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Purpose: This study describes a nose prosthetic rehabilitation using computer-aided design and manufacturing (CAD-CAM) technology after facial disfigurement because of a total rhinectomy.Methods: A patient with a total rhinectomy was scheduled for a nasal prosthesis. Based on the 3-D model of the patient's face reconstructed with the CT data, a four-piece mould for the nasal prosthesis was prototyped using a CAD-CAM procedure. Conventional silicone was processed with this physical mould to fabricate the definitive nasal prosthesis.Results: A silicone nasal prosthesis was manufactured. The size, shape, and cosmetic look of the prosthesis were satisfactory and matched the nasal defect area well.Conclusions: The protocol presented herein illustrates favorable clinical treatment outcomes in the prosthetic rehabilitation after a total rhinectomy by means of CAD-CAM technology. [ABSTRACT FROM AUTHOR]

Study Question: Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion?, Summary Answer: Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects., What Is Known Already: Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited., Study Design, Size, Duration: We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding., Participants/materials, Setting, Methods: Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up., Main Results and the Role of Chance: The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05)., Limitations, Reasons for Caution: Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements., Wider Implications of the Findings: Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health., Study Funding/competing Interest(s): This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co., Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests., Trial Registration Number: CHiCTR2100053565., Trial Registration Date: 24 November 2021., Date of First Patient’s Enrolment: 9 March 2022., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3-E1 cells in vitro., Results: Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress., Conclusion: Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO 2 /EPM) is designed and fabricated with porous structures and 3D VO 2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO 2 /EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO 2 . Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO 2 /EPM before and after the phase transition. Moreover, the application of VO 2 /EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices., (© 2024 Wiley‐VCH GmbH.)

Objectives: To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients. Methods: From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires. Results: The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95% CI : 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P =0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P <0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P =0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P =0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P =0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P <0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P <0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P =0.007], arousal disorder [3% (1/40) vs 3% (1/40); P >0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P =0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P =0.051], sexual pain [30% (12/40) vs 15% (6/40); P =0.108]. Conclusions: MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t -test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups ( P >0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P >0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P >0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P <0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm 2 , significantly different from that in the combination therapy group [(0.34±0.16) mm 2 ] at 12 months ( P <0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification., (© 2024. The Author(s).)

Non-traditional intrinsic luminescent (NTIL) polymer is an emerging field, and its color-tunable modification is highly desirable but still rarely investigated. Here, a click chemistry approach for the color-tunable modifications of NTIL polymers by introducing clickable polymerization-induced emission luminogen (PIEgen), is demonstrated. Through Cu-catalyzed azide-alkyne cycloaddition click chemistry, a series of PIEgens is successful prepared, which is further polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Interestingly, after clickable modification, these monomers are nonemissive in both solution and aggregation states; while, the corresponding polymers exhibit intriguing aggregation-induced emission (AIE) characteristics, confirming their PIEgen characteristics. By varying alkynyl substitutions, color-tunable NTIL polymers are achieved with emission wavelength varying from 448 to 498 nm, revealing a series of PIEgens and verifying the importance of modification of NTIL polymers. Further luminescence energy transfer application is carried out as well. This work therefore designs a series of clickable PIEgens and opens a new avenue for the modification of NTIL polymers via click chemistry, which may cause inspirations to the research fields including luminescent polymer, NTIL, click chemistry, AIE and modification., (© 2024 Wiley‐VCH GmbH.)

As a result of innovations in bicycle styles and an increase in the number of women cyclists, the medical community and mass media have begun to pay attention to a condition known as " bicycle face". Women were thought to be the main victims of this condition. Many people believe that cycling has other health consequences. This article examined the history of bicycle face, using medical journals from the late nineteenth and early twentieth centuries in Europe and the United States as primary sources. Articles from popular journals and secondary sources were also reviewed. On this basis, this study analyzes the discussion of women's cycling-related issues in the medical community, and the cultural and social factors behind them, and examines the interaction between the medical community's attitudes towards women's cycling and social and cultural backgrounds, so as to further enrich the relevant research on women's body history and social history.

Recent research on the water content of large igneous provinces (LIPs) has revealed that water has a significant impact on the formation of LIPs. However, most studies focus on the water content of mafic-ultramafic rocks, while relatively little attention has been paid to the water content of continental flood basalts (CFB), which form the major part of LIPs and are characterized by huge volumes (> 1 × 10 5 km 3 ) and short eruption times. Here, we determined water contents of clinopyroxene crystals from the Akesu diabase, which is co-genetic with flood basalts of the Tarim LIP in China. Based on these measurements, we obtained a water content of higher than 1.23 ± 0.49 wt.% for the parental magma to the Tarim CFB and a minimum water content of 1230 ± 490 ppm for the mantle source, thus indicating the presence of a hydrous mantle plume. Combined with previous studies, our results suggest that water plays a key role in the formation of the Tarim LIP. Additionally, the whole-rock compositions of the Akesu diabase indicate a contribution of pyroxenite in the mantle source. This is consistent with a model, in which water was brought into the Tarim mantle plume by a subducted oceanic plate that entered the deep mantle., (© 2024. The Author(s).)

Cinnamic ester is a common and abundant chemical substance, which can be extracted from natural plants. Compared with traditional esters, cinnamic ester contains α,β-unsaturated carbonyl structure with multiple reactive sites, resulting in more abundant reactivities and chemical structures. Here, a versatile polymerization-induced emission (PIE) is successfully demonstrated through Barbier polymerization of cinnamic ester. Attributed to its abundant reactivities of α,β-unsaturated carbonyl structure, Barbier polymerization of cinnamic esters with different organodihalides gives polyalcohol and polyketone via 1,2-addition and 1,4-addition, respectively, which is also confirmed by small molecular model reactions. Meanwhile, these organodihalides dependant polyalcohol and polyketone exhibit different non-traditional intrinsic luminescence (NTIL) from aggregation-induced emission (AIE) type to aggregation-caused quenching (ACQ) type, where novel PIE luminogens (PIEgens) are revealed. Further potential applications in explosive detection are carried out, where it achieves TNT detection sensitivity at ppm level in solution and ng level on the test paper. This work therefore expands the structure and functionality libraries of monomer, polymer and NTIL, which might cause inspirations to different fields including polymer chemistry, NTIL, AIE and PIE., (© 2024 Wiley‐VCH GmbH.)

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 10 5  S m -1 , and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 μm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices., (© 2024. The Author(s).)

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12 , increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β =-2.30, 95% CI -4.43--0.16, P =0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β =-7.39, 95% CI -11.50--3.21, P <0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR =1.05, 95% CI 1.01-1.08, P =0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Knowledge on runoff transport of manure-sourced antibiotics from farmland soil to aquatic environment is limited due to complexity of hydrological regime and pathways. This study monitored natural rainfalls in sloping orchard plots with free-range chickens, with an attempt to investigate the migration characteristics of typical antibiotics via surface runoff as well as the impact of manure presence. Results showed that rainstorms continuously carried away antibiotics in surface runoff and all target antibiotics including those with high affinities to soil were detected at the beginning of runoff production. Concentration of antibiotics was found to respond strongly to the instantaneous rainfall intensity, showing consistent fluctuations during rainfalls. Concentrations of sulfonamides and florfenicol were two orders of magnitude higher than that of tetracyclines and fluoroquinolones. Compared to the control without raising chickens, antibiotics migration was considerably increased with the increased runoff production due to soil surface changes caused by chicken activities. Additionally, dynamics of antibiotic concentration significantly correlated with variations of fluorescent DOM components. Chicken manure-derived DOM mainly contained tryptophan moiety, and laboratory fluorescence quenching test with 2D-COS analysis indicated that all antibiotics interacted more strongly and preferentially with tryptophan than humic-like species. Antibiotics bonded to manure DOM with an affinity corresponding to the significance level of their correlations. In this light, potential use of fluorescence indices based on the established correlations may provide a convenient tool for tracing runoff migration of antibiotics during rainfalls., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chen Liu reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ 2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P <0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P >0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Background: The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24 +0 -31 +6  weeks' gestation age (GA)., Methods: This was a retrospective cross-sectional study. The source population was infants born at 24 +0 -31 +6  weeks' GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O 2 /CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression., Results: Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O 2 /CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation (P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation., Conclusions: Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed., (© 2023. The Author(s).)

Background: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear., Methods: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation., Conclusion: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke., (© 2023. The Author(s).)

This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8-21 days, adjusted OR = 1.98 (1.59, 2.45); 22-35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8-21 days, adjusted OR = 8.42 (3.22, 22.01); 22-35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy., (© 2023. The Author(s).)

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI ( P =0.650). The PDA treatment rate decreased with increasing gestational age ( P <0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95% CI 0-0.3) to 3.4 (95% CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

Tumor-derived exosomes (TDEs) play critical roles in many aspects of cancer progression. There have been several advances in cancer immunotherapy in recent years. A major challenge, however, has been addressed to the role of TDEs in tumor cell immune escape through their influence on the antitumor immunity of natural killer (NK) cells, a key type of immune cell. In this review, we present our overview of the effects of different TDEs on NK cell activation and NK cell toxicity. Studies on mechanism suggest that TDEs mainly affect the immune response of NK cells by inhibiting activated receptors on the surface of NK cells and downregulating the NK recognition ligand MICA/B on the tumor cell surface. In addition, a summary was documented on how to restore the cytotoxicity of NK cells and improve the drug's ability to recognize tumor cells, and a detailed explanation was also provided on the mechanism of action of the drug.

Microplastics emerge as a new environmental and human health crisis. Minimal research exists on effects of microplastic ingestion on the oral bioavailability of minerals (Fe, Ca, Cu, Zn, Mn, and Mg) in the gastrointestinal tract via impacting intestinal permeability, mineral transcellular transporters, and gut metabolites. Here, mice were exposed to polyethylene spheres of 30 and 200 μm (PE-30 and PE-200) in diet (2, 20, and 200 μg PE g -1 ) for 35 d to determine the microplastic effects on mineral oral bioavailability. Results showed that for mice fed diet amended with PE-30 and PE-200 at 2-200 μg g -1 , Ca, Cu, Zn, Mn, and Mg concentrations in the small intestine tissue were 43.3-68.8 %, 28.6-52.4 %, 19.3-27.1 %, 12.9-29.9 %, and 10.2-22.4 % lower compared to control mice, suggesting hampered bioavailability of these minerals. In addition, Ca and Mg concentrations in mouse femur were 10.6 % and 11.0 % lower with PE-200 at 200 μg g -1 . In contrast, Fe bioavailability was elevated, as suggested by significantly (p < 0.05) higher Fe concentration in the intestine tissue of mice exposed to PE-200 than control mice (157-180 vs. 115 ± 7.58 μg Fe g -1 ) and significantly (p < 0.05) higher Fe concentrations in liver and kidney with PE-30 and PE-200 at 200 μg g -1 . Following PE-200 exposure at 200 μg g -1 , genes coding for duodenal expression of tight junction proteins (e.g., claudin 4, occludin, zona occludins 1, and cingulin) were significantly up-regulated, possibility weakening intestinal permeability to Ca, Cu, Zn, Mn, and Mg ions. The elevated Fe bioavailability was possibly related to microplastic-induced greater abundances of small peptides in the intestinal tract, which inhibited Fe precipitation and elevated Fe solubility. Results showed that microplastic ingestion may cause Ca, Cu, Zn, Mn, and Mg deficiency but Fe overload via altering intestinal permeability and gut metabolites, posing a threat to human nutrition health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Home oxygen therapy (HOT) is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia (BPD). There is a lack of evidence-based consensus on the indication for HOT among these infants. Because wide variation in the institutional use of HOT exists, little is known about the role of regional social-economic level in the wide variation of HOT., Methods: This was a secondary analysis of Chinese Neonatal Network (CHNN) data from January 1, 2019 to December 31, 2019. Infants at gestational ages < 32 weeks, with a birth weight < 1500 g, and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study. Infants with major congenital anomalies and those who were discharged against medical advice were excluded., Results: Of 1768 preterm infants with BPD, 474 infants (26.8%) were discharged to home with oxygen. The proportion of HOT use in participating member hospitals varied from 0 to 89%, with five of 52 hospitals' observing proportions of HOT use that were significantly greater than expected, with 14 hospitals with observing proportions significantly less than expected, and with 33 hospitals with appropriate proportions. We noted a negative correlation between different performance groups of HOT and median GDP per capita (P = 0.04)., Conclusions: The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels. A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China., (© 2022. The Author(s).)

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Background: Organizing pneumonia (OP) is a rare interstitial lung disease. Secondary organizing pneumonia (SOP) caused by Mycobacterium tuberculosis (MTB) is extremely rare. Migratory MTB-associated SOP is more deceptive and dangerous. When insidious tuberculosis (TB) is not recognized, SOP would be misdiagnosed as cryptogenic organizing pneumonia (COP). Use of steroid hormone alone leads to the progression of TB foci or even death. Clues of distinguishing atypical TB at the background of OP is urgently needed., Case Presentation: A 56-year-old female patient was hospitalized into the local hospital because of cough and expectoration for more than half a month. Her medical history and family history showed no relation to TB or other lung diseases. Community-acquired pneumonia was diagnosed and anti-infection therapy was initialized but invalid. The patient suffered from continuous weigh loss. More puzzling, the lesions were migratory based on the chest computed tomography (CT) images. The patient was then transferred to our hospital. The immunological indexes of infection in blood and pathogenic tests in sputum and the bronchoalveolar lavage fluid were negative. The percutaneous lung puncture biopsy and pathological observation confirmed OP, but without granulomatous lesions. Additionally, pathogen detection of the punctured lung tissues by metagenomics next generation sequencing test (mNGS) were all negative. COP was highly suspected. Fortunately, the targeted next-generation sequencing (tNGS) detected MTB in the punctured lung tissues and MTB-associated SOP was definitely diagnosed. The combined therapy of anti-TB and prednisone was administrated. After treatment for 10 days, the partial lesions were significantly resorbed and the patient was discharged. In the follow-up of half a year, the patient was healthy., Conclusions: It is difficult to distinguish SOP from COP in clinical practice. Diagnosis of COP must be very cautious. Transient small nodules and cavities in the early lung image are a clue to consider TB, even though all pathogen tests are negative. tNGS is also a powerful tool to detect pathogen, ensuring prompt diagnosis of TB-related SOP. For clinicians in TB high burden countries, we encourage them to keep TB in mind before making a final diagnosis of COP., (© 2023. The Author(s).)

This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

Piwi-interacting RNAs (piRNAs), a class of small non-coding RNAs (ncRNAs), play pivotal roles in maintaining the genomic stability and modulating biological processes such as growth and development via the regulation of gene expression. However, the piRNAs in the Asian honeybee ( Apis cerana ) are still largely unknown at present. In this current work, on the basis of previously gained high-quality small RNA-seq datasets, piRNAs in the larval gut of Apis cerana cerana , the nominated species of A. cerana , were identified for the first time, followed by an in-depth investigation of the regulatory roles of differentially expressed piRNAs (DEpiRNAs) in the developmental process of the A. c. cerana . Here, a total of 621 piRNAs were identified in A. c. cerana larval guts, among which 499 piRNAs were shared by 4-(Ac4 group), 5-(Ac5 group), and 6-day-old (Ac6 group) larval guts, while the numbers of unique ones equaled 79, 37, and 11, respectively. The piRNAs in each group ranged from 24 nucleotides (nt) to 33 nt in length, and the first base of the piRNAs had a cytosine (C) bias. Additionally, five up-regulated and five down-regulated piRNAs were identified in the Ac4 vs. Ac5 comparison group, nine of which could target 9011 mRNAs; these targets were involved in 41 GO terms and 137 pathways. Comparatively, 22 up-regulated piRNAs were detected in the Ac5 vs. Ac6 comparison group, 21 of which could target 28,969 mRNAs; these targets were engaged in 46 functional terms and 164 pathways. The results suggested an overall alteration of the expression pattern of piRNAs during the developmental process of A. c. cerana larvae. The regulatory network analysis showed that piR-ace-748815 and piR-ace-512574 in the Ac4 vs. Ac5 comparison group as well as piR-ace-716466 and piR-ace-828146 in the Ac5 vs. Ac6 comparison group were linked to the highest number of targets. Further investigation indicated that targets of DEpiRNAs in the abovementioned two comparison groups could be annotated to several growth and development-associated pathways, such as the Jak/STAT, TGF-β, and Wnt signaling pathways, indicating the involvement of DEpiRNAs in modulating larval gut development via these crucial pathways. Moreover, the expression trends of six randomly selected DEpiRNAs were verified using a combination of stem-loop RT-PCR and RT-qPCR. These results not only provide a novel insight into the development of the A. c. cerana larval gut, but also lay a foundation for uncovering the epigenetic mechanism underlying larval gut development.

Toxoplasmosis is an important zoonotic parasitic disease caused by Toxoplasma gondii ( T. gondii ). However, the functions of circRNAs and miRNAs in response to T. gondii infection in the livers of mice at acute and chronic stages remain unknown. Here, high-throughput RNA sequencing was performed for detecting the expression of circRNAs and miRNAs in livers of mice infected with 20 T. gondii cysts at the acute and chronic stages, in order to understand the potential molecular mechanisms underlying hepatic toxoplasmosis. Overall, 265 and 97 differentially expressed (DE) circRNAs were found in livers at the acute and chronic infection stages in comparison with controls, respectively. In addition, 171 and 77 DEmiRNAs were found in livers at the acute and chronic infection stages, respectively. Functional annotation showed that some immunity-related Gene ontology terms, such as "positive regulation of cytokine production", "regulation of T cell activation", and "immune receptor activity", were enriched at the two infection stages. Moreover, the pathways "Valine, leucine, and isoleucine degradation", "Fatty acid metabolism", and "Glycine, serine, and threonine metabolism" were involved in liver disease. Remarkably, DEcircRNA 6:124519352|124575359 was significantly correlated with DEmiRNAs mmu-miR-146a-5p and mmu-miR-150-5p in the network that was associated with liver immunity and pathogenesis of disease. This study revealed that the expression profiling of circRNAs in the livers was changed after T. gondii infection, and improved our understanding of the transcriptomic landscape of hepatic toxoplasmosis in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zou, Meng, Wei, Gu, Chen, Geng, Yang, Zhang and Cao.)

Identification of lysine (symbol Lys or K) succinylation (Ksucc) sites centralizes the basis for disclosing the mechanism and function of lysine succinylation modifications. Traditional experimental methods for Ksucc site ientification are often costly and time-consuming. Therefore, it is necessary to construct an efficient computational method to prediction the presence of Ksucc sites in protein sequences. In this study, we proposed a novel and effective predictor for the identification of Ksucc sites based on deep learning algorithms that was termed as Deep&#95;KsuccSite. The predictor adopted Composition, Transition, and Distribution (CTD) Composition (CTDC), Enhanced Grouped Amino Acid Composition (EGAAC), Amphiphilic Pseudo-Amino Acid Composition (APAAC), and Embedding Encoding methods to encode peptides, then constructed three base classifiers using one-dimensional (1D) convolutional neural network (CNN) and 2D-CNN, and finally utilized voting method to get the final results. K-fold cross-validation and independent testing showed that Deep&#95;KsuccSite could serve as an effective tool to identify Ksucc sites in protein sequences. In addition, the ablation experiment results based on voting, feature combination, and model architecture showed that Deep&#95;KsuccSite could make full use of the information of different features to construct an effective classifier. Taken together, we developed Deep&#95;KsuccSite in this study, which was based on deep learning algorithm and could achieved better prediction accuracy than current methods for lysine succinylation sites. The code and dataset involved in this methodological study are permanently available at the URL https://github.com/flyinsky6/Deep&#95;KsuccSite., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xu, Lu, Yang, Gu, Wang and Liu.)

Objective: This study aimed to estimate the causal effects of Coronavirus disease 2019 susceptibility and hospitalization on cardiovascular disease death using two-sample Mendelian randomization analysis., Methods: We used statistics from a genome-wide association study. A total of 2,568,698 participants were assessed in this study, including 1,299,010 in Coronavirus disease 2019 susceptibility databases, 908,494 in Coronavirus disease 2019 hospitalization database, and 361,194 in a cardiovascular disease death database. We performed two-sample Mendelian randomization analysis using the inverse variance weighted method. As sensitivity analysis techniques, Mendelian randomization-Egger regression, heterogeneity analyses, and Leave-one-out analysis were employed. Reverse Mendelian randomization analysis was used to detect reverse causality. Statistical significance was defined as P < 0.05., Results: Coronavirus disease 2019 susceptibility may be a causal factor for cardiovascular disease death (β = 2.188 × 10 -3 , P = 0.002), which involves five common single nucleotide polymorphisms. Similarly, Coronavirus disease 2019 hospitalization may also be a causal factor for cardiovascular disease death (β = 8.626 × 10 -4 , P = 0.010), which involves nine common single nucleotide polymorphisms. Furthermore, sensitivity and reverse Mendelian randomization analysis suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between Coronavirus disease 2019 and cardiovascular disease death., Conclusion: Our bidirectional Mendelian randomization analysis showed a causal relationship between Coronavirus disease 2019 susceptibility and hospitalization associated with an increased risk of cardiovascular disease death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miao, Gu and Shi.)

Objective: To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence., Methods: We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set., Results: Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively., Conclusion: Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio., (© 2022 John Wiley & Sons Ltd.)

Paternal stress exposure-induced high corticosterone (CORT) levels may contribute to depression in offspring. Clinical studies disclose the association of depressive symptoms in fathers with their adolescent offspring. However, there is limited information regarding the intervention for intergenerational inheritance of depression. In this study we evaluated the intervention of cinnamaldehyde, a major constituent of Chinese herb cinnamon bark, for intergenerational inheritance of depression in CORT- and CMS-induced mouse models of depression. Depressive-like behaviors were induced in male mice by injection of CORT (20 mg·kg -1 ·d -1 , sc) for 6 weeks or by chronic mild stress (CMS) for 6 weeks. We showed that co-administration of cinnamaldehyde (10, 20, or 40 mg·kg -1 ·d -1 , ig) for 6 weeks in F0 males prevented the depressive-like phenotypes of F1 male offspring. In addition, co-administration of cinnamaldehyde (20 mg·kg -1 ·d -1 , ig) for 4 weeks significantly ameliorated depressive-like behaviors of chronic variable stress (CVS)-stimulated F1 offspring born to CMS mice. Notably, cinnamaldehyde had no reproductive toxicity, while positive drug fluoxetine showed remarkable reproductive toxicity. We revealed that CMS and CORT significantly reduced testis glucocorticoid receptor (GR) expression, and increased testis and sperm miR-190b expression in F0 depressive-like models. Moreover, pre-miR-190b expression was upregulated in testis of F0 males. The amount of GR on miR-190b promoter regions was decreased in testis of CORT-stimulated F0 males. Cinnamaldehyde administration reversed CORT-induced GR reduction in testis, miR-190b upregulation in testis and sperm, pre-miR-190b upregulation in testis, and the amount of GR on miR-190b promoter regions of F0 males. In miR-190b-transfected Neuro 2a (N2a) cells, we demonstrated that miR-190b might directly bind to the 3'-UTR of brain-derived neurotrophic factor (BDNF). In the hippocampus of F1 males of CORT- or CMS-induced depressive-like models, increased miR-190b expression was accompanied by reduced BDNF and GR, which were ameliorated by cinnamaldehyde. In conclusion, cinnamaldehyde is a potential intervening agent for intergenerational inheritance of depression, probably by regulating GR/miR-190b/BDNF pathway., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

MicroRNAs can regulate the function of ion channels in many organs. Based on our previous study we propose that miR-142a-39, which is highly expressed in denervated skeletal muscle, might affect cell excitability through similar mechanisms. In this study, we overexpressed or knocked down miR-142a-3p in C2C12 cells using a lentivirus method. After 7 days of differentiation culture, whole-cell currents were recorded. The results showed that overexpression of miR-142a-3p reduced the cell membrane capacitance, increased potassium current density and decreased calcium current density. Knockdown of miR-142a-3p reduced sodium ion channel current density. The results showed that change in miR-142a-3p expression affected the ion channel currents in C2C12 cells, suggesting its possible roles in muscle cell electrophysiology. This study was approved by the Animal Ethics Committee of Peking University in July 2020 (approval No. LA2017128)., Competing Interests: None

The present study prepared shell-core nanoparticles comprising poly(lactic-co-glycolic acid)(PLGA) cores encapsulated by shells composed of mixed lipids(Lipoid S100 and DSPE-PEG 2000) or polymer F127 to investigate the effects of shell composition on overcoming physiological barriers of gastrointestinal mucus and intestinal epithelial cells and improving bioavailability.The results are expected to provide references for the research on the improvement of the oral bioavailability of Chinese medicine by nanocar-riers. Silibinin(SLB) was used as a model drug to prepare PLGA nanoparticles coated with the shell of mixed lipids(SLB-LPNs) or F127(SLB-FPNs) via a modified nanoprecipitation method.Transmission electron microscopy showed that both LPNs and FPNs were spherical with a core-shell structure.The average particle sizes of SLB-LPNs and SLB-FPNs were(94.13±2.23) and(95.42±4.91) nm, respectively.The Zeta potential values were(-39.3±2.8) and(-17.0±0.2) mV, respectively.X-ray diffraction analysis revealed the presence of SLB in the two types of nanoparticles in a molecular or amorphous state.The ability of nanoparticles to cross both the mucus and epithelial barriers were evaluated using the cellular internalization kinetics assay.LPNs showed a higher rate of cell internalization than FPNs, indicating that LPNs could penetrate the mucus layer and become internalized by cells more rapidly.As revealed by the in vivo pharmacokinetic assay in rats with SLB suspension as the reference, the relative oral bioavailability of SLB-LPNs and SLB-FPNs was 400.37% and 923.31%, respectively.The effect of SLB-FPNs in improving oral bioavailability was more significant than that of SLB-LPNs.In summary, shell composition can influence the ability of nanoparticles to overcome oral physiological bar-riers, such as the mucus layer and intestinal epithelial cells, and improve oral bioavailability.Shell-core structured nanoparticles are promising nanocarriers for oral drug delivery systems.

During the COVID-19 pandemic, online education has become an important approach to learning in the information era and an important research topic in the field of educational technology as well as that of education in general. Teacher-student interaction in online education is an important factor affecting students' learning performance. This study employed a questionnaire survey to explore the influence of teacher-student interaction on learning effects in online education as well as the mediating role of psychological atmosphere and learning engagement. The study involved 398 college students studying at Chinese universities as the research object. Participants filled out a self-report questionnaire. The study found that (1) the level of teacher-student interaction positively affected students' learning effects ( r  = 0.649, p  < 0.01). (2) The psychological atmosphere mediated the positive effect of the level of teacher-student interaction on learning effects with mediating effect value of 0.1248. (3) Learning engagement mediated the positive effect of teacher-student interaction on learning effects with a mediating effect value of 0.1539. (4) The psychological atmosphere and learning engagement play a chain-mediating role in the mechanism of teacher-student interaction affecting students' learning effects; that is, teacher-student interaction promotes students' learning engagement by creating a good psychological atmosphere, which, in turn, influences learning effects. The mediating effect value was 0.0403. The results indicate that teacher-student interaction not only directly affects students' learning effects but also influences students' learning effects through the mediating effect of the psychological atmosphere and learning engagement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Sun, Sha, Gu, Hou, Zhu and Fang.)

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t -test, rank-sum test or χ 2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age ( Z =17.62, P< 0.01), lower birth weight ( t =18.64, P <0.01), higher proportion of small-for-gestation age (χ 2 =31.06, P< 0.01), multiple birth (χ²=12.82, P <0.01) and intensive resuscitation in delivery room (χ²=287.52, P< 0.01), as well as lower proportion of females (χ²=10.68, P <0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P <0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P <0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

β-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the β-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify β-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a β-galactosidase gene named bgaQ, encoded for high β-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr 801 and Pro 802 around the active sites of BgaQ with His 801 and Gly 802 , the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of β-galactosidase from Strep. thermophilus for GOS-enriched yogurt making., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: This study aimed to describe length of stay (LOS) to discharge and site variations among very preterm infants (VPIs) admitted to 57 Chinese neonatal intensive care units (NICUs) and to investigate factors associated with LOS for VPIs., Methods: This retrospective multicenter cohort study enrolled all infants < 32 weeks' gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network, within 7 days after birth in 2019. Exclusion criteria included major congenital anomalies, NICU deaths, discharge against medical advice, transfer to non-participating hospitals, and missing discharge date. Two multivariable linear models were used to estimate the association of infant characteristics and LOS., Results: A total of 6580 infants were included in our study. The overall median LOS was 46 days [interquartile range (IQR): 35-60], and the median corrected gestational age at discharge was 36 weeks (IQR: 35-38). LOS and corrected gestational age at discharge increased with decreasing gestational age. The median corrected gestational age at discharge for infants at 24 weeks, 25 weeks, 26 weeks, 27-28 weeks, and 29-31 weeks were 41 weeks, 39 weeks, 38 weeks, 37 weeks and 36 weeks, respectively. Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals., Conclusions: The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents. Large variation of LOS independent of infant characteristics existed, indicating variation of care practices requiring further investigation and quality improvement., (© 2021. The Author(s).)

Motor endplates (MEPs) are important sites of information exchange between motor neurons and skeletal muscle, and are distributed in an organized pattern of lamellae in the muscle. Delayed repair of peripheral nerve injury typically results in unsatisfactory functional recovery because of MEP degeneration. In this study, the mouse tibial nerve was transected and repaired with a biodegradable chitin conduit, immediately following or 1 or 3 months after the injury. Fluorescent α-bungarotoxin was injected to label MEPs. Tissue optical clearing combined with light-sheet microscopy revealed that MEPs were distributed in an organized pattern of lamellae in skeletal muscle after delayed repair for 1 and 3 months. However, the total number of MEPs, the number of MEPs per lamellar cluster, and the maturation of single MEPs in gastrocnemius muscle gradually decreased with increasing denervation time. These findings suggest that delayed repair can restore the spatial distribution of MEPs, but it has an adverse effect on the homogeneity of MEPs in the lamellar clusters and the total number of MEPs in the target muscle. The study procedures were approved by the Animal Ethics Committee of the Peking University People's Hospital (approval No. 2019PHC015) on April 8, 2019., Competing Interests: None

A new Brønsted acid-catalyzed oxo-cyclization of propargyl alcohols with azlactones to synthesize C 2 -azlactonized 2 H -chromenes has been established that uses 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BiNPO 4 H) as the catalyst and gives excellent diastereoselectivities (≥19:1 dr) in most cases. This protocol has a high compatibility with various substituents of substrates, offering a catalytic and useful entry to the fabrication of the synthetically important C 2 -functionalized 2 H -chromene scaffold.

Objective: To investigate the effect of platelet-rich plasma on tendon-bone healing after anterior cruciate ligament reconstruction., Methods: This retrospective study included 85 patients (range, 18-50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet-rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively., Results: The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet-rich plasma group than in the normal saline group at all follow-up time points (P < 0.05). The signal/noise quotient values of the tibial and femoral ends in both groups were significantly different at 3, 6, and 12 months postoperatively (P < 0.05). Additionally, the signal/noise quotient values of the tibia were significantly lower than those of the femur in both groups (P < 0.05). The Lysholm and International Knee Documentation Committee scores were significantly better in the platelet-rich plasma group than in the normal saline group only at 3 months postoperatively. No complications, such as knee joint infection or vascular and nerve injuries, occurred in any of the 85 patients. The knee flexion of all patients were more than 90°, and the straight degree was 0°. No joint stiffness was observed in all patients., Conclusion: Platelet-rich plasma can promote tendon-bone healing in grafts and can improve early postoperative knee joint function., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematological malignancies, but relapse resulting predominantly from residual disease in the bone marrow (BM) remains the major cause of treatment failure. Using immunodeficient mice grafted with laboratory-generated human B-ALL, our previous study suggested that leukemia cells within the BM are resistant to graft-versus-leukemia (GVL) effects and that mobilization with CXCR4 antagonists may dislodge leukemia cells from the BM, enabling them to be destroyed by GVL effects. In this study, we extended this approach to patient-derived xenograft (PDX) and murine T-ALL and AML models to determine its clinical relevance and effects on GVHD and donor hematopoietic engraftment. We found that posttransplant treatment with the CXCR4 antagonist AMD3100 significantly improved the eradication of leukemia cells in the BM in PDX mice grafted with B-ALL cells from multiple patients. AMD3100 also significantly improved GVL effects in murine T-ALL and AML models and promoted donor hematopoietic engraftment in mice following nonmyeloablative allo-HCT. Furthermore, posttransplant treatment with AMD3100 had no detectable deleterious effect related to acute or chronic GVHD. These findings provide important preclinical data supporting the initiation of clinical trials exploring combination therapy with CXCR4 antagonists and allo-HCT., (© 2021. The Author(s), under exclusive licence to CSI and USTC.)

Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3 on colorectal cancer (CRC) remains unclear. In this study, HOXA-AS3 was significantly over-expressed in CRC clinical samples and human CRC cell lines (SW480, SW620, HCT116, COLO205, and LOVO). HOXA-AS3 knockdown was further achieved by specific siRNAs in COLO205 and LOVO cell lines. The depletion of HOXA-AS3 remarkably inhibited cell proliferation, induced cell cycle arrest, and promoted cell apoptosis in CRC cell lines. Additionally, HOXA-AS3 knockdown was determined to facilitate miR-4319 expression and reduce expression level of sphingolipid transporter 2 (SPNS2) in CRC cell lines. The dual luciferase reporter assay suggested that HOXA-AS3 acted as a sponge of miR-4319, and miR-4319 further directly targeted SPNS2 for expression regulation. Besides, HOXA-AS3 was determined to mediate CRC cell proliferation and apoptosis via miR-4319/SPNS2 axis. Moreover, tumorigenesis experiment validated that HOXA-AS3 promoted CRC progression in vivo by regulating miR-4319, SPNS2, and protein kinase B (AKT) signaling. In summary, this study reveals the novel role of HOXA-AS3 in pathogenesis of CRC and provides a candidate for CRC therapeutic target., (© 2021. University of Navarra.)

Objective: To evaluate the efficacy and safety of drospirenone and ethinylestradiol tablets (Ⅱ) in Chinese women with dysmenorrhea. Methods: This was a single-arm, open-label, interventional, multicenter, post-authorization safety/effectiveness study of drospirenone and ethinylestradiol tablets (Ⅱ) across 6 treatment cycles, a total of 526 patients were included in the dysmenorrhea subgroup. Visual analog scale (VAS) was used to assess the severity of menstrual pain. Secondary outcomes included unintended pregnancies, bleeding pattern, cycle control and safety. Results: After treated with drospirenone and ethinylestradiol tablets (Ⅱ), VAS of pain had decreased significantly compared with baselines [(49.5±23.7) vs (32.3±24.9) vs (20.7±19.4) vs (18.4±18.7) mm, P <0.01]. From the second cycle to the fifth cycle, the incidence of scheduled bleeding increased from 93.9% (450/479) to 96.4% (431/447). The duration of scheduled bleeding decreased from (5.7±2.7) to (5.4±1.8) days. The incidence of intermenstrual bleeding decreased from 9.0% (43/479) to 5.6% (25/447). 17.5% (92/526) patients reported adverse drug reactions, most frequently reported adverse events were breast pain, nausea, breast swelling, headache, and uterine bleeding. No death occurred during the study. Conclusion: Drospirenone and ethinylestradiol tablets (Ⅱ) is effective for the treatment of dysmenorrhea and has good safety.

Background: Congenital atrial appendage aneurysm (AAA) is a rare malformation which can coexist with potentially lethal complications. We aimed to summary echocardiographic characteristics and prognosis of fetal AAA., Methods: We retrospectively analyzed the echocardiographic data of 17 fetuses with AAA，and their outcomes or pathological reports were also collected., Results: Eight fetuses with left AAA (LAAA) and 9 fetuses with right AAA (RAAA) were identified. Five fetuses were diagnosed with other cardiac defects. Two fetuses with RAAA presented with arrhythmias, including atrial premature beats (n = 1) and bradyarrhythmia (n = 1). LAAA could be detected by four-chamber view (50.0%) and short-axis view (100.0%). RAAA could be detected by four-chamber view (100.0%), and view of right ventricular inflow tract (33.3%). There were three cases with mild pericardial effusion. Three cases with complex cardiac defects were selectively terminated, with confirmation of LAAA by autopsy in one case. Fourteen fetuses were born. After following 2 (range, 1-5) years, the AAA disappeared in one case with LAAA and two cases with RAAA. While, 11 cases were still diagnosed with AAA. Atrial premature beats with RAAA, which appeared in prenatal period, still persisted after birth., Conclusion: Congenital AAA is a rare abnormality in utero. The short-axis view and the four-chamber view were the most useful views to detect fetal AAA. Fetal AAA may disappear in childhood. Atrial tachyarrhythmias in utero may exist persistently after birth. Patients with AAA should be followed up closely and appropriate intervention should be taken when complications appeared., (© 2021 Wiley Periodicals LLC.)