Background: Melasma is an acquired pigmentation disorder with challenges in treatment because of its refractory nature and high risk of recurrence.Objectives: This study aimed to compare the efficacy and side effects of 14 common therapies for melasma using a systematic review and network meta-analysis (NMA).Methods: The PubMed, Embase, and Cochrane Library databases were searched till December 2020 using the melasma area and severity index as a therapeutic index. A total of 59 randomized controlled trials (RCTs) met the inclusion criteria and were selected.Results: The ranking of relative efficacy compared with placebo in descending order was Q-switched Nd:Yag 1,064-nm laser (QSND), intense pulsed light, ablative fractional laser (AFL), triple combined cream (TCC), topical vitamin C, oral tranexamic acid (oTA), peeling, azelaic acid, microneedles (MNs), topical tranexamic acid (tTA), tretinoin, picosecond laser, hydroquinone (HQ), and non-AFL. Moreover, QSND was more effective than HQ and tTA against melasma. The ranking of percentage (%) of side effects in ascending order for each of 14 therapies with more than 80 participants was tretinoin (10.1%), oTA (17.6%), HQ (18.2%), AFL (20.0%), QSND (21.5%), TCC (25.7%), tTA (36.75%), peeling (38.0%), and MN (52.3%). Taking both efficacy and safety into consideration, TCC was found to be the most favorable selection among the topical drugs for melasma. QSND and AFL were still the best ways to treat melasma among photoelectric devices. oTA as system administration was a promising way recommended for melasma. Among 31 studies, 87% (27/31) studies showed that the efficacy of combination therapies is superior to that of single therapy. The quality of evidence in this study was generally high because of nearly 50% of split-face RCTs.Conclusions: Based on the published studies, this NMA indicated that QSND, AFL, TCC, and oTA would be the preferred ways to treat melasma for dermatologists. However, more attention should be paid to the efficacy and safety simultaneously during the clinical application. Most of the results were in line with those of the previous studies, but a large number of RCTs should be included for validation or update.Systematic Review Registration: identifier: CRD42021239203.

BackgroundThe efficacy of topical minoxidil (MX) alone on female pattern hair loss (FPHL) is limited. Combination therapy based on topical MX is currently expected to provide better outcomes.ObjectivesThis study aimed to assess whether the combined therapies including MX plus oral spironolactone (SPT) and MX plus microneedling (MN) have advantages in efficacy and safety over topical MX alone on mild-to-moderate FPHL with normal hormone levels in the blood and regular menstrual cycle.MethodsA prospective, single-center, parallel-group, evaluator blinded, randomized trial including 120 non-menopause women with proven FPHL (Sinclair class II-III) was performed in China. Patients were randomly assigned to three groups, namely, the MX group (5% topical MX alone, once daily), the MX + SPT group (MX plus SPT 80–100 mg daily), and the MX+MN group (MX plus MN every 2 weeks, 12 sessions). The change from the baseline to week 24 was assessed in hair growth (hair density and diameter under dermoscope), scalp tissue structure (epidermal thickness, dermis thickness, and average hair follicle diameter under ultrasound biomicroscopy), physician's global assessment (using a 7-point global-assessment scale and Sinclair's stage change), patient evaluation (Women's Androgenetic Alopecia Quality of Life Questionnaire and Sinclair's hair-shedding score) and side effects.ResultsIn total, 115 participants completed the trial. At week 24, the hair density increased most in MX + MN group and increased least in MX group (p < 0.001 for MX + MN group vs. MX + SPT group; p = 0.009 for MX + SPT group vs. MX group). The hair shaft diameter significantly increased in all groups (p < 0.001, respectively), but there were no significant differences among the three groups (p = 0.905). The epidermal thickness and average hair follicle diameter only increased in MX + MN group. Dermis thickness increased in all groups, but there were no significant differences among the three groups. Both physician's and patient assessments showed improvement in all three groups. Scalp pruritus was the most common side effect. The MX + SPT group had the most reported adverse effects.LimitationsThe main limitations of this study are the relatively small sample size, the exclusion of severe FPHL patients, and the potential bias from unblinded treatments among the 3 groups.ConclusionTopical MX combined with MN is a better choice than either MX plus oral SPT or MX alone for the treatment of mild-to-moderate FPHL patients.

Background: Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells. Objectives: We aim to investigate the influence of opioids on recurrence and metastasis of breast cancer in nude mice. Methods: Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco’s Modified Eagle’s Medium, (ii) morphine (10 μmol/mL), (iii) morphine plus naloxone (10 + 10 μmol/mL), and (iv) naloxone (10 μmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting. Results: Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p < 0.05). Furthermore, the MDA-MB-231 cells in the morphine group showed an increase in p-Akt, c-Myc, and thrombosponin-1 expression. Conclusion: In the current study, we found that morphine promotes the angiogenesis of the recurrent postoperative tumors of nude mice with breast cancer and the proliferation of tumor cells and such promotion may be related to the PI3K-c-Myc signaling pathway.