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Objective: To compare effectiveness of topical 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA PDT) and loop electrosurgical excision procedure (LEEP) among patients with cervical intraepithelial neoplasia (CIN). Methods: We retrospectively identified patients who underwent either 5-ALA PDT or LEEP from Sep. 2012 to Dec. 2019 in Chinese PLA general hospital. Patients' outcomes were compared according to the HPV genotyping, cytological tests within 3–6-month follow-up post-treatment, the pathological examination would be performed if the cytological results indicated the risk of CIN. Propensity score matching (PSM) was adapted to pair the baseline. Complete remission (CR), partial remission (PR) and the remission rate of HPV infections were used to evaluate the efficacy of 5-ALA PDT versus LEEP. Results: In total, 30 pairs were matched as the matching tolerance was set as 0.03. There was no significant difference about the CR and PR between 5-ALA PDT and LEEP group (73.33% vs 84.00%, P = 0.340; 3.33% vs 4.00%, P = 1.000). Among different CIN group, there was no statistic difference between 5-ALA PDT and LEEP. Moreover, in terms of HPV remission rate, 5-ALA PDT showed the same efficacy as LEEP (59.26% vs 53.85%, P = 0.691). Conclusions: In essence, topical 5-ALA PDT emerges as a non-invasive, repeatable procedure with minimal side effects for cervical lesions, preserving cervical structure. Overall, the efficacy of 5-ALA PDT is comparable to LEEP in achieving successful outcomes. [ABSTRACT FROM AUTHOR]

Highlights • JA may mediate ALA alleviation of cold-induced oxidative stress in tomato. • H 2 O 2 interacts with JA to regulate cold stress in tomato. • NO may act downstream of H 2 O 2 along with JA to improve cold tolerance in tomato. Abstract Low temperature is a limiting factor in tomato production during early spring and winter in North China. Plants perceive low temperature through activation of cold-sensitive signaling pathways, which up-regulate cold-responsive gene expression and increase plant cold tolerance. Many studies reported that 5-aminolevulinic acid (ALA) protect plants against environmental stresses. We showed that ALA pretreatment enhanced cold-triggered oxidative stress tolerance in tomato via hydrogen peroxide (H 2 O 2) signaling and subsequent cross-talk with redox signals. Here, we investigated whether ALA induced the jasmonic acid (JA) and nitric oxide (NO) signaling in response to cold stress in tomato, and evaluated the relationships between JA, NO, and H 2 O 2. Tomato plants were pretreated with inhibitors of JA synthesis [salicylhydroxamic acid (SHAM) and diethyldithiocarbamic acid (DIECA)] or NO synthesis [tungstate and NG-nitro-L-arginine methyl ester (L-NAME)] as well as scavengers of NO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO)] or H 2 O 2 [dimethylthiourea (DMTU)]. Then, these plants were treated with exogenous ALA, JA, or H 2 O 2. Finally, plants were grown under normal or low temperature conditions. The results showed that ALA dramatically elevated JA levels under normal-and low-temperature conditions. Exogenous JA and H 2 O 2 dramatically increased superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) activities and reduced membrane lipid peroxidation. The JA synthesis inhibitors SHAM and DIECA did not significantly affect membrane lipid damage and SOD, CAT, and GR activities, compared with cold-treated plants alone. Whereas ALA significantly attenuated the inhibition effects of SHAM and DIECA. In contrast, JA and H 2 O 2 mitigated the DMTU-, SHAM-, and DIECA-mediated reduction in antioxidation. ALA, JA, and H 2 O 2 up-regulated nitrate reductase (NR) and nitric oxide synthase (NOS) transcript levels and NR and NOS activities, thereby triggering the NO bust. cPTIO, tungstate and L-NAME weakened JA-mediated, and essentially abolished H 2 O 2 -mediated antioxidase activity and mitigated membrane lipid damage. These results indicate that ALA induced H 2 O 2 and JA displayed independent but synergistic roles in regulating tomato antioxidation. NO may act downstream of H 2 O 2 along with JA to regulate antioxidant enzyme gene expression and increase tomato cold tolerance. In conclusion, NO is a downstream signal of H 2 O 2 which cooperated with JA, mediated ALA-regulated oxidative stress tolerance under low temperatures in tomato. [ABSTRACT FROM AUTHOR]

A variety of evidence suggest that 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is clinically effective in management of acne vulgaris. Several clinical guidelines for acne recommend PDT as an alternative treatment modality for severe acne. However, there is a lack of detailed clinical guideline for PDT in acne treatment. To propose up-to-date, evidence-based and practical recommendations on application of ALA-PDT for acne vulgaris, dermatologists and PDT experts from the Photodynamic Therapy Research Center of the CMA and Photodynamic Therapy Rehabilitation Training Center of CARD achieved consensus and guidelines based on careful evaluation of published literature, expert opinions and experience. ALA-PDT plays a therapeutic role in all four major pathogenesis of acne, and is suitable for moderate to severe acne and scar-prone acne, especially for patients who cannot tolerate or refused systemic antibiotics and isotretinoin. The efficacy and adverse reactions of ALA-PDT are closely related to therapeutic parameters including ALA concentration, incubation time, light source and dosage. Proper pretreatment helps to improve transdermal absorption of ALA and enhances its efficacy. We reviewed and proposed recommended protocols for four PDT procedures including conventional PDT (C-PDT), modified painless PDT (M-PDT), intense pulsed light PDT (IPL-PDT) and daylight PDT (DL-PDT). M-PDT with lower ALA concentration (3-5%), shorter incubation time (30 mins), and lower dose but prolonged illumination (630nm, 40-60 mW/cm 2 , 150 J/cm 2 ) can improve lesions of moderate to severe acne vulgaris effectively with minimal pain and easier manipulation, and thus was recommended by Chinese dermatologists. Lastly, management of adverse reactions were addressed., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Litchi chinensis Sonn. cv. ‘Feizixiao’ is commonly cultivated in orchards in Hainan Island of tropical China; however, its commodity value was reduced due to the non-synchronized pericarp coloration and low aril nutritional quality. 5-Aminolevulinic acid (5-ALA), a key precursor in the biosynthesis of porphyrin compounds, is known to be an effective plant growth regulator for improving fruit coloration and nutritive quality. In this study, 5-ALA solution was exogenously sprayed at concentrations of 80, 100, 120, 140, and 160 mg L −1 on the fruit peel of ‘Feizixiao’ litchi at 45 days after full bloom. Fruit growth, coloration and nutritive quality were determined. The treatment with 5-ALA at 80 mg L −1 maintained the vitamin C content of the aril at a higher level than that of the control. The application of 5-ALA significantly increased fruit length and diameter compared with that of the control, but there was no significant effect on the titratable acid content. At 20 days after 5-ALA treatment, anthocyanin contents of the pericarp were significantly higher and the hue angle (h°) was significantly lower than those of the control. Redundancy analysis showed that 5-ALA improved the skin color of ‘Feizixiao’ litchi by promoting anthocyanin accumulation, but not chlorophyll degradation, in the pericarp during the time of harvest. This study showed that 5-ALA significantly improved the skin color at harvest time and fruit quality by promoting the growth of fruit, delaying the degradation of soluble solids, increasing the edible rate, and shortening the interval of aril development and skin coloration. [ABSTRACT FROM AUTHOR]

Photodynamic Therapy with 5-aminolevulinic acid (ALA-PDT) has been widely applied in the treatment of skin diseases in China. To further standardize, guide, and promote the clinical applications of ALA-PDT in dermatology, the Chinese Society of Dermatology, Chinese Association of Rehabilitation Dermatology, Photomedicine Therapeutic Equipment Group of Committee on Skin Disease, and Cosmetic Dermatology of China Association of Medical Equipment invited relevant experts engaged in ALA-PDT to revise and update the first edition of "Clinical application of 5-aminolevulinic acid-based photodynamic therapy: an expert consensus statement" and establish a more current edition, to provide an updated reference for Chinese dermatologists in clinical practice. In the guideline, the expert group reached consensus opinions on ALA-PDT with regard to mechanisms of action, therapeutic protocol, clinical applications, adverse reactions and countermeasures, precautions, care, and evaluation of efficacy., (Copyright © 2021. Published by Elsevier B.V.)

Extracorporeal photopheresis (ECP), a modality that exposes isolated leukocytes to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light, is used to treat conditions such as cutaneous T-cell lymphoma and graft-versus-host disease. However, the current procedure of ECP has limited selectivity and efficiency; and produces only partial response in the majority of treated patients. Additionally, the treatment is expensive and time-consuming, so the improvement for this modality is needed. In this study, we used the concept of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor of an endogenously synthesized photosensitizer protoporphyrin IX (PpIX) in combination with blue light to explore the possibility of targeting activated human blood T cells ex vivo. With various T-cell activation protocols, a high ALA-induced PpIX production took place in activated CD3+, CD4+CD25+, and CD8+ T cell populations with their subsequent killing after blue light exposure. By contrast, resting T cells were much less damaged by the treatment. The selective and effective killing effect on the activated cells was also seen after co-cultivating activated and resting T cells. Under our clinically relevant experimental conditions, ALA-PDT killed activated T cells more selectively and efficiently than 8-MOP/UV-A. Monocyte-derived dendritic cells (DCs) were not affected by the treatment. Incubation of ALA-PDT damaged T cells with autologous DCs induced a downregulation of the co-stimulatory molecules CD80/CD86 and also upregulation of interleukin 10 (IL-10) and indoleamine 2,3-dioxygenase expression, two immunosuppressive factors that may account for the generation of tolerogenic DCs. Overall, the data support the potential use of ALA-PDT strategy for improving ECP by selective and effective killing of activated T cells and induction of immune tolerance. [ABSTRACT FROM AUTHOR]

Background: The benefits of fluorescent light (FL) cystoscopy with 5-aminolevulinic acid (5-ALA) or hexaminolevulinate (HAL) in non-muscle-invasive bladder cancer (NMIBC) have been mentioned in many trials. Meanwhile, several problems need to be addressed such as the rate of residual disease following these procedures., Objective: To assess the effects of FL cystoscopy compared with white light (WL) cystoscopy on the rate of residual Ta, T1, and carcinoma in situ (CIS) tumors, recurrence-free survival (RFS) and progression-free survival (PFS)., Methods: A search in the databases PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) was undertaken. Studies were included if their outcomes included the residual tumor rate, PFS or RFS. The data was analyzed by REVMAN 5.3 and STATA 14.0., Results: The residual tumor rate of the FL group was lower than that of the WL group (relative risk [RR] 0.42; 95 % confidence interval [CI] 0.26-0.80; P = 0.007), which was consistent with the residual Ta rate (RR 0.44; 95 % CI 0.28-0.69; P = 0.0004), the residual T1 rate (RR 0.42; 95 % CI 0.21-0.83; P = 0.01) and the residual CIS rate (RR 0.39; 95 % CI 0.19-0.80; P = 0.01). RFS at the 12-month follow-up (RR 1.15; 95 % CI 1.08-1.28; P = 0.0002) and 24-month follow-up (RR 1.26; 95 % CI 1.17-1.35; P < 0.00001) in the FL group was significantly higher than that in the WL group. However, no statistically significant differences were found in PFS at the 12-month follow-up (RR 1.01; 95 % CI 0.99-1.03; P = 0.17) or 24-month follow-up (RR 1.00; 95 % CI 0.97-1.03; P = 0.95)., Conclusion: FL cystoscopy was related to a reduced residual tumor rate compared with WL cystoscopy in NMIBC, which was also consistent with the Ta, T1 and residual CIS rates. RFS was higher in patients with FL cystoscopy at the 12- to 24-month follow-up., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) is an effective and safe treatment modality for acne vulgaris, and a variety of light sources have been investigated. Sunlight has been used as a PDT light source in a limited number of acne studies . However, to date, a comparative study of conventional PDT (C-PDT) and daylight PDT (DL-PDT) on acne is still lacking., Objectives: This study aims to assess the efficacy and safety of DL-PDT vs. C-PDT in the treatment of acne vulgaris., Methods: Eighty patients with facial moderate-to-severe acne vulgaris were randomly assigned to either DL-PDT group or C-PDT group. All patients got two to three treatment sessions at two-week intervals. The lesions were photographed with VISIA digital imaging system at baseline and weeks 2, 4, and 6. Follow-up monthly for 3 months. The endpoints include efficacy (lesion response), safety (VAS pain score) and patient satisfaction., Results: A total of 77 patients completed the study. There was no statistical difference in objective response rate between DL-PDT group and C-PDT group at weeks 2, 4, and 6, respectively (40.0 %, 90.0 %, and 94.7 % vs. 45.0 %, 85.0 %, and 92.3 %, p > 0.05). The IGA score of DL-PDT group has no difference from C-PDT at baseline and at weeks 6, respectively (3.3 ± 0.4, 1.5 ± 0.7 vs. 3.4 ± 0.5, 1.6 ± 0.7, p > 0.05). The VAS pain score of DL-PDT group was lower than that of C-PDT group (1.8 ± 0.2, vs. 5.8 ± 0.3, p < 0.05). Adverse reactions such as mild burning sensation, erythema, dryness, crusting, scales and hyperpigmentation were all tolerated. Patient satisfaction was similar between the two groups (p > 0.05)., Conclusions: DL-PDT is an effective and well-tolerated regimen for moderate-to-severe acne vulgaris compared with C-PDT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background : Rosacea is difficult to cure and frequently recurs. Topical photodynamic therapy (PDT) has been tentatively used, with only preliminary results reported. Objective : To evaluate the efficacy and safety of topical PDT in Chinese patients with rosacea. Methods & Materials : Seventeen participants with rosacea were treated three times using 5-aminolevulinic acid (ALA)-PDT at intervals of 7-10 days. Papule and pustule numbers, erythema severity, telangiectasia severity, physician's global assessment (PGA) score (1 [best]-6), and patient satisfaction score (0-3 [highest]) were assessed. Rosacea improvement and the total effective rate were calculated. Stratum corneum hydration and sebum levels, and the melanin index (MI) and erythema index (EI) were measured non-invasively. Results : After three treatments with ALA-PDT, the total effective rate (≥50% improvement) was 64.71%, mean PGA score was 2.88 ± 0.93, and mean patient satisfaction score was 1.71 ± 0.69. The EI significantly decreased 1 month after the final treatment (from 468 ± 80.61 to 439 ± 77.78 for the forehead and from 507.65 ± 92.51 to 483.27 ± 78.32 for the nasal ala). Four participants received three additional treatments. They achieved 50-74% improvement after three treatments and ≥75% improvement after six treatments. Conclusion : ALA-PDT is safe and effective for treating rosacea.

Background: Rosacea is a common chronic cutaneous disorder which is characterized by flushing, erythema, papulopustules and telangiectasia. The pathogenesis of the disease is still unknown. A multifaceted approach is necessary to control the disease because of its tendency to relapse. New more effective treatment options are desirable to achieve a complete remission. Aminolevulinic acid-photodynamic therapy (ALA-PDT) is a well-established treatment for non-melanoma skin cancer and precancerous lesions. ALA- PDT can also be used for inflammatory disease, including acne vulgaris. However, little is known about the efficacy and safety of ALA-PDT for rosacea in Chinese patients with Fitzpatrick skin types III and IV., Objectives: To investigate the efficacy and safety of ALA-PDT in the treatment of rosacea classified as erythematotelangiectatic type or papulopustular type., Methods: Twenty rosacea patients with either erythematotelangiectatic or papulopustular types were enrolled. 5% 5-Aminolevulinic acid in an oil-in-water emulsion was applied to the lesions under occlusion with plastic film for 2 h, and the lesions were irradiated with 100 mW/cm2, 80-90 J/cm2, LED red light (635 ± 15 nm) over 15 min in each session with four sessions at 10-day intervals. Objective measures (severity of flushing, erythema and telangiectasia, number of inflammatory lesions, VISIA Red Complexion Analysis images), subjective symptoms (including itching, prickling, burning, etc.) were recorded at baseline and at 4, 12 and 24 weeks after the last treatment. Adverse effects were recorded at each treatment and follow-up visit., Results: During the follow-up period, all patients showed gradual objective clinical improvement compared with baseline (P < 0.01). Clinical inflammatory lesions disappeared completely in all patients after 24 weeks. Subjective symptoms, including flushing, itching, prickling, burning et al, had vanished and did not show any relapse during the follow-up period. The main side effects of ALA-PDT were pain, erythema, swelling and post- inflammatory hyperpigmentation. All side-effects were transient and tolerated by all the patients. No patients were dissatisfied with the therapeutic outcome., Conclusions: ALA-PDT is an effective and safe approach for the treatment of rosacea of erythematotelangiectatic or papulopustular types, to control clinical manifestations and reduce subjective symptoms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objective: Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients., Patients and Methods: Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation., Results: The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial., During Irradiation: The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes)., After Irradiation: The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056)., Conclusions: Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain., (© 2014 Wiley Periodicals, Inc.)