Nomogram models for predicting overall and cancer-specific survival in early-onset gastric cancer patients: a population-based cohort study.

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo.

Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this "breast-to-breast" metastasis that might promote breast cancer distant spread. One somatic mutation acquired was SIVA-D160N that displayed pro-metastatic phenotypes in vivo and in vitro. Over-expression of SIVA-D160N promoted migration and invasion of human MB-MDA-231 breast cancer cells in vitro, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing SIVA-D160N displayed enhanced distant spread on IVIS imaging. Over-expression of SIVA-D160N promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells in vitro. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of SIVA-D160N in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of SIVA-D160N in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

High capacities of carbon capture and photosynthesis of a novel organic carbon-fixing microalgae in municipal wastewater: From mutagenesis, screening, ability evaluation to mechanism analysis.

The development of wastewater treatment processes capable of reducing and fixing carbon is currently a hot topic in the wastewater treatment field. Microalgae possess a natural carbon-fixing advantage, and microalgae that can symbiotically coexist with indigenous bacteria in actual wastewater attract more significant attention. Ultraviolet (UV) mutagenesis and dissolved organic carbon (DOC) acclimation were applied to strengthen the carbon-fixing performance of microalgae in this study. The mechanisms associated with microalgal water purification ability, gene regulation at the molecular level and photosynthetic potential under different trophic modes resulting from carbon fixation and transformation were disclosed. The superior performance of Chlorella sp. MHQ2 was eventually screened out among a large number of mutants generated from 3 wild-type Chlorella strains. Results indicated that the dry cell weight of the optimal species Chlorella sp. HQ mutant MHQ2 was 1.91 times that of the wild strain in the pure algal system, more carbon from municipal wastewater (MW) were transferred to the microalgae and re-entered into the biological cycle through resource utilization. In addition, COD, NH3-N and TP removal efficiencies of MW by Chlorella sp. MHQ2 were found to increase to 95.8% (1.1-times), 96.4% (1.4-times), and 92.9% (1.2-times), respectively, under the extra DOC supply and the assistance of indigenous bacteria in the MW. In the transcriptome analysis of the logarithmic phase, the glycolytic pathway was inhibited, and the pentose phosphate pathway was mainly carried out for microalgal life activities, further promoting efficient energy utilization. Upon analysis of carbon capture capacity and photosynthetic potential in trophic mode, the addition of NaHCO3 increased the photosynthetic rate of Chlorella sp. MHQ2 in mixotrophy whereas it was attenuated in autotrophy. This study could provide a new perspective for the study of resource utilization and microalgae carbon- fixing mechanisms in the actual wastewater treatment process.

Mechanically strained osteocyte-derived exosomes contained miR-3110-5p and miR-3058-3p and promoted osteoblastic differentiation.

BACKGROUND: Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. RESULTS: A mechanical tensile strain of 2500 µÎµ at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). CONCLUSIONS: In osteocytes, a mechanical tensile strain of 2500 µÎµ at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

Enhancing the stability of a novel D-allulose 3-epimerase from Ruminococcus sp. CAG55 by interface interaction engineering and terminally attached a self-assembling peptide.

D-allulose, a highly desirable sugar substitute, is primarily produced using the D-allulose 3-epimerase (DAE). However, the availability of usable DAE enzymes is limited. In this study, we discovered and engineered a novel DAE Rum55, derived from a human gut bacterium Ruminococcus sp. CAG55. The activity of Rum55 was strictly dependent on the presence of Co2+, and it exhibited an equilibrium conversion rate of 30.6 % and a half-life of 4.5 h at 50 °C. To enhance its performance, we engineered the interface interaction of Rum55 to stabilize its tetramer structure, and the best variant E268R was then attached with a self-assembling peptide to form active enzyme aggregates as carrier-free immobilization. The half-life of the best variant E268R-EKL16 at 50 °C was dramatically increased 30-fold to 135.3 h, and it maintained 90 % of its activity after 13 consecutive reaction cycles. Additionally, we identified that metal ions played a key role in stabilizing the tetramer structure of Rum55, and the dependence on metal ions for E268R-EKL16 was significantly reduced. This study provides a useful route for improving the thermostability of DAEs, opening up new possibilities for the industrial production of D-allulose.

Clinical influencing factors of vital pulp therapy on pulpitis permanent teeth with 2 calcium silicate-based materials: A randomized clinical trial.

BACKGROUND: Compared with traditional root canal therapy (RCT), vital pulp therapy (VPT) is a personalized and minimally invasive method for the treatment of pulpitis caused by dental caries. However, there are still no clear guidelines for VPT because high-quality randomized clinical trials are scarce. This prospective cohort study evaluated the clinical efficacy of VPT with the light-curable calcium silicate-based material TheraCal LC (TH) and bioceramic material iRoot BP Plus (BP) in reversible and irreversible pulpitis permanent teeth with carious exposures. METHODS: 115 teeth with reversible or irreversible pulpitis caused by deep care were randomly divided into 2 groups. TheraCal LC and iRoot BP Plus were used for the pulp capping. Direct pulp capping (DPC), partial pulpotomy (PP) and full pulpotomy (FP) were performed based on observation of the exposed pulp. Postoperative discomforts were enquired and recorded via follow-up phone calls. Clinical and radiographic evaluations were performed 3, 6, and 12 months postoperatively. RESULTS: The overall clinical success rate in the first year was 90.4% (47/52) in both groups. The TH group required less operating time, showed lower levels of pain, and had shorter pain duration post-operative (P < .001). According to the binary logistic regression model, preoperative pain duration was significantly correlated with the prognosis of VPT (P = .011). CONCLUSION: VPT with TheraCal LC and iRoot BP Plus in pulpitis permanent carious teeth both achieved good clinical outcomes, and TheraCal LC can be easily operated for clinical use. Preoperative pain duration of the affected tooth might have a significant correlation with the prognosis of VPT.

Overexpressing Bcl-2 enhances murine chimeric antigen receptor T cell therapy against solid tumor.

Chimeric antigen receptor T (CART) cell therapy has demonstrated promising potential in the treatment of hematologic malignancies. However, its application to solid tumors is limited due to the restrictive nature of the tumor microenvironment, resulting in functional failure and poor persistence of CART cells. Overexpression of Bcl-2 in human CART cells (hCART) has been found to significantly enhance their anti-apoptotic effects both in vitro and in vivo. Nevertheless, the evaluation of hCART cells in preclinical studies has predominantly relied on immunodeficient mice xenograft tumor models, making it challenging to assess the impact of hCART cells on normal tissues and the immune system. We established a murine CART (mCART) that overexpresses Bcl-2 and targets the epidermal growth factor receptor variant III (EGFRvIII), named EGFRvIII·mCART-Bcl2. It demonstrated superior proliferation, cytotoxicity, and anti-apoptotic capabilities in vitro. In an immunocompetent mouse model of abdominal metastasis of colorectal cancer, EGFRvIII·mCART-Bcl2 exhibited improved survival of CART in the abdomen, increased tumor clearance, and significantly prolonged overall mouse survival. In summary, our study provides evidence that the introduction of Bcl-2 into mCART cells can enhance their therapeutic efficacy against solid tumors while ensuring safety.

Inflammatory bowel disease alters in vivo distribution of orally administrated nanoparticles: Revealing via SERS tag labeling technique.

Nanoparticles (NPs) could be uptake orally and exposed to digestive tract through various sources such as particulate pollutant, nanomedicine and food additive. Inflammatory bowel disease (IBD), as a global disease, induced disruption of the intestinal mucosal barrier and thus altered in vivo distribution of NPs as a possible consequence. However, related information was relatively scarce. Herein, in vivo distribution of typical silica (SiO2) and titania (TiO2) NPs was investigated in healthy and IBD models at cell and animal levels via a surface-enhanced Raman scattering (SERS) tag labeling technique. The labeled NPs were composed of gold SERS tag core and SiO2 (or TiO2) shell, demonstrating sensitive and characteristic SERS signals ideal to trace the NPs in vivo. Cell SERS mapping revealed that protein corona from IBD intestinal fluid decreased uptake of NPs by lipopolysaccharide-induced RAW264.7 cells compared with normal intestinal fluid protein corona. SERS signal detection combined with inductively coupled plasma mass spectrometry (ICP-MS) analysis of mouse tissues (heart, liver, spleen, lung and kidney) indicated that both NPs tended to accumulate in lung specifically after oral administration for IBD mouse (6 out of 20 mice for SiO2 and 4 out of 16 mice for TiO2 were detected in lung). Comparatively, no NP signals were detected in all tissues from healthy mice. These findings suggested that there might be a greater risk associated with the oral uptake of NPs in IBD patients due to altered in vivo distribution of NPs.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND: The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. METHOD: This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10 mmHg. RESULT: A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15 kPa and platelet count ≥ 150 × 109/L] OR SSM < 21 kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25 kPa OR SSM ≥ 50 kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. CONCLUSION: Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Detection of uridine diphosphate glucuronosyltransferase 1A1 for pancreatic cancer imaging and treatment via a "turn-on" fluorescent probe.

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is expressed ubiquitously in cancer cells and can metabolize exogenous substances. Studies show higher UGT1A1 levels in pancreatic cancer cells than normal cells. Therefore, we need a method to monitor the activity level of UGT1A1 in pancreatic cancer cells and in vivo. Here, we report a fluorescent probe, BCy-panc, for UGT1A1 imaging in cells and in vivo. Compared with other molecular probes, this probe is readily prepared, with high selectivity and sensitivity for the detection of UGT1A1. Our results show that BCy-panc rapidly detects UGT1A1 in pancreatic cancer. In addition, there is an urgent need for evidence to clarify the relationship between UGT1A1 and pancreatic cancer development. The present investigation found that the increase of UGT1A1 by chrysin was effective in inducing apoptosis in pancreatic cancer cells. These results indicate that the synergistic effect of chrysin and cisplatin at the cellular level is superior to that of cisplatin alone. The UGT1A1 level may be a biomarker for early diagnosis of cancer. Meanwhile, UGT1A1 plays a crucial role in pancreatic cancer, and the combination of chrysin and cisplatin may provide effective ideas for pancreatic cancer treatment.

Molecular imprinting-based triple-emission ratiometric fluorescence sensor with aggregation-induced emission effect for visual detection of doxycycline.

The development of high-performance sensors for doxycycline (DOX) detection is necessary because its residue accumulation will cause serious harm to human health and the environment. Here, a novel tri-emission ratiometric fluorescence sensor was proposed by using "post-mixing" strategy of different emissions fluorescence molecularly imprinted polymers with salicylamide as dummy template (DMIPs). BSA was chosen as assistant functional monomer, and also acted as sensitizers for the aggregation-induced emission (AIE) effect of DOX. The blue-emitting carbon dots and the red-emitting CdTe quantum dots were separately introduced into DMIPs as the response signals. Upon DOX recognition within 2 min, blue and red fluorescence of the tri-emission DMIPs sensor were quenched while green fluorescence of DOX was enhanced, resulting in a wide range of color variations observed over bluish violet-rosered-light pink-orange-yellow-green with a detection limit of 0.061 µM. The sensor possessed highly selective recognition and was successfully applied to detect DOX in complicated real samples. Moreover, with the fluorescent color collection and data processing, the smartphone-assisted visual detection of the sensors showed satisfied sensitivity with low detection limit. This work provides great potential applications for rapid and visual detection of antibiotics in complex substrates.

Weakened Mn-O bond in Mn-Ce catalysts through K doping induced oxygen activation for boosting benzene oxidation at low temperatures.

K-doped Mn-Ce solid solution catalysts were synthesized using a combination of coprecipitation and hydrothermal methods, demonstrating excellent performance in benzene oxidation. The catalyst K1Ce5Mn5 exhibited comparable activity to noble metal catalysts, achieving a 90 % benzene conversion at approximately 194 ℃. Durable tests under dry and moist conditions revealed that the catalyst could maintain its activity for 50 h at 218 ℃ and 236 ℃, respectively. Characterization results indicated that the catalyst's enhanced activity resulted from the weakened Mn-O bonding caused by the introduction of K+, facilitating the activation of oxygen and its involvement in the reaction. CeOx, the main crystalline phase of Mn-Ce solid solutions, provided abundant oxygen vacancies for capturing and activating oxygen molecules for the weakened Mn-O structures. This conclusion was further supported by partial density of state analysis from density functional theory computations, revealing that the introduction of K+ weakened the orbital hybridization of Mn3d and O2p. Finally, in situ diffuse reflectance infrared Fourier-transform spectroscopy (in situ DRIFTS) studies on Ce5Mn5 and K1Ce5Mn5 catalysts suggested that the introduction of K+ promoted the conversion of adsorbed benzene. Furthermore, intermediate products were transformed more rapidly for K1Ce5Mn5 compared to Ce5Mn5.

Robust Thiazole-Linked Covalent Organic Frameworks for Water Sensing with High Selectivity and Sensitivity.

The rational design of covalent organic frameworks (COFs) with hydrochromic properties is of significant value because of the facile and rapid detection of water in diverse fields. In this report, we present a thiazole-linked COF (TZ-COF-6) sensor with a large surface area, ultrahigh stability, and excellent crystallinity. The sensor was synthesized through a simple three-component reaction involving amine, aldehyde, and sulfur. The thiazole and methoxy groups confer strong basicity to TZ-COF-6 at the nitrogen sites, making them easily protonated reversibly by water. Therefore, TZ-COF-6 displayed color change visible to the naked eye from yellow to red when protonated, along with a red shift in absorption in the ultraviolet-visible diffuse reflectance spectra (UV-vis DRS) when exposed to water. Importantly, the water-sensing process was not affected by polar organic solvents, demonstrating greater selectivity and sensitivity compared to other COF sensors. Therefore, TZ-COF-6 was used to detect trace amounts of water in organic solvents. In strong polar solvents, such as N,N-dimethyl formamide (DMF) and ethanol (EtOH), the limit of detection (LOD) for water was as low as 0.06% and 0.53%, respectively. Even after 8 months of storage and 15 cycles, TZ-COF-6 retained its original crystallinity and detection efficiency, displaying high stability and excellent cycle performance.

Best acupuncture method for mammary gland hyperplasia: Evaluation of randomized controlled trials and Bayesian network meta-analysis.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

The value of ultrasound in combination with 99mTc-MIBI imaging department of ultrasound medicine, for the diagnosis of ectopic parathyroid glands in the thyroid gland in patients with secondary hyperparathyroidism.

To investigate the value of preoperative ultrasound combined with 99mTc-MIBI imaging for the diagnosis of ectopic intrathyroid parathyroid gland (ETPG) in patients with secondary hyperparathyroidism (SHPT). One hundred and eleven patients with SHPT who underwent total parathyroidectomy plus forearm transplantation from January 2015 to January 2022 in the Third Hospital of Hebei Medical University were selected. All patients underwent routine preoperative ultrasonography and 99mTc-MIBI imaging, and with pathological diagnosis as the gold standard, the clinical data of ETPG patients were selected, including clinical manifestations, laboratory tests, preoperative ultrasonography and 99mTc-MIBI imaging for localization and diagnosis, intraoperative exploration and postoperative pathology, and postoperative follow-up. To analyze the ultrasound manifestations of preoperative parathyroid hyperplasia and the results of 99mTc-MIBI imaging in patients with ETPG. Among 111 patients with SHPT, there were 5 patients with ETPG, 1 male and 4 females with a mean age of (45.00 ±â€…5.05) years, and 6 ectopic parathyroid glands were located in the thyroid gland. The incidence of ETPG was 4.5% (5/111), 4 were detected by ultrasound, 2 were not detected with a diagnostic accuracy of 66.7% (4/6), 3 were positive for 99mTc-MIBI imaging, 3 were negative with a diagnostic accuracy of 50.0% (3/6). Among them, one was not detected by ultrasound, but was positive for 99mTc-MIBI imaging, 2 with negative 99mTc-MIBI imaging, but all were detected by ultrasound, and one with negative 99mTc-MIBI imaging was detected by ultrasound but misdiagnosed as a thyroid nodule. A total of 5 ETPGs were detected by ultrasound combined with 99mTc-MIBI imaging, with a diagnostic accuracy of 83.3% (5/6). Patients' postoperative serum calcium and serum parathyroid hormone (PTH) levels were normalized or significantly decreased from preoperative levels. Ultrasound combined with 99mTc-MIBI imaging can achieve higher accuracy than either examination alone in the preoperative localization and diagnosis of ETPG in SHPT patients.

T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets.

BACKGROUND: Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown. METHODS: Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes. RESULTS: Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma. CONCLUSION: Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.

3D reconstruction of a gastrulating human embryo.

Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.

Associations of education attainment with gestational diabetes mellitus and the mediating effects of obesity: A Mendelian randomization study.

We aim to assess the causal association between educational attainment and gestational diabetes mellitus, and the mediating effect of obesity on this association. We estimated the causal effects of educational attainment on gestational diabetes mellitus using European ancestry genome-wide association study summary data with two-sample univariate Mendelian randomization (UVMR) approach. Two-stage Mendelian randomization analysis was performed to assess the potential mediating role of obesity traits in this association and to calculate the mediating proportion. UVMR analysis demonstrated that higher educational attainment was associated with a reduced risk of GDM (OR 0.76, 95% CI 0.67-0.86; p < 0.01). EA has also been associated with decreased obesity in women. Mediation Mendelian randomization results indicated that body mass index (BMI) was the most significant mediating factor in the relationship between educational attainment and GDM, accounting for 42.52% (95% CI 37.75-55.44%) of the effect, followed by waist-to-hip ratio (WHR) at 34.35% (95% CI 29.82-46.41%), body fat percentage at 28.95% (95% CI 35.99-46.81%), and WHR adjusted for BMI (WHRadjBMI) at 12.51% (95% CI 36.2-58.5%). educational attainment exerts a potential causal protective effect against gestational diabetes mellitus, and obesity-related risk factors play a mediating role. Attention should be paid to the educational attainment of women, and obese women with lower educational attainment may represent a higher risk group for GDM than those with higher educational attainment.