The clinical characteristics of cerebral small vessel disease patients with motoric cognitive risk syndrome during single- and dual-task walking.

Objective: We aimed to (1) identify neuroimaging biomarkers of distinguishing motoric cognitive risk syndrome (MCRS) risk among older Chinese adults with cerebral small vessel disease (CSVD) and (2) detect differences in gait parameters and neuroimaging biomarkers between CSVD individual with and without MCRS, especially during dual-task walking (DTW). Methods: We enrolled 126 inpatients with CSVD who were divided into two groups according to MCRS status. Data on basic parameters, variability, asymmetry, and coordination were collected during single-task walking (STW) and DTW. Neuroimaging features (white matter hyperintensities, lacunes, and microbleeds) and total disease burden were calculated. Analysis of variance and logistic regression analyses were applied to assess the role of STW, DTW, and neuroimaging biomarkers in MCRS. Results: In total, 126 consecutive inpatients with CSVD were included (84 and 42 patients were classified as MCRS-negative and MCRS-positive, respectively). The MCRS-positive group showed poorer performance for nearly all gait parameters compared with the MCRS-negative group during cognitive DTW. Meanwhile, all gait parameters except asymmetry were assessed in participants with MCRS for significant deterioration during cognitive DTW compared with that during STW. However, only basic parameters differed between STW and cognitive DTW in participants without MCRS. A significant independent association between total CSVD scores and MCRS was also detected. Conclusions: For CSVD patients, with higher total CSVD burden rather than any single neuroimaging marker, was linked to a greater risk of MCRS. In addition, CSVD individuals with MCRS had higher variability and phase coordination index (PCI), especially in cognitive DTW. Thus, they should concentrate more on their gait variability or coordination and reduce secondary task loads while walking in daily life, especially in cognitive secondary tasks.

Imaging Transcriptomics of the Brain for Schizophrenia.

Schizophrenia is a severe mental disorder with a neurodevelopmental origin. Although schizophrenia results from changes in the brain, the underlying biological mechanisms are unknown. Transcriptomics studies quantitative expression changes or qualitative changes of all genes and isoforms, providing a more meaningful biological insight. Magnetic resonance imaging (MRI) techniques play roles in revealing brain structure and function. We give a narrative focused review on the current transcriptome combined with MRI studies related to schizophrenia and summarize the research methodology and content of these studies to identify the research commonalities as well as the implications for future research, in an attempt to provide new insights into the mechanism, clinical diagnosis, and treatments of schizophrenia.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Application of ionic liquid ultrasound-assisted extraction (IL-UAE) of lycopene from guava (Psidium guajava L.) by response surface methodology and artificial neural network-genetic algorithm.

Lycopene-rich guava (Psidium guajava L.) exhibits significant economic potential as a functional food ingredient, making it highly valuable for the pharmaceutical and agro-food industries. However, there is a need to enhance the extraction methods of lycopene to fully exploit its beneficial uses. In this study, we evaluated various ionic liquids to identify the most effective one for extracting lycopene from guava. Among thirteen ionic liquids with varying carbon chains or anions, 1-butyl-3-methylimidazolium chloride demonstrated the highest productivity. Subsequently, a single-factor experiment was employed to test the impact of several parameters on the efficiency of lycopene extraction using this selected ionic liquid. These parameters included extraction time, ultrasonic power, liquid-solid ratio, concentration of the ionic liquid, as well as material particle size. Moreover, models of artificial neural networks using genetic algorithms (ANN-GA) and response surface methodology (RSM) were employed to comprehensively assess the first four key parameters. The optimized conditions for ionic liquid ultrasound-assisted extraction (IL-UAE) were determined as follows: 33 min of extraction time, 225 W of ultrasonic power, 22 mL/g of liquid-solid ratio, 3.0 mol/L of IL concentration, and extraction cycles of three. Under these conditions, lycopene production reached an impressive yield of 9.35 ± 0.36 mg/g while offering advantages such as high efficiency, time savings, preservation benefits, and most importantly environmental friendliness.

Proline-derived quinoline formamide compounds as human urate transporter 1 inhibitors with potent uric acid-lowering activities.

We report the design and synthesis of a series of proline-derived quinoline formamide compounds as human urate transporter 1 (URAT1) inhibitors via a ligand-based pharmacophore approach. Structure-activity relationship studies reveal that the replacement of the carboxyl group on the polar fragment with trifluoromethanesulfonamide and substituent modification at the 6-position of the quinoline ring greatly improve URAT1 inhibitory activity compared with lesinurad. Compounds 21c, 21e, 24b, 24c, and 23a exhibit potent activities against URAT1 with IC50 values ranging from 0.052 to 0.56 µM. Furthermore, compound 23a displays improved selectivity towards organic anion transporter 1 (OAT1), good microsomal stability, low potential for genotoxicity and no inhibition of the hERG K+ channel. Compounds 21c and 23a, which have superior pharmacokinetic properties, also demonstrate significant uric acid-lowering activities in a mouse model of hyperuricemia. Notably, 21c also exhibits moderate anti-inflammatory activity related to the gout inflammatory pathway. Compounds 21c and 23a with superior druggability are potential candidates for the treatment of hyperuricemia and gout.

Sequential transplantation of exosomes and BMSCs pretreated with hypoxia efficiently facilitates perforator skin flap survival area in rats.

Bone marrow mesenchymal stem cells (BMSC) are promising candidates for the treatment of trans-territory perforator flap necrosis. However, the low retention and survival rate of engrafted BMSCs limit their therapeutic efficacy. Strategies either modifying BMSCs or alleviating the inflammatory environment may solve this problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and hypoxia pretreated BMSCs on flap necrosis. After the perforator flap model was created, the exosomes derived from BMSCs were injected immediately into choke zone II followed by transplantation of hypoxia pretreated BMSCs on Day 2. Gross view was performed to assess the flap survival, enzyme-linked immunosorbent assay was performed to evaluate the inflammatory factor level, microvessel number was assessed and quantitative polymerase chain reaction (qPCR) was performed to assess angiogenesis. We found that exosome delivery significantly reduced inflammatory cytokines levels on Day 1 and Day 3 and promoted the engrafted BMSCs' survival on Day 7. After combining with transplantation of hypoxia pretreated BMSCs, the flap survival rate and the angiogenesis-related gene expression were significantly higher than in the other three groups; the von Willebrand factor (vWF) vascular diameter and vWF vascular count were significantly higher than in the phosphate buffered saline (PBS) group. Thus, we concluded that sequential transplantation of exosomes and BMSCs combinatorially pretreated with hypoxia further facilitated flap survival. This sequential transplantation approach provides novel insights into the clinical treatment of flap necrosis.

Restoring long-lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study.

BACKGROUND: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface. METHODS: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1-point improvement from baseline on both sides of the face. RESULTS: HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL. Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. CONCLUSIONS: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.

Relationship between Body Composition and Gait Characteristics in Patients with Cerebral Small Vessel Disease.

BACKGROUND: This study aims to explore the correlation between body composition, encompassing factors such as muscle mass and fat distribution, and gait performance during both single-task walking (STW) and dual-task walking (DTW) in patients diagnosed with cerebral small vessel disease (CSVD). METHODS: The data of hospitalized patients diagnosed with CSVD, including cadence, stride time, velocity and stride length, as well as information on variability, asymmetry and coordination during both STW and DTW, were assessed. The number of falls reported by each participant was also assessed. RESULTS: A total of 95 CSVD patients were assessed, and the results showed that individuals with low appendicular skeletal muscle mass (ASM), which includes both the low ASM group and the combination of low ASM and high body fat (BF) group, had reduced velocity or cadence, shortened stride length, and prolonged stride time across all walking modalities compared to the control group. Only the combination of the low ASM and high BF group exhibited a deterioration in the coefficient of variation (CV) for all basic parameters and the Phase Coordination Index (PCI) compared to the control group across all walking patterns. Conversely, patients in the high BF group displayed a decline in basic parameters, primarily during cognitive DTW. Concurrently, the high BF group showed a significant increase in the CV and the PCI compared to the control group only during cognitive DTW. Furthermore, regardless of gender, both ASM and BF independently correlated with the occurrence of falls. CONCLUSIONS: CSVD patients with varying.

Handwriting Movement Abnormalities in Older Adults with Silent Cerebral Small Vessel Disease-A Preliminary Study.

BACKGROUND: The features of cerebral small vessel disease (CSVD) range from occurrence of asymptomatic radiological markers to symptomatic characteristics that include cognitive deficits and gait decline. The aim of the present study was to examine whether handwriting movement is abnormal in older people with CSVD through handwriting and drawing tasks using digitized handwriting kinematic assessment technology. METHODS: Older subjects (n = 60) were grouped according to Fazekas score, with 16 in the Severe CSVD group, 12 in the Non-severe group and 32 in the Healthy group. Kinematic data were recorded and analyzed during handwriting and drawing tasks: signature; writing of Chinese characters ("" and ""); and Archimedes' spiral drawing. RESULTS: The Severe CSVD group showed lower velocity and higher tortuosity during signature writing, lower velocity of stroke #4 of "" and vertical size of "" than did the Non-severe and Healthy groups. Both Severe CSVD and Non-severe CSVD subjects displayed higher average normalized jerk than did the Healthy group. Partial correlation analysis adjusting for age, gender, education, and mini-mental state evaluation (MMSE) showed that CSVD burden was positively associated with tortuosity of signature and average normalized jerk of Archimedes' spiral, and was negatively associated with velocity of strokes #3 and #4 of "", as well as vertical size of "". CONCLUSIONS: Older adults with CSVD showed abnormal handwriting movement. And the handwriting abnormalities captured by digitized handwriting analysis were correlated with CSVD severity in users of simplified Chinese characters.

Performance of the walking trail making test in older adults with white matter hyperintensities.

BACKGROUND: Several studies have reported that the walking trail making test (WTMT) completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments. We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities (WMH). AIM: To explore the performance in the WTMT in older people with WMH. METHODS: In this single-center, observational study, 25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age, gender, and educational level who were undergoing physical examination in our hospital during the same period served as the control group. The participants completed the WTMT-A and WTMT-B to obtain their gait parameters, including WTMT-A completion time, WTMT-B completion time, speed, step length, cadence, and stance phase percent. White matter lesions were scored according to the Fazekas scale. Multiple neuropsychological assessments were carried out to assess cognitive function. The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis. RESULTS: Patients with WMH performed significantly worse on the choice reaction test (CRT) (0.51 ± 0.09 s vs 0.44 ± 0.06 s, P = 0.007), verbal fluency test (VFT, 14.2 ± 2.75 vs 16.65 ± 3.54, P = 0.012), and digit symbol substitution test (16.00 ± 2.75 vs 18.40 ± 3.27, P = 0.010) than participants in the control group. The WMH group also required significantly more time to complete the WTMT-A (93.00 ± 10.76 s vs 70.55 ± 11.28 s, P < 0.001) and WTMT-B (109.72 ± 12.26 s vs 82.85 ± 7.90 s, P < 0.001). WTMT-A completion time was positively correlated with CRT time (r = 0.460, P = 0.001), while WTMT-B completion time was negatively correlated with VFT (r = -0.391, P = 0.008). On the WTMT-A, only speed was found to statistically differ between the WMH and control groups (0.803 ± 0.096 vs 0.975 ± 0.050 m/s, P < 0.001), whereas on the WTMT-B, the WMH group exhibited a significantly lower speed (0.778 ± 0.111 vs 0.970 ± 0.053 m/s, P < 0.001) and cadence (82.600 ± 4.140 vs 85.500 ± 5.020 steps/m, P = 0.039), as well as a higher stance phase percentage (65.061 ± 1.813% vs 63.513 ± 2.465%, P = 0.019) relative to controls. CONCLUSION: Older adults with WMH showed obviously poorer WTMT performance. WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.

Chin Augmentation and Treatment of Chin Retrusion with a Flexible Hyaluronic Acid Filler in Asian Subjects: A Randomized, Controlled, Evaluator-Blinded Study.

BACKGROUND: Aesthetic improvement of the chin is increasingly requested by patients, including those of Chinese origin. METHODS: A randomized, evaluator-blinded, no-treatment controlled study evaluated the effectiveness and safety of a flexible hyaluronic acid (HA) filler, Restylane® DefyneTM (HADEF), in the correction of chin retrusion in a Chinese adult population over 12 months after treatment. On Day 1, subjects were randomized 3:1 into two groups, HADEF or delayed-treatment controls, and those in the HADEF group were administered treatment. An optional touch-up treatment was administered 1 month after treatment to obtain optimal chin augmentation. The initially untreated control group was offered delayed-treatment after 6 months (including 1-month touch-up). RESULTS: HADEF was superior to no-treatment in improving chin retrusion according to the blinded evaluator at 6 months [Galderma Chin Retrusion Scale (GCRS) responder rate (≥ 1-point improvement from baseline) of 81% vs. 5% for untreated controls; p < 0.001, meeting the primary effectiveness objective. A majority of subjects maintained improvement at 12 months (61% in the HADEF group). All subjects reported satisfaction with results at 6 months after treatment with HADEF and aesthetic improvement rates per the global aesthetic improvement scale (GAIS) were high for 12 months following treatment, with an acceptable safety profile. CONCLUSIONS: These results demonstrated HADEF to be effective and safe for the correction of mild-to-moderate chin retrusion in Chinese subjects, confirming findings previously observed in a western population. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Variability, asymmetry and bilateral coordination of gait during single- and dual-task walking of patients with cerebral small vessel disease.

OBJECTIVE: We investigated coefficient of variation (CV), gait asymmetry (GA) and phase coordination index (PCI) in cerebral small vessel disease (CSVD) patients during single-task walking (STW) and dual-task walking (DTW) and explored the relationship between above parameters with disease severity and cognitive function. METHODS: This cross-sectional study collected cognitive function indices and gait parameters from 23 healthy controls and 94 patients with CSVD during STW and DTW. According to the Fazekas scales, the severity of CSVD valued by white matter hyperintensity (WMH) were divided into control, mild, moderate, severe and control group. MRIs were analyzed for WMHs, CMB, lacunes, etc. RESULTS: The control group showed lower PCI than CSVD patients during STW; no differences were detected among the disease severity groups. During DTW, all four groups exhibited significant differences in PCI and CV. For the moderate and severe groups, coordination and variation significantly differed between the two walking methods. There were correlations between the PCI and GA in the moderate and severe groups (R = 0.376, R = 0.573 during DTW; R = 0.414, R = 0.643 during STW) and no correlations in the control group and mild CSVD group. CONCLUSION: PCI and CV may be vital for detecting the symptoms in the early stage of CSVD disease. We also verified that the PCI could become the bridge across the cognition and motor disorder in CSVD, which was helpful for evaluating clinical symptoms comprehensively.

Anticancer effect of covalent purine-containing EGFR TKI, ZZC4 and its mechanism of action through network pharmacology.

AIMS: Epidermal growth factor receptor (EGFR) has been documented in many malignancies as participating in the progression of cancer cells. Here, we present a novel EGFR tyrosine kinase inhibitor, ZZC4, and examine its effect on cancer cell proliferation, migration, and tumor-bearing xenograft models. MAIN METHODS: The antiproliferative effect of ZZC4 was assessed in vitro by MTT assay, colony formation, and wound healing assay and in vivo with tumor-bearing xenograft nude mice. Further, Western blotting analysis and computational network pharmacology were used to explore and understand the mechanism of ZZC4. KEY FINDINGS: The results showed that ZZC4 potently inhibited the proliferation of lung, breast, and melanoma cells, and was more sensitive to lung cancer cells HCC827, H1975, and breast cancer cell T47D. In vitro findings were corroborated in vivo as results showed the suppressive effect of ZZC4 on HCC827 and H1975 tumor growth. Western blotting analysis confirmed that ZZC4 is an effective inhibitor of the EGFR pathways as it down-regulated p-EGFR, p-Akt, and p-MAPK. Computational molecular docking confirmed the strong binding affinity between ZZC4 and EGFR. Moreover, network pharmacology suggested that ZZC4 might play a suppressive role in the progression of malignancies with EGFR/PI-3K/Akt axis dysregulation or in cancer-related drug resistance. SIGNIFICANCE: Our study showed that ZZC4 is an anticancer drug candidate.

Spatiotemporal gait characteristics during single- and dual-task walking are associated with the burden of cerebral small vessel disease.

Introduction: Gait impairment is a common symptom among individuals with cerebral small vessel disease (CSVD). However, performance differences between single-task walking (STW) and dual-task walking (DTW) among individuals with CSVD remain unclear. Therefore, we aimed to examine differences in gait characteristics during STW and DTW as well as the association between gait performance and neuroimaging markers. Methods: We enrolled 126 older individuals with CSVD. The speed, cadence, stride length, stride time, and their dual-task cost (DTC) or variability were measured under the STW, motor-cognitive DTW (cognitive DTW), and motor-motor DTW (motor DTW) conditions. We examined neuroimaging features such as white matter hyperintensities (WMHs), lacunes, microbleeds, and total burden. Further, we analysed the association of neuroimaging markers with gait performance, including gait variability and DTC. Results: Almost all spatiotemporal characteristics, as well as their DTCs or variabilities, showed significant among-group differences according to disease severity in the cognitive DTW condition; however, relatively lesser differences were observed in the STW and motor DTW conditions. The total CSVD burden score was moderately correlated with all the spatial parameters, as well as their DTCs or variabilities, in the cognitive DTW condition. Moreover, WMHs showed a correlation with speed, stride time, and cadence, as well as their DTCs, in the cognitive DTW condition. Furthermore, lacunes showed a moderate correlation with speed, stride length, and the DTC of speed, whilst microbleeds were only related to the DTC of stride length in the cognitive DTW condition. Neuroimaging biomarkers were not correlated with spatiotemporal parameters in STW and motor DTW conditions after Bonferroni correction. Moreover, the correlation coefficient between the total CSVD burden score and gait parameters was greater than those of other biomarkers. Discussion: Parameters in the cognitive DTW condition are more appropriate than those in the motor DTW condition for the evaluation of gait abnormalities in patients with CSVD. Moreover, the total CSVD burden score might have better predictive utility than any single neuroimaging marker. Patients with CSVD, especially those with moderate-to-severe disease, should concentrate more on their gait patterns and reduce the load of secondary cognitive tasks whilst walking in daily life.

The relationship between apathy and nonparametric variables of rest activity rhythm in older adults with cerebral small vessel disease.

The goal of the current study was to demonstrate if the rest-activity rhythm (RAR) was altered in apathetic older adults with cerebral small vessel disease (CSVD) and find out the relationship between apathy/depression severity and RAR features in CSVD patients. This is a cross-sectional observational investigation including 53 CSVD cases (54.74% men), aged 70.70 ± 6.18 years old. The participants were assessed by neuropsychiatric inventory (NPI) subscale of apathy (NPI-apathy) and depression (NPI-depression) in succession, according to updated diagnostic criteria for apathy (DCA). Each subject wore an actigraph device (ActiGraph GT3X) in their nondominant hand for 7 days to collect raw data. Using a non-parametric methodological analysis, this study determined RAR variables such as interdaily stability (IS), intraday variability (IV) and relative amplitude (RA). Patients in the apathy-positive group had a higher Fazekas score than those in the apathy-negative group. IS, but not IV, RA, or objective sleep variables, differed between elderly patients with varying degrees of CSVD burden. Furthermore, apathy severity was statistically correlated with RA after adjusting for age, gender and education level, whereas depression severity was not associated with RAR variables. Finally, we discovered that the severity of apathy had no significant relationship with the severity of depression. All these findings indicated that the RAR altered in apathetic older adults with CSVD, and apathy was associated with decreased RAR amplitude.

Modification of osimertinib to discover new potent EGFRC797S-TK inhibitors.

The EGFRC797S mutation is a dominant mechanism of acquired resistance after the treatment of non-small cell lung cancer (NSCLC) with osimertinib in clinic. To date, there is no inhibitor approved to overcome the resistance caused by osimertinib. In this study, a series of compounds with phenylamino-pyrimidine scaffold deriving from osimertinib were designed, synthesized and evaluated as fourth-generation EGFRC797S-TK inhibitors. Consequently, compound Os30 exhibited potent inhibitory activities against both EGFRDel19/T790M/C797S TK and EGFRL858R/T790M/C797S TK with IC50 values of 18 nM and 113 nM, respectively. Moreover, Os30 can powerfully inhibit the proliferation of KC-0116 (BaF3-EGFRDel19/T790M/C797S) and KC-0122 (BaF3-EGFRL858R/T790M/C797S) cells. In addition, Os30 can suppress EGFR phosphorylation in a concentration-dependent manner in KC-0116 cells, arrest KC-0116 cells at G1 phase and induce the apoptosis of KC-0116 cells. More importantly, Os30 showed potent antitumor efficacy in the KC-0116 cells xenograft nude mice tumor model with the tumor growth inhibitory rate of 77.6% at a dosage of 40 mg/kg. These findings demonstrate that modification of osimertinib can discover new potent EGFRC797S-TK inhibitors, and compound Os30 is a potent fourth-generation EGFR inhibitor to treat NSCLC with EGFmRC797S mutation.

Centrifugal Microfluidic Synthesis of Nickel Sesquioxide Nanoparticles.

Nickel sesquioxide (Ni2O3) nanoparticles were synthesized using centrifugal microfluidics in the present study. The obtained nanoparticles were characterized using SEM to investigate their morphology and microstructure, and XRD was employed to analyze their purity. The nanoparticle size data were measured and analyzed using ImageJ (v1.8.0) software. The flow process and mixing procedure were monitored through computational fluid dynamics simulation. Among the synthesized Ni2O3 nanoparticles, those obtained at the rotation speed of 1000 rpm for 10 min with angular acceleration of 4.2 rad/s2 showed the best performance in terms of high purity, complete shape and microstructure, small diameter, and narrow diameter distribution. The experimental results demonstrate that the rotation speed of the microfluidic chip and reaction time contribute to a decrease in particle diameter and a narrower diameter distribution range. In contrast, an increase in acceleration of the rotation speed leads to an expanded nanoparticle size range and, thus, a wider distribution. These findings contribute to a comprehensive understanding of the effects exerted by various factors in centrifugal microfluidics and will provide new insights into nanoparticle synthesis using centrifugal microfluidic technology.

Design, synthesis and evaluation of new pyrimidine derivatives as EGFRC797S tyrosine kinase inhibitors.

The clinical use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer was limited by the drug resistance caused by EGFRC797S mutation. Therefore, in order to overcome the drug resistance, we designed and synthesized a series of 2-aminopyrimidine derivatives as EGFRC797S-TKIs. Among these compounds, compounds A5 and A13 showed significant anti-proliferative activity against the KC-0116 (EGFRdel19/T790M/C797S) cell line with high selectivity. A5 inhibited EGFR phosphorylation and induced apoptosis of KC-0116 cell, arrested KC-0116 cell at G2/M phase. Molecular docking results showed that A5 and brigatinib bind to EGFR in a similar pattern. In addition to forming two important hydrogen bonds with Met793 residue, A5 also formed a hydrogen bond with Lys745 residues, which may play an important role for the potent inhibitory activity against EGFRdel19/T790M/C797S. Based on these results, A5 turned out to be effective reversible EGFRC797S-TKIs which can be further developed.

Comparison of the efficacy and safety of a 730 nm picosecond titanium sapphire laser and a 755 nm picosecond alexandrite laser for the treatment of freckles in Asian patients: A two-center randomized, split-face, controlled trial.

OBJECTIVE: The 730 nm picosecond titanium sapphire laser is a novel laser that shows promising results in treating freckles. This study aimed to further investigate the efficacy and safety of the 730 nm picosecond titanium sapphire laser for treating freckles in Asian patients compared with those of the 755 nm picosecond alexandrite laser. METHODS: Each face of 86 participants was split into two parts and randomly assigned either one session of 730 or 755 nm picosecond-laser treatment each. Efficacy and safety were determined based on blinded visual evaluations and self-reports at each follow-up visit. RESULTS: The treatment outcomes of the 730 nm picosecond laser for the treatment of freckles were comparable to those of the 755 nm picosecond laser, with 68.99 ± 7.42% and 69.27 ± 7.75% clearance, respectively (p > 0.05). Participants achieved similar Global Aesthetic Improvement Scale scores (4.04 ± 0.31 vs. 4.02 ± 0.30, respectively [p > 0.05]). Additionally, the 730 nm picosecond laser was perceived to be less painful than the 755 nm picosecond laser (4.69 ± 1.63 vs. 5.65 ± 1.80 nm, p < 0.0001). CONCLUSION: The 730 nm picosecond laser is safe and effective for the treatment of freckles in Asian patients. Besides, the 730 nm picosecond laser is less painful than the 755 nm picosecond laser.

Efficacy and Safety of Picosecond Laser in the Treatment of Melasma: A Network Meta-analysis.

BACKGROUND: The role of lasers in the treatment of melasma and acquired hyperpigmentation disease of the skin has been suggested by clinicians. However, there is no consensus on the most efficient and safe treatment method. OBJECTIVE: To systematically evaluate the efficacy and safety of picosecond laser in the treatment of melasma. METHODS AND MATERIALS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese scientific journal database, and Wanfang database were searched. The data for therapeutic efficacy, melasma area and severity score, and incidence rate of adverse reactions were extracted from the included studies. RESULTS: A total of 20 studies involving 1,182 patients were included in this network meta-analysis. Combined therapy with carbamic acid and 1064-nm picosecond laser was the best measure. Melasma area and severity index score of patients after low-power fractional CO2 laser treatment was higher than that of patients after the treatment with 1064-nm picosecond laser. CONCLUSION: Aminomethyl cyclic acid combined with 1064-nm picosecond laser may have the highest effective rate after treatment. Low-power fractional CO2 laser provided the lowest melasma area and severity index score after treatment, and the incidence rate of adverse reactions after treatment, was highest when intense pulsed light was used.