Percutaneous Transforaminal Endoscopic Lumbar Foraminotomy in Stable Degenerative Lumbar Isthmic Spondylolisthesis with Radicular Leg Pain: A Retrospective Study.

Objective: Endoscopic surgery is a minimally invasive option for effectively addressing lumbar degenerative diseases. This study aimed to describe the specific technology of percutaneous transforaminal endoscopic lumbar foraminotomy (PTELF) as a therapeutic intervention for managing radicular leg pain (RLP) resulting from stable degenerative lumbar isthmic spondylolisthesis (DLIS) and to present the associated clinical results. Methods: From March 2022 and April 2023, 25 patients were diagnosed with single-level stable DLIS with RLP and underwent PTELF. Clinical assessments utilized the visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab criteria. All endoscopic surgery videos were reviewed to interpret the pathology associated with DLIS. Results: The mean age of the cohort was 65.3 ± 11.0 years. The mean preoperative ODI score, VAS score for low back, and VAS score of the leg were 64.1 ± 8.2, 7.0 ± 0.7, and 7.3 ± 0.8, respectively. These scores significantly improved to 16.3 ± 10.4, 2.0 ± 0.6, and 1.7 ± 1.0 at the final follow-up, respectively (P<0.01). The modified MacNab criteria indicated "good" or "excellent" outcomes in 92.0% of cases. Analysis of 23 surgical videos revealed 15 patients with disc herniation, nine with lower vertebral endplate involvement, consistent presence of uneven bone spurs (at the proximal lamina stump and around the foramen), and accumulated scars. Two patients experienced postoperative dysesthesia, and one encountered a recurrence of RLP. Conclusion: PTELF emerges as a potentially safe and effective procedure for alleviating RLP in patients with stable DLIS. However, additional evidence and extended follow-up periods are imperative to evaluate the feasibility and potential risks associated with PTELF.

Transforaminal Endoscopic Lumbar Foraminotomy for the Treatment of L5-S1 Isthmic Lumbar Spondylolisthesis with Foraminal Stenosis: A 1-Year Follow-Up.

BACKGROUND: Isthmic lumbar spondylolisthesis (ILS) is a prevalent spinal pathology. Radicular pain in patients is often attributed to L5-S1 ILS combined with foraminal stenosis (FS), making such patients prime candidates for surgical intervention. We herein aimed to elucidate the surgical technique and clinical outcomes of transforaminal endoscopic lumbar foraminotomy (TELF) in the treatment of L5-S1 ILS with FS. METHODS: From September 2021 to December 2022, 20 consecutive patients were diagnosed with L5-S1 ILS with FS and underwent TELF. All patients were followed up for at least 12 months. The clinical outcomes were evaluated using the visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria. RESULTS: The mean age of the patients was 62.4 ± 10.9 years. The mean preoperative VAS score for low back, VAS score of the leg, and Oswestry Disability Index score was 5.1 ± 1.7, 7.4 ± 0.7, and 58.0 ± 8.4, respectively. These scores significantly improved to 1.8 ± 0.7, 1.5 ± 0.6, and 15.3 ± 7.1 at 12 months postoperatively, respectively (P < 0.01). Evaluation based on the modified MacNab criteria revealed that 95.0% of patients achieved a good-to-excellent outcome. One patient underwent revision surgery. CONCLUSIONS: TELF emerges as a potentially safe and effective surgical option for alleviating radicular pain in patients with L5-S1 stable ILS combined with FS. While our short-term clinical results are satisfactory, it is necessary to expand the sample size and extend the follow-up time to validate the effectiveness and long-term efficacy of TELF.

Structural Elucidation of a Polysaccharide from Flammulina velutipes and Its Lipid-Lowering and Immunomodulation Activities.

FVPT1, a novel heteropolysaccharide, was purified from the fruiting body of Flammulina velutipes using magnetic-field-assisted three-phase partitioning and gel permeation chromatography. The structure was characterized using monosaccharide composition and methylation analysis, infrared spectroscopy and nuclear magnetic resonance (NMR). The FVPT1 (~1.64 × 104 Da) was composed of L-fucose, D-galactose, D-glucose and D-mannose at a molar ratio of 1.0:3.5:1.0:1.4. The polysaccharide repeating unit of FVPT1 was established with methylation analyses and NMR spectroscopy. Moreover, a zebrafish larva hyperlipidemia model test demonstrated that FVPT1 can show appreciable lipid-lowering effects. In addition, the FVPT1 exhibited remarkable immunoregulatory activity by increasing nitric oxide, interleukin (IL)-1ß and IL-1 secretion in macrophages. Therefore, these results suggest that FVPT1 has the potential to be developed into a new immune or hypolipidemic health product.

Quantifying uncertainty: Air quality forecasting based on dynamic spatial-temporal denoising diffusion probabilistic model.

Air pollution constitutes a substantial peril to human health, thereby catalyzing the evolution of an array of air quality prediction models. These models span from mechanistic and statistical strategies to machine learning methodologies. The burgeoning field of deep learning has given rise to a plethora of advanced models, which have demonstrated commendable performance. However, previous investigations have overlooked the salience of quantifying prediction uncertainties and potential future interconnections among air monitoring stations. Moreover, prior research typically utilized static predetermined spatial relationships, neglecting dynamic dependencies. To address these limitations, we propose a model named Dynamic Spatial-Temporal Denoising Diffusion Probabilistic Model (DST-DDPM) for air quality prediction. Our model is underpinned by the renowned denoising diffusion model, aiding us in discerning indeterminacy. In order to encapsulate dynamic patterns, we design a dynamic context encoder to generate dynamic adjacency matrices, whilst maintaining static spatial information. Furthermore, we incorporate a spatial-temporal denoising model to concurrently learn both spatial and temporal dependencies. Authenticating our model's performance using a real-world dataset collected in Beijing, the outcomes indicate that our model eclipses other baseline models in terms of both short-term and long-term predictions by 1.36% and 11.62% respectively. Finally, we conduct a case study to exhibit our model's capacity to quantify uncertainties.

Acupuncture combined with ondansetron for prevention of postoperative nausea and vomiting in high-risk patients undergoing laparoscopic gynaecological surgery: A randomised controlled trial.

BACKGROUND: Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality. OBJECTIVE: This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk. METHODS: This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups. CONCLUSION: Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients.

Effect of Adjunctive Acupuncture on Pain Relief Among Emergency Department Patients With Acute Renal Colic Due to Urolithiasis: A Randomized Clinical Trial.

Importance: Renal colic is described as one of the worst types of pain, and effective analgesia in the shortest possible time is of paramount importance. Objectives: To examine whether acupuncture, as an adjunctive therapy to analgesics, could accelerate pain relief in patients with acute renal colic. Design, Setting, and Participants: This single-center, sham-controlled, randomized clinical trial was conducted in an emergency department in China between March 2020 and September 2020. Participants with acute renal colic (visual analog scale [VAS] score ≥4) due to urolithiasis were recruited. Data were analyzed from October 2020 to January 2022. Interventions: After diagnosis and randomization, all patients received 50 mg/2 mL of diclofenac sodium intramuscular injection immediately followed by 30-minute acupuncture or sham acupuncture. Main Outcomes and Measures: The primary outcome was the response rate at 10 minutes after needle manipulation, which was defined as the proportion of participants whose VAS score decreased by at least 50% from baseline. Secondary outcomes included response rates at 0, 5, 15, 20, 30, 45, and 60 minutes, rescue analgesia, and adverse events. Results: A total of 115 participants were screened and 80 participants (66 men [82.5%]; mean [SD] age, 45.8 [13.8] years) were enrolled, consisting of 40 per group. The response rates at 10 minutes were 77.5% (31 of 40) and 10.0% (4 of 40) in the acupuncture and sham acupuncture groups, respectively. The between-group differences were 67.5% (95% CI, 51.5% to 83.4%; P < .001). The response rates of acupuncture were also significantly higher than sham acupuncture at 0, 5, 15, 20 and 30 minutes, whereas no significant difference was detected at 45 and 60 minutes. However, there was no difference between the 2 groups in rescue analgesia rate (difference 2.5%; 95% CI -8.8% to 13.2%; P > .99). No adverse events occurred during the trial. Conclusions and Relevance: These findings suggest that acupuncture plus intramuscular injection of diclofenac is safe and provides fast and substantial pain relief for patients with renal colic compared with sham acupuncture in the emergency setting. However, no difference in rescue analgesia was found, possibly because of the ceiling effect caused by subsequent but robust analgesia of diclofenac. Acupuncture can be considered an optional adjunctive therapy in relieving acute renal colic. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900025202.

Smart phone-based transcutaneous electrical acupoint stimulation as adjunctive therapy for hypertension (STAT-H trial): protocol for a cluster randomised controlled trial.

INTRODUCTION: Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension. METHODS AND ANALYSIS: This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure <140/90 mm Hg), proportion of patients taking antihypertensive drugs, change in number of antihypertensive drugs and changes in 12-item Short-Form. Tertiary outcomes will include change in body mass index, change in waist circumference, physical activity and medication adherence. Safety outcomes will be any serious adverse events and clinical events. ETHICS AND DISSEMINATION: This study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2000039400.

[Factors associated with positive results in English literature of acupuncture for chronic pain].

OBJECTIVE: To analyze the main factors affecting the positive results of acupuncture for chronic pain in English literature of randomized controlled trial (RCT), in order to provide reference for the design of acupuncture clinical research. METHODS: The RCTs of acupuncture for chronic pain published before March 26, 2020 were searched in PubMed, EMbase and Cochrane Library by computer. A total of 21 factors were analyzed by single-factor analysis, and the factors with statistically significant difference were selected for multivariate Logistic regression analysis. RESULTS: A total of 69 RCTs were included, including 47 RCTs (68.12%) with positive results and 22 RCTs (31.88%) with non-positive results. The multivariate Logistic regression analysis was performed with the three screened factors (publication year, treatment frequency and intervention form) selected by single-factor analysis, and the results showed that the positive results were related to the frequency of acupuncture treatment. The positive rate of RCT with frequency≥2 times a week was 3.24 times of that with frequency<2 times a week (OR=3.24, 95%CI =[1.07,9.83], P<0.05). CONCLUSION: Acupuncture frequency may be the main factor affecting the positive results of RCT in English literature of acupuncture for chronic pain. More researches are needed in the future to explore the influence of acupuncture frequency on the curative effect.

Acupuncture for chronic sciatica: protocol for a multicenter randomised controlled trial.

BACKGROUND: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks. METHODS AND ANALYSIS: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults.

The complete mitochondrial genome of the edible mushroom Grifola frondosa.

The culinary-medicinal mushroom Grifola frondosa is widely cultivated in East Asia. In this study, the complete mitochondrial genome of G. frondosa was determined using Illumina sequencing. The circular molecule was 197,486 bp in length with a content of 25.01% GC, which was one of the largest mitochondrial genomes in the order Polyporales. A total of 39 known genes encoding 13 common mitochondrial genes, 24 tRNA genes, 1 ribosomal protein s3 gene (rps3), and 1 DNA polymerase gene (dpo) were predicted in this genome. The phylogenetic analysis showed that G. frondosa clustered together with Sparassis crispa, Laetiporus sulphureus, Wolfiporia cocos, and Taiwanofungus camphoratus. The complete mitochondrial genome reported here may provide new insight into genetic information and evolution for further studies.

[Application of "patient and public involvement" in acupuncture clinical research].

In order to explore the application of "patient and public involvement" (PPI) in acupuncture clinical research, the connotation, reporting standards and research status of PPI at home and abroad are collated, and the key problems of PPI encountered in acupuncture clinical research are deeply considered and summarized. It is suggested that the short-form checklist of the Guidance for Reporting Involvement of Patients and the Public (GRIPP) of the 2nd edition should be applied to acupuncture clinical research. PPI provides a new perspective for acupuncture clinical research. It is beneficial for each stage of research, contributes to the improvement of acupuncture medical service mode and increases the success rate and cost-effectiveness of research so that the innovation and development of acupuncture science can be promoted.

Overall Reporting Descriptions of Acupuncture for Chronic Pain in Randomized Controlled Trials in English Journals.

BACKGROUND: Whether the clinical effect of acupuncture in chronic pain is effective has always been a hot topic of research, which has a great relationship with the overall reporting descriptions of acupuncture, especially the sham acupuncture intervention. To confirm the effectiveness of acupuncture, more clinical studies are often required. Therefore, it is necessary to report high-quality and complete descriptions of acupuncture in clinical trials. This study aims to assess the overall reporting quality of acupuncture for chronic pain in randomized controlled trials (RCTs). METHODS: Three databases from inception to March 2020 were searched, to assess the quality of acupuncture reports included the RCTs based on the pain-specific supplement to Consolidated Standards for Reporting Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. The quality of sham acupuncture descriptions was evaluated based on the Template for Intervention Description and Replication (TIDieR)-placebo checklist. Descriptive statistics and analysis of the results were carried out according to the percentage of each item. RESULTS: A total of 74 RCTs were included which met the inclusion criteria. Based on the pain-specific CONSORT, the reporting rates of "Statistical methods", "Participant flow", and "Blinding" were "52.70%", "70.27%", and "77.03%", respectively. The weakest reported items in STRICTA were related to the depth of insertion (Item 2c, 54.05%) and the setting and context of treatment (Item 4b, 0.00%). Based on the TIDieR-placebo checklist, the reporting rates of "Item 12", "Item 11", "Item 13", "Item 3", and "Item 4" were "8.11%", "10.81%", "29.73%", " 44.59% ", and "47.30%", respectively. CONCLUSION: At present, the overall report quality of acupuncture treatment for chronic pain in English journals is acceptable, but the report rate in some aspects is still low. In the future, researchers should report RCTs of acupuncture following cleaner checklists and guidelines.

Acupuncture for persistent atrial fibrillation after catheter ablation: study protocol for a pilot randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA). METHODS AND DESIGN: This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3 months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded. DISCUSSION: This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

Effect of tetracaine on dynamic reorganization of lipid membranes.

To understand the intrinsic influence of a drug on lipid membranes is of critical importance in pharmacological science. Herein, we report fluorescence microscopy analysis of the interaction between the local anesthetic tetracaine (TTC) and planar supported lipid bilayers (SLBs), as model membranes. Our results show that TTC increases lipid chain mobility, destabilizes the SLBs and remarkably induces membrane disruption and solubilization. Upon TTC binding, a local curvature change in the bilayer was observed, which led to the subsequent formation of up to 20-µm-long flexible lipid tubules as well as the formation of micron-size holes. Quantitative analysis revealed that membrane solubilization process can be divided into two distinct different stages as a function of TTC concentration. In the first stage (<800 µM), the bilayer disruption profiles fit well to a Langmuir isotherm, while in the second stage (800 µM-25 mM), TTC solubilizes the membrane in a detergent-like manner. Notably, the onset of membrane solubilization occurred below the critical micelle concentration (cmc) of TTC, indicating a local accumulation of the drug in the membrane. Additionally, cholesterol increases the insertion of TTC into the membrane and thus promotes the solubilization effect of TTC on lipid bilayers. These findings may help to elucidate the possible mechanisms of TTC interaction with lipid membranes, the dose dependent toxicity attributed to local anesthetics, as well as provide valuable information for drug development and modification.

EFFECTS OF TEST-BOLUS AND LOW-DOSE SCAN ON CT PULMONARY ANGIOGRAPHY IMAGE QUALITY IN PATIENTS WITH DIFFERENT BODY MASS INDEXES.

This study aimed to investigate different methods of obtaining high-quality Computed Tomography pulmonary angiography (CTPA) images using low-dose scanning in patients with different body mass index (BMI) values. Sixty patients with suspected pulmonary embolism were grouped based on their BMI values (BMI < 25, designated N, and BMI ≥ 25, designated O) and were assigned to receive either test bolus (TB) or bolus tracking (BT) at conventional (C) or low (L) dose. The effective dose (ED) in the N-TB-L group was lower than in the group N-TB-C (0.56 ± 0.05 vs. 3.78 ± 1.16, p < 0.001), with similar image quality (4.90 ± 0.31 vs. 4.70 ± 0.47, p = 0.120). The ED in the O-TB-L group was lower than in the O-TB-C group (0.54 ± 0.03 vs. 5.14 ± 1.34, p < 0.001), but the group O-TB-C's image quality was higher (4.65 ± 0.59 vs. 3.95 ± 0.89, p = 0.006). Groups N-TB-L versus O-TB-L, groups N-TB-L versus N-BT-L and groups O-TB-C versus O-BT-C had similar EDs (all ps > 0.05), but the image quality was different (all ps < 0.05). In conclusion, the results showed that the image quality of low-dose CTPA scanning using TB was similar to that of the conventional-dose CTPA in patients with BMI < 25 but was lower in patients with BMI ≥ 25. TB was better than BT for all patients, regardless of BMI, when receiving the same ED.

[Observation on therapeutic effect of acupuncture at "experienced ten acupoints" for postprandial distress syndrome].

OBJECTIVE: To observe the clinical effect of acupuncture at "experienced ten acupoints" for postprandial distress syndrome. METHODS: A total of 62 patients with postprandial distress syndrome were randomly divided into an observation group (31 cases, 5 cases dropping off) and a control group (31 cases, 6 cases dropping off ). Acupuncture was applied at Baihui (GV 20), Zhongwan (CV 12), Qihai (CV 6), Tianshu (ST 25), Neiguan (PC 6), Zusanli (ST 36), Gongsun (SP 4), Danzhong (CV 17) in the observation group. In the control group, 6 non-acupoint points were intervened with shallow puncture. The treatment was given 20 min each time, once every other day, 3 times a week for a total of 4 weeks in the two groups. Symptom index of dyspepsia (SID) and Nepean dyspepsia index (NDI) scores were compared before and after treatment, and the efficacy was evaluated in the two groups. RESULTS: The effective rate in the observation group was 76.9% (20/26), which was higher than 28.0% in the control group (7/25, P<0.01). After treatment, the SID and NDI scores in the two groups were lower than those before treatment (P<0.01, P<0.05), and the SID and NDI scores in the observation group were lower than those in the control group (P<0.01, P<0.05). CONCLUSION: Acupuncture at "experienced ten acupoints" can significantly reduce the symptoms of dyspepsia and improve the quality of life in patients with postprandial distress syndrome.

T7 Peptide-Conjugated Lipid Nanoparticles for Dual Modulation of Bcl-2 and Akt-1 in Lung and Cervical Carcinomas.

Expression of Bcl-2 and Akt-1 has been associated with human cancer. G3139 and RX-0201, targeting Bcl-2 and Akt-1, respectively, are antisense oligonucleotides (ASOs) that have shown limited efficacy in clinical trials. Herein, we report a combination of newly designed ASOs based on these agents and was delivered by tumor cell-targeting lipid nanoparticles (LNPs). A "Gapmer" design strategy was applied to these ASOs with the addition of 2'-O-methyl modifications on the nucleotides at 5' and 3' ends. A dual-channel syringe pump-based system was developed for the synthesis of the LNPs. ASO-LNPs composed of DODMA, egg PC, cholesterol, T7-PEG-DSPE, and PEG-DMG at a molar ratio of 35:39.5:20:0.5:5 and carrying either individual ASOs or co-loaded ASO combinations (Co-ASOs) were synthesized and evaluated in both KB and A549 cancer cells and in an A549 murine xenograft model to determine their antitumor effects and biological activities. The ASO-LNPs exhibited excellent colloidal stability and high ASO encapsulation efficiency with relatively small mean particle sizes and moderately positive zeta potentials. Transferrin receptor-targeting T7-conjugated LNPs showed enhanced cellular uptake compared to nontargeted LNPs. In addition, both T7-conjugated Co-ASOs-LNPs and non-T7-conjugated Co-ASOs-LNPs at a molar ratio of (G3139-GAP to RX-0201-GAP at 1:2) showed efficient downregulation of both Bcl-2 and Akt-1 in both A549 and KB cells. Furthermore, T7-conjugated Co-ASOs-LNPs (Co-ASOs-LNPs) produced superior antitumor activity, prolonged the overall survival time, and demonstrated tumor targeting activity in an A549 xenograft model.

Tumor-Targeted and Clearable Human Protein-Based MRI Nanoprobes.

Biocompatibility, targeting, and clearance are key challenges in the design of new MRI contrast agents. Herein, we report on a tumor-targeting, gadolinium biomineralized human transferrin (Tf) protein-based nanoparticle (Gd@Tf NP) for MRI use. As compared to the conventionally used gadolinium chelates, the resultant Gd@Tf NPs possess outstanding chemical stability and exhibited superior longitudinal relaxation. More importantly, our MR images show that Gd@Tf indeed retained the natural tumor targeting ability and the subsequent tumor retrieval biofunctions of Tf. Thus, such Tf protein-based MR NPs integrate T1 signal amplification, precise tumor targeting, and systematic clearance capabilities. They offer a new approach to design biocompatible multifunctional MRI contrast agents for a wide range of clinical imaging and treatment applications.

Could ADC values be a promising diagnostic criterion for differentiating malignant and benign hepatic lesions in Asian populations: A meta-analysis.

BACKGROUND: Liver cancer exhibits geographic and ethnic differences in its prevalence and biology, which implies that it is impractical to develop universal guidelines for all patients. Thus, a meta-analysis was conducted to identify the accuracy of apparent diffusion coefficients (ADCs) for discriminating malignant from benign liver lesions in Asians. METHODS: Eligible studies published in PubMed, Ovid, and Embase/Medline were updated onto October 2014. STATA 12.0 and Meta-Disc 1.4 were used to perform this meta-analysis. RESULTS: Eight studies comprising 661 benign liver lesions and 598 malignant liver lesions fulfilled all the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.88 (95% confidence interval [CI] 0.75-0.95), 0.93 (95% CI 0.86-0.97), 12.42 (95% CI 6.09-25.31), 0.13 (95% CI 0.06-0.29), and 95.58 (95% CI 35.29-258.89), respectively. Overall, the area under the summary receiver-operating characteristic curve was 0.96 (95% CI 0.94-0.98). Heterogeneity was found to originate potentially from the type of benign lesion. A subgroup analysis showed that differentiating between hemangiomas, cysts, and malignant liver lesions produced a significantly higher diagnostic accuracy than that of solid liver lesions. CONCLUSION: Our meta-analysis indicated that ADC could be promising for characterizing liver lesions among Asians, indicating that the ADC value is a promising diagnostic criterion candidate. Meanwhile, the use of dual b values could be sufficient for liver lesion characterization. However, large-scale, high-quality trials should be conducted to identify specific standards, including cut-off values for further development of diffusion-weighted imaging as a routine clinical application among Asian populations.

miR-98 protects endothelial cells against hypoxia/reoxygenation induced-apoptosis by targeting caspase-3.

Endothelial dysfunction is one of the main pathophysiological processes involved in renal ischemia reperfusion injury. Our previous microarray study demonstrated that miR-98 was upregulated in the kidney with ischemia reperfusion injury (IRI). The present study was performed to investigate whether miR-98 was involved in the regulation of endothelial apoptosis under hypoxia and re-oxygenation (H/R) conditions. The dynamic changes of miR-98 in mouse IRI kidney and H/R HUVECs was measured. HUVECs were treated with HIF-1α siRNA to investigate the role of HIF-1α on miR-98 expression. The potential target genes of miR-98 were predicted by bioinformatics analyses. HUVECs were transfected with miR-98 mimics or inhibitor to confirm the role of miR-98 on the expression of target genes and hypoxia-induced apoptosis. The target gene was finally confirmed by dual-luciferase reporter assay. Both of IRI and H/R induced significantly up-regulation of miR-98 in the ischemic kidney and hypoxic HUVECs. HIF-1α siRNA remarkably down-regulated the expression of miR-98 in both normal and hypoxic HUVECs. The putative target genes of miR-98 included IL-6, IL-10 and caspase-3. MiR-98 mimics significantly inhibit caspase-3 expression in HUVECs, while anti-miR-98 significantly up-regulated it. But no change of IL-6 and IL-10 levels was observed after miRNA transfection. miR-98 protected HUVECs against apoptosis induced by hypoxia, while anti-miR-98 had the reverse effect. Furthermore, the dual-luciferase reporter assay confirmed that miR-98 decreased the luciferase activity by targeting the 3' untranslated region of caspase-3. In conclusion, Renal IRI induces up-regulation of miR-98 dependent on HIF-1α, which protects endothelial cells against apoptosis by targeting caspase-3.