Scoring and validation of a simple model for predicting diabetic retinopathy in patients with type 2 diabetes based on a meta-analysis approach of 21 cohorts.

AIM: To develop and validate a model for predicting diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: All risk factors with statistical significance in the DR prediction model were scored by their weights. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve, Kaplan-Meier curve, calibration curve and decision curve analysis. The prediction model was externally validated using a validation cohort from a Chinese hospital. RESULTS: In this meta-analysis, 21 cohorts involving 184,737 patients with type 2 diabetes were examined. Sex, smoking, diabetes mellitus (DM) duration, albuminuria, glycated haemoglobin (HbA1c), systolic blood pressure (SBP) and TG were identified to be statistically significant. Thus, they were all included in the model and scored according to their weights (maximum score: 35.0). The model was validated using an external cohort with median follow-up time of 32 months. At a critical value of 16.0, the AUC value, sensitivity and specificity of the validation cohort are 0.772 ((95% confidence interval (95%CI): 0.740-0.803), p < .01), 0.715 and 0.775, respectively. The calibration curve lied close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated that the model had notably higher net benefits. The external validation results proved the reliability of the risk prediction model. CONCLUSIONS: The simple DR prediction model developed has good overall calibration and discrimination performance. It can be used as a simple tool to detect patients at high risk of DR.

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Risks associated with cognitive function and management strategies in the clinical use of ADT: a systematic review from clinical and preclinical studies.

Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT.

The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials.

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine theory, and its feasibility in aiding gastrointestinal recovery after abdominal surgery is supported by both Traditional Chinese Medicine theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations, and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in gastrointestinal recovery after abdominal surgery and discusses related issues and operations, with the aim to provide new insights and prospects for the incorporation of acupuncture into the Enhanced Recovery After Surgery protocol.

Determinants of Parental Intention to Vaccinate Young Adolescent Girls against the Human Papillomavirus in Taiwan: An Online Survey Study.

Since 2018, Taiwan has included the human papillomavirus (HPV) vaccination into its national immunization program for junior high school girls. However, the reports of side effects following vaccination have increased parental concerns. This study investigated parental intentions regarding the HPV vaccination for their daughters and related factors in Taiwan. A total of 213 parents of girls aged between 12 and 15 years participated in an online survey. The survey collected data on various factors, including the parental intention to vaccinate their daughters against HPV; the motivation behind the vaccinations, as measured using the Motors of Human Papillomavirus Vaccination Acceptance Scale; an understanding of the reasons behind the government's promotion of HPV vaccinations; concerns regarding the side effects of vaccinations for their daughters; an awareness of the reported side effects of HPV vaccines experienced by some individuals; the exposure to information on HPV vaccines from social media; and mental health status, measured using the Brief Symptom Rating Scale. The associations between these variables and the parental intention to vaccinate their daughters against HPV were examined using a multivariable linear regression analysis model. The findings revealed a moderate to high level of intention among participants to vaccinate their daughters against HPV. Parents who perceived a greater value in HPV vaccination for their daughters' health (B = 0.524, standard error [se] = 0.039, p < 0.001) and had greater autonomy in decision-making regarding vaccination (B = 0.086, se = 0.038, p = 0.026) exhibited a higher intention to vaccinate their daughters against HPV. Conversely, parents who expressed greater concern regarding the side effects of HPV vaccines for their daughters had a lower intention to vaccinate (B = -0.762, se = 0.203, p < 0.001). Based on these findings, this study recommends integrating these factors into the design of intervention programs aimed at enhancing parental intentions to vaccinate their daughters against HPV.

Association of clinical characteristics and recurrence of conventional colorectal adenomas with patient age: a single-center study.

OBJECTIVES: We performed a clinical study comparing early-onset and late-onset conventional colorectal adenomas (CCRAs) since little is known about the differences in their characteristics. METHODS: Pearson's chi-square test and the Kruskal‒Wallis test were used to compare basic information. MCAR tests and multiple imputation were performed to complete missing values. Multivariate logistic analysis and propensity score matching were used to identify the risk factors for recurrence. RESULTS: We included 2793 patients (688 with early-onset CCRAs and 2105 with late-onset CCRAs) from January 2017 to December 2021. Patients with early-onset CCRAs had higher levels of Hb, ALB, and triglycerides but lower HDL levels and N/L ratios. Moreover, we found that more early-onset CCRAs were in the left colon than late-onset CCRAs, and the size of early-onset CCRAs was larger. Early-onset CCRAs tended to lack pedicles compared to late-onset CCRAs. Additionally, the ratio of EMR and APC in early-onset CCRAs was higher than that in late-onset CCRAs, and the ratio of ESD and surgery for late-onset CCRAs was higher. We found that age ≥ 50 years, abnormal vessels, drinking alcohol, and DB and ALB levels may be risk factors for recurrence, while the LDL level may be a protective factor. Finally, analysis of cumulative recurrence rates after PSM showed that patients with late-onset CCRAs exhibited higher recurrence rates (P < 0.05). CONCLUSION: Compared with late-onset CCRAs, early-onset CCRAs were associated with higher triglyceride levels, lower HDL levels, and larger tumor volumes. Age ≥ 50 years, abnormal vessels, alcohol consumption, and DB and ALB levels were independent risk factors for recurrence of CCRAs.

Manual Reduction and Plaster External Fixation for the Treatment of Closed Total Talus Dislocation: Case Report and Literature Review.

BACKGROUND: Total dislocation of the talus from all its surrounding joints (talonavicular, tibiotalar, subtalar) is one kind of serious injury of the lower extremity with rare occurrence. It is usually accompanied by fractures of the talus and its periphery, as well as severe soft tissue injury, which is difficult to reset. Complications such as skin necrosis and infection are prone to occur in the early stage, and talus necrosis are prone to occur in the late stage, all of which aggravate disease severity and increase difficulties for its treatment. CASE PRESENTATION: Herein, we reported a case of right talus total dislocation accompanied by medial malleolus fracture and posterior tubercle fracture caused by traffic accident. One hour after injury, the doctor tried to perform manual reduction but failed. Then, we successfully performed manual reduction and plaster external fixation on this patient under anesthesia 6 h after injury, followed by the oral administration of Chinese medicine for 3 months. Twenty months of follow-up investigations revealed that no skin necrosis, talus dislocation, talus necrosis, or other complications occurred; no obvious joint degeneration was observed and the fractures of medial malleolus and talus healed well. MRI of ankle joint indicated the disappearance of ankle effusion caused by injury, and the bone marrow edema had also subsided at talus, medial malleolus, and lateral malleolus and calcaneus. Patient presented with no ligament relaxation, ankle instability, pain, swelling, or functional limitation of the injured limb. AOFAS score reached 100. Daily functions and recreation activities were recovered back to the normal level. CONCLUSION: For patients with closed total dislocation of the talus, fine therapeutic effects can be achieved by early closed manual reduction and plaster external fixation under anesthesia, in combination with oral Chinese herbal medicine afterwards. It is worthy of reference for clinicians.

ChREBP-ß/TXNIP aggravates frucose-induced renal injury through triggering ferroptosis of renal tubular epithelial cells.

High fructose intake is an essential risk factor for kidney injury. However, the specific mechanism underlying high fructose-induced kidney injury remains unclarified. Carbohydrate response element-binding protein (ChREBP) is a key transcriptional activator that regulates fructose metabolism. ChREBP-ß exhibits sustained activity due to the lack of a low glucose inhibitory domain, and is thus described as the active form of ChREBP. In this study, a mouse model with specific overexpression of ChREBP-ß in the renal tubule was established by using the Cre/LoxP method. Quantitative proteomic analysis and experimental verification results suggest that ChREP-ß overexpression leads to ferroptosis of renal tubular epithelial cells and kidney injury. ChREPB-ß promotes the gene transcription of thioredoxin-interacting protein (TXNIP) and thereby increases its expression level. TXNIP is associated with activation of ferroptosis. TXNIP can initiate ferroptosis and eventually contribute to high fructose-induced renal tubular epithelial cell damage. Through down-regulating ChREBP-ß, metformin can inhibit gene transcription of TXNIP, attenuate high fructose-induced ferroptosis in renal tubular epithelial cells, and alleviate kidney injury. In conclusion, ChREBP-ß mediates fructose-induced ferroptosis of renal tubular epithelial cells, and metformin with a ChREBP-ß inhibitory effect may be a potential treatment for ferroptosis of renal tubular epithelial cells.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Monitoring Neovascularization of Malignant Solid Tumors with Horseradish Peroxidase-Functionalized Near-Infrared-II PbS Quantum Dots.

The growth and metastasis of malignant solid tumors depend closely on new blood vessels. Vasculogenic mimicry provides a special pathway of blood supply during the early growth of malignant tumors, and real-time monitoring of its occurrence and development in vivo is important to clinical applications. However, there are few labels with sufficient brightness and stability in vivo to achieve high spatiotemporal resolution imaging of deep tissue for noninvasive optical detection of vasculogenic mimicry in tumor tissues. In this study, we constructed a high-brightness fluorescent label with fluorescence in the near-infrared-II region, which can be used not only for in vivo tumor imaging but also for tissue section imaging. Real-time high-resolution imaging of tumor vessels has been achieved with PbS quantum dots (QDs) surface-coupled with horseradish peroxidase (HRP) (HRP-QDs) by taking advantage of the low background autofluorescence of tissue at the near-infrared-II wavelength for in vivo and tissue section imaging. Qualitative and quantitative analysis of early blood supply patterns of tumor growth enables monitoring neovascularization to accurate noninvasive identification of benign and malignant solid tumors.

Body mass index-based predictions and personalized clinical strategies for colorectal cancer in the context of PPPM.

Currently colorectal cancer (CRC) is the third most prevalent cancer worldwide. Body mass index (BMI) is frequently used in CRC screening and risk assessment to quantitatively evaluate weight. However, the impact of BMI on clinical strategies for CRC has received little attention. Within the framework of the predictive, preventive, and personalized medicine (3PM/PPPM), we hypothesized that BMI stratification would affect the primary, secondary, and tertiary care options for CRC and we conducted a critical evidence-based review. BMI dynamically influences CRC outcomes, which helps avoiding adverse treatment effects. The outcome of surgical and radiation treatment is adversely affected by overweight (BMI ≥ 30) or underweight (BMI < 20). A number of interventions, such as enhanced recovery after surgery and robotic surgery, can be applied to CRC at all levels of BMI. BMI-controlling modalities such as exercise, diet control, nutritional therapy, and medications may be potentially beneficial for patients with CRC. Patients with overweight are advised to lose weight through diet, medication, and physical activity while patients suffering of underweight require more focus on nutrition. BMI assists patients with CRC in better managing their weight, which decreases the incidence of adverse prognostic events during treatment. BMI is accessible, noninvasive, and highly predictive of clinical outcomes in CRC. The cost-benefit of the PPPM paradigm in developing countries can be advanced, and the clinical benefit for patients can be improved with the promotion of BMI-based clinical strategy models for CRC.

A universal strategy for the fabrication of single-photon and multiphoton NIR nanoparticles by loading organic dyes into water-soluble polymer nanosponges.

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes (molar masses of 479.1-1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). The result showed a substantial improvement over the loading of commercial dyes (3.7-50% loading) while preventing their spontaneous aggregation in aqueous solutions. This packaging strategy includes our newly synthesized organic dyes (> 85% loading) designed for OPVs (242), DSSCs (YI-1, YI-3, YI-8), and OLEDs (ADF-1-3, and DTDPTID) applications. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to near-infrared (NIR) emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

Low expression of FOXP2 predicts poor survival and targets caspase-1 to inhibit cell pyroptosis in colorectal cancer.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that FOXP2 functions as a tumour suppressor. However, to date, it remains unclear how FOXP2 influences CRC occurrence. Methods: We took advantage of CRC tissue samples and compared the expression of FOXP2 via immunohistochemistry assays. We elucidated the underlying function of FOXP2 in CRC cells by constructing a cell model with FOXP2 depletion. Co-IP experiments and immunofluorescence (IF) assays were conducted, and the results demonstrated that FOXP2 can promote the activation of caspase-1 to enhance cell pyroptosis. Results: We used tissue RNA sequencing analysis in a colitis-associated cancer mouse model, and found that FOXP2 was downregulated in colitis and tumour tissues. We also found that CRC patients with low FOXP2 expression had poorer survival. Cell viability assays and electron microscopic examination showed that depletion of FOXP2 could enhance cell growth and inhibit cell pyroptosis. At the same time, knocking down FOXP2 expression was able to promote the protein expression of PCNA and cyclin D1 and downregulate the expression of the caspase family of proteins and GSDMD, which are markers of pyroptosis. A series of co-IP and IF assays revealed that FOXP2 interacts with caspase-1 and promotes its expression. Conclusion: Our findings reveal a key role for FOXP2 in CRC cell pyroptosis and provide a mechanism explaining how FOXP2 promotes cell pyroptosis.

A comparative study on the secretion of various cytokines by pulp stem cells at different passages and their neurogenic potential.

AIMS: By measuring the extent of cytokines secreted by human dental pulp stem cells (hDPSCs) from passages 2 through 10, the optimal passage of hDPSCs was determined. This offers a potential theoretical basis for the treatment of neurological disorders. METHOD: After isolation and culture of hDPSCs from human teeth, the morphological features of the cells were observed under an inverted microscope. hDPSCs were identified by their immunophenotypes and their multiple differentiation capability. Cytokine concentrations secreted in the supernatants at passages 2-10 were detected by ELISA. RESULTS: hDPSCs were viewed as fusiform or polygonal in shape, with a bulging cell body, homogenized cytoplasm, and a clear nucleus. Moreover, they could differentiate into neuroblasts in vitro. hDPSCs at passage 3 were positive for CD29 (91.5%), CD73 (94.8%) and CD90 (96.7%), but negative for the hematopoietic markers CD34 (0.13%). ELISA results showed that hDPSCs at passage 3 had the highest secretion levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), with the highest secretion level of Neurotrophin-3 (NT-3) being at passage 2. CONCLUSION: hDPSCs have steady biological features of stem cells and exhibit optimal proliferation potential. hDPSCs at different passages have different capacities in the secretion of VEGF, BDNF, NGF, and NT-3. In conclusion cytokines secreted by hDPSCs may prove to be appropriate in the treatment of neurological diseases.

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice.

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

Submucosal Saline Injection Followed by Endoscopic Ultrasound versus Endoscopic Ultrasound Only for Distinguishing between T1a and T1b Esophageal Cancer.

PURPOSE: To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: Patients with T1N0M0 stage ESCC (n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3-5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases]. RESULTS: Among the per-protocol population, the SSI+EUS group (n = 81) was superior to the EUS-only group (n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6-99.1) vs. 65.9% (95% CI, 55.8-76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1-100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001]. CONCLUSIONS: SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER.

Transcatheter embolization of hepatocellular carcinoma with epirubicin-loaded DC beads in Chinese patients.

BACKGROUND: This study evaluated the safety and efficacy of transcatheter chemoembolization with drug eluting beads (DEB-TACE) and compared it to the conventional TACE (cTACE) therapy method for hepatocellular carcinoma (HCC) in Chinese patients. METHODS: Seventy-four patients were treated with DEB-TACE using the DC bead, and 80 patients were treated with cTACE for HCC. The modified response evaluation criteria in solid tumors (mRECIST) criteria were used to evaluate clinical response, with adverse events assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Post-TACE, 9 patients (12.2%) achieved complete response (CR) and 44 (59.5%) achieved partial response (PR), with an overall tumor response rate (ORR) of 71.6% in the DEB-TACE group. Twelve patients (15%) achieved CR, and 38 (47.5%) achieved PR, with an ORR of 62.5% in the cTACE group. However, there was no significant difference in ORR between the two groups (P=0.229). Univariate logistic regression analysis determined that more than 3 nodules, higher Barcelona clinic liver cancer (BCLC) stage, portal vein invasion, previous chemotherapy (cTACE), and previous surgery were correlated with a worse ORR. Most common adverse events were not severe. CONCLUSIONS: DEB-TACE by DC bead was efficient and well-tolerated compared to cTACE in Chinese HCC patients. However, the present study showed no significant difference in ORR between the DEB-TACE and cTACE in the patient group with HCC. The BCLC stage, number of nodules, portal vein invasion, cTACE, and surgery history could possibly be a predictive factor for HCC treatment response.

Collimated ultrabright gamma rays from electron wiggling along a petawatt laser-irradiated wire in the QED regime.

Even though high-quality X- and gamma rays with photon energy below mega-electron volt (MeV) are available from large-scale X-ray free electron lasers and synchrotron radiation facilities, it remains a great challenge to generate bright gamma rays over 10 MeV. Recently, gamma rays with energies up to the MeV level were observed in Compton scattering experiments based on laser wakefield accelerators, but the yield efficiency was as low as [Formula: see text], owing to low charge of the electron beam. Here, we propose a scheme to efficiently generate gamma rays of hundreds of MeV from submicrometer wires irradiated by petawatt lasers, where electron accelerating and wiggling are achieved simultaneously. The wiggling is caused by the quasistatic electric and magnetic fields induced around the wire surface, and these are so high that even quantum electrodynamics (QED) effects become significant for gamma-ray generation, although the driving lasers are only at the petawatt level. Our full 3D simulations show that directional, ultrabright gamma rays are generated, containing [Formula: see text] photons between 5 and 500 MeV within a 10-fs duration. The brilliance, up to [Formula: see text] photons [Formula: see text] per 0.1% bandwidth at an average photon energy of 20 MeV, is second only to X-ray free electron lasers, while the photon energy is 3 orders of magnitude higher than the latter. In addition, the gamma ray yield efficiency approaches 10%-that is, 5 orders of magnitude higher than the Compton scattering based on laser wakefield accelerators. Such high-energy, ultrabright, femtosecond-duration gamma rays may find applications in nuclear photonics, radiotherapy, and laboratory astrophysics.

Effect of celastrol on toll­like receptor 4­mediated inflammatory response in free fatty acid­induced HepG2 cells.

Toll­like receptor 4 (TLR4)­mediated immune and inflammatory signaling serves a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study demonstrated that celastrol treatment was able to improve hepatic steatosis and inhibit the TLR4 signaling cascade pathway in type 2 diabetic rats. The present study aimed to investigate the effects of celastrol on triglyceride accumulation and inflammation in steatotic HepG2 cells, and the possible mechanisms responsible for the regulation of cellular responses following TLR4 gene knockdown by small interfering RNA (siRNA) in vitro. A cell model of hepatic steatosis was prepared by exposing the HepG2 cells to free fatty acid (FFA) in the absence or presence of celastrol. Intracellular triglycerides were visualized by Oil red O staining, and the TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor­κB (NF­κB) signaling cascade pathway were investigated. To directly elucidate whether TLR4 was the blocking target of celastrol upon FFA exposure, the cellular response to inflammation was determined upon transfection with TLR4 siRNA. The results revealed that celastrol significantly reduced triglyceride accumulation in the steatotic HepG2 cells, and downregulated the expression levels of TLR4, MyD88 and phospho­NF­κBp65, as well as of the downstream inflammatory cytokines interleukin­1ß and tumor necrosis factor α. Knockdown of TLR4 also alleviated FFA­induced inflammatory response. In addition, co­treatment with TLR4 siRNA and celastrol further attenuated the expression of inflammatory mediators. These results suggest that celastrol exerts its protective effect partly via inhibiting the TLR4­mediated immune and inflammatory response in steatotic HepG2 cells.

Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients.

BACKGROUND: This study aimed to investigate the efficacy and safety of drug eluting beads transarterial chemoembolization (DEB-TACE) treatment by CalliSpheres® in Chinese patients with hepatocellular carcinoma (HCC) as well as the predicting factors for response. METHODS: 99 patients with HCC were consecutively enrolled in this study. All participants were treated by CalliSpheres® DEB-TACE. Clinical response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Common Terminology Criteria for Adverse Events (CTCAE) was used to assess the adverse events and liver dysfunction during and after the operation. RESULTS: Post treatment, 16 patients (16.2%) achieved CR and 59 (59.6%) achieved PR, the ORR was 75.8%. Subgroup analysis showed that patients with higher BCLC stage were of worse CR and ORR rates, and the CR as well as ORR between patients with cTACE history and patients without cTACE history were similar. Univariate logistic regression analysis displayed that number of nodules > 3, higher BCLC stage and previous cTACE might be correlated with worse ORR but with no statistical significance. As to liver function, CTCAE grades of laboratory indexes for liver function were increased at 1 week compared to baseline and recovered to the baseline grades at 1-3 months post operation. Besides, most of the common adverse events were light and moderate in our study. CONCLUSIONS: In conclusion, DEB-TACE by CalliSpheres® was efficient and well tolerated in Chinese HCC patients, and BCLC stage, number of nodules and cTACE history were possibly correlated with treatment response.