Increased LACTB2 Expression Regulates Oxidative Phosphorylation and mTORC1 Signaling of Colorectal Cancer.

This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression.

[Reversal Effect of Arctigenin on the Drug Resistance in Leukemia K562/A02 Cells and Its Mechanism].

OBJECTIVE: To study the effect of arctigenin(ARG) on adriamycin(ADM) resistance of leukemia cell line K562/A02 and the underlying mechanism. METHODS: Human leukemia cell line K562 and ADM-resistant cell line K562/A02 were cultured and treated with 2.5-50 µmol/L ADM. Cell proliferation was measured using CCK-8 method, and half maximal inhibitory concentration (IC50) was calculated. K562/A02 cells were treated with different concentrations of ARG (1, 2, 4, 8, 16 mmol/L) to detect the effect of ARG on K562/A02 cells, and a suitable concentration (2 mmol/L) was selected for subsequent experiments. K562/A02 cells were treated with 2 mmol/L ARG and 5 µmol/L ADM, and cell apoptosis was detected by flow cytometry, the expression of P-gp, MRP, cleaved caspase-3, Bax, Bcl-2 proteins and the TLR4/NF-κB signaling pathway-related proteins were measured by Western blot. TLR4 overexpression plasmid was transfected into K562/A02 cells which were co-treated with ARG and ADM, then drug sensitivity and cell apoptosis were measured. RESULTS: The IC50 value of ADM on K562/A02 cells was 36.57 µmol/L, which was significantly higher than that on K562 cells (1.30 µmol/L). ARG with a concentration of ≤2 mmol/L did not have a significant effect on K562/A02 cells. 2 mmol/L ARG significantly reduced the IC50 of ADM on K562/A02 cells. In 5 µmol/L ADM-treated K562/A02 cells, compared with the control group, the apoptosis rate of K562/A02 cells in the ARG group was significantly increased, the expressions of cleaved caspase-3, Bax proteins were significantly upregulated, the expressions of P-gp, MRP, Bcl-2, TLR4, MyD88, and p-NF-κB proteins were significantly downregulated, and the differences were statistically significant (P < 0.05). After transfection with TLR4 overexpression plasmid, the sensitivity of ARG-treated K562/A02 cells to ADM was reduced (P < 0.05), the cell apoptosis was decreased, and the expressions of P-gp, MRP, Bcl-2 and TLR4/NF-κB signaling pathway-related proteins were significantly elevated, while the expressions of cleaved caspase-3 and Bax proteins were significantly decreased (all P < 0.05). CONCLUSION: ARG may reverse the resistance of human leukemia cell line K562/A02 to ADM by inhibiting TLR4/NF-κB signaling pathway.

Mitigation of retinol-induced skin irritation by physiologic lipids: Evidence from patch testing.

BACKGROUND: There is a dearth of effective treatments to counter retinol-induced skin irritation. OBJECTIVE: This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol. METHODS: An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double-blind, and vehicle-controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post-test. Subsequently, a 4-week consumer in-use test, randomized and double-blind in nature, was executed to substantiate the soothing effects of PLG. RESULTS: Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol-induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol-induced discomfort. The subsequent consumer in-use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone. CONCLUSION: To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol-induced irritation. Given their capacity to counter retinol-induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia-CR a* value can serve as a robust objective measure for interpreting patch test outcomes.

Topological wetting states of microdroplets on closed-loop structured surfaces: Breakdown of the Gibbs equation at the microscale.

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.

Mechanistic insight into the competition between interfacial and bulk reactions in microdroplets through N2O5 ammonolysis and hydrolysis.

Reactive uptake of dinitrogen pentaoxide (N2O5) into aqueous aerosols is a major loss channel for NOx in the troposphere; however, a quantitative understanding of the uptake mechanism is lacking. Herein, a computational chemistry strategy is developed employing high-level quantum chemical methods; the method offers detailed molecular insight into the hydrolysis and ammonolysis mechanisms of N2O5 in microdroplets. Specifically, our calculations estimate the bulk and interfacial hydrolysis rates to be (2.3 ± 1.6) × 10-3 and (6.3 ± 4.2) × 10-7 ns-1, respectively, and ammonolysis competes with hydrolysis at NH3 concentrations above 1.9 × 10-4 mol L-1. The slow interfacial hydrolysis rate suggests that interfacial processes have negligible effect on the hydrolysis of N2O5 in liquid water. In contrast, N2O5 ammonolysis in liquid water is dominated by interfacial processes due to the high interfacial ammonolysis rate. Our findings and strategy are applicable to high-chemical complexity microdroplets.

Ultrasound for monitoring different stages of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and review of the literature.

RATIONALE: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication in patients with kidney transplantation, which poses challenges in diagnosis and poor prognosis due to its low incidence and nonspecific clinical manifestations. As a routine follow-up examination method for kidney transplant patients, ultrasound (US) plays a significant role in the diagnosis of PTLD. Therefore, it is critical to evaluate the ultrasonic characteristics of PTLD in transplanted kidney patients for early detection and diagnosis. PATIENT CONCERNS: A 59-year-old female patient was unexpectedly found with a mass in the hilum of the transplanted kidney 12th month after transplantation, which gradually grew up in the following 4 months. The latest US examination found hydronephrosis. Contrast-enhanced ultrasound (CEUS) demonstrated a hypo-enhancement pattern in arterial and parenchymal phases and showed a new irregular area lacking perceivable intensification within the mass, which was considered necrosis. Meanwhile, the patient developed an acute increase in serum creatinine from 122 to 195 µmol/L. DIAGNOSIS: A US-guided biopsy was conducted with the final pathological diagnosis of PTLD (polymorphic). INTERVENTIONS: After receiving 3 times of rituximab and symptomatic treatment, blood creatinine returned to normal but the mass was still progressing in the patient. Therefore, the treatment approach was modified to immune-chemotherapy. OUTCOMES: The patient was in a stable condition to date. LESSONS: PTLD is a rare complication in a transplanted kidney. US and CEUS are the preferred imaging methods in renal transplant patients due to their good repeatability and no nephrotoxicity. This case demonstrates that continuous dynamic monitoring by using US and CEUS has significant value in the detection and diagnosis of PTLD in a transplanted kidney, suggesting early clinical intervention to avoid further progression.

Diagnostic Value of Serum Adenosine Deaminase in Myelodysplastic Syndromes: an Observational Study.

BACKGROUND: This study aimed to explore the diagnostic value of serum adenosine deaminase (ADA) in patients with myelodysplastic syndromes (MDS) and identify potential risk factors for MDS. METHODS: Eighty patients with MDS and 80 healthy individuals were included. The serum ADA level was found to be significantly higher in patients with MDS compared with that of healthy controls (p = 0.014). RESULTS: The receiver operator characteristic curve (ROC) for ADA had an area under curve (AUC) of 0.807 (p = 0.0018). Serum ADA level of 4.5 U/L had a sensitivity of 71.43% and specificity of 80% for MDS diagnosis. The multivariate analysis showed hemoglobin (Hb, OR = 1.322, 95% CI: 1.035 - 2.323, p = 0.039), prothrombin time (PT, OR = 1.524, 95% CI: 1.156 - 3.280, p = 0.042), fibrinogen (OR = 1.335, 95% CI: 1.022 - 2.775, p = 0.027), calculated international normalized ration (INR, OR = 2.212, 95% CI: 1.320 - 3.085, p = 0.038), D-dimer (OR = 2.043, 95% CI: 1.623 - 4.293, p = 0.038), fibrin degradation product (FDP, OR = 2.525, 95% CI: 1.129 - 3.340, p = 0.029), and serum ADA (OR = 2.057, 95% CI: 1.248 - 3.572, p = 0.033) were independently associated with MDS. CONCLUSIONS: Serum ADA might be a potential biomarker in the diagnosis of MDS. Serum ADA level, Hb level, PT, fibrinogen level, INR, D-dimer, and FDPs were independent risk factors of MDS.

Accelerated Photolysis of H2O2 at the Air-Water Interface of a Microdroplet.

Photochemical homolysis of hydrogen peroxide (H2O2) occurs widely in nature and is a key source of hydroxyl radicals (·OH). The kinetics of H2O2 photolysis play a pivotal role in determining the efficiency of ·OH production, which is currently mainly investigated in bulk systems. Here, we report considerably accelerated H2O2 photolysis at the air-water interface of microdroplets, with a rate 1.9 × 103 times faster than that in bulk water. Our simulations show that due to the trans quasiplanar conformational preference of H2O2 at the air-water interface compared to the bulk or gas phase, the absorption peak in the spectrum of H2O2 is significantly redshifted by 45 nm, corresponding to greater absorbance of photons in the sunlight spectrum and faster photolysis of H2O2. This discovery has great potential to solve current problems associated with ·OH-centered heterogeneous photochemical processes in aerosols. For instance, we show that accelerated H2O2 photolysis in microdroplets could lead to markedly enhanced oxidation of SO2 and volatile organic compounds.

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

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

Automatic detection and differential diagnosis of age-related macular degeneration from color fundus photographs using deep learning with hierarchical vision transformer.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, highlighting the need for early and accurate detection. In this study, we proposed DeepDrAMD, a hierarchical vision transformer-based deep learning model that integrates data augmentation techniques and SwinTransformer, to detect AMD and distinguish between different subtypes using color fundus photographs (CFPs). The DeepDrAMD was trained on the in-house WMUEH training set and achieved high performance in AMD detection with an AUC of 98.76% in the WMUEH testing set and 96.47% in the independent external Ichallenge-AMD cohort. Furthermore, the DeepDrAMD effectively classified dryAMD and wetAMD, achieving AUCs of 93.46% and 91.55%, respectively, in the WMUEH cohort and another independent external ODIR cohort. Notably, DeepDrAMD excelled at distinguishing between wetAMD subtypes, achieving an AUC of 99.36% in the WMUEH cohort. Comparative analysis revealed that the DeepDrAMD outperformed conventional deep-learning models and expert-level diagnosis. The cost-benefit analysis demonstrated that the DeepDrAMD offers substantial cost savings and efficiency improvements compared to manual reading approaches. Overall, the DeepDrAMD represents a significant advancement in AMD detection and differential diagnosis using CFPs, and has the potential to assist healthcare professionals in informed decision-making, early intervention, and treatment optimization.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Thieno[3,4-d]pyrimidin-4(3H)-thione: an effective, oxygenation independent, heavy-atom-free photosensitizer for cancer cells.

All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen, and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4-d]pyrimidin-4(1H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(3H)-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions. It is demonstrated that thieno[3,4-d]pyrimidin-4(3H)-thione efficiently populates the long-lived and reactive triplet state generating singlet oxygen with a quantum yield of about 80% independent of solvent. It is further shown that thieno[3,4-d]pyrimidin-4(3H)-thione exhibits high photodynamic efficacy against monolayer melanoma cells and cervical cancer cells both under normoxic and hypoxic conditions. Our combined spectroscopic, computational, and in vitro data demonstrate the excellent potential of thieno[3,4-d]pyrimidin-4(1H)-thione as a heavy-atom-free PDT agent and paves the way for further development of photosensitizers based on the thionation of thieno[3,4-d]pyrimidine derivatives. Collectively, the experimental and computational results demonstrate that thieno[3,4-d]pyrimidine-4(3H)-thione stands out as the most promising thiobase photosensitizer developed to this date.

A nomogram based on radiomics intermuscular adipose analysis to indicate arteriosclerosis in patients with newly diagnosed type 2 diabetes.

Objective: Early identifying arteriosclerosis in newly diagnosed type 2 diabetes (T2D) patients could contribute to choosing proper subjects for early prevention. Here, we aimed to investigate whether radiomic intermuscular adipose tissue (IMAT) analysis could be used as a novel marker to indicate arteriosclerosis in newly diagnosed T2D patients. Methods: A total of 549 patients with newly diagnosed T2D were included in this study. The clinical information of the patients was recorded and the carotid plaque burden was used to indicate arteriosclerosis. Three models were constructed to evaluate the risk of arteriosclerosis: a clinical model, a radiomics model (a model based on IMAT analysis proceeded on chest CT images), and a clinical-radiomics combined model (a model that integrated clinical-radiological features). The performance of the three models were compared using the area under the curve (AUC) and DeLong test. Nomograms were constructed to indicate arteriosclerosis presence and severity. Calibration curves and decision curves were plotted to evaluate the clinical benefit of using the optimal model. Results: The AUC for indicating arteriosclerosis of the clinical-radiomics combined model was higher than that of the clinical model [0.934 (0.909, 0.959) vs. 0.687 (0.634, 0.730), P < 0.001 in the training set, 0.933 (0.898, 0.969) vs. 0.721 (0.642, 0.799), P < 0.001 in the validation set]. Similar indicative efficacies were found between the clinical-radiomics combined model and radiomics model (P = 0.5694). The AUC for indicating the severity of arteriosclerosis of the combined clinical-radiomics model was higher than that of both the clinical model and radiomics model [0.824 (0.765, 0.882) vs. 0.755 (0.683, 0.826) and 0.734 (0.663, 0.805), P < 0.001 in the training set, 0.717 (0.604, 0.830) vs. 0.620 (0.490, 0.750) and 0.698 (0.582, 0.814), P < 0.001 in the validation set, respectively]. The decision curve showed that the clinical-radiomics combined model and radiomics model indicated a better performance than the clinical model in indicating arteriosclerosis. However, in indicating severe arteriosclerosis, the clinical-radiomics combined model had higher efficacy than the other two models. Conclusion: Radiomics IMAT analysis could be a novel marker for indicating arteriosclerosis in patients with newly diagnosed T2D. The constructed nomograms provide a quantitative and intuitive way to assess the risk of arteriosclerosis, which may help clinicians comprehensively analyse radiomics characteristics and clinical risk factors more confidently.

Spontaneous Oxidation of Thiols and Thioether at the Air-Water Interface of a Sea Spray Microdroplet.

The transport of dissolved organic sulfur, including thiols and thioethers, from the ocean surface to the atmosphere through sea spray aerosol (SSA) is of great importance for the global sulfur cycle. Thiol/thioether in SSA undergoes rapid oxidation that is historically linked to photochemical processes. Here, we report the discovery of a non-photochemical, spontaneous path of thiol/thioether oxidation in SSA. Among 10 investigated naturally abundant thiol/thioether, seven species displayed rapid oxidation in SSA, with disulfide, sulfoxide, and sulfone comprising the major products. We suggest that such spontaneous oxidation of thiol/thioether was mainly fueled by thiol/thioether enrichment at the air-water interface and generation of highly reactive radicals by the loss of an electron from ions (e.g., glutathionyl radical produced from ionization of deprotonated glutathione) at or near the surface of the water microdroplet. Our work sheds light on a ubiquitous but previously overlooked pathway of thiol/thioether oxidation, which could contribute to an accelerated sulfur cycle as well as related metal transformation (e.g., mercury) at ocean-atmosphere interfaces.

TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis.

Tumor necrosis factor receptor-related factor 7 (TRAF7) can regulate cell differentiation and apoptosis, but its specific functional mechanism in the pathological process of acute myeloid leukemia (AML) closely related to differentiation and apoptosis disorders is largely unclear. In this study, TRAF7 was found to be lowly expressed in AML patients and a variety of myeloid leukemia cells. TRAF7 was overexpressed in AML Molm-13 and chronic myeloid leukemia (CML) K562 cells by transfection with pcDNA3.1-TRAF7. CCK-8 assay and flow cytometry analysis showed that TRAF7 overexpression induced growth inhibition and apoptosis in K562 and Molm-13 cells. Measurements of glucose and lactate suggested that TRAF7 overexpression impaired glycolysis of K562 and Molm-13 cells. Cell cycle analysis indicated that most of K562 and Molm-13 cells were captured in G0/G1 phase by TRAF7 overexpression. PCR and western blot assay revealed that TRAF7 increased Kruppel-like factor 2 (KLF2) expression but decreased 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression in AML cells. KLF2 knockdown can counteract TRAF7-triggered PFKFB3 inhibition, and abolish TRAF7-mediated glycolysis inhibition and cell cycle arrest. KLF2 knockdown or PFKFB3 overexpression both can partially neutralize TRAF7-induced growth inhibition and apoptosis of K562 and Molm-13 cells. Moreover, Lv-TRAF7 decreased human CD45+ cells in mouse peripheral blood in the xenograft mice established by NOD/SCID mice. Taken together, TRAF7 exerts anti-leukemia effects by impairing glycolysis and cell cycle progression of myeloid leukemia cells via modulating the KLF2-PFKFB3 axis.

Evaluation of Cutoff Values of RHE and MRV on Diagnosis for Iron Deficiency Anemia in Chinese Adults of Chengdu.

BACKGROUND: Our aim was to evaluate the cutoff values of RHE and MRV as markers to diagnose IDA in healthy Han ethnic adults of Chengdu. METHODS: A total of 263 Han adults who needed bone marrow aspiration for diagnosis were enrolled according to the inclusive and exclusive criteria. The cutoff values of RHE and MRV were determined by receiver operating curves. RESULTS: According to statistical analysis, the cutoff values of RHE and MRV in male and female groups were 26.75 pg, 89.60 fL and 26.65 pg, 88.55 fL respectively. The areas under the curve (AUC) of RHE and MRV were 0.941, 0.939 and 0.925, 0.909 in male and female groups, respectively. CONCLUSIONS: In our study, we explored the cutoff values of RHE and MRV to diagnose IDA in the Han ethnic population in Chengdu for the first time.

A prospective multi-center randomized comparative trial evaluating outcomes of transrectal ultrasound (TRUS)-guided 12-core systematic biopsy, mpMRI-targeted 12-core biopsy, and artificial intelligence ultrasound of prostate (AIUSP) 6-core targeted biopsy for prostate cancer diagnosis.

BACKGROUND: Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group. METHODS: Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate. RESULTS: AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001). CONCLUSIONS: AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future. REGISTRATION: This trial was registered in ISRCTN (ISRCTN18033113).

WDHD1 is over-expressed in nasopharyngeal carcinoma and may control the expression of ITGAV.

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.

Surgical treatment for perihilar cholangiocarcinoma:a single-center experience / 中华外科杂志

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism / 中华创伤杂志(英文版)

PURPOSE@#Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS.@*METHODS@#A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference.@*RESULTS@#In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy.@*CONCLUSION@#The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.