Enabling Ultrafine Ru Nanoparticles with Tunable Electronic Structures via a Double-Shell Hollow Interlayer Confinement Strategy toward Enhanced Hydrogen Evolution Reaction Performance.

Engineering of the catalysts' structural stability and electronic structure could enable high-throughput H2 production over electrocatalytic water splitting. Herein, a double-shell interlayer confinement strategy is proposed to modulate the spatial position of Ru nanoparticles in hollow carbon nanoreactors for achieving tunable sizes and electronic structures toward enhanced H2 evolution. Specifically, the Ru can be anchored in either the inner layer (Ru-DSC-I) or the external shell (Ru-DSC-E) of double-shell nanoreactors, and the size of Ru is reduced from 2.2 to 0.9 nm because of the double-shell confinement effect. The electronic structures are efficiently optimized thereby stabilizing active sites and lowering the reaction barrier. According to finite element analysis results, the mesoscale mass diffusion can be promoted in the double-shell configuration. The Ru-DSC-I nanoreactor exhibits a much lower overpotential (η10 = 73.5 mV) and much higher stability (100 mA cm-2). Our work might shed light on the precise design of multishell catalysts with efficient refining electrostructures toward electrosynthesis applications.

Trifunctional L-Cysteine Assisted Construction of MoO2/MoS2/C Nanoarchitecture Toward High-Rate Sodium Storage.

The volume collapse and slow kinetics reaction of anode materials are two key issues for sodium ion batteries (SIBs). Herein, an "embryo" strategy is proposed for synthesis of nanorod-embedded MoO2/MoS2/C network nanoarchitecture as anode for SIBs with high-rate performance. Interestingly, L-cysteine which plays triple roles including sulfur source, reductant, and carbon source can be utilized to produce the sulfur vacancy-enriched heterostructure. Specifically, L-cysteine can combine with metastable monoclinic MoO3 nanorods at room temperature to encapsulate the "nutrient" of MoOx analogues (MoO2.5(OH)0.5 and MoO3·0.5H2O) and hydrogen-deficient L-cysteine in the "embryo" precursor affording for subsequent in situ multistep heating treatment. The resultant MoO2/MoS2/C presents a high-rate capability of 875 and 420 mAh g-1 at 0.5 and 10 A g-1, respectively, which are much better than the MoS2-based anode materials reported by far. Finite element simulation and analysis results verify that the volume expansion can be reduced to 42.8% from 88.8% when building nanorod-embedded porous network structure. Theoretical calculations reveal that the sulfur vacancies and heterointerface engineering can promote the adsorption and migration of Na+ leading to highly enhanced thermodynamic and kinetic reaction. The work provides an efficient approach to develop advanced electrode materials for energy storage.

Assessing the Feasibility of Simplifying the Scanning Protocol for Spinal Metastases With Vertebral Compression Fractures Using Only the Dixon T2-Weighted Sequence.

OBJECTIVE: Conventional imaging protocols, including sagittal T1-weighted imaging (T1WI) and water-only T2-weighted imaging (T2WI), are time consuming when screening for spinal metastases with vertebral compression fractures (VCFs). In this study, we aimed to assess the accuracy of using only the Dixon T2-weighted sequence in the diagnosis of spinal metastases with VCFs to determine its suitability as a simplified protocol for this task. METHODS: This retrospective study included 27 patients diagnosed with spinal metastases and VCFs. Qualitative analysis was performed separately by two musculoskeletal radiologists, who independently performed diagnostic evaluations of each vertebra using both conventional and simplified protocols. McNemar's test was then used to compare the differences in diagnostic results, and Cohen's kappa coefficient was used to assess interobserver and interprotocol agreement. Diagnostic performance values for both protocols, including sensitivity, specificity, and area under the curve, were then determined based on the reference standard. Quantitative image analysis was performed randomly for 30 metastases on T1WI and fat-only T2WI to measure the signal intensity, signal-to-noise ratio, and contrast-to-noise ratio. RESULTS: The diagnosis of VCFs by both radiologists was in full agreement with the reference standard. The classification of spinal metastases and diagnostic performance values determined by both radiologists were not significantly different between the two protocols (all P > 0.05), and the consistency between observers and protocols was excellent (κ = 0.973-0.991). The contrast-to-noise ratio of fat-only T2WI was significantly higher than that of T1WI (P < 0.001). CONCLUSIONS: The Dixon T2-weighted sequence alone performed well in diagnosing spinal metastases with VCFs, performing no worse than the conventional protocol (T1WI and water-only T2WI). This suggests that the Dixon T2-weighted sequence alone can serve as a simplified protocol for the diagnosis of spinal metastases with VCFs, thereby avoiding the need for more intricate scanning procedures.

Universal Sub-Nanoreactor Strategy for Synthesis of Yolk-Shell MoS2 Supported Single Atom Electrocatalysts toward Robust Hydrogen Evolution Reaction.

The coordination structure determines the electrocatalytic performances of single atom catalysts (SACs), while it remains a challenge to precisely regulate their spatial location and coordination environment. Herein, we report a universal sub-nanoreactor strategy for synthesis of yolk-shell MoS2 supported single atom electrocatalysts with dual-anchored microenvironment of vacancy-enriched MoS2 and intercalation carbon toward robust hydrogen-evolution reaction. Theoretical calculations reveal that the "E-Lock" and "E-Channel" are conducive to stabilize and activate metal single atoms. A group of SACs is subsequently produced with the assistance of sulfur vacancy and intercalation carbon in the yolk-shell sub-nanoreactor. The optimized C-Co-MoS2 yields the lowest overpotential (η10 =17 mV) compared with previously reported MoS2 -based electrocatalysts to date, and also affords a 5-9 fold improvement in activity even comparing with those as-prepared single-anchored analogues. Theoretical results and in situ characterizations unveil its active center and durability. This work provides a universal pathway to design efficient catalysts for electro-refinery.

Magnetic resonance imaging of focal fibrocartilaginous dysplasia - findings derived from a three-dimensional gradient echo sequence.

BACKGROUND: Focal fibrocartilaginous dysplasia is a rare benign bone lesion of young children that causes deformities in the extremities. However, the pathogenesis and treatments have not been defined and the MR manifestations have been less well described. OBJECTIVE: To describe the MR manifestations of focal fibrocartilaginous dysplasia, especially on the T1-W three-dimensional (3-D) volumetric interpolated breath-hold examination (VIBE) sequence. MATERIALS AND METHODS: In this retrospective study, the authors reviewed the MR and radiographic images, pathology and medical records of 21 cases of focal fibrocartilaginous dysplasia. All cases were evaluated by spin-echo MRI sequence. Among them, 17 cases were evaluated by T1-W 3-D VIBE sequence. RESULTS: The cohort consisted of 13 boys and 8 girls ages 4-75 months. In 14 cases, focal fibrocartilaginous dysplasia was located in the tibia, 3 in the femur and 4 in the ulna. MRI 3-D VIBE sequence findings showed all cases had hypointense fiber band structures in the bone defect areas. The fibrous bands in the lower extremities ended in the epiphysis or epiphyseal plate, and in the upper extremities the epiphysis or carpal bone. Ten cases had hyperintensities that might represent cartilage composition. Four cases had cartilage signals that were continuous with the epiphyseal cartilage. MR spin-echo sequence findings showed that bone marrow edema of the adjacent joint was observed in eight cases, enlargement of the epiphyseal plate in three cases and medial meniscus injury in five cases. CONCLUSION: The 3-D VIBE sequence reveals useful details in focal fibrocartilaginous dysplasia.

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

Double-Color-Image Compression-Encryption Algorithm Based on Quaternion Multiple Parameter DFrAT and Feature Fusion with Preferable Restoration Quality.

To achieve multiple color images encryption, a secure double-color-image encryption algorithm is designed based on the quaternion multiple parameter discrete fractional angular transform (QMPDFrAT), a nonlinear operation and a plaintext-related joint permutation-diffusion mechanism. QMPDFrAT is first defined and then applied to encrypt multiple color images. In the designed algorithm, the low-frequency and high-frequency sub-bands of the three color components of each plaintext image are obtained by two-dimensional discrete wavelet transform. Then, the high-frequency sub-bands are further made sparse and the main features of these sub-bands are extracted by a Zigzag scan. Subsequently, all the low-frequency sub-bands and high-frequency fusion images are represented as three quaternion signals, which are modulated by the proposed QMPDFrAT with three quaternion random phase masks, respectively. The spherical transform, as a nonlinear operation, is followed to nonlinearly make the three transform results interact. For better security, a joint permutation-diffusion mechanism based on plaintext-related random pixel insertion is performed on the three intermediate outputs to yield the final encryption image. Compared with many similar color image compression-encryption schemes, the proposed algorithm can encrypt double-color-image with higher quality of image reconstruction. Numerical simulation results demonstrate that the proposed double-color-image encryption algorithm is feasibility and achieves high security.

A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib.

An inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue mass with intramuscular penetration that is primarily treated via a surgical procedure. However, with unclear boundaries and a high rate of relapse, there is no standard treatment for recurrence or unresectable tumors. It is noteworthy that approximately half of IMTs harbor genetic rearrangements of the anaplastic lymphoma kinase (ALK). ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. Here, we present a case of a 15-year-old patient with IMT around the hip. Next-generation sequencing (NGS) revealed an LRRFIP1-ALK fusion, which has not yet been reported in the literature. Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions. This report expands the list of gene fusions in IMTs and highlights a new target for treatment.

Tetramethylpyrazine Protects Blood-Spinal Cord Barrier Integrity by Modulating Microglia Polarization Through Activation of STAT3/SOCS3 and Inhibition of NF-кB Signaling Pathways in Experimental Autoimmune Encephalomyelitis Mice.

We previously reported that tetramethylpyrazine (TMP) alleviates experimental autoimmune encephalomyelitis (EAE) by decreasing glia activation. Activated microglia has been shown to mediate blood-spinal cord barrier (BSCB) disruption, which is a primary and continuous pathological characteristic of multiple sclerosis (MS). Therefore, in this study, we further investigated whether TMP protects the BSCB integrity by inhibition of glia activation to alleviate EAE. Extravasation of evans blue was used to detect the BSCB disruption. Tumor necrosis factor-α (TNF-α)/interlukine-1ß (IL-1ß) and interlukine-4 (IL-4)/interlukine-10 (IL-10) were determined by enzyme-linked immunosorbent assay. BV2 glial cells stimulated by interferon-γ (IFN-γ) were co-cultured with human brain microvascular endothelial cells to investigate the effect of TMP on the BSCB disruption. Flow cytometry was used to analyze the microglia phenotype. Western blot was performed to reveal the signaling pathways involved in the microglia activation. In this study, most importantly, we found that TMP protects the BSCB integrity by modulating microglia polarization from M1 phenotype to M2 phenotype through activation of STAT3/SOCS3 and inhibition of NF-кB signaling pathways. Moreover, TMP significantly preserves the tight junction proteins, reduces the secretion of pro-inflammatory cytokines (TNF-α, IL-1ß) and increases the secretion of anti-inflammatory cytokines (IL-4, IL-10) from IFN-γ-stimulated BV2 microglia cells. Consequently, protection of the BSCB integrity leads to alleviation of clinical symptoms and demyelination in EAE mice. Therefore, TMP might be an effective therapeutic agent for cerebral disorders with BBB or BSCB disruption, such as ischemic stroke, MS, and traumatic brain injury.

Variations in active outflow along the trabecular outflow pathway.

Previous tracer studies have shown segmental outflow in the trabecular meshwork (TM) and along the inner wall (IW) of Schlemm's canal (SC). Whether segmental outflow is conserved distal to SC has not yet been investigated. This study aims to investigate whether the segmented pattern of outflow is conserved in distal outflow pathways by using a newly developed global imaging method and to evaluate variations of active outflow in three distinct regions along trabecular outflow pathway. Six normal whole globe human eyes were first perfused at 15 mmHg to establish a stable baseline outflow facility. The anterior chamber was then exchanged (5 mL) and perfused with fluorescent microspheres (0.002% v/v, 200 µL) to label areas of active outflow. All eyes were perfusion fixed and dissected into anterior segments. The TM and scleral surface were en face imaged globally. Effective filtration area (EFA) and fluorescent tracer distribution and intensity were analyzed in global images for both the TM and episcleral veins (EPVs). Anterior segments were further dissected into a minimum of 16 radial wedges, from which frontal sections were cut, stained, and imaged, using confocal microscopy. EFA from all three locations along the trabecular outflow pathway were measured and compared. Additionally, TM thickness, SC height, and total number of collector channels (CC) were analyzed and compared between active and inactive areas of outflow. Statistical analysis was performed using Student's t-tests and Wilcoxon signed-rank test with a required significance of p ≤ 0.05. All three locations showed a segmental outflow pattern. The TM had a significantly higher mean EFA (86.3 ± 3.5%) compared to both the IW (34.7 ± 2.9%; p ≤ 0.01) and EPVs (41.1 ± 3.8%; p ≤ 0.01). No significant difference in mean EFA was found between IW and EPVs. Preferential active outflow was observed in the nasal and inferior quadrants. TM thickness was significantly larger in areas of active outflow (103.3 ± 4.0 µm; p ≤ 0.01) compared to areas of inactive outflow (78.5 ± 6.5 µm), but there was no significant difference in SC height between active and inactive outflow areas. Among all eyes, a total of 80 CCs were counted with 63 associated with active outflow and 17 associated with inactive outflow. A higher number of CCs associated with areas of active outflow were found in the nasal (26 of 63) and inferior (20 of 63) quadrants compared to the temporal (9 of 63) and superior (8 of 63) quadrants. A segmental nature of outflow is conserved along the trabecular outflow pathway with variations in three distinct locations (TM, IW, and EPVs). IW and EPVs showed a similar mean EFA. Preferential active outflow was observed in the nasal and inferior quadrants of the eye, which are associated with more expanded TM and higher number of CCs. Normal outflow patterns and its variations along the outflow pathway reported in this study will provide the basis for future studies of the outflow changes in eyes with glaucoma.

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

OBJECTIVE: Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. METHODS: Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). RESULTS: MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. CONCLUSION: Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.

[High Throughput Screening Analysis of Preservatives and Sweeteners in Carbonated Beverages Based on Improved Standard Addition Method].

Simulated water samples of 3 kinds of preservatives and 4 kinds of sweeteners were formulated by using orthogonal design. Kernel independent component analysis (KICA) was used to process the UV spectra of the simulated water samples and the beverages added different amounts of the additive standards, then the independent components (ICs), i. e. the UV spectral profiles of the additives, and the ICs' coefficient matrices were used to establish UV-KICA-SVR prediction model of the simulated preservatives and sweeteners solutions using support vector regression (SVR) analysis. The standards added beverages samples were obtained by adding different amounts level of additives in carbonated beverages, their UV spectra were processed by KICA, then IC information represented to the additives and other sample matrix were obtained, and the sample background can be deducted by removing the corresponding IC, other ICs' coefficient matrices were used to estimate the amounts of the additives in the standard added beverage samples based on the UV-KICA-SVR model, while the intercept of linear regression equation of predicted amounts and the added amounts in the standard added samples is the additive content in the raw beverage sample. By utilization of chemometric "blind source separation" method for extracting IC information of the tested additives in the beverage and other sample matrix, and using SVR regression modeling to improve the traditional standard addition method, a new method was proposed for the screening of the preservatives and sweeteners in carbonated beverages. The proposed UV-KICA-SVR method can be used to determine 3 kinds of preservatives and 4 kinds of sweetener in the carbonate beverages with the limit of detection (LOD) are located with the range 0.2-1.0 mg · L⁻¹, which are comparable to that of the traditional high performance liquid chromatographic (HPLC) method.

Survivin status affects prognosis and chemosensitivity in epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to explore the clinical significance of survivin expression in epithelial ovarian cancer (EOC) and the effect of survivin small hairpin RNA (shRNA) on survivin expression, apoptosis, and chemosensitivity in the human ovarian cancer cell line OVCAR3. METHODS: A retrospective review of 90 consecutive EOC patients with a median follow-up time of 51 months was conducted. Survivin expression was examined by immunohistochemistry. OVCAR3 cells were transfected in vitro with survivin shRNA. Survivin mRNA expression levels were detected using reverse transcription-polymerase chain reaction. Flow cytometry was applied to determine survivin protein expression levels and cell apoptotic rates. The MTT method was used to examine the effects of survivin shRNA on chemosensitivity in OVCAR3 cells. RESULTS: Positive cytoplasmic expression of survivin was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, nonmucinous type, high grade, and recurrence. Positive survivin expression was also associated with platinum resistance (r = 0.306, P = 0.003). Statistical results indicated that FIGO stage (hazard rate = 1.649, P = 0.047) and cytoplasmic expression of survivin (hazard rate = 1.734, P = 0.010) were independent prognostic factors. Survivin mRNA and protein levels were lower in OVCAR3S (ovarian cancer cells transfected with a survivin recombinant vector) cells at 24 hours after transfection as compared with controls. The flow cytometric analysis revealed that survivin shRNA induced accumulation of cells in the G0/Gl phase, with a decrease in G2/M phase cells following 24 hours of culture as compared with a nontransfected group (P < 0.01). Furthermore, survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel 15-fold (P < 0.05), whereas it had no significant effect on cisplatin (P > 0.05). CONCLUSIONS: In addition to FIGO stage, cytoplasmic survivin protein expression is an independent molecular marker for predicting EOC prognosis. Sequence-specific shRNA targeting survivin can effectively suppress survivin expression, enhance apoptosis, and increase the sensitivity of ovarian cancer cells to paclitaxel but not to cisplatin.

Chronic neck pain is associated with increased mortality in individuals with osteoarthritis: results from the NHANES database prospective cohort study.

BACKGROUND: Neck pain (NP) is a common symptom reported in the elderly. However, no study has examined the relationship between NP and osteoarthritis (OA) so far, and this study aimed to investigate the association of neck pain with the prevalence and mortality of OA. METHODS: A total of 5965 participants were included in this cohort study based on the National Health and Nutrition Examination Survey data set of the USA (NHANES). Death outcomes follow-up information was ascertained by linkage to National Death Index (NDI). The association between NP and OA was studied by multi-various logistic regression models after adjusting for potential confounding factors. Cox proportional hazards models were used to elucidate the relationship between NP and all-cause mortality in OA patients. RESULTS: Among all participants, 8.18% had osteoarthritis, and 5.92% suffered from neck pain. Neck pain was associated with osteoarthritis [1.932 (1.232, 3.028), p < 0.01], which still reminded significant after adjustments [2.519 (1.325, 4.788), p < 0.01] and stratified analysis by sex, race, and smoke status. In OA patients, chronic neck pain (over 1 year) was significantly associated with higher risks of all-cause mortality before [2.94 (1.61, 5.37), p < 0.01] and after adjustment [3.30 (1.23, 45.85), p < 0.05]. CONCLUSION: Neck pain was strongly associated with osteoarthritis. Moreover, chronic neck pain over 1 year significantly increased the mortality of OA patients. Our study demonstrates the need to screen osteoarthritis in the neck pain population and select a more appropriate treatment strategy promptly for those patients.

Single-cell and bulk tissue sequencing unravels the heterogeneity of synovial microenvironment in arthrofibrosis.

Arthrofibrosis (AF) is a debilitating complication that occurs after trauma or surgery, leading to functional impairment and surgical failures worldwide. This study aimed to uncover the underlying mechanism of AF. A total of 141 patients were enrolled, and synovial samples were collected from both patients and animal models at different time points. Single-cell RNA-sequencing (scRNA-seq) and bulk tissue RNA sequencing (bulk-seq) were employed to profile the distinct synovial microenvironment. This study revealed changes in cell proportions during AF pathogenesis and identified Engrailed-1 (EN1) as a key transcription factor strongly associated with disease severity and clinical prognosis. Additionally, the researchers discovered a specific type of synovial fibroblast called DKK3-SLF, which played a critical role in driving AF development. These findings shed light on the composition and heterogeneity of the synovial microenvironment in AF, offering potential avenues for identifying therapeutic targets and developing clinical treatments for AF and other fibrotic diseases.

Two cases of spindle cell tumors with S100 and CD34 co-expression showing novel RAF1 fusions.

BACKGROUND: Recently, a novel group of CD34 and S100 co-expression spindle cell tumors with distinctive stromal and perivascular hyalinization harboring recurrent gene fusions involving RET, RAF1, BRAF, and NTRK1/2 gene has been identified. CASE PRESENTATION: In this study, we reported two Chinese male patients with soft tissue tumors presenting in the right knee joint and the left thigh, respectively. For both patients, the tumors were completely excised with clear margin. Microscopically, case 1showed morphological overlap with neurofibroma, and case 2 showed overlap with lipomatous solitary fibrous tumor. Both tumors showed co-expression of S100 and CD34, and absence of SOX10. Genomic profiling with DNA-based next-generation sequencing (NGS) assay was performed and revealed KIF5B-RAF1 (K16:R8) and TLN2-RAF1 (T54:R8) rearrangements. RNA-based NGS and RT-PCR were performed to confirm the gene fusion. CONCLUSIONS: Though systemic therapy was not indicated in these two patients, identification of targetable kinase fusions may help to refine tumors with an ambiguous immunoprofile, and provides suggestions for targeted therapy in rare aggressive cases.

The expression of hydrogen sulfide-producing enzymes in primary and lung metastatic osteosarcoma.

BACKGROUND: Hydrogen sulfide (H2S) is a novel gas transmitter signaling molecule. H2S is synthesized by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). There have been no reports about the roles of these enzymes in osteosarcoma and its metastases. We detected H2S synthase expression levels in human primary osteosarcoma and lung metastatic osteosarcoma. METHODS: Immunohistochemistry was performed in primary osteosarcoma (n=19), lung metastatic osteosarcoma (n=11), osteoblastoma (n=10) and bony callus (n=2). The expression of CBS, CSE, and MST was defined as negative, moderately positive and strongly positive. RESULTS: MST staining was moderately to strongly positive in all cases. CSE staining was negative in 94.7% (18/19) of primary osteosarcoma cases and 90.9% (10/11) of lung metastatic osteosarcoma cases. CBS staining was strongly positive in 68.4% (13/19) of primary osteosarcoma cases, moderately positive in 15.8% (3/19) of cases, and negative in 15.8% (3/19) of cases. In lung metastatic osteosarcoma, the proportions of negative, moderately positive and strongly positive cases were 63.6% (7/11), 18.2% (2/11) and 18.2% (2/11), respectively. CONCLUSIONS: CBS and CSE expression, especially CSE expression, decreased in both primary osteosarcoma and lung metastatic osteosarcoma, which may suggest that CBS and CSE play roles in osteoblast cell malignant transformation and osteosarcoma progression. These enzymes could be used as new prognostic assessment factors and may represent new therapeutic targets for osteosarcoma and metastasis prevention.

Prevalence and risk factors of diabetic retinopathy among Chinese adults with type 2 diabetes in a suburb of Shanghai, China.

BACKGROUND: To investigate the prevalence and risk factors of diabetic retinopathy (DR) in a Chinese population with type 2 diabetes mellitus (T2DM) in a suburb (Qingpu) of Shanghai, China. METHODS: A population-based cross-sectional study. A total of 7462 residents with T2DM in Qingpu were enrolled according to the resident health archives from January 2020 to December 2020. Blood and urine samples of the subjects were collected. Disc- and macula-centred retinal images were taken to assess DR. SPSS was used to analyse and investigate the prevalence and risk factors of DR. RESULTS: The fundus images of 6380 (85.5%) subjects were of sufficiently good quality for grading. The average (range) age of 6380 subjects was 63.46±7.77 (28-92) years. Six hundred forty-four subjects were diagnosed with DR. The prevalence of DR was 10.1% (95% CI 9.4%-10.8%), with mild, moderate, and severe non-proliferative retinopathy and proliferative retinopathy being 2.1%, 6.3%, 1.3% and 0.4%, respectively. The prevalence of bilateral DR was 6.5%. Higher T2DM duration (OR, 1.057), fasting plasma glucose (OR, 1.063), glycated hemoglobinA1c (OR, 1.269), urea nitrogen (OR, 1.059), and urinary albumin (OR, 1.001) were associated with the higher DR prevalence. CONCLUSION: The prevalence of DR among Chinese adults with T2DM in Qingpu was 10.1%, in which non-proliferative DR was more common. Higher fasting plasma glucose and glycated hemoglobinA1c are well-known risk factors of DR, consistent with the findings in our study. Our study didn't find the risk between lipid indicators and DR. However, several renal function indicators, like higher urea nitrogen and urinary albumin, were risk factors for DR in this study. Appropriate diagnosis and intervention should be taken in time to prevent and control DR development.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model.

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult Chinese rabbits were randomly divided into normal diet (Ca:P, 1:0.7) group (control group) or a high-phosphate diet (Ca:P, 1:7) group (experimental group). The thyroid and parathyroid complexes were harvested for 1-month interval from month 1 to month 6. The expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and cyclin-D1, and B cell lymphoma-2 (Bcl-2), were evaluated by immunohistochemistry in thyroid and parathyroid tissues. Apoptosis was quantified by DNA-fragment terminal labeling. Our results demonstrated that parathyroid cells in the experimental group started proliferating from the end of the 2nd month, the expression of PCNA, Bcl-2, and cyclin-D1 were significantly higher in the PHPT group than those of the control group (p<0.05). Furthermore, the apoptosis index (AI) was positively correlated with the glandular cell count and expression of PCNA in the 6th month in the PHPT group. Overall, our results suggested that excessive proliferation and apoptosis of parathyroid cells may contribute to the pathogenesis of PHPT through PCNA-related, Bcl-2-related, and cyclin-D1-related pathways.

H3F3A G34 mutation DNA sequencing and G34W immunohistochemistry analysis in 366 cases of giant cell tumors of bone and other bone tumors.

H3F3A mutations and the expression of glycine 34 to tryptophan (G34W) mutants in giant cell tumors of bone (GCTBs) and other bone tumors were detected to compare H3F3A mutation types and the expression of G34W-mutant protein in order to provide a theoretical basis for using H3F3A mutations as a diagnostic and differential-diagnostic tool for GCTBs. A total of 366 bone tumor cases were investigated. The cases involved 215 men and 151 women, whose median age was 29 years (3-84). The cases included GCTB (n=180), recurrent GCTB (n=19), GCTB with lung metastasis (n=5), pediatric GCTB (n=15), primary malignant GCTB (n=5), chondroblastoma (CB, n=61), chondrosarcoma grade II (n=15), dedifferentiated chondrosarcoma (n=17), chondromyxoid fibroma (n=9), aneurysmal bone cyst (n=9), nonossifying fibroma (n=9), osteosarcoma (n=16), and undifferentiated sarcoma (n=6). Sanger DNA sequencing analysis was used to detect H3F3A mutations. Immunohistochemistry was used to assess the expression of the G34W-mutated protein in these bone tumors. DNA sequencing results revealed H3F3A mutations in 95.00% of GCTBs (171/180), including glycine 34 to tryptophan (G34W, 163/180, 90.56%), glycine 34 to leucine (G34L, 3/180, 1.67%), glycine 34 to valine (G34V, 3/180, 1.67%), and glycine 34 to arginine (G34R, 2/180, 1.11%). Recurrent GCTBs mostly had the H3F3A G34W mutation (18/19, 94.74%), and GCTBs with lung metastasis all had the H3F3A G34W mutation (5/5, 100%). Pediatric GCTBs had a mutation rate of 93.33% (14/15), including one case with G34L. Four cases of primary malignant GCTB showed the H3F3A G34W mutation (4/5, 80.00%), and the classical GCTB component and malignant component showed consistent mutation types. Immunohistochemistry showed that GCTBs harboring G34W also expressed the mutant protein in tumor cell nuclei. Furthermore, one case of GCTB and one case of recurrent GCTB showed positive G34W immunostaining results despite being negative for the genetic mutation. Other bone tumors all showed wild-type expression in both DNA sequencing and immunohistochemistry. Our large-sample DNA sequencing analysis detected four different forms of mutations in GCTBs, including three rare mutation forms. The most common mutation of H3F3A was G34W, which was in accordance with the expression of G34W in GCTBs detected by immunohistochemistry. Although DNA sequencing analysis detected rare mutation types of H3F3A, false-negative results were also present due to the small number of cells in the samples. Detection of the most common (G34W) mutant protein by immunohistochemistry was more convenient. Given the high prevalence of these driver mutations, the detection of H3F3A mutant proteins can assist in the diagnosis of GCTB and its differential diagnosis from other bone tumors.