NAD+ supplementation improves mitochondrial functions and normalizes glaucomatous trabecular meshwork features.

Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.

Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis.

Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α-smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.

Choline Derivative as a Multifunctional Interfacial Bridge through Synergistic Effects for Improving the Efficiency and Stability of Perovskite Solar Cells.

The interfacial carrier non-radiative recombination caused by buried defects in electron transport layer (ETL) material and the energy barrier severely hinders further improvement in efficiency and stability of perovskite solar cells (PSCs). In this study, the effect of the SnO2 ETL doped with choline chloride (CC), acetylcholine chloride (AC), and phosphocholine chloride sodium salt (PCSS) are investigated. These dopants modify the interface between SnO2 ETL and perovskite layer, acting as a bridge through synergistic effects to form uniform ETL films, enhance the interface contact, and passivate defects. Ultimately, compared with CC (which with ─OH) and AC (which with C═O), the PCSS with P═O and sodium ions groups is more beneficial for improving performance. The device based on PCSS-doped SnO2 ETL achieves an efficiency of 23.06% with a high VOC of 1.2 V, which is considerably higher than the control device (20.55%). Moreover, after aging for 500 h at a temperature of 25 °C and relative humidity (RH) of 30-40%, the unsealed device based on SnO2-PCSS ETL maintains 94% of its initial efficiency, while the control device only 80%. This study provides a meaningful reference for the design and selection of ideal pre-buried additive molecules.

Metformin-induced PCSK9 inhibition further decreases LDL-C following statin treatment in patients with coronary artery disease and without diabetes.

In vitro investigations have established metformin's capacity to downregulate PCSK9 expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (Cholesterol-Lowering Agents alone: atorvastatin+/-ezetimibe, n=38) and Met+CLA groups (metformin plus CLA, n=33) at a 1:1 ratio. The primary endpoint was the therapeutic impact of one-month metformin combination treatment on LDL-C and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL-1 and 80.54 ng·mL-1, respectively. After one month, metformin significantly reduced LDL-C (-20.81%, P<0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P<0.001) were observed. Moreover, Met+CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs 1.45%, P=0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a one-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression.

Melatonin Increases Root Cell Wall Phosphorus Reutilization via an NO Dependent Pathway in Rice (Oryza sativa).

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.

BcWRKY1 confers Botrytis cinerea susceptibility via inhibiting JA biosynthesis.

WRKYs play important roles in plant stress resistance. However, the role of WRKYs in non-heading Chinese cabbage (Brassica campestris ssp. chinensis) against Botrytis cinerea (B. cinerea) remains poorly understood. Herein, the expression of BcWRKY1 was induced by B. cinerea. Further, the role of BcWRKY1 in B. cinerea infection was identified. Silencing of BcWRKY1 in non-heading Chinese cabbage enhanced plant resistance to B. cinerea. After B. cinerea inoculation, BcWRKY1-silencing plants exhibited lower reactive oxygen species (ROS) content, higher jasmonic acid (JA) content, and the expression level of JA biosynthesis genes, BcOPR3, BcLOX3-1 and BcLOX3-2 were upregulated. Overexpression of BcWRKY1 in Arabidopsis exhibited a complementary phenotype. By directly targeting W-boxes in the promoter of BcLOX3-2, BcWRKY1 inhibited the transcription of this gene. In addition, 13 candidate interacting proteins of BcWRKY1 were identified by yeast two-hybrid (Y2H) screening, and the interaction between BcWRKY1 and BcCaM6 weakened the inhibition of BcLOX3-2. In summary, our findings suggest that BcWRKY1 interacts with BcCaM6 to negatively regulate disease resistance.

A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression.

PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI). METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes. RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups. CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.

Estimation of genetic heritabilities of human traits in case-control studies.

It is of great interest to detect missing heritability for human complex traits. Additive genetic effects (ADD), maternal genetic effects (MGE), and parent-of-origin effects (POE) play important roles in genetic mechanisms. Methods have been developed in the literature to analyze heritabilities due to ADD, POE, and MGE separately but not simultaneously. In this paper, a new model termed APM is proposed based on mother-child duos genetic data, which orthogonally decomposes heritabilities due to ADD, POE, and MGE. This orthogonal decomposition is biologically interpretable since it ideally characterizes independent contributions due to the three effects. We focus on case-control data that are widely adopted in genetics studies and develop a novel method R-PCGC by adjusting estimation biases due to sampling bias in case-control studies and imposing nonnegative constraints on the heritability estimates. Large sample properties such as consistency and asymptotic normality are established for R-PCGC. The desired properties of R-PCGC (i.e., asymptotic unbiasedness and nonnegativity) are confirmed through simulations. Finally, R-PCGC regression is applied to a case-control study of preterm births from the Danish National Birth Cohort (DNBC).

BcNAC056 Interacts with BcWRKY1 to Regulate Leaf Senescence in Pak Choi.

Senescence is the final stage of leaf development. For leafy vegetables such as pak choi, leaf senescence is adverse to yield due to the harvest period shortening. However, the regulatory mechanisms of leaf senescence are largely unknown in leafy vegetables. Here, we isolated and characterized a NAC gene, BcNAC056, in pak choi [Brassica campestris (syn. Brassica rapa) ssp. chinensis cv. 49caixin]. BcNAC056-GFP was located in the nucleus at the subcellular level, and BcNAC056 was responsive to leaf senescence and different hormones at the transcriptional level. Heterologous overexpression of BcNAC056 in Arabidopsis promoted leaf senescence, accompanied by the increased expression of senescence-associated genes (SAGs), whereas virus-induced gene silencing-based silencing in pak choi delayed leaf senescence. The following transcriptome analysis showed that heterologous overexpression of BcNAC056 enhanced some AtSAG transcripts in Arabidopsis. Electrophoretic mobility shift assay (EMSA) and dual-luciferase (LUC) reporter assay revealed that BcNAC056 activated SAG12 by directly binding to the promoter. In addition, with the LUC reporter and transient overexpression assays, we proposed that BcNAC056-BcWRKY1 interaction promoted the activation of BcSAG12. Taken together, our findings revealed a new regulatory mechanism of leaf senescence in pak choi.

Postoperative Overtriage to an Intensive Care Unit Is Associated With Low Value of Care.

OBJECTIVE: We test the hypothesis that for low-acuity surgical patients, postoperative intensive care unit (ICU) admission is associated with lower value of care compared with ward admission. BACKGROUND: Overtriaging low-acuity patients to ICU consumes valuable resources and may not confer better patient outcomes. Associations among postoperative overtriage, patient outcomes, costs, and value of care have not been previously reported. METHODS: In this longitudinal cohort study, postoperative ICU admissions were classified as overtriaged or appropriately triaged according to machine learning-based patient acuity assessments and requirements for immediate postoperative mechanical ventilation or vasopressor support. The nearest neighbors algorithm identified risk-matched control ward admissions. The primary outcome was value of care, calculated as inverse observed-to-expected mortality ratios divided by total costs. RESULTS: Acuity assessments had an area under the receiver operating characteristic curve of 0.92 in generating predictions for triage classifications. Of 8592 postoperative ICU admissions, 423 (4.9%) were overtriaged. These were matched with 2155 control ward admissions with similar comorbidities, incidence of emergent surgery, immediate postoperative vital signs, and do not resuscitate order placement and rescindment patterns. Compared with controls, overtraiged admissions did not have a lower incidence of any measured complications. Total costs for admission were $16.4K for overtriage and $15.9K for controls ( P =0.03). Value of care was lower for overtriaged admissions [2.9 (2.0-4.0)] compared with controls [24.2 (14.1-34.5), P <0.001]. CONCLUSIONS: Low-acuity postoperative patients who were overtriaged to ICUs had increased total costs, no improvements in outcomes, and received low-value care.

Consolidated bioprocessing for bioethanol production by metabolically engineered cellulolytic fungus Myceliophthora thermophila.

Using cellulosic ethanol as fuel is one way to help achieve the world's decarbonization goals. However, the economics of the present technology are unfavorable, especially the cost of cellulose degradation. Here, we reprogram the thermophilic cellulosic fungus Myceliophthora thermophila to directly ferment cellulose into ethanol by mimicking the aerobic ethanol fermentation of yeast (the Crabtree effect), including optimizing the synthetic pathway, enhancing the glycolytic rate, inhibiting mitochondrial NADH shuttles, and knocking out ethanol consumption pathway. The final engineered strain produced 52.8 g/L ethanol directly from cellulose, and 39.8 g/L from corncob, without the need for any added cellulase, while the starting strain produced almost no ethanol. We also demonstrate that as the ethanol fermentation by engineered M. thermophila increases, the composition and expression of cellulases that facilitate the degradation of cellulose, especially cellobiohydrolases, changes. The simplified production process and significantly increased ethanol yield indicate that the fungal consolidated bioprocessing technology that we develop here (one-step, one-strain ethanol production) is promising for fueling sustainable carbon-neutral biomanufacturing in the future.

Astroglial Connexin 43-Mediated Gap Junctions and Hemichannels: Potential Antidepressant Mechanisms and the Link to Neuroinflammation.

Major depression disorder (MDD) is a neuropsychiatric disorder associated with a high suicide rate and a higher disability rate than any other disease. Evidence suggests that the pathological mechanism of MDD is related to astrocyte dysfunction. Depression is mainly associated with the expression of connexin 43 (Cx43) and the function of Cx43-mediated gap junctions and hemichannels in astrocytes. Moreover, neuroinflammation has been a hotspot in research on the pathology of depression, and Cx43-mediated functions are thought to be involved in neuroinflammation-related depression. However, the specific mechanism of Cx43-mediated functions in neuroinflammation-related depression pathology remains unclear. Therefore, this review summarizes and discusses Cx43 expression, the role of gap junction intercellular communication, and its relationship with neuroinflammation in depression. This review also focuses on the effects of antidepressant drugs (e.g., monoamine antidepressants, psychotropic drugs, and N-methyl-D-aspartate receptor antagonists) on Cx43-mediated function and provides evidence for Cx43 as a novel target for the treatment of MDD. The pathogenesis of MDD is related to astrocyte dysfunction, with reduced Cx43 expression, GJ dysfunction, decreased GJIC and reduced BDNF expression in the depressed brain. The effect of Cx43 on neuroinflammation-related depression involving inflammatory cytokines, glutamate excitotoxicity, and HPA axis dysregulation. Antidepressant drugs targeting Cx43 can effectively relieve depressive symptoms.

Neurocan regulates vulnerability to stress and the anti-depressant effect of ketamine in adolescent rats.

Depression is more prevalent among adolescents than adults, but the underlying mechanisms remain largely unknown. Using a subthreshold chronic stress model, here we show that developmentally regulated expressions of the perineuronal nets (PNNs), and one of the components, Neurocan in the prelimbic cortex (PrL) are important for the vulnerability to stress and depressive-like behaviors in both adolescent and adult rats. Reduction of PNNs or Neurocan with pharmacological or viral methods to mimic the expression of PNNs in the PrL during adolescence compromised resilience to stress in adult rats, while virally mediated overexpression of Neurocan reversed vulnerability to stress in adolescent rats. Ketamine, a recent-approved drug for treatment-resistant depression rescued impaired function of Parvalbumin-positive neurons function, increased expression of PNNs in the PrL, and reversed depressive-like behaviors in adolescent rats. Furthermore, we show that Neurocan mediates the anti-depressant effect of ketamine, virally mediated reduction of Neurocan in the PrL abolished the anti-depressant effect of ketamine in adolescent rats. Our findings show an important role of Neurocan in depression in adolescence, and suggest a novel mechanism for the anti-depressant effect of ketamine.

Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Genome-wide association analysis of kernel nutritional quality in two natural maize populations.

As one of the three staple crops, nutritional traits in maize are important for human and animal nutrition. Grain quality-related traits are closely related to grain commercial value. Understanding the genetic basis of quality-related traits in maize would be helpful for breeding high-quality maize varieties. In this study, two association panels (AM122 and AM180) were subjected to genome-wide association analysis of grain quality-related traits, including protein content, oil content, starch content, and fiber content. In total, 98 SNPs (P < 1 × 10-4) were identified to be significantly associated with these four grain quality-related traits. By integrating two sets of public transcriptome data, 31 genes located in 200 kb regions flanking the associated SNP showed high expression during kernel development and were differentially expressed in two maize inbred lines, KA225 and KB035, with significantly different quality. These genes might regulate maize grain quality by participating in plant hormone processes, autophagy processes, and others. All these results could provide important reference information for breeding high­quality maize varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01360-w.

The impact of the chalcogen-substitution element and initial spectroscopic state on excited-state relaxation pathways in nucleobase photosensitizers: a combination of static and dynamic studies.

The substitution of oxygen with chalcogen in carbonyl group(s) of canonical nucleobases gives an impressive triplet generation, enabling their promising applications in medicine and other emerging techniques. The excited-state relaxation S2(ππ*) → S1(nπ*) → T1(ππ*) has been considered the preferred path for triplet generation in these nucleobase derivatives. Here, we demonstrate enhanced quantum efficiency of direct intersystem crossing from S2 to triplet manifold upon substitution with heavier chalcogen elements. The excited-state relaxation dynamics of sulfur/selenium substituted guanines in a vacuum is investigated using a combination of static quantum chemical calculations and on-the-fly excited-state molecular dynamics simulations. We find that in sulfur-substitution the S2 state predominantly decays to the S1 state, while upon selenium-substitution the S2 state deactivation leads to simultaneous population of the S1 and T2,3 states in the same time scale and multi-state quasi-degeneracy region S2/S1/T2,3. Interestingly, the ultrafast deactivation of the spectroscopic S3 state of both studied molecules to the S1 state occurs through a successive S3 → S2 → S1 path involving a multi-state quasi-degeneracy S3/S2/S1. The populated S1 and T2 states will cross the lowest triplet state, and the S1 → T intersystem crossing happens in a multi-state quasi-degeneracy region S1/T2,3/T1 and is accelerated by selenium-substitution. The present study reveals the influence of both the chalcogen substitution element and initial spectroscopic state on the excited-state relaxation mechanism of nucleobase photosensitizers and also highlights the important role of multi-state quasi-degeneracy in mediating the complex relaxation process. These theoretical results provide additional insights into the intrinsic photophysics of nucleobase-based photosensitizers and are helpful for designing novel photo-sensitizers for real applications.

Swept-source optical coherence tomography and ultrasound biomicroscopy study of anterior segment parameters in primary angle-closure glaucoma.

PURPOSE: To evaluate the agreement between swept-source OCT (CASIA2) and UBM in primary angle-closure glaucoma. METHODS: Eighty eyes of 40 participants diagnosed with primary angle-closure glaucoma were examined. Parameters measured included angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), trabecular iris angle (TIA), lens vault (LV), anterior chamber depth (ACD), and anterior chamber width (ACW). Angle images of nasal, temporal, superior, and inferior were acquired by the anterior segment mode of CASIA2 and UBM. One-way analysis of variance and paired t-test were used for statistical analysis, and the agreement was analyzed by internal correlation coefficient (ICC) and Bland-Altman method. RESULTS: One-way ANOVA pairwise comparison showed that CASIA2 or UBM had the narrowest superior chamber angle and the widest temporal chamber angle in patients with primary angle-closure glaucoma. The paired t-test showed that inter-device AOD, TIA, ARA, and TISA of superior chamber angle had significant differences (p < 0.001). There was no significant difference in the measured values of LV, ACD, and ACW (p > 0.05). The agreement of all parameters is good through the Bland-Altman method comparison. ICC result showed moderate agreement in other angle parameters except for superior ARA500 (0.739). CONCLUSION: In the anterior chamber angle measurement process, we should pay more attention to the superior chamber angle covered by eyelids. Although the agreement is acceptable between CASIA2 and UBM, the measurements could not be considered interchangeable due to the tremendous statistical difference between the two devices.

Trimester-specific reference intervals of hemostasis biomarkers for healthy pregnancy.

Physiological changes in hemostasis during pregnancy have been reported by several authors. This study aimed at establishing reference intervals for the hemostasis biomarkers thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (tPAI-C), in healthy pregnancies. After excluding outliers, a total of 496 healthy pregnant women (128 first-trimester, 142 second-trimester, 107 third-trimester and 119 pre-labor) and 103 healthy nonpregnant women were enrolled from Shenzhen Bao'an Women's and Children's Hospital. Hemostasis biomarkers, TAT, PIC, TM and tPAI-C, were measured by using a quantitative chemiluminescence enzyme immunoassay performed on HISCL automated analysers. The median and reference intervals (the 2.5th and 97.5th percentiles) were calculated to establish trimester-specific reference intervals for healthy pregnant women. The reference intervals for TAT, PIC, TM and tPAI-C in the first trimester were 0.7-7.6 1 µg/L, 0.2-0.9 mg/L, 2.8-11.0 TU/ml, and 1.2-6.5 1 µg/L, respectively. The reference intervals in the second trimester were 1.7-12.0 1 µg/L, 0.2-1.0 mg/L, 3.7-11.6 TU/ml, and 2.8-8.8 1 µg/L, respectively. The reference intervals in the third trimester were 2.7-16.1 1 µg/L, 0.1-1.4 mg/L, 2.9-12.9 TU/ml, and 1.9-8.0 1 µg/L, respectively. At pre-labor, the reference intervals were 4.8-32.9 1 µg/L, 0.2-1.9 mg/L, 4.2-12.6 TU/ml, and 2.8-15.4 1 µg/L, respectively. Gestational reference intervals for TAT, PIC, TM and tPAI-C in healthy pregnancies are provided, but only for TAT with increasing concentrations throughout pregnancy, the reference intervals for non-pregnant were not applicable.

Efficacy and safety of low-dose oral isotretinoin monotherapy versus combined therapy with picosecond laser for the treatment of acne scars in Asian population.

PURPOSE: Acne scars are common in patients with moderate to severe acne. Isotretinoin is the first-line treatment for those patients, but whether oral isotretinoin can improve acne scar is not clear. Picosecond lasers (FxPico) has been reported to improve acne scars. In the present study, we evaluated the clinical efficacy of low-dose isotretinoin with or without FxPico treatment for acne scars. MATERIALS AND METHODS: A total of 48 patients with acne scars were enrolled and were randomly assigned to receive low dose oral isotretinoin or not. For all the patients in both treatment groups, one side of face were randomly assigned to be treated with picosecond laser. Assessments, including photos, échelle d'évaluation clinique des cicatrices d'acné (ECCA) and Global Acne Grading System (GAGS) score, the number of lesions, melanin and erythema indexes, transepidermal water loss were assessed at 0, 1, 2, and 3 month. Side effects, Dermatology Life Quality Index (DLQI) and satisfaction were recorded before and after the study. RESULTS: A total of 44 patients completed the study (24 received oral low dose isotretinoin and 20 did not). Low dose oral isotretinoin treated group showed significant improvement on ECCA (from 112.5 [50-180] to 105 [50-160]), GAGS score (from 12.6 ± 3.3 to 10.1 ± 3.0), the count of papules (from 4.3 ± 3.7 to 1.0 ± 1.5) than the blank group, and higher improvement were noticed after isotretinoin combined with FxPico. All the side effects were temporary and tolerable, no adverse effects were observed. Higher DLQI and patients' satisfaction were achieved by oral isotretinoin alone and isotretinoin combined with FxPico. CONCLUSIONS: This is the first paper showing the improvement of scars by early low dose-isotretinoin intervention with or without the combination of picosecond laser. Early intervention with oral low-dose isotretinoin is effective for the treatment and prevention of acne scars, the combined therapy with FxPico can achieve better outcome.

Early acne scar intervention with 1064 nm picosecond laser in patients receiving oral isotretinoin: a randomized split-face controlled pilot study.

Early acne scar intervention is important. Oral isotretinoin is widely used in patients with moderate to severe acne. Picosecond laser has shown a promising effect on scar clearance. However, there is a lack of reports on the efficacy and safety of early acne scar management by using 1064-nm picosecond laser in patients receiving low-dose oral isotretinoin. Twenty-four patients with atrophic acne scars of Fitzpatrick skin type III to V were enrolled. All patients were receiving low-dose oral isotretinoin (0.12-0.22 mg/kg/day) during the treatment. The face of the participants was randomly assigned to receive 2 sessions of fractional picosecond 1064 nm Nd: YAG laser (FxPico) treatment and 2 follow-ups, with an interval of 1 month (month 0-3). Clinical efficacy and safety were assessed by photographs, ECCA grading scale, the number of scar lesions melanin and erythema indexes (MI and EI), TEWL, DLQI, and patient satisfaction and the adverse events were recorded on every visit. FxPico significantly decreased the ECCA score and showed higher improvement in the ECCA score. FxPico treated side achieved a significant reduction in all acne scar types, while only boxcar scars and rolling scars showed higher improvement. TEWL but not MI or EI were significantly improved. DLQI and patient satisfaction were higher with the FxPico-treated side than control side. No adverse effects were observed and all the side effects observed were temporary and tolerable. Early intervention by FxPico on patients receiving low-dose oral isotretinoin is a safe and effective modality to improve atrophic acne scars.