Clinicopathologic features and surgical treatment prognosis of esophageal carcinosarcoma.

Background: Carcinosarcoma is a rare esophageal tumor, accounting for approximately 0.27-2.8% of malignant esophageal tumors. This study aims to investigate the clinical pathological characteristics, surgical treatment outcomes, and analysis of prognostic factors in esophageal carcinosarcoma (ECS). Methods: Clinical data from sixteen patients diagnosed with esophageal sarcomatoid carcinoma who underwent surgical interventions were retrospectively analyzed. Clinical and pathological features, treatment modalities, and postoperative outcomes were systematically examined. Results: Out of the 1261 patients who underwent surgical treatment for esophageal cancer, 16 cases were pathologically confirmed as carcinosarcoma. Among them, two underwent neoadjuvant chemotherapy, six received postoperative chemotherapy. Carcinosarcomas predominantly occurred in the middle (43.75%) and lower (50%) segments of the esophagus. Among the 16 cases, 10 presented as polypoid, 4 as ulcerative, and 2 as medullary types. Microscopic examination revealed coexistence and transitional transitions between sarcomatous and carcinoma components. Pathological staging showed 5 cases in stage T1, 2 in stage T2, and 9 in stage T3, with lymph node metastasis observed in 8 cases (50%). TNM staging revealed 2 cases in stage I, 9 in stage II, and 5 in stage III. The overall 1, 3, and 5-year survival rates were 86.67%, 62.5%, and 57.14%, respectively. Univariate analysis indicated that pathological N staging influenced survival rates, while multivariate analysis demonstrated that pathological N staging was an independent prognostic factor. Conclusions: Carcinosarcoma is a rare esophageal tumor, accounting for approximately 0.27-2.8% of malignant esophageal tumors. Histologically, the biphasic pattern is a crucial diagnostic feature, although the carcinomatous component may not always be evident, especially in limited biopsies, leading to potential misclassification as pure sarcoma or squamous cell carcinoma. Despite its large volume and cellular atypia, carcinosarcoma carries a favorable prognosis. Complete surgical resection of the tumor and regional lymph node dissection is the preferred treatment approach for esophageal carcinosarcoma.

Development and validation of a competency evaluation index system for nurse endoscopists with different stages performing endoscopy nursing in China: A modified Delphi study.

BACKGROUND: The advancement of endoscopic techniques has resulted in an increasing need for comprehensive competency in endoscopy nursing. However, there is currently no unified competency evaluation index system for nurse endoscopists in China. AIMS: To develop and validate of a competency evaluation index system for nurse endoscopists with different stages performing endoscopy nursing in China. DESIGN: A modified Delphi study. SETTINGS: Data were collected in a medical university affiliated hospital. PARTICIPANTS: A total of 569 participants in different fields were included at various phases of this research. METHODS: The preliminary indicators were designed after conducting a literature review, semi-structured interviews and questionnaires. Two rounds of correspondence with 30 experts using the Delphi method were conducted to evaluate the content of the index followed by reliability and validity tests. The competency evaluation index system for nurse endoscopists at different stages was developed through expert meetings based on the Delphi consultation results according to the novice-to-expert model. RESULTS: After two rounds of Delphi method consultation, we have established 4 first-level indicators ('Cognitive skill', 'Practice professional skills', 'Professional development skills' and 'Personal characteristics and inner qualities') and 21 s-level indicators, which are the detailed description of first-level indicators. According to the index weight analysis, the four first-level indicators are ranked from the largest to the smallest as practical professional skills, cognitive skills, professional development skills, personal characteristics and intrinsic qualities. Three different stages of nurse endoscopists competency evaluation forms and criteria were developed: primary stage (New skilled), intermediate stage (Capable) and advanced stage (Expert). CONCLUSIONS: The establishment of a competency evaluation index system based on the novice-to-expert model can accurately assess competency levels and help to effectively train the nurse endoscopists at different stages. Future research should focus on imbedding these competencies in nurse education.

Regio- and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes.

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

Thirteen New Patients of PPP2R5D Gene Mutation and the Fine Profile of Genotype-Phenotype Correlation Unraveling the Pathogenic Mechanism Underlying Macrocephaly Phenotype.

BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of diseases that severely affect the physical and mental health of children. The PPP2R5D gene encodes B56δ, the regulatory subunit of protein phosphatase 2A (PP2A). NDDs related to the PPP2R5D gene have recently been defined as Houge-Janssens syndrome 1. METHODS: Clinical/whole exome sequencing was performed on approximately 3000 patients with NDDs from 2017 to 2023. In vitro experiments were performed to assess the impairment of variants to protein expression and the assembly of PP2A holoenzyme. The genetic information and phenotypes of the reported patients, as well as patients in this study, were summarized, and the genotype-phenotype relationship was analyzed. The probability of pathogenic missense variants in PPP2R5D was predicted using AlphaMissense (AM), and the relationship between certain phenotype and 3D protein structural features were analyzed. RESULTS: Thirteen new patients carrying twelve PPP2R5D gene variants were detected, including five novel missense variants and one novel frameshift variant. In vitro experiments revealed that the frameshift variant p.H463Mfs*3 resulted in a ~50 kDa truncated protein with lower expression level. Except for E420K and T536R, other missense variants impaired holoenzyme assembly. Furthermore, we found that pathogenic/likely pathogenic (P/LP) variants that have been reported so far were all missense variants and clustered in three conserved regions, and the likelihood of P/LP mutations located in these conserved regions was extremely high. In addition, the macrocephaly phenotype was related to negatively charged residues involved in substrate recruitment. CONCLUSIONS: We reported thirteen new patients with PPP2R5D gene variants and expanded the PPP2R5D variant spectrum. We confirmed the pathogenicity of novel variants through in vitro experiments. Our findings in genotype-phenotype relationship provide inspiration for genetic counseling and interpretation of variants. We also provide directions for further research on the mechanism of macrocephaly phenotype.

Fructose-1,6-bisphosphatase deficiency: estimation of prevalence in the Chinese population and analysis of genotype-phenotype association.

Objective: Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inborn error due to mutations in the FBP1 gene. The genetic spectrum of FBP1D in China is unknown, also nonspecific manifestations confuse disease diagnosis. We systematically estimated the FBP1D prevalence in Chinese and explored genotype-phenotype association. Methods: We collected 101 FBP1 variants from our cohort and public resources, and manually curated pathogenicity of these variants. Ninety-seven pathogenic or likely pathogenic variants were used in our cohort to estimate Chinese FBP1D prevalence by three methods: 1) carrier frequency, 2) permutation and combination, 3) Bayesian framework. Allele frequencies (AFs) of these variants in our cohort, China Metabolic Analytics Project (ChinaMAP) and gnomAD were compared to reveal the different hotspots in Chinese and other populations. Clinical and genetic information of 122 FBP1D patients from our cohort and published literature were collected to analyze the genotype-phenotypes association. Phenotypes of 68 hereditary fructose intolerance (HFI) patients from our previous study were used to compare the phenotypic differences between these two fructose metabolism diseases. Results: The estimated Chinese FBP1D prevalence was 1/1,310,034. In the Chinese population, c.490G>A and c.355G>A had significantly higher AFs than in the non-Finland European population, and c.841G>A had significantly lower AF value than in the South Asian population (all p values < 0.05). The genotype-phenotype association analyses showed that patients carrying homozygous c.841G>A were more likely to present increased urinary glycerol, carrying two CNVs (especially homozygous exon1 deletion) were often with hepatic steatosis, carrying compound heterozygous variants were usually with lethargy, and carrying homozygous variants were usually with ketosis and hepatic steatosis (all p values < 0.05). By comparing to phenotypes of HFI patients, FBP1D patients were more likely to present hypoglycemia, metabolic acidosis, and seizures (all p-value < 0.05). Conclusion: The prevalence of FBP1D in the Chinese population is extremely low. Genetic sequencing could effectively help to diagnose FBP1D.

Using Clinical-based Discharge Criteria to Discharge Patients After Endoscopy Procedures Under Drug-induced Intravenous Sedation in the Outpatient Care Unit: An Observational Study.

PURPOSE: To verify the feasibility of clinical-based discharge (CBD) criteria and to find out the reasons for the delayed discharge of outpatients after endoscopy procedures under drug-induced intravenous sedation. DESIGN: A prospectively observational study conducted at a tertiary endoscopy center. METHODS: Medical records were collected from outpatients admitted for endoscopy procedures under drug-induced intravenous sedation from June 1, 2021 to December 30, 2021. Patients were scheduled to discharge at least 30 minutes based on the time-based discharge (TBD) method. Postanesthetic discharge scoring system in the outpatient post-anesthesia care unit (PACU) recorded the time of patients discharged home on the CBD criteria. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate analysis was applied to identify the factors relating to late discharges. FINDINGS: 10,597 patients were safely and successfully discharged home, and we were informed of no serious emergency or accidental readmissions to the hospital. The mean CBD time (21.77 ± 11.35 minutes) was compared with the TBD time (30 minutes) and actual TBD discharge time (61.56 ± 4.93 minutes), which were statistically significant, without changes in the patient's vital signs (P < .01). Primarily, further univariate and multivariate analyses showed that abdominal pain and fatigue were key factors accountable for delay in PACU discharge (P < .05). CONCLUSIONS: The study concluded that in patients undergoing ambulatory endoscopy procedures with drug-induced intravenous sedation, discharge times based on physiological scoring systems can efficiently and safely guide ambulatory patient discharge as compared to the traditional TBD method. Postoperative fatigue and pain were the main factors affecting patients discharge associated with a relatively long PACU length of stay.

Proton Transfer Processes in 2-Butenenitrile Dimer Cation Studied by Mass-Selective Infrared Spectroscopy.

2-Butenenitrile (2-Bu) is a recently discovered crucial interstellar molecule. Herein, an abnormal NH band was observed in the infrared spectrum of the 2-Bu dimer cation, suggestive of a proton transfer reaction within the cluster. Through a comprehensive theoretical analysis of the IR spectrum of (2-Bu)2+, we discovered not only the formation of a new C-N bond through the attachment of one 2-Bu to another but also the occurrence of a proton transfer reaction in the cluster. This proton was identified as originating from the methyl group of the attaching 2-Bu in the cluster based on the analysis of IR spectra of (2-Bu)+ and [2-Bu-acrylonitrile (AN)]+. Furthermore, the detailed reaction process of this ion-molecule reaction is examined with theoretical calculation. This finding contributes significantly to our deeper understanding of ion-molecule reactions in the gas phase and the formation of nitrogen-containing prebiotic molecules in the interstellar medium.

Characterization of a human induced pluripotent stem cell line (FDCHi015-A) derived from PBMCs of a patient harbouring ALDOB mutation.

Hereditary fructose intolerance (HFI) is an autosomal recessive metabolic disease associated with a mutation in the aldolase B gene on chromosome 9q31. In this study, we generated a human-induced pluripotent stem cell (hiPSC) line, FDCHi015-A, from peripheral blood mononuclear cells (PBMCs) of a patient carrying the compound heterozygous mutations c.360_364delCAAA and c.1013C > T in exons 4 and 9 of the ALDOB gene, respectively. The iPSCs with the confirmed patient-specific mutation demonstrate pluripotency markers expression, a normal karyotype, and the ability to differentiate into derivatives of three germ layers.

Development and Validation of a Discharge Assessment Scale for Outpatients Undergoing Sedative Anesthesia in the Ambulatory Postanesthesia Care Unit: A Comprehensive Delphi Study.

PURPOSE: The purpose of this study was to develop a discharge assessment scale tailored for outpatients undergoing sedative anesthesia treatment in the ambulatory postanesthesia care unit and validate its agreement with the Post-Anesthetic Discharge Scoring System. DESIGN: The Delphi method. METHODS: A Delphi survey was conducted with 30 experts focusing on the evaluation of outpatient discharges following treatment under ambulatory anesthesia. Subsequently, a cross-sectional observational study employing convenience sampling selected 2,579 outpatients who had undergone painless ambulatory gastrointestinal endoscopy at a tertiary hospital to analyze the level of agreement with the Post-Anesthesia Discharge Scoring System. FINDINGS: The study conducted three rounds of expert consultations to create the ambulatory discharge assessment scale. Twenty-five experts from 12 provinces and municipalities in our country were interviewed. The discharge assessment form encompassed five aspects: consciousness level, vital signs, directional stability, mobility, and adverse reactions. According to the scale, if the total score exceeded 9 points, with none of the items scoring 0 points, the ambulatory patient could be discharged from the hospital with the accompaniment of family members. Patients assessed using this newly constructed scale were able to leave the hospital earlier compared to those assessed using the comparative scale. No significant differences were observed in vital signs at the time of discharge or the occurrence of adverse events within 24 hours after the procedure. CONCLUSIONS: This assessment tool for discharging ambulatory patients after the ambulatory anesthesia from the postanesthesia outpatient care unit can be considered a valuable addition to formalize the discharge process in outpatient services.

Antimicrobial resistance prediction by clinical metagenomics in pediatric severe pneumonia patients.

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

A survey of skin failure perceptions amongst pressure injury management staff in China: A cross-sectional study.

This study sought to evaluate the perceptions of pressure injury (PI) management staff regarding skin failure (SF). Additionally, an analysis of influencing factors based on the collected data was conducted to establish a foundation for targeted SF training. A descriptive, cross-sectional survey was undertaken in October-November 2023, utilising a convenience sampling method involving selected management staff of PI from 16 provinces in China. A total of 501 nursing participants were included, exhibiting an overall perception level that was moderately low. Although the majority were aware of the possibility of SF (n = 417, 83.23%), only 60% reported an understanding of the fundamentals of SF, with the lowest level of comprehension observed in differentiating between SF and PI (n = 212, 42.31%). Overall attitudes were generally positive. Regarding behaviour, active learning was more prevalent (n = 340, 67.86%), but training is less (n = 287, 57.29%). Family education (n = 401, 80.04%) and nursing record monitoring (n = 426, 85.03%) demonstrated better behaviour. Further analysis revealed that training (t = 13.937, p < 0.001) and professional title (F = 4.681, p = 0.010) had a significant effect on participants' perceptions. These findings underscore that there remains a substantial lack of perception about SF amongst participants. Overall, participants exhibited a positive attitude towards SF, highlighting the need for future improvements in SF training.

Derivation of an induced pluripotent stem cell line (FDCHi014-A) from PBMCs of a seven-year-old patient with a truncating NOVA2 variant (c.625del).

Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB) is a rare autosomal dominant disorder caused by a heterozygous mutation in the NOVA2 gene on chromosome 19q13. Here, we describe the generation and characterization of an iPSC line derived from the peripheral blood of a 7-year-old patient carrying a novel heterozygous mutation in NOVA2 (c.625 del). The iPSCs with the confirmed patient-specific mutation were demonstrated by pluripotency markers, a normal karyotype, and the ability to differentiate into three germ layers. This NOVA2-mutant iPSC line could facilitate disease modeling and therapy development studies for NEDASB.

Tailoring d-band center of high-valent metal-oxo species for pollutant removal via complete polymerization.

Polymerization-driven removal of pollutants in advanced oxidation processes (AOPs) offers a sustainable way for the simultaneous achievement of contamination abatement and resource recovery, supporting a low-carbon water purification approach. However, regulating such a process remains a great challenge due to the insufficient microscopic understanding of electronic structure-dependent reaction mechanisms. Herein, this work probes the origin of catalytic pollutant polymerization using a series of transition metal (Cu, Ni, Co, and Fe) single-atom catalysts and identifies the d-band center of active site as the key driver for polymerization transfer of pollutants. The high-valent metal-oxo species, produced via peroxymonosulfate activation, are found to trigger the pollutant removal via polymerization transfer. Phenoxyl radicals, identified by the innovative spin-trapping and quenching approaches, act as the key intermediate in the polymerization reactions. More importantly, the oxidation capacity of high-valent metal-oxo species can be facilely tuned by regulating their binding strength for peroxymonosulfate through d-band center modulation. A 100% polymerization transfer ratio is achieved by lowering the d-band center. This work presents a paradigm to dynamically modulate the electronic structure of high-valent metal-oxo species and optimize pollutant removal from wastewater via polymerization.

Generation of a human induced pluripotent stem cell line (FDCHi012-A) from a patient with DYRK1A-related intellectual disability syndrome carrying DYRK1A mutation (c.1024G > T).

DYRK1A haploinsufficiency causes a neurodevelopmental syndrome termed DYRK1A-related intellectual disability syndrome which is associated with a range of symptoms including microcephaly, epileptic seizures, and autism spectrum disorder. Here, we generated an induced Pluripotent Stem Cell (iPSC) line with a de novo missense mutation (DYRKIA c.1024G > T) from the peripheral blood mononuclear cells of a patient with DYRK1A-related intellectual disability syndrome. This iPSC line showed normal karyotype, exhibited pluripotency, and has three embryonic germ layers differentiation capacity. This iPSC line will be of great use in investigating the disease mechanisms and drug screening for patients with DYRK1A-related intellectual disability syndrome.

PICOTEES: a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts.

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://birthdefectlab.cn:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.

Comprehensive assessment of the genetic characteristics of small for gestational age newborns in NICU: from diagnosis of genetic disorders to prediction of prognosis.

BACKGROUND: In China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors. METHODS: A cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children's Hospital of Fudan University, Shanghai, China. RESULTS: Among the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84-0.96] vs. AUC=0.74 [0.64-0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6-0.93] vs. AUC=0.53[0.29-0.76]; P=0.0117). CONCLUSION: SGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.

CCDC146 is required for sperm flagellum biogenesis and male fertility in mice.

Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.

[A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites]. / æ–°ç”Ÿå„¿æœŸèµ·ç— ä¼´è¡€æ€§è ¹æ°´çš„â 型高脂蛋白血症1例.

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.