Inertial microfluidics,as a microfluidic technology with the ability to precisely manipulate particles and cells with high throughput,has attracted widespread attention.However,challenges remain in achieving particle focusing with insensitivity to flow rates in large-scale channels,mainly due to the instability of secondary flows within the inertial microfluidic chip.This study developed a microstructure-assisted ultra-low aspect ratio spiral microchannel,which utilized the stability and acceleration of secondary flows to achieve inertial particle focusing.The research results demonstrated successful particle focusing within a 1 mm-wide spiral channel chip,for different diameter sizes(7.3 μm and 15.5 μm),within a wide range of flow rates(0.5-3 mL/min).The focusing efficiencies for these particles were measured to be above 94%and 99%,respectively.Additionally,it was observed that the particle focusing position was approximately 100 μm away from the channel walls,significantly larger than other inertial focusing chips.Consequently,by incorporating ordered microstructures within the spiral channel chip,the stability and enhancement of secondary flows were achieved,resulting in flow rate and particle size-insensitive inertial focusing.Compared to traditional methods of inertial focusing,this design had advantages of not requiring additional sheath flow operations,and boasted high throughput and ease of manufacturing.This innovative structure opened up vast prospects for the development of portable inertial microfluidic chips,and could be used in the fields such as cell analysis and detection,flow cytometry,and online sample processing.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-β1 (TGF-β1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
Humans ; Animals ; Mice ; Aged ; Histone Deacetylase 6 ; Skin ; Wound Healing ; Cell Movement ; Collagen/pharmacology* ; Fibroblasts ; Mice, Knockout ; Cells, Cultured

OBJECTIVE: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development. METHODS: The mice with Synapsin1-Cre recombinase were bred with RESULTS: The mice with CONCLUSIONS Deletion of
Animals ; Blotting, Western ; Histone Deacetylase 1/genetics* ; Histone Deacetylase 2 ; Histone Deacetylases/genetics* ; Immunohistochemistry ; Mice ; Neurons/metabolism* ; Signal Transduction

Objective: To observe the clinical efficacy of mind-refreshing and balance-restoring needling method combined with Frenkel exercises in treating ataxia after cerebral stroke. Methods: The recruited 120 patients were randomized into an observation group and a control group, with 60 cases in each group. The control group was intervened by mind-refreshing and balance-restoring needling method, while the observation group was given additional lower-limb Frenkel exercises. Before and after treatment and at the follow-up, the ataxic lower-limb function was scored using Berg balance scale (BBS) and international cooperative ataxia rating scale (ICARS), and Barthel index (BI) was adopted to score the activities of daily living (ADL). Results: After treatment, the markedly effective rate was 70.2％ and the total effective rate was 96.5％ in the observation group, versus 39.7％ and 87.9％ in the control group, and the differences in the markedly effective rate and the total effective rate were statistically significant (P<0.01, P<0.05). The intra-group comparisons showed that the BBS, ICARS and BI scores after treatment and at the follow-up were significantly different from those before treatment in both groups (all P<0.01).There were significant differences in the BBS score between the two groups after treatment and at the follow-up (P<0.05, P<0.01); the between-group differences in the ICARS and BI scores were statistically insignificant after treatment (both P>0.05), while the between-group differences in the ICARS and BI scores were statistically significant at the follow-up (both P<0.05). The interaction effects between the scoring time of BBS and BI and the group factor were statistically significant (P<0.01, P<0.05). Conclusion: Mind-refreshing and balance-restoring needling can effectively improve the lower-limb ataxic symptoms and ADL after stroke; when combined with Fenkel exercises, this needling method can produce more significant efficacy.

BACKGROUNDCurrently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up.

METHODSInstitutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE.

RESULTSTechnical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0-72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 106.0 ± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P < 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P < 0.05).

CONCLUSIONSTAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

Objective To evaluate the safety and efficacy of cross-linked hyaluronic acid Revanesse Ultra for treatment of nasolabial folds in Chinese population .Methods A total of 120 participants were enrolled in this prospective , randomized , positive controlled , non-inferiority clinical trial in accordance to inclusion and ex-clusion criteria , and signed informed consents were obtained .The participants were numbered in the order of en-rollment and randomized into Restylane group and Revanesse group , receiving hyaluronic acid injection to correct bilateral nasolabial folds .Each person received 1 or 2 times of injection ( a touch-up injection could be adminis-tered 4 weeks post the first injection ) .According to the original depth of the wrinkles , no more than 2 ml hyalu-ronic acid was injected into each side .All the participants were followed up at 1, 3, 6, and 12 months after the last injection and standardized photographs were taken at each visit .All the participants were asked to fill the form of local adverse events within the first 15 days after injection.Investigators and the participants both evalu-ated wrinkles based on Wrinkle Severity Rating Scale ( WSRS) .The WSRS score according to the pictures of 6 months post-injection were compared with the pictures which were taken before the injection ( baseline) by in-dependent staff at the end of the trial .One or more grades of WSRS improvement compared with the baseline was considered as effective .Laboratory tests including blood and urine routine , liver and renal function tests were carried out at screening visit and 6 months after injection.Results The baseline features between the two groups were comparable (all P>0.05).There was no significant difference in the WSRS 6 months after injec-tion between the two groups ( P>0.05 ) .There was no significant difference in the WSRS improvement com-pared with baseline between the two groups ( P=0.105 ) .There was no significant difference in the rate of ef-fectiveness between the two groups ( 93.0% vs.96.7%, P=0.431 ) .Two participants reported minor ad-verse events, although both of which might not be associated with the product or procedure .No laboratory test change was found during the trial .Conclusions No severe adverse event associated with the injection material was observed during this clinical trial .According to the result , Revanesse Ultra may have good histocompati-bility and tolerance .It could provide obvious improvement in the nasolabial folds , with effectiveness comparable to that of Restylane .

OBJECTIVETo observe the direct regulation of miR-127 on Bcl-6 and the effect of Bcl-6 in rescuing miR-127-induced cell cycle and cell growth inhibition.

METHODSThe 3'UTR and coding region of human bcl-6 gene were amplified by PCR and cloned into pcDNA3.0-Luc and pcDNA3.0-Flag vectors, respectively. Mutations were introduced into the seed sequences of the predicted miR-127 target sites within the Bcl-6 3'UTR using recombinant PCR. Luciferase assay was used to verify the direct targeted regulation of miR-127 on Bcl-6. In HepG2 cell models with overexpression or knockdown of miR-12, the changes of cell cycle and cell growth were investigated after transfection with the constructed vectors.

RESULTSThe recombinant plasmids were successfully obtained as confirmed by double digestion and sequence identification. Luciferase assay showed that in 293T and HepG2 cells, miR-127 inhibited the activation of wild-type Bcl-6 3'UTR reporter vector but not mutated Bcl-6 3'UTR vector. Overexpression of miR-127 induced cell cycle arrest at G(2)/M phase and suppressed the growth of HepG2 cells, and these effects were reversed by Bcl-6 overexpression.

CONCLUSIONWe successfully cloned wild-type and mutated 3'UTR reporter vectors and expression vector of bcl-6 gene and confirmed their biological functions.

3' Untranslated Regions ; Cell Cycle ; Cell Proliferation ; DNA-Binding Proteins ; genetics ; Genes, Reporter ; Genetic Vectors ; Hep G2 Cells ; Humans ; Luciferases ; MicroRNAs ; genetics ; Proto-Oncogene Proteins c-bcl-6 ; Transfection