Our experience diagnosing 225 patients with cervical glandular lesions: current technologies, lessons learned, and areas for improvement.

OBJECTIVE: To explore the relative sensitivity of different methods for detecting cervical glandular lesions. METHODS: A total of 225 patients with cervical glandular lesions diagnosed from January 2018 to February 2023 were retrieved from the pathology database of Guangdong Maternal and Child Health Hospital, and their clinicopathological features were reviewed. RESULTS: Four human papillomavirus (HPV) genotypes: HPV18, 16, 45, and 52, dominated all glandular lesions, and accounting for 74.10% of HPV-positive tumors. Furthermore, 36.89% of abnormal squamous cells were diagnosed as abnormal based on cytological examinations leading to the detection of cervical glandular lesions; only 16.89% were diagnosed based on the initial detection of abnormal glandular cytology. The most common abnormal cervical screening result was ASC-US on cytology (14.22%), followed by HSIL (11.56%). Only few number of patients were diagnosed with or suspected of having cervical adenopathy via a Pap test (18.22%). Nearly one-third of cervical glandular lesions cases were not detected on the Pap test; but were diagnosed upon cervical biopsy or based on the histological examination of ECC, LEEP, or CKC specimens. The LEEP or CKC biopsy specimens had negative margins in 49 cases (40.83%), while the margins were positive in the other 71 cases (59.17%). Five cases (10.20%) with negative margins still had residual lesions following total hysterectomy, and 19 (26.76%) with positive margins had no residual lesions after total hysterectomy. CONCLUSION: The ability to detect cervical glandular lesions varies for routine HPV genotyping, Pap test, or biopsy/ECC, with different sensitivities and advantages and disadvantages for each method.

Prognostic factor analysis and clinical significance of HER­2­positive breast cancers with negative lymph nodes and a tumor diameter ≤1 cm.

The 2021 National Comprehensive Cancer Network guidelines recommend that adjuvant chemotherapy combined with trastuzumab be considered for human epidermal growth factor receptor 2 (HER-2)-positive breast cancer patients with small tumors (tumor diameter ≤1 cm) and negative lymph nodes. Additionally, the prognostic factors and clinical significance of HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm remain unclear. In the present study, the clinical data and prognostic factors of 87 patients with HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm admitted to Guangdong Women and Children Hospital from January 2013 to December 2019 were retrospectively analyzed. The median follow-up time was 70 months, the disease-free survival (DFS) of all patients was 94.3% and the overall survival (OS) was 100%. Univariate analysis of prognosis demonstrated that patients aged ≤40 years had significantly lower DFS than those aged >40 (80.8 vs. 100.0%, P<0.001). DFS was significantly improved in patients who were hormone-receptor-positive and patients who received endocrine therapy compared with patients who were estrogen receptor negative and patients who did not receive endocrine therapy (100.0 vs. 89.6%, P=0.039; 100.0 vs. 90.0%, P=0.049). Prognostic univariate analysis demonstrated that patient age, hormone receptor status and use of endocrine therapy were significantly related to the DFS (P<0.05), while none of these were independent factors related to the DFS in the prognostic multivariate analysis (P=0.240, P=0.976 and P=0.925). The proportion of patients with a tumor diameter 0.5-1 cm receiving adjuvant anti-HER-2 treatment was significantly greater compared with patients with tumors with a diameter ≤0.5 cm (46.4 vs. 18.6%, P<0.05). There was no significance difference in the DFS of patients treated with adjuvant chemotherapy with or without anti-HER-2 therapy with tumor diameters ≤0.5 cm (P>0.05), but there was a significant difference in the DFS of patients with a tumor diameter 0.5-1 cm (P<0.05). These results suggested that adjuvant chemotherapy, with or without anti-HER-2 therapy, may affect the prognosis of HER-2-positive breast cancer patients with negative lymph nodes and a tumor diameter of 0.5-1 cm. Therefore, it could be recommended that such patients receive adjuvant chemotherapy and anti-HER-2 therapy in the future.

Infantile fibrosarcoma of the perineum with dorsal metastasis in a neonate: a case report original.

BACKGROUND: Infantile fibrosarcoma is a rare pediatric soft tissue tumor and usually appears in children before one year of age. Distal extremities constitute the most frequently affected locations, and other tissues such as the trunk, head and neck, gut, sacrococcygeal region, and viscera are uncommon sites. CASE PRESENTATION: We describe a rare case of infantile fibrosarcoma arising from the perineum. First, a cystic mass was detected using prenatal ultrasonography, and then an echo was changed in serial ultrasound examinations. A solid cystic lesion was found at term; a hypoechoic lesion occurred in the back. The tumor became so large that massive bleeding occurred, which then underwent surgical resection. Pathological examination confirmed infantile fibrosarcoma. CONCLUSION: Our report demonstrates not all ultrasonographic findings in cases of infantile fibrosarcoma exhibit a solid mass during the initial examination - an early-stage lesion may reveal a cystic echo. Infantile fibrosarcoma has a good prognosis and surgery constitute the main treatment, with adjuvant chemotherapy being received if necessary.

Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.

Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44-56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.

Phosphorus-Doped directly interconnected networks of amorphous Metal-Organic framework nanowires for efficient methanol oxidation.

Developing high-performance and low-cost electrocatalysts toward methanol oxidation reaction (MOR) is essential for fuel cell applications. Herein, we report a defect engineering strategy integrating amorphization and phosphorization to construct directly interconnected networks of amorphous NiCo-based metal-organic framework nanowires (a-NiCo-MOFNWs) with phosphorus (P) doping. The resulting P-doped a-NiCo-MOFNWs (a-NiCo-MOFNWs-P) network displays superior MOR efficiency and long-term durability over 1000 cyclic voltammetry (CV) measurements. The special structure of directly interconnected networks and the synergistic effect between the amorphous MOFs and dispersed phosphorus species give rise to abundant exposed active sites, accelerated electron transport, and increased porosity for mass transfer, thus boosting the reaction kinetics of MOR. This work provides additional insights into the network assembly and structural evolution of one-dimensional (1D) MOFs, and also opens up new avenues for the design of highly reactive and robust non-precious metal-based electrocatalysts.

Malignant Peripheral Nerve Sheath Tumor in the Nasal Cavity of a Neonate: A Case Report.

Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that can develop on the lining of nerves and within the network of nerve fibers in different organs, and it is commonly found in the head and neck, limbs, and trunk. These tumors can occur in patients of any age. They most commonly occur in adults aged 20 to 50 years; however, fewer cases of this tumor in children have been reported. To date, no neonatal case of MPNST in the nasal cavity has been reported. Here, we report the case of a 4-day-old female newborn who presented with a nasal mass that re-enlarged after surgery and was diagnosed as MPNST of the nasal cavity on the basis of pathological results. This is the first report of MPNST in the nasal cavity of a neonate. Differential diagnosis and treatment of nasal masses have been proposed in the related literature.

Engineering a precise adenine base editor with minimal bystander editing.

Adenine base editors (ABEs) catalyze A-to-G transitions showing broad applications, but their bystander mutations and off-target editing effects raise safety concerns. Through structure-guided engineering, we found ABE8e with an N108Q mutation reduced both adenine and cytosine bystander editing, and introduction of an additional L145T mutation (ABE9), further refined the editing window to 1-2 nucleotides with eliminated cytosine editing. Importantly, ABE9 induced very minimal RNA and undetectable Cas9-independent DNA off-target effects, which mainly installed desired single A-to-G conversion in mouse and rat embryos to efficiently generate disease models. Moreover, ABE9 accurately edited the A5 position of the protospacer sequence in pathogenic homopolymeric adenosine sites (up to 342.5-fold precision over ABE8e) and was further confirmed through a library of guide RNA-target sequence pairs. Owing to the minimized editing window, ABE9 could further broaden the targeting scope for precise correction of pathogenic single-nucleotide variants when fused to Cas9 variants with expanded protospacer adjacent motif compatibility. bpNLS, bipartite nuclear localization signals.

A novel MOFs-induced strategy for preparing anatase-free hierarchical TS-1 zeolite:synthesis routes, growth mechanisms and enhanced catalytic performance.

Titanosilicate-1 zeolites (TS-1) as one of the most commonly used catalysts for alkene epoxidation, construction of hierarchical pores as well as elimination of anatase to promote mass transportation and avoid invalid decomposition of hydrogen peroxide are always desirable yet challenging goals. Here, a novel and unique Ti-based metal organic frameworks (MOFs)-induced synthetic strategy for fabricating anatase-free hierarchical TS-1 was first proposed. All the components of MOFs perform different functions: the uniformly distributed Ti nodes replace conventional tetrabutyl titanate (TBOT) to serve as sole Ti source for constructing zeolite crystal; the separated ligands can be embedded in the zeolite framework and act as template to in situ build hierarchical pore structure; the coordination interaction between Ti nodes and ligands can efficiently avoid the anatase generation by balancing the forming rates of Ti-OH and Si-OH. This synthetic strategy is of general applicability, and two different synthetic routes including traditional hydrothermal process and steam assisted crystallization (SAC) procedure are successfully adopted. The obtained hydrothermal TS-1 and SAC anatase-free samples all possess abundant intercrystalline mesopores of 20-50 nm and even macropores between 50 and 150 nm, improving the conversion over 25 % for 1­hexene epoxidation than TS-1 sample prepared by conventional route. The influences of the amount of Ti MOFs precursor and the crystallization process are studied in detail, and possible synthesis mechanisms are proposed. This MOFs-induced strategy might open up an avenue for the rational design of ideal and hierarchical zeolite to boost the catalytic efficiency.

Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing.

Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion. The introduction of an N46L variant in TadA-8e eliminates its adenine deaminase activity and results in a TadA-8e-derived C-to-G base editor (Td-CGBE) capable of highly efficient and precise C·G-to-G·C editing. Through fusion with uracil glycosylase inhibitors and further introduction of additional variants, a series of Td-CBEs was obtained either with a high activity similar to that of BE4max or with higher precision compared to other reported accurate CBEs. Td-CGBE/Td-CBEs show very low indel effects and a background level of Cas9-dependent or Cas9-independent DNA/RNA off-target editing. Moreover, Td-CGBE/Td-CBEs are more efficient in generating accurate edits in homopolymeric cytosine sites in cells or mouse embryos, suggesting their accuracy and safety for gene therapy and other applications.

Electrostatic potential-derived charge: a universal OER performance descriptor for MOFs.

Metal-organic frameworks (MOFs) provide opportunities for the design of high-efficiency catalysts attributed to their high compositional and structural tunability. Meanwhile, the huge number of MOFs poses a great challenge to experimental-intensive development of high-performance functional applications. By taking the computationally feasible and structurally representative trigonal prismatic secondary building units (SBUs) of MOFs as the entry point, we introduce a descriptor-based approach for designing high-performance MOFs for the oxygen evolution reaction (OER). The electrostatic potential-derived charge (ESPC) is identified as a robust and universal OER performance descriptor of MOFs, showing a distinct linear relationship with the onset potentials of OER elemental steps. Importantly, we establish an ESPC-based physical pattern of active site-intermediate binding strength, which interprets the rationality of ESPC as an OER performance descriptor. We further reveal that the SBUs with Ni/Cu as active site atoms while Mn/Fe/Co/Ni as spectator atoms have excellent OER activity through the variation pattern of ESPC along with metal composition. The universal correlation between ESPC and OER activity provides a rational rule for designing high-performance MOF-based OER electrocatalysts and can be easily extended to design functional MOFs for a rich variety of catalytic applications.

Analysis of the Influencing Factors of Sentinel Lymph Node Metastasis in Breast Cancer.

Objective: To analyze and discuss the influencing factors of sentinel lymph node metastasis in breast cancer. Methods: A total of 469 breast cancer patients admitted in the Department of Pathology of Guangdong Women and Children Hospital from October 2016 to December 2021 were retrospectively analyzed. The general information, immunohistochemical expression, tumor molecular subtype, tumor size, histological grade, pathological type, and tumor location were collected and the relationship with sentinel lymph node metastasis was analyzed. Results: For patients with different age, Ki-67 and Human epidermal growth factor receptor-2 (HER-2) immunohistochemical expression level (invasive cancer), molecular subtype (invasive cancer), tumor size, histological grade (invasive cancer) and pathological type. The results of multivariate logistic regression analysis showed that the age was less than or equal to 40 years; the molecular subtype was Luminal B and HER-2 overexpression (invasive cancer); tumor was larger; the histological grade (invasive cancer) was higher; the pathological type was invasive carcinoma, there were independent risk factors for sentinel lymph node metastasis in breast cancer. The sentinel lymph node metastasis rates of invasive lobular carcinoma, invasive micropapillary carcinoma, and metaplastic carcinoma (all met the criteria for squamous cell carcinoma and histological grade III) were higher than 50% in special invasive carcinomas. Conclusion: Age, expression level of Ki 67 and HER-2, molecular typing, tumor volume and histological grade are all high-risk factors related to sentinel lymph node metastasis of breast cancer. When one or more of the above factors are involved in an examination, pathologists should be more cautious in making a sentinel lymph node frozen diagnosis. By standardizing the sampling and increasing the number of frozen sections (slicing more frozen tissue layers), the section quality can be improved. This may be conducive to reducing the false negative rate and reducing the pain and risk of secondary surgery.

An efficient factor for fast screening of high-performance two-dimensional metal-organic frameworks towards catalyzing the oxygen evolution reaction.

Two-dimensional (2D) metal-organic frameworks (MOFs) are promising materials for catalyzing the oxygen evolution reaction (OER) due to their abundant exposed active sites and high specific surface area. However, how to rapidly screen out highly-active 2D MOFs from numerous candidates is still a great challenge. Herein, based on the high-throughput density functional theory (DFT) calculations for 20 kinds of different transition metal-based MOFs, we propose a factor for fast screening of 2D MOFs for the OER under alkaline conditions (pH = 14.0), that is, when the Gibbs free energy change of the O-O bond formation (defined as ΔG 1) is located at ∼1.15 eV, the peak OER performance would be achieved. Based on the high-throughput calculation results, the prediction factor can be further simplified by replacing the Gibbs free energy with the sum of the associated single point energy (SPE) and a binding energy-dependent term. Guided by this factor, we successfully predicted and then obtained the high-performance Ni-based 2D MOFs. This factor would be a practical approach for fast screening of 2D MOF candidates for the OER, and also provide a meaningful reference for the study of other materials.

Base-free catalytic aerobic oxidation of mercaptans over MOF-derived Co/CN catalyst with controllable composition and structure.

The oxidation of mercaptans under mild and base-free conditions is of vital importance in terms of economy and environment for petroleum processing industry. Here, we developed a series of MOF-derived cobalt-based nitrogen-doped (N-doped) carbon (Co/CN-x) catalysts for the base-free catalytic oxidation of mercaptans. The optimal Co/CN-900 showed excellent catalytic activity for the oxidation of mercaptans under base-free conditions, yielding complete conversion of various mercaptans and > 99.0% selectivity of disulfides. The high performance can be contributed to the advantages of hierarchical pore structure for the diffusion and migration of substrates, self-carrying alkalinity for the formation of mercaptide anion, abundant active Co sites for catalytic oxidation of mercaptans as well as the synergistic effects between the Co nanoparticles (NPs) and N-doped carbon supports. Furthermore, a possible mechanism for base-free catalytic oxidation of mercaptans over Co/CN-x catalysts is proposed based on a set of control experiments and density functional theory (DFT) calculations.

Metalloporphyrin-Decorated Titanium Dioxide Nanosheets for Efficient Photocatalytic Carbon Dioxide Reduction.

In photocatalysis, the most efficient way to separate photogenerated electron-hole pairs has been extensively studied. However, the methods to increase the quantities of free electrons are neglected. Herein, we used a self-assembly method to fabricate MTCPP/TiO2 composite materials with a series of metalloporphyrins (MTCPPs, M = Fe, Co, Zn) as sensitizers to modify TiO2 nanosheets. First, abundant carboxyl and hydroxyl on porphyrin were adsorbed by metal ions. Then, the remaining carboxyl and hydroxyl on porphyrin were anchored on the surface of TiO2 nanosheets. Finally, MTCPP/TiO2 was obtained by a layer-by-layer self-assembly process. MTCPP broadens the light response of TiO2 from ultraviolet light to visible light and enhances the CO2 adsorption ability. Moreover, metal ions coordinating with porphyrin regulate the electron density of the porphyrin ring and provide a stronger π feedback bond, which promote charge separation. Consequently, by optimizing the type of metal ion, the yield of ZnTCPP/TiO2 composites reached 109.33 µmol/(g h) of CO and 9.94 µmol/(g h) of CH4, which was more than 50 times that of pure TiO2. This study proposes a possible visible-light-induced CO2 reduction mechanism of metal-ion-based photocatalysis, which provides great insights into optimizing the designation of efficient photocatalysis.

Molecular alterations differentiate microinvasive carcinoma from ductal carcinoma in situ and invasive breast carcinoma: retrospective analysis of a large single-center series.

Microinvasive carcinoma (MIC) of the breast is a rare lesion. The clinicopathologic features and biologic behavior of MIC are unclear. Whether MIC is a distinct entity or an interim stage in the progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) remains to be determined. A retrospective review of clinicopathologic features and analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in patients with MIC (90 cases), DCIS (268 cases) and IBC (1504 cases) was performed. Most MICs (93.3%) exhibited an intermediate to high nuclear grade, and this proportion was larger than that of DCIS (62.7%, P < 0.001) or IBC (85.4%, P = 0.036). The incidence of sentinel lymph node metastasis in MIC (12.5%) was higher than that of DCIS (1.6%, P < 0.001), but much lower than that of IBC (39.7%, P < 0.001). MICs had higher expression of HER-2 and lower expression of ER and PR compared to DCIS and IBC; and MIC was more likely to present with a HER-2+ subtype. Furthermore, DCIS exhibited greater HER-2 overexpression or gene amplification (P < 0.001) levels and lower proliferation index of Ki-67 (P < 0.001) compared to IBC. Our results suggest that the clinicopathologic and molecular phenotype of MIC are different from DCIS and IBC. Thus, MIC may be a distinct entity rather than an interim stage in the progression from DCIS to IBC. The prognosis of MIC and the biologic behavior of this uncommon subset need to be further explored.

Hybrid AI-assistive diagnostic model permits rapid TBS classification of cervical liquid-based thin-layer cell smears.

Technical advancements significantly improve earlier diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various factors. We develop an artificial intelligence assistive diagnostic solution, AIATBS, to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria. We train AIATBS with >81,000 retrospective samples. It integrates YOLOv3 for target detection, Xception and Patch-based models to boost target classification, and U-net for nucleus segmentation. We integrate XGBoost and a logical decision tree with these models to optimize the parameters given by the learning process, and we develop a complete cervical liquid-based cytology smear TBS diagnostic system which also includes a quality control solution. We validate the optimized system with >34,000 multicenter prospective samples and achieve better sensitivity compared to senior cytologists, yet retain high specificity while achieving a speed of <180s/slide. Our system is adaptive to sample preparation using different standards, staining protocols and scanners.

Carbon-Based Composite Phase Change Materials for Thermal Energy Storage, Transfer, and Conversion.

Phase change materials (PCMs) can alleviate concerns over energy to some extent by reversibly storing a tremendous amount of renewable and sustainable thermal energy. However, the low thermal conductivity, low electrical conductivity, and weak photoabsorption of pure PCMs hinder their wider applicability and development. To overcome these deficiencies and improve the utilization efficiency of thermal energy, versatile carbon materials have been increasingly considered as supporting materials to construct shape-stabilized composite PCMs. Despite some carbon-based composite PCMs reviews regarding thermal conductivity enhancement, a comprehensive review of carbon-based composite PCMs does not exist. Herein, a systematic overview of recent carbon-based composite PCMs for thermal storage, transfer, conversion (solar-to-thermal, electro-to-thermal and magnetic-to-thermal), and advanced multifunctional applications, including novel metal organic framework (MOF)-derived carbon materials are provided. The current challenges and future opportunities are also highlighted. The authors hope this review can provide in-depth insights and serve as a useful guide for the targeted design of high-performance carbon-based composite PCMs.

Toward Tailoring Chemistry of Silica-Based Phase Change Materials for Thermal Energy Storage.

Efficient thermal energy harvesting using phase change materials (PCMs) has great potential for thermal energy storage and thermal management applications. Benefiting from these merits of pore structure diversity, convenient controllability, and excellent thermophysical stability, SiO2-based composite PCMs have comparatively shown more promising prospect. In this regard, the microstructure-thermal property correlation of SiO2-based composite PCMs is still unclear despite the significant achievements in structural design. To enrich the fundamental understanding on the correlations between the microstructure and the thermal properties, we systematically summarize the state-of-the-art advances in SiO2-based composite PCMs for tuning thermal energy storage from the perspective of tailoring chemistry strategies. In this review, the tailoring chemistry influences of surface functional groups, pore sizes, dopants, single shell, and hybrid shells on the thermal properties of SiO2-based composite PCMs are systematically summarized and discussed. This review aims to provide in-depth insights into the correlation between structural designs and thermal properties, thus showing better guides on the tailor-made construction of high-performance SiO2-based composite PCMs. Finally, the current challenges and future recommendations for the tailoring chemistry are also highlighted.