The effect of autophagy on hemoporfin-mediated photodynamic therapy in human umbilical vein endothelial cells.

SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.

Effective treatment of corticosteroid-induced facial erythema using fractional radiofrequency microneedling.

OBJECTIVES: To investigate the efficacy of Fractional Radiofrequency Microneedling (FRM) in treating corticosteroid-induced facial erythema. METHODS: A retrospective study was conducted involving eight patients diagnosed as corticosteroid-induced facial erythema. Each patient underwent a single session of FRM. Evaluative measures included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), assessment of telangiectasia severity, procedure-associated pain (10-point scale), patient satisfaction (3-point scale) and secondary outcomes. RESULTS: The study found a 75% success rate and 100% effectiveness rate in alleviating erythema symptoms. CEA and PSA scores decreased by 67.7% and 78.1%, respectively. No cases of erythema rebound were recorded during the 3-month follow-up period. CONCLUSIONS: FRM demonstrated effectiveness and safety in treating facial erythema, offering promising advancement in dermatologic therapeutics.

Hemoporfin-mediated photodynamic therapy for the treatment of port-wine stain: A multicenter, retrospective study.

BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) has been approved for port-wine stain (PWS) in China in 2017. This study evaluated the efficacy and safety of Hemoporfin-PDT for PWS in a real life setting and investigated factors that influence the efficacy. METHODS: A multicenter retrospective study included patients with PWS who underwent Hemoporfin-PDT in 29 hospitals across China and completed at least two months of follow-up. The efficacy was evaluated based on patien photographs. RESULTS: A total of 1679 patients were included. After the first and second sessions of Hemoporfin-PDT, 63.5 and 75.3% of patients responded, respectively. The response rate of purple-type PWS was significantly lower than that of pink-type PWS (OR: 0.71, 95% CI: 0.54-0.94, P < 0.05), and there was no significant difference between thick- and pink-type (OR: 0.72, 95% CI: 0.42-1.22, P > 0.05). The response rate of PWS on the limbs was significantly lower than that on the mid-face (OR: 0.35, 95% CI: 0.23-0.53, P < 0.0001), while no significant difference was observed between PWS on the peripheral part of the face, neck or other parts of the body and PWS on the mid-face (P > 0.05). The response rate was lower in male patients with an age > 3 years or ≤ 6 years (P < 0.05). Previous treatment history did not affect the efficacy (P > 0.05). Hemoporfin-PDT was well tolerated. CONCLUSION: Patients with PWS have a good response and good tolerance to Hemoporfin-PDT.

The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: An updated systematic review and meta-analysis of randomized controlled trials.

Background: Amyotrophic lateral sclerosis (ALS) has attracted widespread attention because of its unknown pathogenesis, rapid progression, and life-threatening and incurable characteristics. A series of complementary therapies, including Chinese herbal medicine (CHM), is available for use in the clinic and has been the focus of much research. However, it is unclear as to whether supplementary CHM relieves disease symptoms or extends life span; thus, we conducted this updated meta-analysis to validate the efficacy and safety of this practice. Methods: We searched six electronic databases for randomized controlled trials involving CHM and patients with ALS that were published up to April 2022. Two researchers independently screened the literature, assessed the risk of bias for each trial, and then extracted data. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool, and a pooled data analysis was performed using RevMan 5.3. Results: A total of 14 trials led to the publication of 15 articles featuring 1,141 participants during the study period; the articles were included in the systematic review. In terms of increasing ALS functional rating scale (ALSFRS) scores, CHM was superior to the placebo after 3 months of treatment [mean difference (MD):0.7; 95% CI:0.43 to 0.98; P < 0.01] and to riluzole after 4 weeks of treatment (MD: 2.87; 95% CI: 0.81 to 4.93; P < 0.05), and it was superior to conventional medicine (CM) alone when used as an add-on therapy after 8 weeks of treatment (MD: 3.5; 95% CI: 0.51 to 6.49; P < 0.05). The change in the modified Norris score (m-Norris) from baseline to the end of more than 3 months of treatment was significantly different when compared between the CHM plus CM group and the CM alone group (MD: 2.09; 95% CI: 0.62 to 3.55; P < 0.01). In addition, CHM had a significantly better effect on increase in clinical effective rate (RR: 1.54; 95% CI: 1.23 to 1.92; P < 0.01) and improvement in forced vital capacity (MD: 7.26; 95% CI: 2.92 to 11.6; P < 0.01). However, there was no significant difference between the CHM therapy and CM in terms of improving life quality (MD: 5.13; 95% CI: -7.04 to 17.31; P = 0.41) and decreasing mortality (RR: 0.41; 95% CI: 0.04 to 4.21; P = 0.46). Conclusion: The analysis suggested that the short-term adjunct use of CHM could improve the ALSFRS score and clinical effect with a good safety profile when compared with the placebo or riluzole alone. However, future research should be centered on the long-term efficacy of patient-oriented outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323047, identifier: CRD42022323047.

Avellis syndrome with ipsilateral prosopalgia, glossopharyngeal neuralgia, and central post-stroke pain: A case report and literature review.

RATIONALE: Avellis syndrome is a rare bulbar syndrome. The main lesions may involve nucleus ambiguus and the lateral spinothalamic tract. The typical reported clinical manifestations are hoarseness, dysphagia, pain, and temperature disturbance of contralateral body. The manifestations, however, may vary. We aim to report new manifestations of Avellis syndrome in this report. PATIENT CONCERNS: A 47-year-old Chinese peasant woman who felt sudden dizziness, nausea when she was doing the laundry was referred to our department from other hospital. She vomited the stomach contents once and complained numbness of the left trunk and limbs as well as coughing while drinking. The patient presented with palatopharyngeal paralysis, Horner syndrome, and diminished pain as well as temperature sensation in the contralateral face, trunk, and limbs. She also presented with ipsilateral prosopalgia, glossopharyngeal neuralgia, and central poststroke pain. DIAGNOSES: T2-weighted MRI images demonstrated a high-signal intensity lesion in the right medulla oblongata which indicated a banded infarction site. The patient was diagnosed with medulla oblongata infarction, Avellis syndrome, Horner syndrome, dysphagia, hemiparesthesia, ipsilateral prosopalgia, glossopharyngeal neuralgia, and central poststroke pain. INTERVENTIONS: The patient was administrated aspirin to prevent the aggregation of platelet and rosuvastatin tablets to regulate lipids as well as to stabilize vascular plaque. She was injected with butylphthalide sodium chloride to improve nerve nutritional status and carbamazepine was prescribed to deal with prosopalgia and glossopharyngeal neuralgia. Gabapentin and pregabalin were administrated to deal with the central poststroke pain. OUTCOMES: The symptoms of prosopalgia as well as glossopharyngeal neuralgia were gone, and dizziness, dysphagia, and Horner syndrome were significantly alleviated when she was discharged from the hospital while the interventions showed little effect on central poststroke pain. LESSONS: We reported a case of Avellis syndrome who manifested as the typical reported manifestations. The patient, what's more, presented with ipsilateral trigeminal, glossopharyngeal neuralgia, and central poststroke pain which were described for the first time. It is of great significance for clinicians to recognize the typical as well as other manifestations which helps to make a clear diagnosis.

EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with the post-stroke shoulder-hand syndrome: A Bayesian network meta-analysis.

Background: Post-stroke shoulder-hand syndrome (SHS), although not a life-threatening condition, may be the most distressing and disabling problem for stroke survivors. Thus, it is essential to identify effective treatment strategies. Physical therapy is used as a first-line option for treating SHS; however, it is unclear which treatment option is preferred, which creates confusion in guiding clinical practice. Our study aims to guide clinical treatment by identifying the most effective physical therapy interventions for improving clinical symptoms in patients with post-stroke SHS using Bayesian network meta-analysis. Methods: We conducted a systematic and comprehensive search of data from randomized controlled trials using physical therapy in patients with SHS from database inception to 1 July 2022. Fugl-Meyer Upper Extremity Motor Function Scale (FMA-UE) and pain visual analog score (VAS) were used as primary and secondary outcome indicators. R (version 4.1.3) and STATA (version 16.0) software were used to analyze the data. Results: A total of 45 RCTs with 3,379 subjects were included, and the intervention efficacy of 7 physical factor therapies (PFT) combined with rehabilitation training (RT) was explored. Compared with the control group, all the PFT + RT included were of statistical benefit in improving limb motor function and pain relief. Also, our study indicated that EMG biofeedback combined with RT (BFT + RT) [the surface under the cumulative ranking curve (SUCRA) = 96.8%] might be the best choice for patients with post-stroke SHS. Conclusion: EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with post-stroke SHS according to our Bayesian network meta-analysis results. However, the above conclusions need further analysis and validation by more high-quality RCTs. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022348743.

Comparison of the efficacy of acupuncture-related Therapies for post-stroke motor aphasia: A Bayesian network meta-analysis.

Background: Motor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA). Methods: Eight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data. Results: A total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA. Conclusion: The NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.

Safety and effectiveness of 5-aminolevulinic acid photodynamic therapy combined with fractional micro-plasma radio-frequency treatment for verrucous epidermal nevus: A retrospective study with long-term follow-up.

Verrucous epidermal nevus (VEN) is a benign skin disease that seriously affects appearance. Numerous therapeutic methods have been tried with varying results. However, there are few reports on the treatment of VEN by photodynamic therapy (PDT). This study aimed to evaluate the efficacy and adverse effects of 5-aminolevulinic acid (ALA)-PDT in VEN treatment with a long-term follow-up. A total of 16 patients with VEN received ALA-PDT and were followed up for more than 1 year to observe the treatment effects, adverse reactions, and patients' satisfaction. Complete improvement of lesions was observed in 11 patients (three to six sessions of ALA-PDT). Two patients obtained 90-99% improvement (five sessions) and 50-89% improvement in three patients (three to six sessions). They were satisfied with the treatment effects, with an average satisfaction of 4.19/5 (±0.91). Long-term follow-up ranging 14-50 months showed a low recurrence rate (2/16) and no scar left after ALA-PDT. The results demonstrate that ALA-PDT is an effective and safe therapy in treating VEN with mild adverse reactions and a low risk of scar formation.

Subfoveal choroidal thickness changes after intravitreal ranibizumab injections in different patterns of diabetic macular edema using a deep learning-based auto-segmentation.

PURPOSE: To evaluate the effect of intravitreal injection of ranibizumab (IVR) on subfoveal choroidal thickness (SFCT) and its relationship with central macular thickness (CMT) and best-corrected visual acuity (BCVA) changes in eyes with center-involving DME (CI-DME) using a deep learning-based auto-segmentation. METHODS: This prospective interventional case series included 68 eyes of 68 patients with CI-DME naive to treatment. Morphological optical coherence tomography (OCT) findings of DME were classified into three patterns of structural change: (i) diffuse retinal thickening (DRT), (ii) cystoid macular edema (CME), and (iii) serous retinal detachment (SRD). All patients underwent 3+prorenata IVR. The treated eyes underwent BCVA evaluation and OCT scanning at baseline and months 1, 3, and 6 after the first injection. Then, the choroid layer was measured using a deep learning-based auto-segmentation. RESULTS: At baseline, the mean SFCT and CMT for SRD, DRT, and CME groups were 324.68 ± 65.58 µm and 624.37 ± 77.92 µm, 348.91 ± 45.81 µm and 443.5 ± 78.33 µm, 361.4 ± 64.62 µm, and 536.5 ± 66.02 µm, respectively. After anti-VEGF treatment, the SFCT and CMT have decreased by varying degrees. At 3 and 6 months of treatment, there were no significant changes among these groups. There was no correlation between baseline SFCT and the resulting BCVA (P = 0.670, P = 0.584). There was also no correlation between changes in SFCT and BCVA, CMT (P = 0.344, P = 0.336). CONCLUSION: After treating CI-DME with IVR, SFCT and CMT significantly decreased. However, there were no significant changes among the SRD, DRT, and CME groups. TRIAL REGISTRATION: Trial registration: ChiCTR, ChiCTR-ROC-17013360. Registered 13 November 2017, http://www.chictr.org.cn/ChiCTR-ROC-17013360 .

5-aminolevulinic acid photodynamic therapy and excision surgery for nevoid basal cell carcinoma syndrome with multiple basal cell carcinomas and PTCH1 mutation.

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS.

Successful treatment of facial hypertrophic scar with HMME-PDT: A case report.

Treating hypertrophic scars is a challenge for clinicians. Herein, we report a case of one female with both a facial port wine stain and a hypertrophic scar treated with Hematoporphyrin monomethyl ether photodynamic therapy. Surprisingly, with the treatment of the facial port wine stain, the other skin lesion, the hypertrophic scar, also alleviated. HMME-PDT has been approved for application in PWS; however, this case showed effective easing of the hypertrophic scar lesion, which indicates that it might be a promising therapeutic method for hypertrophic scars.

Handheld instrument for wound-conformal delivery of skin precursor sheets improves healing in full-thickness burns.

The current standard of care for patients with severe large-area burns consists of autologous skin grafting or acellular dermal substitutes. While emerging options to accelerate wound healing involve treatment with allogeneic or autologous cells, delivering cells to clinically relevant wound topologies, orientations, and sizes remains a challenge. Here, we report the one-step in situ formation of cell-containing biomaterial sheets using a handheld instrument that accommodates the topography of the wound. In an approach that maintained cell viability and proliferation, we demonstrated conformal delivery to surfaces that were inclined up to 45° with respect to the horizontal. In porcine pre-clinical models of full-thickness burn, we delivered mesenchymal stem/stromal cell-containing fibrin sheets directly to the wound bed, improving re-epithelialization, dermal cell repopulation, and neovascularization, indicating that this device could be introduced in a clinical setting improving dermal and epidermal regeneration.

Photodynamic therapy in a patient with facial angiofibromas due to tuberous sclerosis complex.

The facial angiofbromas due to tuberous sclerosis complex produced significant social and emotional distress for affected individuals, but there is no specific therapeutic strategy up to now. Herein, we report a case of facial angiofibromas successfully treated by 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) with no recurrence for 6 years, thus providing a promising therapeutic option.

Interoperable and scalable data analysis with microservices: applications in metabolomics.

MOTIVATION: Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. RESULTS: We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. AVAILABILITY AND IMPLEMENTATION: The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the Virtual Research Environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Successful treatment of verrucous epidermal nevus with fractional micro-plasma radio-frequency technology and photodynamic therapy.

Verrucous epidermal nevus (VEN) is a skin disorder that commonly presents at birth; it is characterized by skin-colored to brown verrucous papules in a linear distribution following Blaschko's lines. Even though it is extremely rare, VEN has been associated with malignant transformation. VEN has been treated by different treatment modalities with varying and frustrating results. We introduce a new type of treatment. The fractional micro-plasma radio-frequency (RF) technology, which uses unipolar RF technology to provoke plasma spars, creating multiple controlled micro-perforations on the skin. Photodynamic therapy (PDT) is a type of technology for disease diagnosis and treatment, in which a photosensitizer gathers within the nidus and kills the diseased cells. In this report, we present a case of VEN that was successfully treated with fractional micro-plasma RF technology and PDT without side effects or complications; a follow-up was conducted after 24 months and no signs of recurrence were observed.

tranSMART-XNAT Connector tranSMART-XNAT connector-image selection based on clinical phenotypes and genetic profiles.

Motivation: TranSMART has a wide range of functionalities for translational research and a large user community, but it does not support imaging data. In this context, imaging data typically includes 2D or 3D sets of magnitude data and metadata information. Imaging data may summarise complex feature descriptions in a less biased fashion than user defined plain texts and numeric numbers. Imaging data also is contextualised by other data sets and may be analysed jointly with other data that can explain features or their variation. Results: Here we describe the tranSMART-XNAT Connector we have developed. This connector consists of components for data capture, organisation and analysis. Data capture is responsible for imaging capture either from PACS system or directly from an MRI scanner, or from raw data files. Data are organised in a similar fashion as tranSMART and are stored in a format that allows direct analysis within tranSMART. The connector enables selection and download of DICOM images and associated resources using subjects' clinical phenotypic and genotypic criteria. Availability and Implementation: tranSMART-XNAT connector is written in Java/Groovy/Grails. It is maintained and available for download at https://github.com/sh107/transmart-xnat-connector.git. Contact: sijin@ebi.ac.uk.

High dimensional biological data retrieval optimization with NoSQL technology.

BACKGROUND: High-throughput transcriptomic data generated by microarray experiments is the most abundant and frequently stored kind of data currently used in translational medicine studies. Although microarray data is supported in data warehouses such as tranSMART, when querying relational databases for hundreds of different patient gene expression records queries are slow due to poor performance. Non-relational data models, such as the key-value model implemented in NoSQL databases, hold promise to be more performant solutions. Our motivation is to improve the performance of the tranSMART data warehouse with a view to supporting Next Generation Sequencing data. RESULTS: In this paper we introduce a new data model better suited for high-dimensional data storage and querying, optimized for database scalability and performance. We have designed a key-value pair data model to support faster queries over large-scale microarray data and implemented the model using HBase, an implementation of Google's BigTable storage system. An experimental performance comparison was carried out against the traditional relational data model implemented in both MySQL Cluster and MongoDB, using a large publicly available transcriptomic data set taken from NCBI GEO concerning Multiple Myeloma. Our new key-value data model implemented on HBase exhibits an average 5.24-fold increase in high-dimensional biological data query performance compared to the relational model implemented on MySQL Cluster, and an average 6.47-fold increase on query performance on MongoDB. CONCLUSIONS: The performance evaluation found that the new key-value data model, in particular its implementation in HBase, outperforms the relational model currently implemented in tranSMART. We propose that NoSQL technology holds great promise for large-scale data management, in particular for high-dimensional biological data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new data model as a basis for migrating tranSMART's implementation to a more scalable solution for Big Data.