sequencing in the clinical diagnosis of infectious diseases after allo-HSCT: a single-center analysis.

BACKGROUND: We investigated the value of metagenomic next-generation sequencing (mNGS) in diagnosing infectious diseases in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fifty-four patients who had fever following allo-HSCT from October 2019 to February 2022 were enrolled. Conventional microbiological tests (CMTs) and mNGS, along with imaging and clinical manifestations, were used to diagnose infection following allo-HSCT. The clinical diagnostic value of mNGS was evaluated. RESULTS: A total of 61 mNGS tests were performed, resulting in the diagnosis of 46 cases of infectious diseases. Among these cases, there were 22 cases of viral infection, 13 cases of fungal infection, and 11 cases of bacterial infection. Moreover, 27 cases (58.7%) were classified as bloodstream infections, 15 (32.6%) as respiratory infections, 2 (4.3%) as digestive system infections, and 2 (4.3%) as central nervous system infections. Additionally, there were 8 cases with non-infectious diseases (8/54, 14.81%), including 2 cases of interstitial pneumonia, 2 cases of bronchiolitis obliterans, 2 cases of engraftment syndrome, and 2 cases of acute graft-versus-host disease. The positive detection rates of mNGS and CMT were 88.9% and 33.3%, respectively, with significant differences (P < 0.001). The sensitivity of mNGS was 97.82%, the specificity was 25%, the positive predictive value was 93.75%, and the negative predictive value was 50%. Following treatment, 51 patients showed improvement, and 3 cases succumbed to multidrug-resistant bacterial infections. CONCLUSIONS: mNGS plays an important role in the early clinical diagnosis of infectious diseases after allo-HSCT, which is not affected by immunosuppression status, empiric antibiotic therapy, and multi-microbial mixed infection.

Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development. METHODS: A prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. RESULTS: The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99-0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02-1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25-2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21-5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36-2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44-2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02-1.91; p = 0.035). CONCLUSIONS: A longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).

DNA polymerase η promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1.

DNA polymerase eta (Pol η) is a eukaryotic member of the Y-family of DNA polymerase involved in translesion DNA synthesis and genome mutagenesis. Recently, several translesion DNA synthesis polymerases have been found to function in repair of DNA double-strand breaks (DSBs). However, the role of Pol η in promoting DSB repair remains to be well defined. Here, we demonstrated that Pol η could be targeted to etoposide (ETO)-induced DSBs and that depletion of Pol η in cells causes increased sensitivity to ETO. Intriguingly, depletion of Pol η also led to a nonhomologous end joining repair defect in a catalytic activity-independent manner. We further identified the scaffold protein Kap1 as a novel interacting partner of Pol η, the depletion of which resulted in impaired formation of Pol η and Rad18 foci after ETO treatment. Additionally, overexpression of Kap1 failed to restore Pol η focus formation in Rad18-deficient cells after ETO treatment. Interestingly, we also found that Kap1 bound to Rad18 in a Pol η-dependent manner, and moreover, depletion of Kap1 led to a significant reduction in Rad18-Pol η association, indicating that Kap1 forms a ternary complex with Rad18 and Pol η to stabilize Rad18-Pol η association. Our findings demonstrate that Kap1 could regulate the role of Pol η in ETO-induced DSB repair via facilitating Rad18 recruitment and stabilizing Rad18-Pol η association.

Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia-Ischemia.

BACKGROUND: Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. PURPOSE: To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. STUDY TYPE: Prospective. POPULATION: A total of 42 neonates (24 males and 18 females). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). STATISTICAL TESTS: One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. RESULTS: For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. DATA CONCLUSION: For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Prediction of tumor budding in patients with rectal adenocarcinoma using b-value threshold map.

OBJECTIVE: To investigate the feasibility of b-value threshold (bThreshold) map in preoperative evaluation of tumor budding (TB) in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC were enrolled and underwent diffusion-weighted imaging (DWI). Contrast-to-noise ratio (CNR) between the lesions and normal tissues was assessed using DWI and bThreshold maps. TB was counted and scored using hematoxylin and eosin staining. Reproducibility for the apparent diffusion coefficient (ADC), bThreshold values, and region-of-interest (ROI) sizes were compared. Differences in ADC and bThreshold values with low-intermediate and high TB grades and the correlations between mean ADC and bThreshold values with TB categories were analyzed. Diagnostic performance of ADC and bThreshold values was assessed using area under the curve (AUC) and decision curve analysis. RESULTS: Fifty-one patients were evaluated. The CNR on bThreshold maps was significantly higher than that on DW images (9.807 ± 4.811 vs 7.779 ± 3.508, p = 0.005). Reproducibility was excellent for the ADC (ICC 0.933; CV 8.807%), bThreshold values (ICC 0.958; CV 7.399%), and ROI sizes (ICC 0.934; CV 8.425%). Significant negative correlations were observed between mean ADC values and TB grades and positive correlations were observed between mean bThreshold values and TB grades (p < 0.05). bThreshold maps showed better diagnostic performance than ADC maps (AUC, 0.914 vs 0.726; p = 0.048). CONCLUSIONS: In LARC patients, bThreshold values could distinguish different TB grades better than ADC values, and bThreshold maps may be a preoperative, non-invasive approach to evaluate TB grades. KEY POINTS: • Compared with diffusion-weighted images, bThreshold maps improved visualization and detection of rectal tumors. • Agreement and diagnostic performance of bThreshold values are superior to apparent diffusion coefficient in assessing tumor budding grades in patients with locally advanced rectal cancer. • bThreshold maps could be used to evaluate tumor budding grades non-invasively before operation.

Stronger susceptibilities to air pollutants of influenza A than B were identified in subtropical Shenzhen, China.

Air pollution was indicated to be a key factor contributing to the aggressive spread of influenza viruses, whereas uncertainty still exists regarding to whether distinctions exist between influenza subtypes. Our study quantified the impact of five air pollutants on influenza subtype outbreaks in Shenzhen, China, a densely populated and highly urbanized megacity. Daily influenza outbreak data of laboratory-confirmed positive cases were obtained from the Shenzhen CDC, from May 1, 2013 to Dec 31, 2015. Concentrations of nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matters ≤2.5 µm (PM2.5), particulate matters ≤10 µm (PM10), and ozone (O3), were retrieved from the 18 national monitoring stations. The generalized additive model (GAM) and distributed lag non-linear model (DLNM) were used to calculate the concentration-response relationships between environmental inducers and outbreak epidemics, respectively for influenza A (Flu-A) and B (Flu-B). There were 1687 positive specimens were confirmed during the study period. The cold season was restricted from Nov. 4th to Apr. 20th, covering all seasons other than the long-lasting summer. Relatively heavy fine particle matter (PM2.5) and NO2 pollution was observed in cold months, with mean concentrations of 46.06 µg/m3 and 40.03 µg/m3, respectively. Time-series analysis indicated that high concentrations of NO2, PM2.5, PM10, and O3 were associated with more influenza outbreaks at short lag periods (0-5 d). Although more Flu-B (679 cases) epidemics occurred than Flu-A (382 cases) in the cold season, Flu-A generally showed higher susceptibility to air pollutants. A 10 µg/m3 increment in concentrations of PM2.5, PM10, and O3 at lag 04, was associated with a 2.103 (95%CI: 1.528-2.893), 1.618 (95%CI: 1.311-1.996), and 1.569 (95%CI: 1.214-2.028) of the relative risk (RR) of Flu-A, respectively. A 5 µg/m3 increase in NO2 was associated with higher risk of Flu-A at lag 03 (RR = 1.646, 95%CI: 1.295-2.092) and of Flu-B at lag 04 (RR = 1.319, 95%CI: 1.095-1.588). Nevertheless, barely significant effect of particulate matters (PM2.5, PM10) on Flu-B and SO2 on both subtypes was detected. Further, the effect estimates of NO2 increased for both subtypes when coexisting with other pollutants. This study provides evidence that declining concentrations of main pollutants including NO2, O3, and particulate matters, could substantially decrease influenza risk in subtropical Shenzhen, especially for influenza A.

A predictive model for preterm infants with bronchopulmonary dysplasia based on ferroptosis-related lncRNAs.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most challenging chronic lung disease for prematurity, with difficulties in early identification. Given lncRNA emerging as a novel biomarker and the regulator of ferroptosis, this study aims to develop a BPD predictive model based on ferroptosis-related lncRNAs (FRLs). METHODS: Using a rat model, we firstly explored mRNA levels of ferroptosis-related genes and ferrous iron accumulation in BPD rat lungs. Subsequently, a microarray dataset of umbilical cord tissue from 20 preterm infants with BPD and 34 preterm infants without BPD were downloaded from the Gene Expression Omnibus databases. Random forest and LASSO regression were conducted to identify diagnostic FRLs. Nomogram was used to construct a predictive BPD model based on the FRLs. Finally, umbilical cord blood lymphocytes of preterm infants born before 32 weeks gestational age and term infants were collected and determined the expression level of diagnostic FRLs by RT-qPCR. RESULTS: Increased iron accumulation and several dysregulated ferroptosis-associated genes were found in BPD rat lung tissues, indicating that ferroptosis was participating in the development of BPD. By exploring the microarray dataset of preterm infants with BPD, 6 FRLs, namely LINC00348, POT1-AS1, LINC01103, TTTY8, PACRG-AS1, LINC00691, were determined as diagnostic FRLs for modeling. The area under the receiver operator characteristic curve of the model was 0.932, showing good discrimination of BPD. In accordance with our analysis of microarray dataset, the mRNA levels of FRLs were significantly upregulated in umbilical cord blood lymphocytes from preterm infants who had high risk of BPD. CONCLUSION: The incorporation of FRLs into a predictive model offers a non-invasive approach to show promise in improving early detection and management of this challenging chronic lung disease in premature infant, enabling timely intervention and personalized treatment strategies.

[Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer].

Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.

Effects of long-term high-altitude exposure on retinal and choroidal microcirculation.

PURPOSE: To quantify the effect of long-term high-altitude (HA) exposure on retinal and choroidal microcirculation and to relate these changes to high-altitude polycythemia (HAPC), as a proxy for etiopathogenesis of high-altitude related retinopathy (HAR). METHODS: Fifty-one HAPC patients, 50 healthy HA residents, and 43 low altitude (LA) residents were recruited in this study. Optical coherence tomography angiography (OCTA) and enhanced depth imaging (EDI)-OCT images were analyzed. Retinal microvascular metrics included vessel density (VD), skeleton density (SD), fractal dimension (FD), and foveal avascular zone (FAZ). Choroidal microvascular metrics included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). All metrics were calculated by ImageJ software and compared among HAPC group, healthy HA group, and LA group. RESULTS: In HAPC group, VD (30.62 ± 3.67%), SD (13.25 ± 1.64%), FD (1.79 ± 0.04), and the CVI (63.01 ± 1.42%) were significant lower and SFCT (403.25 ± 94.3 µm) was significant thicker than healthy HA group (all P < 0.001). FAZ area was comparable between two groups (0.42 ± 0.1 vs. 0.4 ± 0.11 mm2, P = 0.411). However, these metrics were not different between healthy HA group and LA group (all P > 0.05) except for FD was lower in HA group (P < 0.001). Pearson's correlation analyses revealed HGB was negatively related with VD (r = - 0.562, P < 0.001) and positively related with SFCT (r = 0.505, P < 0.001) in healthy HA group; however, no associations between HGB and vascular metrics in HAPC group were detected (all P > 0.05). CONCLUSIONS: Long-term exposure to HA environment induces retinal and choroidal microcirculation disturbance in HAPC patients. However, these changes were not evident in healthy HA residents because of adaptation.

Refractory thrombocytopenia could be a rare initial presentation of Noonan syndrome in newborn infants: a case report and literature review.

BACKGROUND: Noonan syndrome (NS) is a relatively rare inherited disease. Typical clinical presentation is important for the diagnosis of NS. But the initial presentation of NS could be significant variant individually which results in the difficult of working diagnosis. Here we report a rare neonatal case of NS who presented with refractory thrombocytopenia as the initial manifestation. CASE PRESENTATION: This was a preterm infant with refractory thrombocytopenia of unknown origin transferred from obstetric hospital at 6 weeks of age. During hospitalization, typical phenotypes of NS in addition to thrombocytopenia were observed, such as typical facial characteristics, short stature, atrial septal defect, cryptochidism, coagulation defect and chylothorax. Genetic testing showed a pathogenic variant at exon 2 of the PTPN11 gene with c.124A > G (p.T42A). Respiratory distress was deteriorated with progressive chylothorax. Chest tube was inserted for continuous draining. Chemical pleurodesis with erythromycin was tried twice, but barely effective. Finally, parents decided to withdraw medical care and the patient died. CONCLUSIONS: Thrombocytopenia could be the first symptom of Noonan syndrome. After ruling out other common causes of thrombocytopenia, NS should be considered as the working diagnosis.

Predictive Tool for Closure of Ductus Arteriosus with Pharmacologic or Surgical Treatment in Preterm Infants.

To construct a model with the indices obtained by echocardiography to predict whether patent ductus arteriosus (PDA) was required to be treated with pharmacologic treatment or surgical ligation, we performed a prospective observational study, including all neonates with gestational age ≤ 30 weeks and assessed the hemodynamics of PDA by serial daily echocardiography examination at postnatal age of 0-12 h, 24 h, 48 h, and 72 h, respectively. The infants were classified in two groups based on whether they were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or surgical ligation to close the PDA from the second week after birth. We compared the echocardiographic indices between the two groups and utilized the indices to construct a model to predict which premature infants' PDA requires intervention. The results showed that a total of forty-two preterm infants were enrolled in the study. 15 (35.7%) preterms were in the intervention group and 27 (64.3%) preterms were in the non-intervention group. Compared with the non-intervention group, the intervention group had a higher proportion of left ventricular volume overload and systemic shunt effect. In addition, the combined indicators of PDA size/weight > 3.2 mm/kg and LA/Ao > 1.4 at postnatal age of 72 h had a highest value to predict whether PDA requires intervention. These findings denoted that serial daily echocardiographic assessment can be useful in predicting whether a PDA will be closed with NSAIDs and/or surgical ligation in preterm infants with gestational age ≤ 30 weeks.Trial registration Number: IRB No. 2018-IRB-073. Date: 2018/09/21, retrospectively registered.

[Timing of surgical ligation of patent ductus arteriosus in very low birth weight infants]. / æžä½Žå‡ºç”Ÿä½“é‡å„¿åŠ¨è„‰å¯¼ç®¡æœªé—­æ‰‹æœ¯ç»“æ‰Žæ—¶æœºçš„ç ”ç©¶.

OBJECTIVES: To study the effect of timing of surgical ligation of patent ductus arteriosus (PDA) on the prognosis of very low birth weight infants (VLBWI). METHODS: The medical data of VLBWI who underwent transthoracic ligation for PDA from June 2018 to May 2021 were reviewed retrospectively. The infants were divided into early ligation group (≤21 days of age) and late ligation group (>21 days of age) based on the age of ligation. The two groups were compared in terms of perioperative clinical features, complications, and mortality. The risk factors for early surgical ligation were analyzed. RESULTS: A total of 72 VLBWI were enrolled, with 19 infants (26%) in the early ligation group and 53 infants (74%) in the late ligation group. There were significant differences in birth weight, gestational age, weight at operation, days of age at operation, rates of preoperative invasive and noninvasive mechanical ventilation, incidence rate of pulmonary hemorrhage, incidence rate of hypotension, preoperative PDA internal diameter (mm/kg), intraoperative PDA external diameter (mm/kg), incidence rate of post-ligation cardiac syndrome, and duration of postoperative invasive mechanical ventilation between the two groups (P<0.05). A binary logistic regression analysis showed that pulmonary hemorrhage was an indication of early surgical ligation of PDA (P<0.05). There were no significant differences in the incidence rates of post-operative complications and the mortality rate between the early ligation and late ligation groups. CONCLUSIONS: Early surgical ligation may be performed for VLBWI who are experiencing pulmonary hemorrhage and hemodynamically significant PDA confirmed by cardiac ultrasound after birth. However, post-ligation cardiac syndrome should attract enough attention. In addition, early surgical ligation of PDA does not increase the risk of surgery-related and long-term complications or death, indicating that it is a safe and feasible treatment option.

Value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight infants. / ç”ŸåŽæ—©æœŸåºŠæ—å¿ƒè„è¶ å£°é¢„æµ‹æžä½Žå‡ºç”Ÿä½“é‡å„¿åŠ¨è„‰å¯¼ç®¡æŒç»­å¼€æ”¾çš„ç ”ç©¶.

OBJECTIVES: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. METHODS: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days. RESULTS: On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively. CONCLUSIONS: The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

Evaluating treatment response to neoadjuvant chemoradiotherapy in rectal cancer using various MRI-based radiomics models.

BACKGROUND: To validate and compare various MRI-based radiomics models to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal cancer. METHODS: A total of 80 patients with locally advanced rectal cancer (LARC) who underwent surgical resection after nCRT were enrolled retrospectively. Rectal MR images were scanned pre- and post-nCRT. The radiomics features were extracted from T2-weighted images, then reduced separately by least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA). Four classifiers of Logistic Regression, Random Forest (RF), Decision Tree and K-nearest neighbor (KNN) models were constructed to assess the tumor regression grade (TRG) and pathologic complete response (pCR), respectively. The diagnostic performances of models were determined with leave-one-out cross-validation by generating receiver operating characteristic curves and decision curve analysis. RESULTS: Three features related to the TRG and 11 features related to the pCR were obtained by LASSO. Top five principal components representing a cumulative contribution of 80% to overall features were selected by PCA. For TRG, the area under the curve (AUC) of RF model was 0.943 for LASSO and 0.930 for PCA, higher than other models (P < 0.05 for both). As for pCR, the AUCs of KNN for LASSO and PCA were 0.945 and 0.712, higher than other models (P < 0.05 for both). The DCA showed that LASSO algorithm was clinically superior to PCA. CONCLUSION: MRI-based radiomics models demonstrated good performance for evaluating the treatment response of LARC after nCRT and LASSO algorithm yielded more clinical benefit.

MRI-based nomogram analysis: recognition of anterior peritoneal reflection and its relationship to rectal cancers.

BACKGROUND: This study is aimed to explore the factors influencing the visualization of the anterior peritoneal reflection (APR) and evaluated the feasibility of measuring the distance from the anal verge to APR (AV-APR), the tumor height on MRI and the accuracy of determining the tumor location with regard to APR. METHODS: We retrospectively analyzed 110 patients with rectal cancer. A univariate and multivariate logistic regression was performed to identify the independent factors (age, sex, T stage, the degree of bladder filling, pelvic effusion, intraoperative tumor location, BMI, uterine orientation, the distance from seminal vesicle/uterus to rectum) associated with the visualization of the APR on MRI. The nomogram diagram and receiver operating characteristic curve (ROC curve) were established. Intraclass correlation coefficient (ICC) was used to evaluate the consistency of the distance of AV-APR. The Pearson correlation coefficient was used to characterize the agreement between measurements of the tumor height by colonoscopy and MRI. The Kappa statistics was used to evaluate the value of MRI in the diagnosis of the tumor location with regard to the APR. RESULTS: Multivariate logistic regression showed that BMI (P = 0.031, odds ratio, OR = 1.197), pelvic effusion (P = 0.020, OR = 7.107) and the distance from seminal vesicle/uterus to the rectum (P = 0.001, OR = 3.622) were correlated with the visualization of APR. The cut-off point of BMI and the distance from seminal vesicle/uterus to the rectum is 25.845 kg/m2 and 1.15 cm. The area under curve (AUC) (95% Confidence Interval, 95% CI) of the combined model is 0.840 (0.750-0.930). The favorable calibration of the nomogram showed a non-significant Hosmer-Lemeshow test statistic (P = 0.195). The ICC value (95% CI) of the distance of AV-APR measured by two radiologists was 0.981 (0.969-0.989). The height measured by MRI and colonoscopy were correlated with each other (r = 0.699, P < 0.001). The Kappa value was 0.854. CONCLUSIONS: BMI, pelvic effusion, and the distance from seminal vesicle/uterus to rectum could affect the visualization of APR on MRI. Also, it's feasible to measure the distance of AV-APR, the tumor height, and to evaluate the tumor location with regard to APR using MRI.

Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine.

Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad range of applications in biomedical engineering and regenerative medicine functioning as tissue engineering scaffolds, carriers for cell-based therapies, and biomedical devices for delivery of drugs and biologics. The focus of this review is to discuss the properties and clinical indications of polymeric scaffold materials and extracellular matrix technologies for DOC regenerative medicine. More specifically, this review outlines the key properties, advantages and drawbacks of natural polymers including alginate, cellulose, chitosan, silk, collagen, gelatin, fibrin, laminin, decellularized extracellular matrix, and hyaluronic acid, as well as synthetic polymers including polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly (ethylene glycol) (PEG), and Zwitterionic polymers. This review highlights key clinical applications of polymeric scaffolding materials to repair and/or regenerate various DOC tissues. Particularly, polymeric materials used in clinical procedures are discussed including alveolar ridge preservation, vertical and horizontal ridge augmentation, maxillary sinus augmentation, TMJ reconstruction, periodontal regeneration, periodontal/peri-implant plastic surgery, regenerative endodontics. In addition, polymeric scaffolds application in whole tooth and salivary gland regeneration are discussed.

[Dyspnea and situs inversus in a boy aged 3 days].

A boy was admitted on day 3 after birth due to shortness of breath for 2 days and cyanosis for 1 day. He had clinical manifestations of dyspnea in the early postnatal period and situs inversus, and was finally diagnosed with Kartagener syndrome. His condition was improved after oxygen therapy, anti-infective therapy, and aerosol therapy. The genetic testing showed that there was a large-fragment loss of heterozygosity, exon 48_50, and a hemizygous mutation, c.7915C > T(p.R2639X), in the DNAH5 gene. Kartagener syndrome is a rare autosomal recessive disease, and this is the first case of Kartagener syndrome diagnosed in the neonatal period in China.