No Difference in the Pathogenic Microorganisms Among Different Types of Anorectal Abscesses: A Retrospective Study.

OBJECTIVE:  There is limited data on the pathogenic microorganisms associated with anorectal abscesses. The purpose of this study was to retrospectively analyze the types and quantities of pathogenic microorganisms in the pus cultures of patients with anorectal abscesses and to explore the correlation between pathogenic microorganisms and types of anorectal abscesses. METHODS:  A retrospective analysis was conducted on the microbiological data of 517 inpatient surgical patients with anorectal abscesses treated at a single center from January 2017 to December 2021. Chi-square tests were used to analyze whether there were differences in the types and quantities of pathogenic microorganisms among different types of anorectal abscesses. RESULTS:  Among the 517 patients, the mean age was 38.5 years, with an average duration of illness of 7.4 days. Of these, 440 (85.1%) were male and 77 (14.9%) were female. The types of anorectal abscesses included perianal abscesses (54 cases, 10.4%), intersphincteric abscesses (253 cases, 48.9%), ischiorectal abscesses (129 cases, 25.0%), deep posterior anal space (DPAS) abscesses (26 cases, 5.0%), supra-levator abscesses (10 cases, 1.9%), and horseshoe abscesses (45 cases, 8.7%). A total of 23 different microorganisms were cultured from the 517 pus specimens. The most common microorganism was Escherichia coli (323 cases, 62.5%), followed by Klebsiella pneumoniae (77 cases, 14.9%), Bacteroides fragilis (nine cases, 1.7%), Pseudomonas aeruginosa (eight cases, 1.5%), and Staphylococcus aureus (seven cases, 1.4%). Additionally, no microorganisms were cultured from 58 (11.2%) pus specimens. Nine patients (1.7%) were admitted with concomitant necrotizing fasciitis. Among the nine cases of concurrent necrotizing fasciitis, E. coli, K. pneumoniae, and S. aureus were cultured in six (66.7%), two (22.2%), and one (11.1%) case, respectively. Chi-square tests revealed no significant differences in the types and quantities of pathogenic microorganisms among different types of anorectal abscesses (P > 0.05). CONCLUSION:  This study provides a large sample of pus culture microbiological data from patients with anorectal abscesses. Regardless of whether it is a simple anorectal abscess or concurrent necrotizing fasciitis, E. coli was the most common microorganism cultured from the pus of patients with anorectal abscesses. Other common microorganisms include K. pneumoniae, B. fragilis, and S. aureus. These results provide evidence for the precise antibiotic treatment of anorectal abscesses. Additionally, there were no differences in the types and quantities of pathogenic microorganisms among different types of anorectal abscesses.

Isolation of undescribed cladosporols and spirobisnaphthalenes from a plant pathogen Cladosporium cladosporioides F-10-2-A.

Two undescribed cladosporol derivatives, cladosporols J-K (1-2), and three previously unreported spirobisnaphthalenes, urnucratins D-F (3-5), as well as eleven known cladosporols (6-16), were characterized from Cladosporium cladosporioides (Cladosporiaceae), a common plant pathogen isolated from the skin of Chinese toad. Cladosporols J-K (1-2) with a single double bond have been rarely reported, while urnucratins D-F (3-5) featured an unusual benzoquinone bisnaphthospiroether skeleton, contributing to an expanding category of undiscovered natural products. Their structures and absolute configurations were determined using extensive spectroscopic methods, including NMR, HRESIMS analyses, X-ray single crystal diffraction, as well as through experimental ECD analyses. Biological assays revealed that compounds 1 and 2 exhibited inhibitory activity against A549 cells, with IC50 values of 30.11 ± 3.29 and 34.32 ± 2.66 µM, respectively.

Global research landscape on the contribution of de novo mutations to human genetic diseases over the past 20 years: bibliometric analysis.

As the contribution of de novo mutations (DNMs) to human genetic diseases has been gradually uncovered, analyzing the global research landscape over the past 20 years is essential. Because of the large and rapidly increasing number of publications in this field, understanding the current landscape of the contribution of DNMs in the human genome to genetic diseases remains a challenge. Bibliometric analysis provides an approach for visualizing these studies using information in published records in a specific field. This study aimed to illustrate the current global research status and explore trends in the field of DNMs underlying genetic diseases. Bibliometric analyses were performed using the Bibliometrix Package based on the R language version 4.1.3 and CiteSpace version 6.1.R2 software for publications from 2000 to 2021 indexed under the Web of Science Core Collection (WoSCC) about DNMs underlying genetic diseases on 17 September 2022. We identified 3435 records, which were published in 731 journals by 26,538 authors from 6052 institutes in 66 countries. There was an upward trend in the number of publications since 2013. The USA, China, and Germany contributed the majority of the records included. The University of Washington, Columbia University, and Baylor College of Medicine were the top-producing institutions. Evan E Eichler of the University of Washington, Stephan J Sanders of the Yale University School of Medicine, and Ingrid E Scheffer of the University of Melbourne were the most high-ranked authors. Keyword co-occurrence analysis suggested that DNMs in neurodevelopmental disorders and intellectual disabilities were research hotspots and trends. In conclusion, our data show that DNMs have a significant effect on human genetic diseases, with a noticeable increase in annual publications over the last 5 years. Furthermore, potential hotspots are shifting toward understanding the causative role and clinical interpretation of newly identified or low-frequency DNMs observed in patients.

Polyethylene glycol-polyvinylidene fluoride/TiO2 nanocomposite polymer coatings with efficient antifouling strategies: Hydrophilized defensive surface and stable capacitive deionization.

Capacitive deionization (CDI) is flourishing as an energy-efficient and cost-effective water desalination method. However, challenges such as electrode degradation and fouling have hindered the practical deployment of CDI technology. To address these challenges, the key point of our strategy is applying a hydrophilic coating composed of polyethylene glycol (PEG)-functionalized nano-TiO2/polyvinylidene fluoride (PVDF) to the electrode interface (labeled as APPT electrode). The PEG/PVDF/TiO2 layer not only mitigates the co-ion depletion, but also imparts the activated carbon (AC) electrode hydrophilicity. As anticipated, the APPT electrode possessed an enhanced desalination capacity of 83.54 µmol g-1 and a low energy consumption of 17.99 Wh m-3 in 10 mM sodium chloride solution compared with the bare AC electrode. Notably, the APPT maintained about 93.19 % of its desalination capacity after 50 consecutive adsorption-desorption cycles in the presence of bovine serum albumin (BSA). During the trial, moreover, no obvious overall performance decline was noted in concentration reduction (Δc), water recovery (WR) and productivity (P) over 50 cycles. This strategy realizes energy-efficient, antifouling and stable brackish water desalination and has great promise for practical applications.

Comprehensively evaluating the relationships between marital status and other family factors with cardiovascular disease and long-term overall mortality in the elderly: a study of 48 510 Chinese individuals.

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

Clinical and genetic architecture of a large cohort with auditory neuropathy.

Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.

Design and synthesis of nucleotidyl lipids and their application in the targeted delivery of siG12D for pancreatic cancer therapy.

Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.

Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

[Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children].

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.

Anti-Toxoplasma gondii effect of tylosin in vitro and in vivo.

BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.

Easily scale 3D conductive gradient fiber membrane for contaminants removal and fouling mitigation under electrochemical assistance.

An electrochemical membrane filtration system provides an innovative approach to enhance contaminant removal and mitigate membrane fouling. There is an urgent need to develop portable, versatile, and efficient electrochemical membranes for affordable wastewater treatment. Here, a 3D conductive gradient fiber membrane (CC/PVDF) with a gradient porous structure was prepared using a two-step phase inversion method. Methyl orange (MO) was utilized as model organic substance to investigate the electrochemical performance of the CC/PVDF membrane. At applied potentials of +2 V, +3 V, -2 V and -3 V, the removal efficiency of MO was 5.1, 5.3, 4.8, and 5.1 times higher than at 0 V. A dramatic flux loss of 35.02% occurred on the membrane without electrochemistry, interestingly, whereas the flux losses were only 23.59%-10.24% in the applied potential after 30 min of filtration, which were approximately 1.18, 1.28, 1.29 and 1.38 times as high as that without electrochemistry, respectively. The enhanced removal and anti-fouling performances of the membranes were attributed to the functions of electrochemical degradation, electrostatic repulsion, and electrically enhanced wettability. Electrochemical generation of Hydrogen peroxide, along with HO• radicals, was detected and direct electron transfer and HO• were proved to be the dominant oxidants responsible for MO degradation. The intermediate oxidation products were identified by mass spectrometry, and an electrochemical degradation pathway of MO was proposed based on bond-breaking oxidation, ring-opening reactions, and complete oxidation. All the findings emphasize that the ECMF system possesses superior efficiency and creative potential for water purification applications.

[A case of sudden hearing loss combined with familial hyperlipidemia].

Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.

Zinc porphyrin/MXene hybrids with phosphate-induced stimuli-responsive behavior for dual-mode fluorescent/electrochemiluminescent ratiometric biosensing.

Highly sensitive ratiometric biosensors have attracted much attention in biomarker detection, but most rely on single-mode signals, which can affect accuracy. The development of new principles and methods for dual-mode ratiometric sensing can enhance detection accuracy. Herein, the zinc(II) meso-tetra(4-carboxyphenyl) porphyrin/MXene (ZnTCPP/Ti3C2Tx) hybrids with phosphate-induced stimuli-responsive behavior are used to develop a novel dual-mode fluorescent/electrochemiluminescent (FL/ECL) ratiometric biosensor. The composites exhibit FL quenching and enhanced ECL behavior involving dissolved O2. The FL quenching of ZnTCPP/Ti3C2Tx is caused by energy transfer (EnT) and photo-induced electron transfer (PET) from ZnTCPP to Ti3C2Tx. While the introduction of MXene compensates for the inadequate conductivity of ZnTCPP, facilitating electron transfer, which further makes the surface ZnTCPP more capable of activating O2 to produce singlet oxygen (1O2), thereby generating enhanced cathodic ECL. Furthermore, phosphate ions (PO43-) can interact with the Ti sites of ZnTCPP/Ti3C2Tx, leading to competition for coordination with ZnTCPP, which in turn detaches ZnTCPP, resulting in enhanced FL and reduced ECL. On the basis of the phosphate-induced stimuli-responsive behavior, the dual-mode FL/ECL ratiometric biosensing of alkaline phosphatase (ALP) is achieved through ALP-catalyzed production of PO43- cascade effect with ZnTCPP/Ti3C2Tx. The linear detection range for ALP is 0.1-50 mU/mL, with a detection limit as low as 0.0083 mU/mL. This proposed ZnTCPP/Ti3C2Tx composites with stimuli-responsive behavior is expected to provide new ideas for the development of high-sensitivity dual-mode ratiometric biosensors with promising applications in the precise detection of important biomarkers.

NADH improves AIF dimerization and inhibits apoptosis in iPSCs-derived neurons from patients with auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment involving disruptions to inner hair cells (IHCs), ribbon synapses, spiral ganglion neurons (SGNs), and/or the auditory nerve itself. The outcomes of cochlear implants (CI) for ANSD are variable and dependent on the location of lesion sites. Discovering a potential therapeutic agent for ANSD remains an urgent requirement. Here, 293T stable transfection cell lines and patient induced pluripotent stem cells (iPSCs)-derived auditory neurons carrying the apoptosis inducing factor (AIF) p.R422Q variant were used to pursue a therapeutic regent for ANSD. Nicotinamide adenine dinucleotide (NADH) is a main electron donor in the electron transport chain (ETC). In 293T stable transfection cells with the p.R422Q variant, NADH treatment improved AIF dimerization, rescued mitochondrial dysfunctions, and decreased cell apoptosis. The effects of NADH were further confirmed in patient iPSCs-derived neurons. The relative level of AIF dimers was increased to 150.7 % (P = 0.026) from 59.2 % in patient-neurons upon NADH treatment. Such increased AIF dimerization promoted the mitochondrial import of coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4), which further restored mitochondrial functions. Similarly, the content of mitochondrial calcium (mCa2+) was downregulated from 136.7 % to 102.3 % (P = 0.0024) in patient-neurons upon NADH treatment. Such decreased mCa2+ levels inhibited calpain activity, ultimately reducing the percentage of apoptotic cells from 30.5 % to 21.1 % (P = 0.021). We also compared the therapeutic effects of gene correction and NADH treatment on hereditary ANSD. NADH treatment had comparable restorative effects on functions of ANSD patient-specific cells to that of gene correction. Our findings offer evidence of the molecular mechanisms of ANSD and introduce NADH as a potential therapeutic agent for ANSD therapy.

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients.

To retrospectively analyze the efficacy and safety of venetoclax combined with azacitidine (VEN + AZA) in the treatment of elderly patients with acute myeloid leukemia. The clinical data for 57 AML patients treated with the VEN + AZA regimen from December 2019 to November 2022 in the Department of Hematology, General Hospital of Tianjin Medical University, were collected. Of the 57 patients included in this study, the mean age of onset was 69.89 (±8.88) years. The median follow-up time was 8.57 months, and the median OS time was 11.50 months. The ORR, CR rate, and MRD (<0.1%) negativity rate were 87.5%, 68.8%, and 58.3%, respectively. The median OS was longer in patients who achieved CR/CRi and who were MRD-negative than in those who did not. MRD negativity was less likely to be achieved in patients aged ≥75 years and with ECOG scores of ≥3. Compared to traditional intensive chemotherapy, MRD negative was achieved more quickly with VEN + AZA regimens in patients with newly diagnosed AML. Advanced age and ECOG score were risk factors for negative MRD. The dominant adverse reactions were hematological adverse events. VEN + AZA regimens in elderly unfit patients with previously untreated newly diagnosed AML have sufficient efficacy and safety.

Atomic Insights into the Relationship between Molecular Structure and Dispersion Performance of Phenyl Polymer on Graphene Oxide.

The adsorption of organic polymers onto the surface of graphene oxide is known to improve its dispersibility in cement-based materials. However, the mechanism of this improvement at the atomic level is not yet fully understood. In this study, we employ a combination of DFT static calculation and umbrella sampling to explore the reactivity of polymers and investigate the effects of varying amounts of phenyl groups on their adsorption capacity on the surface of graphene oxide. Quantitative analysis is utilized to study the structural reconstruction and charge transfer caused by polymers from multiple perspectives. The interfacial reaction between the polymer and graphene oxide surface is further clarified, indicating that the adsorption process is promoted by hydrogen bond interactions and π-π stacking effects. This study sheds light on the adsorption mechanism of polymer-graphene oxide systems and has important implications for the design of more effective graphene oxide dispersants at the atomic level.

Subacute infective endocarditis due to Lodderomyces elongisporus: a case report and review of the literature.

Lodderomyces elongisporus, a rare emerging pathogen, can cause fungemia often related to immunosuppression or intravenous devices. Herein, we report the case of a 58-year-old woman with subacute infective endocarditis due to Lodderomyces elongisporus identified by blood fungal culture and whole-genome sequencing, who was treated with antifungals, mitral replacement and endocardial vegetation removal surgery.

Introduction of Nanoscale Si3N4 to Improve the Dielectric Thermal Stability of a Si3N4/P(VDF-HFP) Composite Film.

In order to improve the dielectric thermal stability of polyvinylidene fluoride (PVDF)-based film, nano silicon nitride (Si3N4) was introduced, and hence the energy storage performance was improved. The introduction of nano Si3N4 fillers will induce a phase transition of P(VDF-HFP) from polar ß to nonpolar α, which leads to the improved energy storage property. As such, the discharging energy density of Si3N4/P(VDF-HFP) composite films increased with the amount of doped Si3N4. After incorporating 10wt% Si3N4 in Si3N4/P(VDF-HFP) films, the discharging density increased to 1.2 J/cm3 under a relatively low electric field of 100 MV/m. Compared with a pure P(VDF-HFP) film, both the discharging energy density and thermal dielectric relaxor temperature of Si3N4/P(VDF-HFP) increased. The working temperature increased from 80 °C to 120 °C, which is significant for ensuring its adaptability in high-temperature energy storage areas. Thus, this result indicates that Si3N4 is a key filler that can improve the thermal stability of PVDF-based energy storage polymer films and may provide a reference for high-temperature capacitor materials.

Comparative Analysis of Doppler Ultrasound Combined with Serum PAPP-A in Diagnosis and Pathology of Placenta Accreta.

Objective: To explore the value of Doppler ultrasound combined with the serum pregnancy associated plasma protein A (PAPP-A) in the diagnosis and pathology of placenta accreta. Methods: For the method of retrospective study, the data of 250 pregnant women with cesarean section delivery in our hospital from February 2020 to February 2021 were analyzed, and the prenatal examination of pregnant women was performed by Doppler ultrasound and the serum PAPP-A level was determined by serology detection. They were divided into the placenta accreta group (n=152) and non-placenta accreta group (n=98) according to the pathological results after delivery to compare the imaging data and the serum PAPP-A levels in the two groups. The receiver operating characteristic curve (ROC curve) was drawn with the pathological results as the gold standard. Results: The serum PAPP-A level in the placenta accreta group was overtly lower than that in the non-placenta accreta group (698.65±9.65 vs 910.57±9.65, t = 169.52, P < .001). In the placenta accreta group, there were 126 cases (82.89%) with irregular gyrate liquid dark area formed in the placenta of pregnant women, 78 cases (51.32%) with partial or all disappearance of posterior placenta space, 22 cases (14.74%) with the attenuation or disappearance of myometrium in the placental attachment, and 20 cases (13.16%) with abnormal placental thickening. The sensitivity, specificity, positive predictive value and negative predictive value of the Doppler ultrasound combined with serum diagnosis of PAPP-A were 86.84%, 79.59%, 86.84% and 79.59%, respectively. ROC analysis showed that the area under the curve (AUC) of Doppler ultrasound combined with serum diagnosis of PAPP-A was 0.835, with the asymptotic Sig.b < .001 and an asymptotic 95% confidence interval (CI) of 0.780-0.891. Conclusion: Doppler ultrasound could analyze the pathological manifestations of placenta accreta, and serum PAPP-A could be combined to improve the detection rate of placenta accreta, with a certain clinical application value.

Natural History of KCNQ4 p.G285S Related Hearing Loss, Construction of iPSC and Mouse Model.

OBJECTIVE: KCNQ4 is one of the most common disease-causing genes involved in autosomal dominant non-syndromic hearing loss. We previously found that patients with KCNQ4 p.G285S exhibited a much more rapid deterioration in hearing loss than those with other KCNQ4 variants. To determine the rate of hearing loss and assess the disease for further analysis, we performed a long-term follow-up of these patients and generated patient-derived induced pluripotent stem cells (iPSCs), and a mouse model. METHODS: Patients with KCNQ4 p.G285S from a five-generation family with hearing loss were followed up from 2005 to 2022. iPSCs were generated by stimulating peripheral blood mononuclear cells from the proband, and their pluripotency was determined. The Kcnq4 p.G286S mouse model was generated using CRISPR/Cas9, and its genotype and phenotype were identified. RESULTS: (1) The annual rates of hearing loss at the frequencies of speech were 0.96 dB for the proband and 0.87 dB for his father during the follow-up period, which were faster than patients with other KCNQ4 variants. (2) The patient-derived iPSC line carrying KCNQ4 p.G285S, possessed the capacity of differentiation and pluripotency capacities. (3) Mutant mice with Kcnq4 p.G286S exhibited hearing loss and outer hair cell loss at 1 month of age. CONCLUSION: Patients with KCNQ4 p.G285S variant exhibited significantly accelerated progression of hearing loss compared to those with other reported variants. Awareness of the natural history of hearing loss associated with KCNQ4 p.G285S is beneficial for genetic counseling and prognosis. The generation of the iPSCs and mouse model can provide a valuable foundation for further in-depth analyses. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.