Measurement properties of patient-reported outcome measures of mental help-seeking attitude: a systematic review of psychometric properties.

Background: At present, the phenomenon of patients with mental disorders not seeking mental help is very serious, and the mental help-seeking attitude is the central structure of the help process. However, there is no consensus on which patient-reported outcome measure (PROM) should be used to assess mental help-seeking attitudes. Objective: The systematic review aims to critically appraise, compare, and summarize the measurement quality of the all-available PROMs about mental help-seeking attitudes to provide evidence-based guidance and reference for clinical researchers. Methods: A systematic search was conducted in 9 databases (PubMed, Embase, Web of Science, Medline, APA, CINAHL, Sinomed, CNKI, and WanFang) since the establishment of the database until November 30, 2022 to identify articles on the PROMs of mental help-seeking attitudes. We used the COSMIN guidelines to evaluate the methodological quality and measurement properties of all-available PROMs, and a modified Grading, Recommendation, Assessment, Development, and Evaluation (GRADE) system to evaluate the level of evidence supporting each rating. Finally, the recommendation level is given according to the overall quality of each PROM. Results: We identified 29 studies representing 13 PROMs out of 2,828 screening studies. The overall quality of the included PROMs varied, with 6 rated as class B, 6 as class C, and only the Mental Help Seeking Attitudes Scale (MHSAS) as class A. Conclusion: The measurement characteristics of MHSAS have been the most comprehensive evaluation, and it has good reliability and validity, and high feasibility for clinical application, so it can be temporarily recommended for use, but the above conclusions still need to be supported by more high-quality evidence.

PROTAC Degraders of Androgen Receptor-Integrated Dissolving Microneedles for Androgenetic Alopecia and Recrudescence Treatment via Single Topical Administration.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a youth-oriented tendency, but it lacks effective treatment. The binding of androgen receptor (AR) and androgen plays an essential role in the occurrence and progression of AGA. Herein, novel proteolysis targeting chimera degrader of AR (AR-PROTAC) is synthesized and integrated with dissolving microneedles (PROTAC-MNs) to achieve AR destruction in hair follicles for AGA treatment. The PROTAC-MNs possess adequate mechanical capabilities for precise AR-PROTAC delivery into the hair follicle-residing regions for AR degradation. After applying only once topically, the PROTAC-MNs achieve an accelerated onset of hair regeneration as compared to the daily application of the first-line topical drug minoxidil. Intriguingly, PROTAC-MNs via single administration still realize superior hair regeneration in AGA recrudescence, which is the major drawback of minoxidil in clinical practice. With the degradation of AR, the PROTAC-MNs successfully regulate the signaling cascade related to hair growth and activate hair follicle stem cells. Furthermore, the PROTAC-MNs do not cause systemic toxicity or androgen deficiency-related chaos in vivo. Collectively, these AR-degrading dissolving microneedles with long-lasting efficacy, one-step administration, and high biocompatibility provide a great therapeutic potential for AGA treatment.

Chlorogenic Acid Relieves the Lupus Erythematosus-like Skin Lesions and Arthritis in MRL/lpr Mice.

Chlorogenic acid (CGA) is a phenylpropyl substance synthesized through the shikimic acid pathway. In addition to its anti-tumor, anti-inflammatory, and antioxidant abilities, CGA also has immunomodulatory effects. The aim of the present study is to investigate the therapeutic effects of CGA on the skin damage and arthritis caused by systemic lupus erythematosus (SLE) in an MRL/lpr mouse model. In the SLE model, female MRL/lpr mice at the age of 10 weeks old were treated with CGA daily or cyclophosphamide (CTX) weekly via intraperitoneal injection for three months. After treatment, CGA can significantly alleviate the skin and mucous membrane damage caused by SLE and has a certain improvement effect on arthritis. CGA could inhibit dsDNA expression to a certain extent but has no obvious regulation on ANA concentration. The ELISA and BioMAP results indicated that CGA might play an anti-inflammatory role by down-regulating the interleukin (IL)-17 level. In conclusion, our study demonstrates that CGA can alleviate multiorgan damage in MRL/lpr mice by reducing IL-17.

Conditioned media-integrated microneedles for hair regeneration through perifollicular angiogenesis.

Androgenetic alopecia (AGA), the most prevalent type of hair loss in clinic, is induced partly by insufficient perifollicular vascularization. Here we designed a dissolvable microneedles (MNs) patch that was loaded with conditioned media (CM) derived from hypoxia-pretreated mesenchymal stem cells, which contained elevated HIF-1α. The CM-integrated MNs patch (designated as CM-MNs) can puncture the stratum corneum and deliver the pro-angiogenic factors directly into skin in a one-step and minimally invasive manner. Meanwhile, the administration of CM-MNs induced a certain mechanical stimulation on the skin, which can also promote neovascularization. With the combined effects of the pro-angiogenic factors in CM and the mechanical stimulation induced by MNs, CM-MNs successfully boosted perifollicular vascularization, and activated hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. Furthermore, we proved that the inhibition of perifollicular angiogenesis restrained the awakening of hair follicle stem cells, elucidating the tight correlation between perifollicular angiogenesis and the activation of hair follicle stem cells. The innovative integration of CM and MNs holds great promise for clinical AGA treatment and indicates that boosting angiogenesis around hair follicles is an effective strategy against AGA.

Micro/nanorobots for precise drug delivery via targeted transport and triggered release: A review.

Micro/nanorobots that can effectively convert diverse energy sources into movement can revolutionize the field of pharmaceutical, particularly targeted drug delivery. By targeted transport and triggered release, drug can be delivered to targeted tissues or body sites. Targeted transport is discussed with different actuation energy sources including self-propelled (H2O2 and enzymes), external field-propelled (light, electrical, acoustics and magnetic field) and motile microorganism-propelled (bacterium, sperm, and contractile and immune cells) types. Triggered release systems including physiological environment, external fields and other mechanisms categories are also discussed here for the first time. With different transport and triggered release systems, micro/nanorobots achieved the goal of precise delivery of therapeutics. This review may provide a different perspective or referable guidance for the future development of more flexible targeted delivery systems.

A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect.

Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 µg of Ce6 in the needle tips via a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 µm under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions in situ through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.

Ceria Nanozyme-Integrated Microneedles Reshape the Perifollicular Microenvironment for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is highly prevalent in current society but lacks effective treatments. The dysregulation of the hair follicle niche induced by excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment is the leading cause of AGA. Herein, we designed a ceria nanozyme (CeNZ)-integrated microneedles patch (Ce-MNs) that can alleviate oxidative stress and promote angiogenesis simultaneously to reshape the perifollicular microenvironment for AGA treatment. On the basis of the excellent mechanical strength of Ce-MNs, the encapsulated CeNZs with catalase- and superoxide-mimic activities can be efficiently delivered into skin to scavenge excessive ROS. Moreover, the mechanical stimulation induced by the administration of MNs can remodel the microvasculature in the balding region. Compared with minoxidil, a widely used clinical drug for AGA treatment, Ce-MNs exhibited accelerated hair regeneration in the AGA mouse model at a lower administration frequency without inducing significant skin damage. Consequently, such a safe and perifollicular microenvironment-shaping MNs patch shows great potential for clinical AGA treatment.

Recent advances in mechanical force-assisted transdermal delivery of macromolecular drugs.

The transdermal delivery of macromolecular drugs has become one of the focused topics in pharmaceutical research since it enables highly specific and effective delivery, while avoiding the pain and needle phobia associated with injection, or incidences like drug degradation and low bioavailability of oral administration. However, the passive absorption of macromolecular drugs via skin is highly restricted by the stratum corneum owing to high molecular weight. Therefore, various strategies have been extensively developed and conducted to facilitate the transdermal delivery of macromolecular drugs, among which, mechanical force-assisted techniques occupy dominant positions. Such techniques include ultrasound, needle-free jet injection, temporary pressure and microneedles. In this review, we focus on recent transdermal enhancing strategies utilizing mechanical force, and summarize their mechanisms, advantages, limitations and clinical applications respectively.

Multidisciplinary team approach to the prenatal management of orofacial clefts: a single center cohort study in Taiwan.

Advances in ultrasound fetal diagnostics and treatment have created a dilemma for doctors and parents: choosing whether to continue with a pregnancy as well as choosing between various treatment options. A multidisciplinary approach has been widely accepted in the management of other prenatally diagnosed anomalies and has shown superior results compared to routine care. We present a retrospective cohort of patients prenatally diagnosed with orofacial clefts who were offered consultation by an expert multidisciplinary team, including: a fetal medicine specialist, an obstetrician, a plastic surgeon, and a case managing nurse. We analyzed factors influencing parents' decision to utilize a consultation service, as well as their decision about pregnancy continuation. Our results suggest that the presence of other anomalies and maternal age heavily influenced the decision about the uptake of consultations. If consulted by the team, parents tended to continue with the pregnancy, even when accounting for fetal gender and maternal age. On the other hand, having a consultation had varying effects depending on the cleft type. The findings suggest that multidisciplinary consultations may be an efficient approach in managing pregnancies complicated by orofacial cleft anomalies; which may help in preventing unnecessary pregnancy terminations and developing a sufficient postnatal care plan.

Simultaneous Determination of Eight Alkaloids in Rat Plasma by UHPLC-MS/MS after Oral Administration of Coptis deltoidea C. Y. Cheng et Hsiao and Coptis chinensis Franch.

A ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was successfully developed and validated for the identification and determination of eight alkaloids: tetrahydropalmatine (A); palmatine (B); magnoflorine (C); columbamine (D); berberine (E); worenine (F); berberrubine (G) and coptisine (H) in rat plasma, which are the active components in Coptis deltoidea C. Y. cheng et Hsiao (CCY) and Coptis chinensis Franch (CF). The chromatographic separation of analytes was successfully achieved on an Agilent SB-C18 column (1.8 µm, 150 mm × 2.1 mm) using a programme with a mobile phase consisting of acetonitrile and water containing 0.3% acetic acid at a flow rate of 0.25 mL/min. The analytes were detected with a triple quadrupole tandem MS in multiple reaction monitoring (MRM) mode and an electrospray ionization (ESI) source in positive mode. The validated method showed good linearity over a wide concentration range (r² > 0.991), and lower limits of quantification (LLOQ) less than 1.1 ng/mL for all analytes, and matrix effects ranged from 85.2% to 106.8%. The mean extraction recoveries were no less than 86.4%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The method validation results demonstrated that the proposed method was sensitive, specific, and reliable, which could lay a foundation for the pharmacokinetic study of eight analytes after oral administration of CCY and CF in subsequent studies.