Molecular cloning and functional characterization of peroxinectin from red swamp crayfish, Procambarus clarkii.

Peroxinectin, which has both peroxidase and cell adhesion activities, is crucial for invertebrate innate immune responses. In this study, we first cloned the full-length cDNA of Procambarus clarkii Peroxinectin (denoted as Pc-Px) and evaluated its immune roles. The Pc-Px cDNA had 2460 base pairs (bp) and 819 amino acid residues, including peroxidase domain and a putative integrin-binding motif. Pc-Px tissue expression was found to be ubiquitous in all examined tissues under normal physiological conditions. Pc-Px mRNA levels were highest in hemocytes, followed by gills and heart, and were lowest in the gut. The LPS, PGN, and Poly I:C treatment significantly up-regulated the transcript level of Pc-Px gene, but the expression trends were different after the microbials component treatments. Pc-Px knockdown using double-stranded RNA altered the transcription profiles of various immune-related genes in hepatopancreas of P. clarkii. Taken together, Pc-Px is an important component of immune system that likely to modulate immune function of P. clarkii via regulating immune-associated genes.

A nomogram based on ultrasound characteristics to predict large-number cervical lymph node metastasis in papillary thyroid carcinoma.

To establish a nomogram for predicting large-number cervical lymph node metastases (LNMs) of primary papillary thyroid carcinoma (PTC) based on ultrasound characteristics. This retrospective study included patients with PTC diagnosed by pathological examination and who underwent surgery between August 2015 and May 2021 at Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo, China). Large-number LNM was defined as >5 lymph nodes with metastases. The patients were propensity score-matched (PSM) for age and sex. A multivariable analysis was used to determine the risk factors for massive LNM. After PSM, the 78 patients with large-number LNM were matched with 312 patients with small-number LNM. Compared with the patients with small-number LNM, those with large-number LNM had larger tumors (13.0 ± 7.7 vs. 6.8 ± 3.8 mm, p < 0.001), and higher frequencies of multifocal nodules (42.3% vs. 22.4%, p < 0.001), taller-than-wide shape (82.1% vs. 56.7%, p < 0.001), calcifications (76.9% vs. 47.4%, p < 0.001), microcalcifications (68.0% vs. 36.5%, p < 0.001), capsule invasion (32.1% vs. 17.6%, p = 0.005), and ultrasound diagnosis of LNM (44.9% vs. 9.3%, p < 0.001). The multivariable analysis showed that nodule size (OR = 1.19, 95%CI: 1.11-1.27, p < 0.001), multifocal disease (OR = 2.50, 95%CI: 1.30-4.80, p = 0.006), taller-than-wide shape (OR = 0.45, 95%CI: 0.22-0.93, p = 0.032), and ultrasound diagnosis of LNM (OR = 5.57, 95%CI: 2.73-11.37, p < 0.001) were independently associated with large-number LNM. A nomogram was built, and the area under the receiver operating characteristics curve was 0.86 (95%CI: 0.81-0.90). A nomogram was successfully built to predict large-number LNM in patients with PTC, based on nodule size, multifocality, taller-than-wide shape, and ultrasound diagnosis of LNM.

Multimodal ultrasonography of male primary breast lymphoma.

① Gray scale ultrasound showed multiple hypoechoic masses of varying sizes in the right breast. The larger one was 1.8 × 0.7 cm (arrow), oval in shape, with clear boundaries, and lymphatic hilar-like structures. ② Color Doppler ultrasonography showed blood flow signals within the hypoechoic mass, and the larger (arrow) mass showed blood flow signals similar to lymphatic hilum. ③ Elastography showed the mass was soft and blue (short arrow) or green (long arrow) in texture, and the surrounding tissue was hard and red in texture. ④ Contrast-enhanced ultrasound showed that after 19 s of contrast agent injection, the whole breast showed a 'snowflake' high enhancement, but no enhancement was observed in local areas (arrow). ⑤ The ultrasound-guided puncture image clearly showed the puncture needle (arrow) insert into the hypoechoic mass for biopsy. ⑥ The arrow in the pathological image (HE, 20 × 10 times) showed tumor cells.

The value of radiomics model based on ultrasound image features in the differentiation between minimal breast cancer and small benign breast masses.

BACKGROUND: Female breast cancer has surpassed lung cancer as the most common cancer, and is also the main cause of cancer death for women worldwide. Breast cancer <1 cm showed excellent survival rate. However, the diagnosis of minimal breast cancer (MBC) is challenging. OBJECTIVE: The purpose of our research is to develop and validate an radiomics model based on ultrasound images for early recognition of MBC. METHODS: 302 breast masses with a diameter of <10 mm were retrospectively studied, including 159 benign and 143 malignant breast masses. The radiomics features were extracted from the gray-scale ultrasound image of the largest face of each breast mass. The maximum relevance minimum reduncancy and recursive feature elimination methods were used to screen. Finally, 10 features with the most discriminating value were selected for modeling. The random forest was used to establish the prediction model, and the rad-score of each mass was calculated. In order to evaluate the effectiveness of the model, we calculated and compared the area under the curve (AUC) value, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the model and three groups with different experience in predicting small breast masses, and drew calibration curves and decision curves to test the stability and consistency of the model. RESULTS: When we selected 10 radiomics features to calculate the rad-score, the prediction efficiency was the best, the AUC values for the training set and testing set were 0.840 and 0.793, which was significantly better than the insufficient experience group (AUC = 0.673), slightly better than the moderate experience group (AUC = 0.768), and was inferior to the experienced group (AUC = 0.877). The calibration curve and decision curve also showed that the radiomics model had satisfied stability and clinical application value. CONCLUSION: The radiomics model based on ultrasound image features has a satisfied predictive ability for small breast masses, and is expected to become a potential tool for the diagnosis of MBC, and it is a zero cost (in terms of patient participation and imaging time).

Separable and Inseparable Silk Fibroin Microneedles for the Transdermal Delivery of Colchicine: Development, Characterization, and Comparisons.

Colchicine is the first-line option for both the treatment and prophylaxis of gout flares. However, due to potentially severe side effects, the clinical use of colchicine is limited. A well-tolerated and safe delivery system for colchicine is widely desired. For this purpose, colchicine-loaded inseparable microneedles were fabricated using silk fibroin. Additionally, separable microneedles made of silk fibroin as the needle tips and PVP K30 as the base material were developed. Both types of microneedles were evaluated for their mechanical strength, swelling and dissolution characteristics, insertion abilities, degradation properties, in vitro penetration, skin irritation, and in vivo anti-gout effects. The results demonstrated that separable microneedles had greater mechanical strength and insertion ability. Moreover, the separable microneedles separated quickly and caused little skin irritation. In the pharmacodynamic test, mice with acute gouty arthritis responded significantly to treatment with separable microneedles. In conclusion, the separable silk fibroin-based microneedles provide a promising route for colchicine delivery.

Development and validation of a novel immune-related prognostic model in lung squamous cell carcinoma.

Background: The immune system plays an important role in the development of lung squamous cell carcinoma (LUSC). Therefore, immune-related genes (IRGs) expression may be an important predictor of LUSC prognosis. However, a prognostic model based on IRGs that can systematically assess the prognosis of LUSC patients is still lacking. This study aimed to construct a LUSC immune-related prognostic model by using IRGs. Methods: Gene expression data about LUSC were obtained from The Cancer Genome Atlas (TCGA). Differential expression analysis and univariate Cox regression analysis were performed to identify prognostic differentially expressed IRGs. A prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Then we validated the performance of the prognostic model in training and test cohorts. Furthermore, associations with clinical variables and immune infiltration were also analyzed. Results: 593 differentially expressed IRGs were identified, and 8 of them were related to prognosis. Then a transcription factor regulatory network was established. A prognostic model consisted of 4 immune-related genes was constructed by using Lasso and multivariate Cox regression analyses. The prognostic value of this model was successfully validated in training and test cohorts. Further analysis showed that the prognostic model could be used independently to predict the prognosis of LUSC patients. The relationships between the risk score and immune cell infiltration indicated that the model could reflect the status of the tumor immune microenvironment. Conclusions: We constructed a risk model using four PDIRGs that can accurately predict the prognosis of LUSC patients. The risk score generated by this model can be used as an independent prognostic indicator. Moreover, the model can predict the infiltration of immune cells in patients, which is conducive to the prediction of patient sensitivity to immunotherapy.

The Effect of Prim-O-Glucosylcimifugin on Tryptase-Induced Intestinal Barrier Dysfunction in Caco-2 Cells.

The intestinal barrier dysfunction is a critical pathological change in irritable bowel syndrome (IBS). The objective of this study was to evaluate the effect of Prim-O-glucosylcimifugin (POG) on intestinal barrier dysfunction and reveal possible molecular mechanisms. Human colon adenocarcinoma cell line (Caco-2) cell monolayers induced by tryptase (TRYP) were used to establish an intestinal barrier dysfunction model. Caco-2 cell monolayers from both functional and dysfunctional samples were treated with POG (30, 60 and 120 µg/mL) for 2, 8, 24, 36, 48 and 72 h. The Caco-2 cell monolayers were assessed by measurement of trans-epithelial electrical resistance (TEER) and percentage of fluorescein permeation (PFP). The expression of Protease Activated Receptor 2 (PAR-2) and myosin light chain kinase (MLCK) mRNA was analyzed by RT-PCR and the level of Zonula Occludens-1 (ZO-1) protein expression was determined by Western blot. In addition, the impact of POG on the distribution of the tight juction protein of Occludin was performed by immunofluorescence. Our results showed that POG elevated the TEER and decreased the PFP of the functional Caco-2 cell monolayers, as well as the dysfunctional Caco-2 cell monolayers. Furthermore, POG inhibited the expression of PAR-2 mRNA and MLCK mRNA and increased the level of ZO-1 protein expression in dysfunctional Caco-2 cells. The distribution of the Occludin proteins was ameliorated simultaneously. This study demonstrates that POG can enhance the intestinal barrier function of Caco-2 cell monolayers by inhibiting the expression of PAR-2 and MLCK and up-regulating the expression of ZO-1 protein, and ameliorated the distribution of Occludin protein.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

Dissolving microneedle-based intradermal delivery of interferon-α-2b.

The dermal and transdermal delivery of protein pharmaceuticals faces enormous challenges, and at the same time, has very significant potential for the non-invasive treatment of both localized and systemic diseases. To demonstrate the pharmaceutical usefulness of dissolving microneedles (MNs) containing interferon-α-2b (IFN), IFN MNs were prepared using a new method. IFN were encapsulated in MNs with dose from 4.94 ± 0.64 to 23.79 ± 2.48 µg, and in vitro release test showed the efficiency reached 49.2%. After percutaneous administration of IFN MNs to rats, serum IFN levels were measured for 12 h. The peak serum IFN level, maximum drug concentration (Cmax), and the time to reach maximum concentration (Tmax), were 11.58 ± ng/ml and 40 min, respectively, for high-dose MNs group. The area under the curve (AUC) of MNs group was 28.85 ng·h/ml, while intramuscular injection (IM) group with equal dose was 31.17 ng·h/ml. Immunogenicity analysis showed the anti-IFN antibody got back to normal level at ninth week, and there was no difference between male and female rats. IFN MNs showed good stability for 2 months and no damage to the administered rats' skin. The results demonstrated the IFN MNs have a great potential to provide an alternative to IM.

Controllable coating of microneedles for transdermal drug delivery.

Coated microneedles have been paid much attention recently, and several coating strategies have been developed to address the problems during coating process. However, there are still some unresolved issues, such as, precise control requirements, microneedle substrate contamination and high processing temperature. The purpose of this study was to develop a simple and controllable method to make uniform coatings on microneedles at room temperature. This novel method avoids the contamination of microneedle substrate by providing both the adsorption force of thickener and micro-scale coating film produced by a newly design device. Thickeners were screened to enhance the mass of coatings. The parameters that influence the coatings were tested systematically, which made coating process controllable. Finally, three model drugs were coated onto microneedles to prove the method is applicable more broadly. In addition, insertion experiments were carried out to test the drug delivery feasibility of the coated microneedles. In conclusion, this study presents a simple and controllable method to coat microneedles with small molecular chemical drugs or large proteins for rapid skin drug delivery.

Electroacupuncture Facilitates Vascular Normalization by Inhibiting Glyoxalase1 in Endothelial Cells to Attenuate Glycolysis and Angiogenesis in Triple-Negative Breast Cancer.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

Effective transcutaneous immunization against hepatitis B virus by a combined approach of hydrogel patch formulation and microneedle arrays.

Transcutaneous immunization (TCI) has many advantages compared with needle-based administrations. But the conventional TCI shows poor permeation of antigens across the skin barrier. In this study, Functional MicroArray (FMA) system was used to poke the skin and increase the permeability, and the hydrogel patch formulation was used as the carrier for transdermal delivery of hepatitis B surface antigen (HBsAg) and cholera toxin B (CTB) as an adjuvant. In vitro permeation of antigen was studied using porcine ear skin and rat abdominal skin. The results showed that FMA system could significantly increase the permeation of HBsAg across skin compared with conventional TCI. HBsAg loaded hydrogel formulation exhibited better antigenic thermostability than the liquid formulation. In vivo immunization studies were performed in mice, and the serum IgG titer, IgG2a/IgG1 ratio were measured. The results showed that TCI with FMA induced more potent immune responses than the groups without FMA pretreatment. CTB adjuvanted TCI group could induce higher IgG titers compared with the group without CTB. Furthermore, TCI group can maintain a longer duration of stable IgG titers compared with the intramuscular injection (IM) group. In conclusion, the FMA/hydrogel system was proved to be a potential vaccination strategy against hepatitis B virus.

Invasive acupuncture for gastroparesis after thoracic or abdominal surgery: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis aimed to systematically evaluate the efficacy of acupuncture in treating postsurgical gastroparesis syndrome (PGS) after thoracic or abdominal surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Twelve databases (PubMed, Embase, Cochrane Library Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) (from 1946), Web of Science, EBSCO, Scopus, Open Grey, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc (CBM)) and three registration websites (WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR)) were searched from the inception to September 2022, and citations of the included literature were screened. ELIGIBILITY CRITERIA: All randomised controlled trials addressing invasive acupuncture for PGS. DATA EXTRACTION AND SYNTHESIS: Key information on the included studies was extracted by two reviewers independently. Risk ratio (RR) with 95% CI was used for categorical data, and mean difference with 95% CI for continuous data. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Outcomes were conducted with trial sequential analysis (TSA). RESULTS: Fifteen studies with 759 patients met the inclusion criteria. Subgroup analyses revealed that compared with the drug group, the drug and acupuncture group had a greater positive effect on the total effective rate (TER) (nine trials, n=427; RR=1.20; 95% CI 1.08 to 1.32; P-heterogeneity=0.20, I2=28%, p=0.0004) and the recovery rate (RCR) (six trials, n = 294; RR = 1.61; 95% CI 1.30 to 1.98; P-heterogeneity=0.29, I2=19%, p<0.0001) of PGS after abdominal surgery. However, acupuncture showed no significant advantages in terms of the TER after thoracic surgery (one trial, p=0.13) or thoracic/abdominal surgery-related PGS (two trials, n = 115; RR=1.18; 95% CI 0.89 to 1.57; P-heterogeneity=0.08, I2=67%, p=0.24) and the RCR after thoracic/abdominal surgery (two trials, n=115; RR=1.40; 95% CI 0.97 to 2.01; P-heterogeneity=0.96, I2=0%, p=0.07). The quality of evidence for TER and RCR was moderate certainty. Only one study reported an acupuncture-related adverse event, in the form of mild local subcutaneous haemorrhage and pain that recovered spontaneously. TSA indicated that outcomes reached a necessary effect size except for clinical symptom score. CONCLUSION: Based on subgroup analysis, compared with the drug treatment, acupuncture combined drug has significant advantages in the treatment of PGS associated with abdominal surgery, but not with thoracic surgery. PROSPERO REGISTRATION NUMBER: CRD42022299189.

Development of ensemble learning models for prognosis of hepatocellular carcinoma patients underwent postoperative adjuvant transarterial chemoembolization.

Background: Postoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for individualized prognostic prediction and early management. Methods: A total of 274 HCC patients who underwent PA-TACE were enrolled in this study. The prediction performance of five machine learning models was compared and the prognostic variables of postoperative outcomes were identified. Results: Compared with other machine learning models, the risk prediction model based on ensemble learning strategies, including Boosting, Bagging, and Stacking algorithms, presented better prediction performance for overall mortality and HCC recurrence. Moreover, the results showed that the Stacking algorithm had relatively low time consumption, good discriminative ability, and the best prediction performance. In addition, according to time-dependent ROC analysis, the ensemble learning strategies were found to perform well in predicting both OS and RFS for the patients. Our study also found that BCLC Stage, hsCRP/ALB and frequency of PA-TACE were relatively important variables in both overall mortality and recurrence, while MVI contributed more to the recurrence of the patients. Conclusion: Among the five machine learning models, the ensemble learning strategies, especially the Stacking algorithm, could better predict the prognosis of HCC patients following PA-TACE. Machine learning models could also help clinicians identify the important prognostic factors that are clinically useful in individualized patient monitoring and management.

Simultaneous basal-bolus delivery of fast-acting insulin and its significance in diabetes management.

Insulin delivery relies on subcutaneous or intravascular injection, leading to reduced patient compliance. Transdermal delivery of insulin has been successfully demonstrated but dose accuracy and skin irritation are problematic in addition to the complex basal-bolus delivery profile required by insulin therapy. Here we present a novel intraepidermal delivery technology (delivered site at epidermis layer, <150 µm) by combining skin pretreatment with short microneedles (<150 µm in length) and iontophoresis transdermal patch (enhanced transport via electrical field) that can provide a continuous basal dose and on-demand bolus dosing for mealtime insulin needs. To our knowledge, this is the first demonstration of therapeutic equivalence between fast-acting human regular insulin and long-acting insulin with possibilities for on-demand dose adjustment. This new intraepidermal delivery technology is likely to change the therapy regimen of patients suffering from insulin-dependent diabetes mellitus and provide a way to lower cost in comparison with insulin pumps and improve patient compliance. FROM THE CLINICAL EDITOR: The authors present a novel intraepidermal insulin delivery technology by combining skin pretreatment with short microneedles and iontophoresis transdermal patch to provide a continuous basal dose and on-demand bolus dosing. This new method is has the potentials to replace insulin pumps by offering a cost effective alternative with less inconvenience and improved compliance.

Enhanced transdermal delivery of 18ß-glycyrrhetic acid via elastic vesicles: in vitro and in vivo evaluation.

OBJECTIVE: The aim of this work was to develop an elastic vesicular formulation to enhance the skin permeation of a poorly water-soluble 18ß-glycyrrhetic acid (GA) and treat dermatitis. METHODS: Elastic vesicles of GA were prepared by the film method with high pressure homogenizer and characterized by storage stability. In vitro permeation studies were carried on rat skin using Franz diffusion cell. In vivo skin deposition of GA was studied using HPLC assay. Chronic allergic contact dermatitis model was built to evaluate pharmacodynamic of GA elastic vesicles. RESULTS: The GA elastic vesicles developed have high flexibility and the storage stability was at least for 6 months at 4°C and for 4 months at 25°C. In vitro cumulative penetration of GA from elastic vesicles within 8 hours was 5.3-fold and 23.2-fold higher than that of conventional liposomes and saturated solution, respectively. After non-occlusive application to mice ears in vivo, skin deposition of GA increased immediately and reached the C(max) at 3 h (1.95 ± 0.32 µg/cm²) and still detected, even after 16 hours GA removed. In vivo anti-inflammatory activity study, GA elastic vesicles showed significant reduction in ear thickness and mass (25.52% and 49.23%) (P < 0.05). The suppressive activity was comparable to that of positive control group (Triamcinolone Acetonide and Econazole Nitrate cream in market), while few side effects were observed in present model. CONCLUSION: The results suggested that of GA elastic vesicular was safe and effective in treatment of contact dermatitis by transdermal administration.

Global Research on Public Health Emergency Preparedness From 1997 to 2019: A Bibliometric Analysis.

OBJECTIVES: To access the trends and focuses of publications on public health emergency preparedness in the timeframe 1997-2019. METHODS: Publications related to public health emergency preparedness (PHEP) were retrieved from the Web of Science Core Collection database. Bibliometric analyses including output statistics, co-authorship analysis, citation analysis, co-citation analysis, and co-occurrence analysis were performed and mapped using VOSviewer. RESULTS: A total of 1058 publications on PHEP were included in this study. There was an increasing trend of publication output and citations since 2002. A total of 4605 authors from 1587 institutes and 92 countries contributed to the publications, and the United States lead the field. Disaster Medicine and Public Health Preparedness was the most active and co-cited journal among 243 journals. The knowledge foundation mainly focused on the professionals' capacity, education, and conceptions of PHEP. Epidemics, natural disasters, terrorism, education, and communication were the principle topics; while "vulnerable populations," "disaster medicine," and "hurricane" were the recent hotspots in this field. CONCLUSIONS: Significant progresses had been achieved worldwide in the past 2 decades, however, improvement of research activity and international collaboration is still a need for most countries.

Enhanced bioavailability of L-carnitine after painless intradermal delivery vs. oral administration in rats.

PURPOSE: In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system. METHODS: In vitro study was designed to assess the effects of various skins, donor concentration and hydrogels from different carbomer derivatives on the release of LC in a Franz-type diffusion cell. The LC gel patches with carbomer 980 P were prepared and successfully applied to pharmacokinetic study of SD rats with and without FMA. Intravenous injection and oral administration were performed to support pharmacokinetic calculations and comparison of bioavailability. RESULTS: Enhanced delivery of LC using FMA was achieved in skin of different species in vitro studies. The 750 mg LC gel patches were applied to rats over 6 h, and approximately 27% of loaded dose was transported into rat. A 2.8-fold enhancement of absolute bioavailability for LC with FMA intradermal delivery system was observed compared with oral LC administration in vivo study. CONCLUSIONS: Both in vitro and in vivo studies demonstrated that the FMA intradermal delivery system can enhance the delivery and bioavailability of LC.