Transient receptor potential mucolipin 1 circumvents oxidative stress in primary human melanocytes.

BACKGROUND: Transient Receptor Potential Mucolipin 1 (TRPML1) serves as a pivotal reactive oxygen species (ROS) sensor in cells, which is implicated in the regulation of autophagy. However, its function in melanocyte autophagy under oxidative stress remains elusive. METHODS: The expression and ion channel function of TRPML1 were investigated using immunofluorescence and calcium imaging in primary human melanocytes (MCs). After activating TRPML1 with MLSA1 (TRPML1 agonist), autophagy-related molecules were investigated via western blot. ROS level, apoptosis- and autophagy-related molecules were investigated after pretreatment with MLSA1. After interference with TRPML1 expression, mitochondrial structures were visualized by electron microscopy with hydrogen peroxide (H2O2）treatment. RESULTS: TRPML1 was expressed and functionally active in primary human MCs, and its activation promotes elevated expression of LC3-II and reduced apoptosis and ROS levels under oxidative stress. TRPML1 downregulation caused mitochondrial swelling and disruption of cristae structures under oxidative stress in primary human MCs. CONCLUSIONS: TRPML1 might mediate lysosomal autophagy in primary human MCs under oxidative stress, participating in mechanisms that maintain the oxidative and antioxidant systems in balance.

Characterization and therapeutic potential of MRABP9, a novel lytic bacteriophage infecting multidrug-resistant Acinetobacter baumannii clinical strains.

Acinetobacter baumannii is one of the most important pathogens of healthcare-associated infections. The rising prevalence of multidrug-resistant A. baumannii (MRAB) strains and biofilm formation impact the outcome of conventional treatment. Phage-related therapy is a promising strategy to tame troublesome multidrug-resistant bacteria. Here, we isolated and evaluated a highly efficient lytic phage called MRABP9 from hospital sewage. The phage was a novel species within the genus Friunavirus and exhibited lytic activity against 2 other identified MRAB strains. Genomic analysis revealed it was a safe virulent phage and a pectate lyase domain was identified within its tail spike protein. MRABP9 showed potent bactericidal and anti-biofilm activity against MRAB, significantly delaying the time point of bacterial regrowth in vitro. Phage administration could rescue the mice from acute lethal MRAB infection. Considering its features, MRABP9 has the potential as an efficient candidate for prophylactic and therapeutic use against acute infections caused by MRAB strains.

Next-generation probiotic candidates targeting intestinal health in weaned piglets: Both live and heat-killed Akkermansia muciniphila prevent pathological changes induced by enterotoxigenic Escherichia coli in the gut.

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P < 0.05), suggesting the weaning period may be an effective window for A. muciniphila intervention. Following that, 48 crossbred weaned pigs at 28 d old were randomly assigned to five groups: control (CON), high/low live A. muciniphila (HA/LA), and high/low heat-killed A. muciniphila (HIA/LIA). From 1 to 28 d old, the CON group received gastric infusion of anaerobic sterile saline every other day; the HA and LA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL live A. muciniphila, respectively; and the HIA and LIA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL heat-killed A. muciniphila, respectively. At d 29, pigs in the CON group were randomly and equally divided into two groups, one of which was named the enterotoxigenic Escherichia coli (ETEC) group, and all groups except CON received a 5-d ETEC challenge. The supplementation of A. muciniphila numerically reduced the diarrhea rate of weaned pigs compared to the pigs that only received the ETEC challenge (P = 0.57), but the LIA group had a higher diarrhea rate than the CON group (P < 0.05). Consistent with this, the supplementation of A. muciniphila improved the small intestinal morphology and structure, proportion of CD4+ T lymphocytes in the blood, as well as the expression of genes related to intestinal barrier and antioxidant indices of pigs with ETEC challenge, especially for the LA group (P < 0.05). Meanwhile, A. muciniphila supplementation reduced the expression of ETEC virulence factor genes in the ileum and colon of pigs challenged by ETEC (P < 0.05). Therefore, A. muciniphila may protect the intestinal health of weaned piglets from damage caused by ETEC infection, but the effect may vary depending on the concentration and activity of A. muciniphila.

Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice.

Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.

Causal role of immune cells in alopecia areata: A two-sample Mendelian randomization study.

BACKGROUND: Previous research has highlighted an association between alopecia areata (AA) and the collapse of hair follicle immune privilege, however, the causal linkage to specific immune cell traits remains to be elucidated. This study aimed to investigate the causal influence of immune cell traits on AA utilizing a two-sample Mendelian randomization (MR) approach. METHODS: Leveraging GWAS summary statistics of 731 immunological traits (n = 3757) and AA data (n = 211,428), MR analyses were conducted employing inverse-variance weighted (IVW), weighted median, and MR-Egger regression methodologies. Sensitivity analyses were undertaken using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO analysis. A reverse MR analysis was performed for immune cell traits identified in the initial MR analysis. RESULTS: Our study unveiled multiple immune traits associated with AA. Protective associations were observed for CD62L- CD86+ myeloid dendritic cells (DCs), TD CD4+%CD4+ T cells, and others, with ORs ranging from 0.63 to 0.78. Conversely, traits like CD62L on CD62L+ plasmacytoid DCs, HLA-DR on CD14- CD16+ monocytes, HLA-DR on monocytes, and others, were determined to augment the risk of AA, with ORs ranging from 1.13 to 1.46. Reverse MR analysis signified a reduction in BAFF-R on IgD-CD24-B cells post-AA onset (OR: 0.97, 95% CI: 0.95-1.00), with no identified heterogeneity or horizontal pleiotropy among the instrumental variables (IVs). CONCLUSIONS: Our findings suggests that CD62L on certain subpopulations of DCs and HLA-DR on monocytes may epitomize risk factors for AA, offering potential therapeutic targets for alleviating AA.

NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of NF-κB Signaling and Ameliorates Mice's Depressive-like Behavior.

Microglia are believed to be the key immune effectors of the central immune microenvironment, and their dysregulation is associated with neuroinflammation and mood disorders. Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain-containing five (NLRC5) is a new member of the Nod-like receptor family. Recently, NLRC5 has been reported to be expressed by microglia. Nonetheless, the exact roles of NLRC5 in microglial activation and its function in depression have not been investigated yet. Herein, we found that reducing NLRC5 decreased lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) in primary cultured microglia and microglial cell lines but not in bone marrow-derived macrophages (BMDMs). In more detail, reducing NLRC5 diminished the secretion of LPS-induced cytokines by attenuating IKKα/ß phosphorylation and inhibiting NF-κB signaling. Moreover, the expression of Nlrc5 in the hippocampus of LPS- or chronic unpredictable mild stress (CUMS)-induced depressive mice was increased. In line with the in vitro findings, Nlrc5 deficiency inhibited microglial activation in the mouse hippocampus and improved LPS- or CUMS-induced depressive-like behaviors. In summary, we demonstrated the critical role of NLRC5 in LPS-induced microglial activation and LPS- or CUMS-induced depressive mouse models.

New Target for Minoxidil in the Treatment of Androgenetic Alopecia.

Objective: To investigate the mechanism of minoxidil in treating androgenetic alopecia (AGA). Methods: The mechanism of action of minoxidil on AGA was first systematically investigated from the viewpoint of network pharmacology, including minoxidil-AGA target prediction, protein-protein interaction (PPI) network analysis, molecular docking and enrichment analysis of targets related to minoxidil and AGA, and dermal papilla cell assays to confirm the viability of prediction. Results: The combined analysis revealed that minoxidil treatment of AGA not only acts on androgenic receptors (AR) but also on 2 new targets, steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) and aromatase (CYP19A1). The biological processes linked to these targets were concentrated on several pathways, including enzymes and hormones. Further experiments have revealed that minoxidil suppresses the expression of AR and CYP17A1, boosts the activity of CYP19A1, decreases the formation and binding of dihydrotestosterone, and enhances the production of estradiol. Through these changes, minoxidil acts as a treatment for AGA. Conclusion: Minoxidil may act by altering hormonal and enzymatic pathways. Our study finds two new targets (CYP17A1, CYP19A1) of minoxidil and demonstrates that minoxidil inhibits AR. These targets may provide new ideas for drug research.

MAT2A inhibits the ferroptosis in osteosarcoma progression regulated by miR-26b-5p.

Osteosarcoma (OS) is the most frequent primary malignant bone tumor. Ferroptosis, a form of regulated cell death, is a key tumor suppression mechanism. Although methionine adenosyltransferase II alpha (MAT2A) has been reported to inhibit several tumor cells, it is unclear whether inhibition of MAT2A in OS cells can reduce ferroptosis. CCK-8, flow cytometry, and Transwell assays were performed to evaluate cell viability, cell apoptosis/cycle, and cell migration, respectively. The levels of ferrous iron and glutathione (GSH) levels in cells were measured to evaluate the degree of cell ferroptosis. Western blot analysis was performed to detect protein levels of MAT2A, p-STAT3 (Ser727)/STAT3, and solute carrier family 7 member 11 (SLC7A11) in OS cells. MAT2A was significantly upregulated in OS specimens and high MAT2A expression was associated with a poorer prognosis in OS patients. shRNA targeting MAT2A significantly increased OS cell apoptosis, triggered cell cycle arrest in the G2 phase, and attenuated migration ability in vitro. MAT2A depletion dramatically inhibited tumor progression of OS in vivo. Overexpression of MAT2A rescued the tumor inhibition caused by miR-26b-5p. MAT2A knockdown promoted OS cell ferroptosis. miR-26b-5p/MAT2A regulates tumor malignant progression and OS cell ferroptosis by controlling p-STAT3 and SLC7A11 expressions. Taken together, our study displayed that miR-26b-5p/MAT2A triggers ferroptosis in OS cells by increasing intracellular ferrous iron levels and inhibiting the STAT3/SLC7A11 axis. Our results reveal a MAT2A-mediated ferroptosis defense mechanism used by OS cells and propose a potential ferroptosis-inducing strategy for the treatment of OS patients.

A Cone Beam Computed Tomography Analysis of Bone Volume Variations of Extra-alveolar Region Based on Sex, Age, Vertical and Sagittal Facial Patterns.

OBJECTIVES: The goal of this study is to measure mandibular buccal shelf (MBS) concerning angulation, bone volume, and cortical bone volume as well as bone depth and cortical bone depth of infrazygomatic crest (IZC) via cone beam computed tomography and evaluate the measurements according to sex, age, vertical, and sagittal facial types. MATERIALS AND METHODS: This study collected lateral cephalograms and cone beam computed tomography scans from 100 individuals, which were used to observe angulation, bone and cortical bone volume entailing width and depth of MBS as well as the depth of IZC. FH-MP (mandibular plane angle) and A point-Nasion-B point were adopted to determine vertical and sagittal facial patterns respectively. RESULTS: Bone widths at 6 mm and 11 mm to cementoenamel junction (CEJ) and cortical bone width at 6 mm to CEJ in MBS showed significant sex differences, while bone depths and cortical bone depths in IZC show significant age difference( P <0.05). Bone width and cortical bone width at 6 mm to CEJ at the mesial root and 11 mm to CEJ at both roots as well as angulations of MBS in the mandibular first molar region, bone depth and cortical bone depth at the maxillary first molar distal buccal root, and the proximity region were all correlated to FH-MP ( P <0.05). CONCLUSIONS: Short-faced individuals of Asian ethnicity tend to have greater bone width, greater projection in MBS, and greater bone depth in the posterior region of IZC. The optimal implant sites are 11 mm apical to CEJ at the mandibular second molar distal root and 65° at the maxillary first molar mesial root.

Estimating the Distribution and Convergence of County-level Healthcare Resources Allocative Efficiency in China Based on DEA and Spatial Panel Model.

Although China's 2009 New Healthcare Reform aimed to correct the imbalance in the spatial allocation of healthcare resources with a focus on the county level, its impact on county-level allocative efficiency evolution and convergence remains unclear. This paper for the first time performs a spatial analysis to explore the distribution, evolution, and convergence of the allocative efficiency of healthcare resources with county-level data. This paper uses the sample data of 158 countries in Henan Province, China, to evaluate the evolution and convergence of the allocative efficiency of healthcare resources. Based on the estimated Data Envelopment Analysis (DEA) allocative efficiency, analysis of variance (ANOVA), and spatial descriptive analysis, we explore the county heterogeneity and efficiency evolution; a spatial panel model is then utilized to test the county-level convergence of the allocative efficiency of healthcare resources. Although the number of efficient counties has not increased, the number of inefficient individuals keeps decreasing, and the allocative efficiency of municipal districts is lower than that of nonmunicipal counties. There exists a positive spatial correlation of allocative efficiency in Henan Province, and significant and robust convergence results can be found at the county level after China's 2009 reform. This study reveals a diversified picture of China's county-level spatial evolution of allocative efficiency in healthcare resources, showing a more balanced spatial distribution of allocative efficiency since the triggering of China's 2009 reform. However, long-term investment incentives and a targeted allocation of healthcare resources are still needed to promote further efficiency convergence and increase the number of counties with efficiency.

[Serological characteristics of ABO blood group and molecular genetic analysis of a Chinese pedigree with cisAB09 subtype].

OBJECTIVE: To explore the serological characteristics of ABO blood group and molecular genetic mechanism for a Chinese pedigree with cisAB09 subtype. METHODS: A pedigree undergoing ABO blood group examination at the Department of Transfusion, Zhongshan Hospital Affiliated to Xiamen University on February 2, 2022 was selected as the study subjects. Serological assay was carried out to determine the ABO blood group of the proband and his family members. Activities of A and B glycosyltransferases in the plasma of the proband and his mother were measured with an enzymatic assay. Expression of A and B antigens on the red blood cells of the proband was analyzed by flow cytometry. Peripheral blood samples of the proband and his family members were collected. Following extraction of genomic DNA, exons 1 to 7 of the ABO gene and their flanking introns were sequenced, and Sanger sequencing of exon 7 was carried out for the proband, his elder daughter and mother. RESULTS: The results of serological assay suggested that the proband and his elder daughter and mother had an A2B phenotype, whilst his wife and younger daughter had an O phenotype. Measurement of plasma A and B glycosyltransferase activity suggested that the titers of B-glycosyltransferase activity were 32 and 256 for the proband and his mother, which were respectively below and above that of A1B phenotype-positive controls (128). Flow cytometry analysis showed that the expression of A antigen on the red blood cell surface of the proband has decreased, whilst the expression of B antigen was normal. Genetic sequencing confirmed that, in addition to an ABO*B.01 allele, the proband, his elder daughter and mother have harbored a c.796A>G variant in exon 7, which has resulted in substitution of the methionine at 266th position of the B-glycosyltransferase by valine and conformed to the characteristics of ABO*cisAB.09 allele. The genotypes of the proband and his elder daughter were determined as ABO*cisAB.09/ABO*O.01.01, his mother was ABO*cisAB.09/ABO*B.01, and his wife and younger daughter were ABO*O.01.01/ABO*O.01.01. CONCLUSION: The c.796A>G variant of the ABO*B.01 allele has resulted in an amino acid substitution p.Met266Val, which probably underlay the cisAB09 subtype. The ABO*cisA B.09 allele encodes a special glycosyltransferase which can synthesize normal level of B antigen and low level of A antigen on the red blood cells.

Efficacy and safety of different JAK inhibitors in the treatment of alopecia areata: a network meta-analysis.

Background: Alopecia areata (AA) is an immune disease characterized by non-scarring hair loss. With the widespread application of JAK inhibitors in immune-related diseases, attention is being given to their role in the treatment of AA. However, it is unclear which JAK inhibitors have a satisfactory or positive effect on AA. This network meta-analysis aimed to compare the efficacy and safety of different JAK inhibitors in the treatment of AA. Methods: The network meta-analysis was performed according to the PRISMA guidelines. We included randomized controlled trials as well as a small number of cohort studies. The differences in efficacy and safety between the treatment and control groups were compared. Results: Five randomized controlled trials, two retrospective studies, and two prospective studies involving 1689 patients were included in this network meta-analysis. In terms of efficacy, oral baricitinib and ruxolitinib significantly improved the response rate of patients compared to placebo [MD = 8.44, 95% CI (3.63, 19.63)] and [MD = 6.94, 95% CI, (1.72, 28.05)],respectively. Oral baricitinib treatment significantly improved the response rate compared to non-oral JAK inhibitor treatment [MD=7.56, 95% CI (1.32,43.36)]. Oral baricitinib, tofacitinib, and ruxolitinib treatments significantly improved the complete response rate compared to placebo [MD = 12.21, 95% CI (3.41, 43.79)], [MD = 10.16, 95% CI (1.02, 101.54)], and [MD = 9.79, 95% CI, (1.29, 74.27)], respectively. In terms of safety, oral baricitinib, tofacitinib, and ruxolitinib treatments significantly reduced treatment-emergent adverse event rates compared with conventional steroid treatment [MD = 0.08, 95% CI (0.02, 0.42)], [MD = 0.14, 95% CI (0.04, 0.55)], and [MD = 0.35, 95% CI, (0.14, 0.88)], respectively. Conclusion: Oral baricitinib and ruxolitinib are excellent options for the treatment of AA owing to their good efficacy and safety profiles. In contrast, non-oral JAK inhibitors do not appear to have satisfactory efficacy in treating AA. However, further studies are required to verify the optimal dose of JAK inhibitors for AA therapy.

Nested Phosphorothioated Hybrid Primer-Mediated Isothermal Amplification for Specific and Dye-Based Subattomolar Nucleic Acid Detection at Low Temperatures.

Developing dye-based isothermal nucleic acid amplification (INAA) at low temperatures such as 37 °C remains a technical challenge. Here, we describe a nested phosphorothioated (PS) hybrid primer-mediated isothermal amplification (NPSA) assay which only utilizes EvaGreen (a DNA-binding dye) to achieve specific and dye-based subattomolar nucleic acid detection at 37 °C. The success of low-temperature NPSA essentially depends on employing Bacillus smithii DNA polymerase, a strand-displacing DNA polymerase with wide range of activation temperature. However, the NPSA's high efficiency entails nested PS-modified hybrid primers and the additives of urea and T4 Gene 32 Protein. To address the inhibition of urea on reverse transcription (RT), one-tube two-stage recombinase-aided RT-NPSA (rRT-NPSA) is established. By targeting human Kirsten rat sarcoma viral (KRAS) oncogene, NPSA (rRT-NPSA) stably detects 0.2 aM of KRAS gene (mRNA) within 90 (60) min. In addition, rRT-NPSA possesses subattomolar sensitivity to detect human ribosomal protein L13 mRNA. The NPSA/rRT-NPSA assays are also validated to obtain consistent results with PCR/RT-PCR methods on qualitatively detecting DNA/mRNA targets extracted from cultured cells and clinical samples. As a dye-based, low-temperature INAA method, NPSA inherently facilitates the development of miniaturized diagnostic biosensors.

Pterostilbene supresses inflammation-induced melanoma metastasis by impeding neutrophil elastase-mediated thrombospondin-1 degradation.

Objective: Chronic inflammation plays a fatal role in tumor metastasis. Pterostilbene (PTE) is a natural dimethylated analogue of resveratrol with anticancer and anti-inflammatory activities. This study aimed to investigate the inhibitory effect of PTE on inflammation-associated metastasis and explore the underlying mechanisms. Methods: Lipopolysaccharide (LPS)-induced lung inflammation and melanoma metastasis models were established in mice. After PTE treatment for four weeks, the organ index, histological changes, proinflammatory cytokines, and the expression and activity of neutrophil elastase (NE), a biomarker of neutrophil influx in the lungs, were analysed. Additionally, direct effects of PTE on NE-induced B16 cell migration were explored in wound healing and Transwell assays, and the expression of thrombospondin-1 (TSP-1) and epithelial-mesenchymal transition (EMT) markers were also detected. Results: PTE obviously attenuated the LPS-induced metastasis of circulatory B16 cells to lungs by reducing the number of metastatic nodules on the lung surfaces and the lung weight/body weight ratio. PTE treatment also significantly reduced LPS-activated increase levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the lungs of tumor-bearing mice. In addition, increased expression and enzyme activity of NE and decreased expression of TSP-1 were observed, and these were blocked by PTE. In vitro, PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration, prevented NE-induced TSP-1 proteolysis and reversed the expression of vimentin, N-cadherin and E-cadherin. Conclusion: PTE could block inflammation-enhanced tumor metastasis, and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.

Treatment update for vitiligo based on autoimmune inhibition and melanocyte protection.

INTRODUCTION: The treatment of vitiligo remains challenging due to the complexity of its pathogenesis, influenced by genetic factors, oxidative stress and abnormal cell adhesion that collectively impact melanocyte survival and trigger immune system attacks, resulting in melanocyte death. Melanocytes in vitiligo are believed to exhibit genetic susceptibility and defects in cellular mechanisms, such as defects in autophagy, that reduce their ability to resist oxidative stress, leading to increased expression of the pro-inflammatory protein HSP70. The low expression of adhesion molecules, such as DDR1 and E-cadherin, accelerates melanocyte damage and antigen exposure. Consequently, autoimmune attacks centered on IFN-γ-CXCR9/10-CXCR3-CD8+ T cells are initiated, causing vitiligo. AREAS COVERED: This review discusses the latest knowledge on the pathogenesis of vitiligo and potential therapeutic targets from the perspective of suppressing autoimmune attacks and activating melanocytes functions. EXPERT OPINION: Vitiligo is one of the most challenging dermatological diseases due to its complex pathogenesis with diverse therapeutic targets. Immune suppression, such as corticosteroids and emerging JAK inhibitors, has proven effective in disease progression. However, during the early stages of the disease, it is also important to optimize therapeutic strategies to activate melanocytes for alleviating oxidative stress and improving treatment outcomes.

The Effect of Descending Resources Reform on Reallocating Healthcare Resources: An Analysis Based on the Difference-in-Differences Method.

Since 2010, China has been exploring descending resources reform in order to correct the imbalanced allocation of healthcare resources and promote coordinated economic development among regions. This paper for the first time estimates the impact this reform has had on the reallocation of healthcare resources by using prefecture-level cities panel data from Zhejiang Province, China, which implemented the reform province-wide in 2013. The time-varying difference-in-differences (DID) method was used to estimate the reform's policy effects. The data used in this paper is from published statistical yearbooks and local governments, which include panel data from 11 prefecture-level and higher cities in Zhejiang Province as the treated group and 46 prefecture-level cities in Jiangsu, Henan, and Sichuan Province as the control group. The entropy weight method was used to construct the supply index and demand index to incorporate multiple inputs and outputs, and efficiency indicators were constructed using the ratio method. This research found that the reform has had a positive effect on outpatient visits in different prefecture-level cities with vast rural areas. However, this reform exerted no significant impact on inpatient services or supply-side or resource allocation efficiency. Several robust tests support the above conclusions, and one theoretical explanation is provided. The descending health resources reform can be a valuable reform path in promoting more balanced healthcare resource allocation; however, the resultant disparities in its effects should be considered when implementing it.

Effect of fractional laser alone or in combination on alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is characterized by limited non-scarring patchy alopecia, which appears as round or oval patches and is prone to recurrence, causing severe psychological burdens to patients. No specific device has been approved by the FDA for the treatment of baldness, but new treatments are being investigated and treatments such as the excimer laser, He- Ne laser, and excimer lamp have been proposed. A growing number of studies have found that fractional lasers also have great potential in the treatment of AA. METHODS: A literature search and meta-analysis using Review Manager 5.4 software to investigate the efficacy of fractional laser treatment for AA. RESULTS: Fractional laser combined with minoxidil (RR 1.32, 95% CI 1.17-1.49, p < 0.00001) or cortisol (RR 1.39, 95% CI 1.15-1.67, p = 0.00006) was more effective than either drug alone in the treatment of AA. Of course, the fractional laser alone was also effective in the treatment of AA (RR 10.33, 95% CI 2.07-51.36, p = 0.004) and more effective than cortisol alone (RR 1.86, 95% CI 1.36-2.52, p < 0.00001), and there was no effect on the occurrence of adverse effects (p = 0.49 > 0.05). When compared to other physical treatments of a comparable kind, fractional laser therapy's effectiveness was not significantly different (p = 0.15 > 0.05). CONCLUSION: Our results show that the use of fractional lasers can effectively treat alopecia areata.