Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1.

BACKGROUND: Previous studies have shown that the Shi-pi-xiao-ji (SPXJ) herbal decoction formula is effective in suppressing hepatocellular carcinoma (HCC), but the underlying mechanisms are not known. Therefore, this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1 (ACAT1)-regulated cellular stiffness. Through a series of experiments, we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1, lowering the level of cholesterol in the cell membrane, and altering the cellular stiffness, which provides a new idea for the research of traditional Chinese medicine against HCC. AIM: To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC. METHODS: HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice. The apoptotic rate and proliferative, invasive, and migratory abilities of control and SPXJ-treated HCC cells were compared. Atomic force microscopy was used to determine the cell surface morphology and the Young's modulus values of the control and SPXJ-treated HCC cells. Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit. ACAT1 protein levels were estimated using western blotting. RESULTS: Compared with the vehicle group, SPXJ serum considerably reduced proliferation of HCC cells, increased stiffness and apoptosis of HCC cells, inhibited migration and invasion of HCC cells, decreased plasma membrane cholesterol levels, and upregulated ACAT1 protein levels. However, treatment of HCC cells with the water-soluble cholesterol promoted proliferation, migration, and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels, but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control. CONCLUSION: SPXJ formula inhibited proliferation, invasion, and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.

Amentoflavone reverses epithelial-mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis.

Epithelial-mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone-regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK-8 kit, wound healing assay, Transwell assay and annexin V-FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V-FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.

Decoding Subject-Driven Cognitive States from EEG Signals for Cognitive Brain-Computer Interface.

In this study, we investigated the feasibility of using electroencephalogram (EEG) signals to differentiate between four distinct subject-driven cognitive states: resting state, narrative memory, music, and subtraction tasks. EEG data were collected from seven healthy male participants while performing these cognitive tasks, and the raw EEG signals were transformed into time-frequency maps using continuous wavelet transform. Based on these time-frequency maps, we developed a convolutional neural network model (TF-CNN-CFA) with a channel and frequency attention mechanism to automatically distinguish between these cognitive states. The experimental results demonstrated that the model achieved an average classification accuracy of 76.14% in identifying these four cognitive states, significantly outperforming traditional EEG signal processing methods and other classical image classification algorithms. Furthermore, we investigated the impact of varying lengths of EEG signals on classification performance and found that TF-CNN-CFA demonstrates consistent performance across different window lengths, indicating its strong generalization capability. This study validates the ability of EEG to differentiate higher cognitive states, which could potentially offer a novel BCI paradigm.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

Manufacture of potassium chloride from cement kiln bypass dust: An industrial implementation case for transforming waste into valuable resources.

The recirculation of chlorine within the kiln presents a major hurdle in co-processing domestic waste in cement kilns. This chlorine enrichment not only adversely affects the quality of cement, but also pose a serious challenge to the subsequent eco-friendly disposal of kiln dust. To solve this problem, a proper bypass system has been implemented in this study on a 4000 t/d new dry process cement rotary kiln, and the collection of chlorine-rich bypass dust outside the kiln (30 t/d) has been achieved. In addition, a comprehensive and innovative system has been developed, including water washing and subsequent triple-effect salt extraction, to achieve leaching of K+ and Cl from the bypass dust in the water rinsing liquid, while effectively removing harmful metal ions such as Pb2+. Finally, the extraction of high-purity KCl salt (6 tons/day, purity of 90 %) has been successfully achieved. It is worth noting that high-temperature flue gas rich in CO2 has been used to precipitate certain heavy metal ions, while steam from the waste-heat power generation system has been employed as a heat source for the potassium salt evaporation process. More importantly, all the materials, except for the KCl salt product, are returned to the cement kiln system without causing any secondary pollution. This study not only effectively addresses the negative impacts of chlorine element circulation within cement kilns during domestic waste co-processing, but also achieves a highly innovative engineering practice of transforming waste into valuable resources from kiln dust to high-purity KCl products. In brief, this work provides a reference example for future approaches to clean production, carbon reduction and resource utilization in the cement industry.

Effects of biochar application and nutrient fluctuation on the growth, and cadmium and nutrient uptake of Trifolium repens with different planting densities in Cd-contaminated soils.

Biochar has been used to remediate contaminated-soil with heavy metals, however, less is known on how biochar interacts with planting density and nutrient fluctuation to affect the remediation. A pot experiment was conducted in the greenhouse to investigate the effects of biochar application (without vs. with 1% biochar, g/g substrate), nutrient fluctuation (constant vs. pulsed) and planting density (1-, 3- and 6-individuals per pot) on the growth, and cadmium (Cd) and nutrient uptake of Trifolium repens population. Our results found that the growth of T. repens population increased significantly with increasing planting density, and the increment decreased with increasing planting density. Both the Cd and nutrient uptake were higher at higher planting density (e.g., 3- and 6-individuals) than at lower planting density (e.g., 1-individual). Biochar application increased the biomass and shoot Cd uptake, but decreased the ratio of root to shoot and root Cd uptake of T. repens population, the effects of which were significantly influenced by planting density. Although nutrient fluctuation had no effect on the growth of T. repens population, but its interaction with planting density had significant effects on Cd uptake in tissues. Overall, the effects of biochar application and nutrient fluctuation on the growth and Cd uptake were both influenced by planting density in the present study. Our findings highlight that biochar application and constant nutrient supply at an appropriate planting density, such as planting density of 3-individuals per pot in the present study, could promote the growth, and Cd and nutrient uptake of T. repens population.

MYBL2 alternative splicing-related genetic variants reduce the risk of triple-negative breast cancer in the Chinese population.

Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, and studies have found an association between the Myb proto-oncogene like 2 (MYBL2) gene and TNBC development; however, the specific mechanisms underlying development remain unknown. Recent studies have reported the association of alternative splicing (AS) with cancer, providing new approaches to elucidate the carcinogenesis mechanism. This study aimed to identify MYBL2 AS-related genetic variants that influence the risk of developing TNBC, providing new ideas for probing the mechanism of TNBC and novel biomarkers for TNBC prevention. Methods: We conducted a case-control study of 217 patients with TNBC and 401 cancer-free controls. The CancerSplicingQTL database and HSF software were used to screen for MYBL2 AS-related genetic variants. The association of sample genotypes with the risk of TNBC development and with clinicopathological features was analysed via unconditional logistic regression. Combining multiple platforms, the candidate sites were subjected to biological function analysis. Results: Two AS-associated SNPs, rs285170 and rs405660, were identified using bioinformatics analysis. Logistic regression analysis showed that both rs285170 (OR = 0.541; 95% CI = 0.343-0.852; p = 0.008) and rs405660 (OR = 0.642; 95% CI = 0.469-0.879; p = 0.006) exhibited protective effects against TNBC under the additive model. Stratification analysis showed that these two SNPs had more significant protective effects in the Chinese population aged ≧50 years. Additionally, we found that rs405660 was associated with the risk of lymph node metastasis (OR = 0.396, 95% CI = 0.209-0.750, p = 0.005) in TNBC. Functional analysis revealed that both rs285170 and rs405660 are associated with splicing of exon 3 and that the exon 3-deleted spliceosome does not increase breast cancer risk. Conclusion: We found for the first time that MYBL2 AS-related genetic variants are associated with reduced TNBC susceptibility in the Chinese population, especially in women aged ≧50 years.

Antihepatoma peptide, scolopentide, derived from the centipede scolopendra subspinipes mutilans.

BACKGROUND: Centipedes have been used to treat tumors for hundreds of years in China. However, current studies focus on antimicrobial and anticoagulation agents rather than tumors. The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated. It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines. AIM: To purify, characterize, and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism. METHODS: An antihepatoma peptide (scolopentide) was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis, a Sephadex G-25 column, and two steps of high-performance liquid chromatography (HPLC). Additionally, the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity. The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry (QTOF MS), and the sequence was matched by using the Mascot search engine. Based on the sequence and molecular weight, scolopentide was synthesized using solid-phase peptide synthesis methods. The synthetic scolopentide was confirmed by MS and HPLC. The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro. The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo. In the tumor xenograft experiments, qualified model mice (male 5-week-old BALB/c nude mice) were randomly divided into 2 groups (n = 6): The scolopentide group (0.15 mL/d, via intraperitoneal injection of synthetic scolopentide, 500 mg/kg/d) and the vehicle group (0.15 mL/d, via intraperitoneal injection of normal saline). The mice were euthanized by cervical dislocation after 14 d of continuous treatment. Mechanistically, flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro. A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro. Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4 (DR4) and DR5. qRT-PCR was used to measure the mRNA expression of DR4, DR5, fas-associated death domain protein (FADD), Caspase-8, Caspase-3, cytochrome c (Cyto-C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1ß converting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice. Western blot assays were used to measure the protein expression of DR4, DR5, FADD, Caspase-8, Caspase-3, and Cyto-C in the tumor tissues. The reactive oxygen species (ROS) of tumor tissues were tested. RESULTS: In the process of purification, characterization and synthesis of scolopentide, the optimal enzymatic hydrolysis conditions (extract ratio: 5.86%, IC50: 0.310 mg/mL) were as follows: Trypsin at 0.1 g (300 U/g, centipede-trypsin ratio of 20:1), enzymolysis temperature of 46 °C, and enzymolysis time of 4 h, which was superior to freeze-thawing with liquid nitrogen (IC50: 3.07 mg/mL). A peptide with the strongest antihepatoma activity (scolopentide) was further purified through a Sephadex G-25 column (obtained A2) and two steps of HPLC (obtained B5 and C3). The molecular weight of the extracted scolopentide was 1018.997 Da, and the peptide sequence was RAQNHYCK, as characterized by QTOF MS and Mascot. Scolopentide was synthesized in vitro with a qualified molecular weight (1018.8 Da) and purity (98.014%), which was characterized by MS and HPLC. Extracted scolopentide still had an antineoplastic effect in vitro, which inhibited the proliferation of Eca-109 (IC50: 76.27 µg/mL), HepG2 (IC50: 22.06 µg/mL), and A549 (IC50: 35.13 µg/mL) cells, especially HepG2 cells. Synthetic scolopentide inhibited the proliferation of HepG2 cells (treated 6, 12, and 24 h) in a concentration-dependent manner in vitro, and the inhibitory effects were the strongest at 12 h (IC50: 208.11 µg/mL). Synthetic scolopentide also inhibited the tumor volume (Vehicle vs Scolopentide, P = 0.0003) and weight (Vehicle vs Scolopentide, P = 0.0022) in the tumor xenograft experiment. Mechanistically, flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01% (0 µg/mL), 12.13% (10 µg/mL), 16.52% (20 µg/mL), and 23.20% (40 µg/mL). Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells. Molecular docking suggested that scolopentide tightly bound to DR4 and DR5, and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol, respectively. In subcutaneous xenograft tumors from mice, quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD, caspase-8 and caspase-3 through a mitochondria-independent pathway. CONCLUSION: Scolopentide, an antihepatoma peptide purified from centipedes, may inspire new antihepatoma agents. Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.

[Molecular mechanisms of Gupi Xiaoji decoction inducing apoptosis of human hepatoma HepG2 cells].

Objective: To investigate the molecular mechanisms of Gupi Xiaoji decoction on apoptosis of human hepatoma cells HepG2. Methods: HepG2 cells were divided into 4 groups: control group (Control), blank serum group (Blank), Gupi Xiaoji Yin serum group (GPXJY) and cisplatin group (Positive). Eight duplicate holes were set in each group. After treated with Gupi Xiaoji Decoction-containing serum or cisplatin for 24 hours, the cell viability, the number of viable cells, the state of apoptosis, the cell cycle and the mitochondrial membrane potential were detected, and the level of lipid peroxidation (MDA) and glycolysis rate of the cells were detected. The expressions of apoptotic Bax, Bcl-2, and Caspase-3 proteins, and the contents of triacylglycerol (TG), cholesterol (TC), pyruvate and glucose in the cell supernatant were detected. Results: Compared with the control group, in the GPXJY group, the inhibition rate was increased (P＜0.05), the number of cells was decreased, the number of apoptosis-positive cells was increased (P＜0.01), the number of cells in the G1 phase was increased significantly (P＜0.05), and the cell membrane potential was decreased (P＜0.05,P＜0.01), the glycolytic function was inhibited significantly, the MDA level was increased, the expressions of Bax and Caspase-3 in the GPXJY group were increased, and the expression of Bcl-2 was decreased (P＜0.05, P＜0.01). In cell supernatant, the TC, TG and glucose contents were decreased significantly, and the pyruvate content was increased significantly (P＜0.05,P＜0.01). Conclusion: Gupi Xiaoji Decoction can induce apoptosis of HepG2 cells and may play a role in energy metabolism.

Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer.

OBJECTIVE: To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines. METHODS: In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines. RESULTS: Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6. CONCLUSIONS: Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

Huxie Huaji Ointment Induced Apoptosis of Liver Cancer Cells In Vivo and In Vitro by Activating the Mitochondrial Pathway.

Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.

[Clinical features and epidemiological trend of prostate cancer in the Changsha area of Hunan Province: Analysis of 2 877 cases].

OBJECTIVE: To analyze the epidemiological characteristics of PCa in the Changsha area of Hunan Province and provide some reference for the formulation of the strategies for the prevention and control of the malignancy. METHODS: We collected the data on the age, pathological type and TCM syndrome type of 2 877 PCa patients diagnosed and treated in Xiangya Hospital of Central South University, the First Affiliated Hospital of Hunan University of Chinese Medicine and the Affiliated Hospital of Hunan Research Institute of Chinese Medicine from January 1, 2010 to December 31, 2019. We analyzed the data obtained and the current prevalence and epidemiological trend of PCa. RESULTS: Of the total number of cases of PCa diagnosed and treated, there were 291 in 2010, 315 in 2011, 213 in 2012, 220 in 2013, 159 in 2014, 226 in 2015, 199 in 2016, 180 in 2017, 577 in 2018 and 497 in 2019. The age-related incidence rate was the lowest in the <40-year-olds (1.77%) and the highest in the 65- to 79-year-olds (18.4%). The incidence rate was increased year by year in the 65- to 79-year-olds, elevated to 63.9% in the 10 years, and most significantly in the ≥80-year-olds, soaring to 97.9% in the 10 years. As for the pathological types, prostatic adenocarcinoma (PAC) accounted for 50.1% (n = 1 441), acinar cell PAC 7.0% (n = 201), follicular PAC 1.29% (n = 37), ductal PCa 0.94% (n = 27), non-specific PCa 9.49% (n = 273), and other PACs 5.77% (n = 166). TCM syndrome differentiation was performed for 157 cases, which revealed kidney-yin deficiency in 40 cases (25.5%) and kidney-yang deficiency in 69 cases (43.9%). CONCLUSIONS: The incidence of PCa from 2010 to 2019 showed an aging-related trend in the Changsha area of Hunan Province, the highest among 65- to 69-year-olds. Males aged 65－79 years are a high-risk population for PCa, which calls for strengthened health education, early diagnosis and early treatment.

A Care Continuum of Immediate ART for Newly Diagnosed Patients and Patients Presenting Later to Care at a Federally Qualified Health Center in New Orleans.

Rapid-start, immediate antiretroviral therapy (ART) initiation is a novel intervention that leads to earlier viral suppression. Longer-term data is essential before supporting this strategy more widely. CrescentCare, a federally qualified health center in New Orleans, followed 195 patients who received same-day ART; here we present a continuum of care for immediate ART intervention.

Surface Immobilization of Redox-Labile Fluorescent Probes: Enabling Single-Cell Co-Profiling of Aerobic Glycolysis and Oncogenic Protein Signaling Activities.

An analytical method is described for profiling lactate production in single cells via the use of coupled enzyme reactions on surface-grafted resazurin molecules. The immobilization of the redox-labile probes was achieved through chemical modifications on resazurin, followed by bio-orthogonal click reactions. The lactate detection was demonstrated to be sensitive and specific. The method was incorporated into a single-cell barcode chip for simultaneous quantification of aerobic glycolysis activities and oncogenic signaling phosphoproteins in cancer. The interplay between glycolysis and oncogenic signaling activities was interrogated on a glioblastoma cell line. Results revealed a drug-induced oncogenic signaling reliance accompanying shifted metabolic paradigms. A drug combination that exploits this induced reliance exhibited synergistic effects in growth inhibition.

[Ureteroscopic holmium: YAG laser lithotripsy for managing urinary tract calculi].

OBJECTIVE: To evaluate the effectiveness and safety of ureteroscopic holmium: YAG laser lithotripsy for managing ureteral calculi. METHODS: Ureteroscopic holmium: YAG laser lithotripsy was used in 168 ureteral calculi (proximal 27 cases, middle 33 cases, distal 108 cases). Transurethral cystoscopic holmium: YAG laser lithotripsy in 12 bladder calculi. RESULTS: Four to six weeks after operation, The stone-free rate was 93% (25/27) in the proximal ureteral calculi, 94% (31/33) in the middle ureteral calculi, 94% (102/108) in the distal ureteral calculi, respectively. The complication rate was 5% (8 cases). the stone-free rate of bladder calculi was 100% (12/12), no complication. CONCLUSION: Ureteroscopic holmium: YAG laser lithotripsy is a highly effective and safe treatment modality for managing ureteral calculi.