Effect of transdermal drug delivery patches on the stratum corneum: in vivo inspection with a handheld terahertz probe.

Transdermal drug delivery patches are a good alternative to hypodermic drug injection. The drug delivery efficiency depends strongly on the hydration of the skin under treatment, and therefore, it is essential to study the effects on the skin induced by the application of these medical-grade patches. Terahertz (THz) spectroscopy shows great promise for non-invasive skin evaluation due to its high sensitivity to subtle changes in water content, low power and non-ionizing properties. In this work, we study the effects of transdermal drug delivery patches (three fully occlusive and three partially occlusive) applied on the upper arms of ten volunteers for a maximum period of 28 h. Three different levels of propylene glycol (0 %, 3 % and 6 %) are added to the patches as excipient. By performing multilayer analysis, we successfully retrieve the water content of the stratum corneum (SC) which is the outermost layer of skin, as well as its thickness at different times before and after applying the patches. This study demonstrates the potential of using THz sensing for non invasive skin monitoring and has wide applications for skin evaluation as well as the development of skin products.

Evaluation of nintedanib efficacy: Attenuating the lens fibrosis in vitro and vivo.

PURPOSE: Organ fibrosis is a huge challenge in clinic. There are no drugs for fibrotic cataracts treatments in clinic. Nintedanib is approved by the FDA for pulmonary fibrosis treatments. This study aims to investigate the efficacy and mechanism of nintedanib on fibrotic cataracts. METHODS: Drug efficacy was validated through TGFß2-induced cell models and injury-induced anterior subcapsular cataract (ASC) mice. A slit lamp and the eosin staining technique were applied to access the degree of capsular fibrosis. The CCK-8 assay was used to evaluate the toxicity and anti-proliferation ability of the drug. The cell migration was determined by wound healing assay and transwell assay. The anti-epithelial mesenchymal transition (EMT) and anti-fibrosis efficacy were evaluated by qRT-PCR, immunoblot, and immunofluorescence. The inhibition of nintedanib to signaling pathways was certified by immunoblot. RESULTS: Nintedanib inhibited the migration and proliferation of TGFß2-induced cell models. Nintedanib can also repress the EMT and fibrosis of the lens epithelial cells. The intracameral injection of nintedanib can also allay the anterior subcapsular opacification in ASC mice. The TGFß2/ Smad and non-Smad signaling pathways can be blocked by nintedanib in vitro and in vivo. CONCLUSION: Nintedanib alleviates fibrotic cataracts by suppressing the TGFß2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.

Manual reduction in testicular torsion and subsequent treatment after successful reduction: a series of reports in a single institution.

Introduction: To explore the factors affecting the success of testicular torsion manual reduction and the safety of subsequent conservative treatment after successful reduction. Methods: Clinical data of 66 patients with testicular torsion treated in our emergency department from February 2017 to February 2022 were retrospectively collected. Manual reduction without anesthesia was performed in 19 patients. Patients with successful manual reduction chose different subsequent treatments according to the wishes of themselves and their guardians, including continuing conservative treatment and surgical exploration. Relevant clinical data were collected and analyzed. Results: Manual reduction was successful in 11 patients (11/19). Seven of them chose to continue conservative treatment, and four underwent surgical exploration immediately. Among the 7 patients who were treated conservatively, 3 underwent surgical treatment due to scrotal discomfort or testicular torsion at different stages, and the remaining 4 patients showed no recurrence of torsion during follow-up. Compared with other patients, patients with successful manual reduction had the shorter duration of pain (p < 0.05). The time from visiting our hospital to surgery in patients who attempted manual reduction was slightly shorter than those who underwent surgery directly (p > 0.05). The testes of these 11 patients were all successfully preserved. Conclusions: The short duration of pain may contribute to the success of manual reduction, and manual reduction did not increase the preparation time before surgery. Due to the unpredictable risk of recurrence, immediate surgical treatment is still recommended, or postponed elective surgical treatment should be offered in the next days or weeks.

The burden of vision loss due to cataract in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To provide a reference for future policy and measure formulation by conducting a detailed analysis of the burden of vision loss due to cataract by year, age, and gender in China from 1990 to 2019. METHODS: Data on the prevalence and disability-adjusted life-years (DALYs) due to cataract in China and neighboring and other G20 countries were extracted from the 2019 Global Burden of Disease (GBD) study to observe the changing trends of vision loss. RESULTS: The number and rate of all-age prevalence and DALYs for cataract in China increased significantly from 1990 to 2019. The age-standardized DALYs rate witnessed a slowly declining trend by 10.16%. And the age-standardized prevalence increased by 14.35% over the 30-year period. Higher prevalence and DALYs were observed in female population from 1990 through 2019, with little improvement over the decades(all p < 0.001). The disease burden of cataract is higher in middle-aged and elderly people. Blindness accounted for the largest proportion of vision impairment burden caused by cataract in China. The age-standardized prevalence and DALY rate of cataract in China were lower than those in India and Pakistan, but higher than those in Russia, South Korea, North Korea, Singapore, and Japan. CONCLUSIONS: In the past 30 years, although the age-standardized DALYs rate has decreased slightly in China, the all-age prevalence and DALYs have both increased. This study highlights the importance of reducing cataract burden by providing timely and easily accessible quality care, especially in females and the elderly population.

Transcriptome sequencing and microRNA-mRNA regulatory network construction in the lens from a Na2SeO3-induced Sprague Dawley rat cataract model.

BACKGROUND: A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression. METHODS: Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes' targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape. RESULT: In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis. CONCLUSION: We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.

Karyotype and genome size variation in Delphinium subg. Anthriscifolium (Ranunculaceae).

Five taxa of Delphiniumsubg.Anthriscifolium have been karyologically studied through chromosome counting, chromosomal measurement, and karyotype symmetry. Each taxon that we investigated has a basic chromosome number of x = 8, D.anthriscifoliumvar.savatieri, D.anthriscifoliumvar.majus, D.ecalcaratum, and D.callichromum were diploid with 2n = 16, while D.anthriscifoliumvar.anthriscifolium was tetraploid with 2n = 32. Monoploid chromosome sets of the investigated diploid taxa contained 1 metacentric chromosome, 3 submetacentric chromosomes, and 4 subtelocentric chromosomes. Higher interchromosomal asymmetry (CVCL) was present in D.ecalcaratum and D.callichromum than in other taxa. The highest levels of intrachromosomal asymmetry (MCA) and heterogeneity in centromere position (CVCI) were found in D.anthriscifoliumvar.majus. Diploid and tetraploid genome sizes varied by 3.02-3.92 pg and 6.04-6.60 pg, respectively. Karyotype and genome size of D.anthriscifoliumvar.savatieri, D.anthriscifoliumvar.majus, D.callichromum, and D.ecalcaratum were reported for the first time. Finally, based on cytological and morphological data, the classification of Delphiniumanthriscifolium was revised.

CircRNA 06209 inhibits cataract development by sponging miR-6848-5p and regulating ALOX15 expression.

Cataract is the leading cause of blindness in the world, and there is a lack of effective treatment drugs. CircRNA plays an important part in a variety of diseases, however, the role of circRNA in cataracts remains largely unknown. In this study, we constructed a cataract model of rats and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. To investigate the effect and mechanism of circRNA 06209 on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, dual luciferase reporter assay, RIP assay, actinomycin D assay, and Western blot analysis. We identify that a necroptosis-related circRNA, circRNA 06209, is down-regulated in cataracts. Vitro experiments showed that up-regulation of circRNA 06209 could promote cell proliferation and inhibit cell apoptosis. Vivo experiments revealed that circRNA 06209 overexpression could inhibit the development of cataracts. Mechanistically, circRNA 06209 acts as a miRNA sponge and competitively binds to miR-6848-5p to curb the inhibitory effect of miR-6848-5p on ALOX15, thereby affecting cell viability and apoptosis. This study found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts.

Spectroscopic insight on impact of environment on natural photoprotectants.

Biomimicry has become a key player in researching new materials for a whole range of applications. In this study, we have taken a crude extract from the red algae Palmaria palmata containing mycosporine-like amino acids - a photoprotective family of molecules. We have applied the crude extract onto a surface to assess if photoprotection, and more broadly, light-to-heat conversion, is retained; we found it is. Considering sunscreens as a specific application, we have performed transmission and reflection terahertz spectroscopy of the extract and glycerol to demonstrate how one can monitor stability in real-world applications.

Hair embedding after transperineal prostate biopsy: two case reports.

BACKGROUND: Transperineal prostate biopsy is gradually becoming the standard methodology for diagnosing prostate cancer because of its high accuracy and low risk of infection, but careful preparation is not always highlighted before a transperineal biopsy. we reported two cases of hair embedding during transurethral resection of the prostate following transperineal puncture biopsy with a Bard MC1820 disposable biopsy needle. Histological examination did not find the hair follicle structure required for hair growth. The hair source was suspected to be percutaneously brought in by needle during the biopsya simulated experiment was used to analyze and reconstruct the process of hair embedding in prostate tissue. CONCLUSION: Hair embedding caused by perineal prostate biopsy is a consumable-related adverse event, and skin preparation before a transperineal prostate biopsy is recommended.

P2P Cloud Manufacturing Based on a Customized Business Model: An Exploratory Study.

To overcome the problems of long production cycle and high cost in the product manufacturing process, a P2P (platform to platform) cloud manufacturing method based on a personalized custom business model has been proposed in this paper by integrating different technologies such as deep learning and additive manufacturing (AM). This paper focuses on the manufacturing process from a photo containing an entity to the production of that entity. Essentially, this is an object-to-object fabrication. Moreover, based on the YOLOv4 algorithm and DVR technology, an object detection extractor and a 3D data generator are constructed, and a case study is carried out for a 3D printing service scenario. The case study selects online sofa photos and real car photos. The recognition rates of sofa and car were 59% and 100%, respectively. Retrograde conversion from 2D data to 3D data takes approximately 60 s. We also carry out personalized transformation design on the generated sofa digital 3D model. The results show that the proposed method has been validated, and three unindividualized models and one individualized design model have been manufactured, and the original shape is basically maintained.

Quantitative evaluation of transdermal drug delivery patches on human skin with in vivo THz-TDS.

Transdermal drug delivery (TDD) has been widely used in medical treatments due to various advantages, including delivering drugs at a consistent rate. However, variations in skin hydration can have a significant effect on the permeability of chemicals. Therefore, it is essential to study the changes in skin hydration induced by TDD patches for better control of the delivery rate. In this work, in vivo terahertz (THz) spectroscopy is conducted to quantitatively monitor human skin after the application of patches with different backing materials and propylene glycol concentrations. Changes in skin hydration and skin response to occlusion induced by other patches are investigated and compared. Our work demonstrates the potential application of in vivo THz measurements in label-free, non-invasive evaluation of transdermal patches on human skin and further reveals the mechanism behind the effect.

[Mendelian randomization of diabetes and prostate cancer risk in East Asian population].

OBJECTIVE: Mendelian randomization (MR) was used to explore the causal relationship between diabetes (type 1 and type 2) and prostate cancer (PCa) in East Asian population. METHODS: Mendelian randomization is a causal inference method based on genetic variation, which uses the influence of randomly assigned genotypes in nature on phenotype to infer the impact of biological factors on diseases. This study used genetic variation genes related to inflammatory biomarkers as instrumental variables to improve inference, and patient data was obtained from the GWAS database's aggregated association results. In the individual sample, we estimated the correlation between instrumental variables (SNPs) and type 1 and type 2 diabetes, and screened out strongly related SNPs, and excluded SNPs related to prostate cancer. After screening, further sensitivity analysis and visualization of research results were carried out to test the blood glucose level and the causal relationship between diabetes and prostate cancer. RESULTS: Our MR analysis found that there was a negative causal relationship between the risk of prostate cancer and type 2 diabetes.The ratio of type 2 diabetes to prostate cancer causal relationship (OR)=1.0039, 95% confidence interval (CI)=(1.0008, 1.0071), P=0.013, while type 1 diabetes had fewer SNPs screened, Failed to conduct relevant follow-up analysis. CONCLUSIONS: Under Mendel's randomization hypothesis, our research results show that in the East East Asian population, the gene predicted type 2 diabetes and the occurrence of prostate cancer have a negative causal relationship, while the causal relationship between type 1 diabetes and prostate cancer is unknown due to the limited number of instrumental variables.

[Study on the length and quality of prostate biopsy tissue strips].

OBJECTIVE: To improve the diagnostic yield of prostate biopsy, which we can achieve by puncture more sites and number of cores, another way to obtain more tissue is to take longer tissue strips. In this study, we evaluated the effect of strip length on cancer diagnosis by needle biopsy and derived a cutoff value of strip length to improve cancer detection. METHODS: The pathological reports of 754 patients with suspected prostate cancer who underwent transperineal prostate biopsy were retrospectively analyzed. The age, serum prostate specific antigen (PSA), prostate volume, Gleason score and tissue strip length were analyzed. The length of the tissue strip was compared between the biopsy positive patients and the biopsy negative patients, and the patients were divided into group A（biopsy positive group）and group B（biopsy negative group）, respectively. Statistical analysis of tissue strip lengths was performed to determine cutoff values for biopsy length quality. RESULTS: A total of 10 556 tissue strips were obtained from 754 patients, and 45.1 % of the patients were pathologically diagnosed as prostate cancer. The median length of the tissue strip was 10.5 (9.5, 12.5) mm, the median age was 69 (64,75) years, the median PSA was 12.4 (8.6, 20.8) µg/L, and the median prostate volume was 44.8 (30.5, 64.4) ml. The median length of tissue strips in group A and group B was 11 (10,13) mm and 10 (9,12) mm, respectively. Receiver operating characteristic (ROC) curve analysis was performed on the length of tissue strips in all cases, and the cutoff value of quality assurance was 11.8mm, the area under curve (AUC) was 0.82, and the cut-off value of quality assurance was 11.8mm. Sensitivity 71.4%, specificity 73.8%(P<0.001). CONCLUSIONS: In transperineal prostate biopsy, the cancer detection rate of tissue strips may increase with length. The results of ROC analysis showed that 11.8 mm was used as the cut-off value for quality assurance.

The Efficacy of Urinary Continence in Patients Undergoing Robot-Assisted Radical Prostatectomy with Bladder-Prostatic Muscle Reconstruction and Bladder Neck Eversion Anastomosis.

Background and Objectives: To evaluate the efficacy of bladder-prostatic muscle reconstruction and bladder neck eversion anastomosis in the recovery of urinary continence after robot-assisted radical prostatectomy (RARP). Materials and Methods: From January 2020 to May 2022, 69 patients who underwent RARP in our hospital were recruited. Thirty-seven patients underwent RARP with the Veil of Aphrodite technique (control group). On the basis of the control group, 32 patients underwent bladder-prostatic muscle reconstruction and bladder neck eversion anastomosis during RARP (observation group). The recovery of urinary continence was followed up at 24 h and 1, 4, 12, and 24 weeks after catheter removal. Results: There were no significant differences in operative time (127.76 ± 21.23 min vs. 118.85 ± 24.71 min), blood loss (118.27 ± 16.75 mL vs. 110.77 ± 19.63 mL), rate of leakage (3.13% vs. 2.70%), rate of positive surgical margin (6.25% vs. 10.81%), or postoperative Gleason score [7 (6−8) vs. 7 (7−8)] between the observation group and the control group (p > 0.05). After catheter removal, the rates of urinary continence at 24 h, 1 week, 4 weeks, 12 weeks, and 24 weeks were 46.88%, 68.75%, 84.38%, 90.63%, and 93.75% in the observation group, respectively. Meanwhile, the rates of urinary continence in the control group were 21.62%, 37.84%, 62.16%, 86.49%, and 91.89%, respectively. There was a significant difference between the two groups (p = 0.034), especially at 24 h, 1 week, and 4 weeks after catheter removal (p < 0.05). Conclusions: Bladder-prostatic muscle reconstruction and bladder neck eversion anastomosis were beneficial to the recovery of urinary continence after RARP, especially early urinary continence.

Optimized multilayer structure for sensitive THz characterization of thin-film glucose solutions.

Terahertz time-domain spectroscopy (THz-TDS) has shown promise in biomedical sample characterization and high characterization sensitivity is in demand due to the thin-film (TF) feature of the sample. This paper proposes an optimized multilayer structure for sensitive characterization of TF aqueous solutions in reflection THz-TDS. Theoretical simulations are conducted for structural optimization and the 75 µm window-sample-mirror structure displays the best sensitivity compared to other sandwich structures and traditional THz measurement geometries. 0-20% TF glucose solutions are then measured; and a spectral peak introduced by the proposed structure is observed to result in the high sensitivity. Our work provides a new way of customizing multilayer structure for THz thin-film characterization.

Application of single-point prostate biopsy in elderly patients with highly suspected prostate cancer.

Objective: To explore the feasibility of single-point prostate biopsy in elderly patients with highly suspected prostate cancer. Methods: Forty-three patients with a prostate imaging reporting and data system score (PI-RADS) of 5, age ≥ 80 years and/or PSA ≥ 100 ng/ml and/or Eastern Cooperative Oncology Group score ≥ 2 were enrolled in our hospital from March 2020 to June 2022. Targeted surgery of these patients was performed using only precise local anesthesia in the biopsy area. The biopsy tissues were examined by intraoperative frozen section examination (IFSE). If the result of IFSE was negative, traditional systematic biopsy and further routine pathological examination were performed. The positive rate of biopsy, operation time, complications and pain score were recorded. Results: The positive rate of prostate biopsy was 94.7%. The results of IFSE in two patients were negative, and the routine pathological results of further systematic biopsy of those patients were also negative. The visual analog scale and visual numeric scale were 2 (2-4) and 3 (2-3), respectively, during the biopsy procedure. The mean time of operation was 8.5 ± 2.1 min from the beginning of anesthesia to the end of biopsy. It took 35.3 ± 18.7 minutes to obtain the pathological report of IFSE. The incidences of complication hematuria and urinary retention were 10.5% and 2.6%, respectively. Conclusion: For elderly patients with highly suspected prostate cancer, single-point prostate biopsy can be used to quickly and safely obtain pathological results.

Comparison of the Oncological and Functional Outcomes of Brachytherapy and Radical Prostatectomy for Localized Prostate Cancer.

Background and Objectives: To compare the oncological and functional outcomes of brachytherapy (BT) and radical prostatectomy (RP) in patients with localized prostate cancer (PCa). Materials and Methods: We retrospectively analyzed data from 557 patients with localized PCa who were treated with BT (n = 245) or RP (n = 312) at Northern Jiangsu People's Hospital between January 2012 and December 2017. Biochemical relapse-free survival (bRFS) and cancer-specific survival (CSS) were compared by treatment modality. Multivariate Cox regression analysis was used to evaluate bRFS. Health-related quality of life (HRQoL) was measured using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Results: The BT group was older and had a higher initial PSA (iPSA). The 5-year bRFS was 82.9% in the BT group versus 80.1% in the RP group (p = 0.570). The 5-year CSS was 96.4% in the BT group versus 96.8% in the RP group (p = 0.967). Based on multivariate Cox regression analysis, Gleason score ≥ 8 was the main independent prognostic factor for bRFS. Regarding the HRQoL, compared with the baseline, both treatments produced a significant decrease in different aspects of HRQoL at 3, 6, and 12 months after treatment. Patients in the BT group had lower HRQoL with regard to urinary irritation/obstruction and bowel function or bother, while patients in the RP group had lower HRQoL concerning urinary incontinence and sexual function or bother. There was no significant difference in HRQoL aspects between the two groups after follow-up for 2 years compared with the baseline. Conclusions: BT provides equivalent oncological control outcomes in terms of bRFS and CSS for patients with localized PCa compared with RP. Gleason score ≥ 8 was the main independent prognostic factor for bRFS. BT had better HRQoL compared with RP, except for urinary irritation/obstruction and bowel function or bother, but returned to baseline after 2 years.

The Application of Biopsy Density in Transperineal Templated-Guided Biopsy Patients With PI-RADS<3.

Background: In patients with multiparameter magnetic resonance imaging (mpMRI) low-possibility but highly clinical suspicion of prostate cancer, the biopsy core is unclear. Our study aims to introduce the biopsy density (BD; the ratio of biopsy cores to prostate volume) and investigates the BD-predictive value of prostate cancer and clinically significant prostate cancer (csPCa) in PI-RADS<3 patients. Methods: Patients underwent transperineal template-guided prostate biopsy from 2012 to 2022. The inclusion criteria were PI-RADS<3 with a positive digital rectal examination or persistent PSA abnormalities. BD was defined as the ratio of the biopsy core to the prostate volume. Clinical data were collected, and we grouped the patients according to pathology results. Kruskal-Wallis test and chi-square test were used in measurement and enumeration data, respectively. Logistics regression was used to choose the factor associated with positive biospy and csPCa. The receiver operating characteristic (ROC) curve was used to evaluate the ability to predict csPCa. Results: A total of 115 patients were included in our study. Biopsy was positive in 14 of 115 and the International Society of Urological Pathology grade groups 2-5 were in 7 of all the PCa patients. The BD was 0.38 (0.24-0.63) needles per milliliter. Binary logistics analysis suggested that PSAD and BD were correlated with positive biopsy. Meanwhile, BD and PSAD were associated with csPCa. The ROC curve illustrated that BD was a good parameter to predict csPCa (AUC=0.80, 95% CI: 0.69-0.91, p<0.05). The biopsy density combined with PSAD increased the prediction of csPCa (AUC=0.90, 95% CI: 0.85-0.97, p<0.05). The cut-off value of the BD was 0.42 according to the Youden index. Conclusion: In PI-RADS<3 patients, BD and PSAD are related to csPCa. A biopsy density of more than 0.42 needles per millimeter can increase the csPCa detection rate, which should be considered as an alternative biopsy method when we perform prostate biopsy in patients with PI-RADS<3.