Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

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]

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

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

Objective To study the correlation between regional cerebral glucose metabolism and behavioral scores in middle cerebral artery occlusion(MCAO)model rats before and after the intervention of constraint induced movement therapy(CIMT),and the correlation between the natural recovery processand motor function recovery in MCAO model rats and the brain activation after CIMT intervention,and to further explore the mechanism of CIMT. Methods Twenty-two adult male Sprague-Dawley(SD)rats were randomly divided into an ischemic group treated with CIMT (CIMT,n=6),an ischemic group (Control,n=6),a sham-operated group(Sham,n=6),and a blank control group(Normal,n=4). The MCAO models of rats in the CIMT group and Control group were established by thread embolism method. The middle cerebral artery was not blocked during the operation for the Sham group,and the Normal group was not given any special treatment. After operation,rats in the CIMT group and Sham group were treated with CIMT. On the 7th day(d7)and the 22nd day(d22)after surgery,foot-fault test(FFT)and the beam balance and walking (BBW) test were used to evaluate the forelimb motor;micro positron emission tomography-computed tomography (micro PET/CT) imaging with fluorodeoxyglucose (18F-FDG) was used to scan the glucose metabolism in different brain regions of rats;Pearson correlation analysis was used to analyze the correlation between behavioral scores and glucose metabolism level in the CIMT group and Control group. Results On d7,the BBW score in the CIMT group and Control group was negatively correlated with glucose metabolism in the left insular cortex and the auditory cortex,and positively correlated with glucose metabolism in the right posterior hippocampus,superior colliculus,and inferior colliculus,with statistically significant differences;the FFT score was negatively correlated with glucose metabolism in the left somatosensory cortex, insular cortex and orbitofrontal cortex, and positively correlated with glucose metabolism in the right midbrain,with statistically significant differences. On d22, the BBW score in the CIMT group and Control group was positively correlated with glucose metabolism in the amygdala,caudate putamen,insular cortex and entorhinal cortex,and negatively correlated with glucose metabolism in the nucleus accumbens (Acb) core shell and caudate putamen in the right brain region,with statistically significant differences;the FFT score was negatively correlated with the entorhinal cortex in the right hemisphere and the difference was statistically significant. Conclusion The recovery of motor function promoted by CIMT was associated with the activation of both cerebral hemispheres in rats. The improvement of balance function promoted by CIMT in rats with cerebral ischemia was mainly related to the activation of Acb core shell in the right hemisphere. The recovery of fine grasping function promoted by CIMT may be related to the activation of the right entorhinal cortex.

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （n=120） and the control group （n=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（χ²=-3.26，P<0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （P<0.05，P<0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (P<0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

Objective:Based on fingerprint， index component content and dry extract yield， a quality evaluation method for substance benchmark of Xiebaisan was established to study the key quality attributes， to explore the quantitative transfer relationship between decoction pieces and substance benchmark， and to preliminarily formulate the quality standard of substance benchmark of Xiebaisan. Method:The substance benchmark of Xiebaisan was prepared according to the records of ancient formulas， fingerprints of 15 batches of decoction pieces and substance benchmarks were collected by high performance liquid chromatography （HPLC） and the index components were determined with the mobile phase of acetonitrile-0.05% phosphoric acid solution for gradient elution. The dry extract yield， fingerprint similarity and transfer rate of index components were combined to study the quantity value transmitting. Result:Ten characteristic peaks were identified in fingerprint of the substance benchmark and two characteristic peaks from stir-fried Mori Cortex， four characteristic peaks from baked Lycii Cortex， four characteristic peaks from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. Mulberroside A， liquiritin and glycyrrhizic acid were used as index components for the determination， the contents of mulberroside A， liquiritin and glycyrrhizic acid in substance benchmark of Xiebaisan were 2.69%-4.26%， 0.09%-0.17% and 0.09%-0.16%， and their transfer rates were （31.37±4.14）%， （36.12±4.03）% and （12.25±0.88）%， respectively. The similarity of fingerprint of substance benchmarks was good， the fingerprint similarities of 14 batches of substance benchmarks and control fingerprint were >0.9. The dry extract yield of substance benchmark of Xiebaisan ranged from 8.09% to 11.29%. Conclusion:The established quality evaluation method of substance benchmark of Xiebaisan is scientific and reasonable， and the transfer process of decoction pieces to substance benchmarks is stable and controllable. The preliminary quality standard of the substance benchmark can provide basis and reference for the development of modern preparations of Xiebaisan in the future.

【Objective】 To investigate and summarize the clinical and imaging features of a few patients with coronavirus disease 2019 (COVID-19) in Lanzhou City. 【Methods】 We carried out a retrospective analysis of the epidemiological data, laboratory results and clinical imaging features of eight hospitalized patients with confirmed COVID-19 in The First Hospital of Lanzhou University from January 23 to February 23, 2020. 【Results】 The sex ratio (men to women) of the 8 patients was 5∶3 while their age ranged from 24 to 57 years old. The incubation period was 1-10 days. Of the 8 patients, 7(87.5%) had COVID-19 brought in from other places in China and 1(12.5%) was a secondary infection case. The main clinical manifestations included cough in 6 cases (75%), fever in 4 cases (50%), expectoration in 3 cases (37.5%), and fatigue in 2 cases (25%). All the 8 cases indicated abnormal manifestations in blood routine examinations, 4 cases (50%) decreased in WBC, 7 cases (87.5%) decreased in Lym count, 5 cases (62.5%) increased in LDH, 1 case (12.5%) increased in CK, 1 case(12.5%) increased in CK-MB, 4 cases (50%) increased in CRP, 2 cases (25%) increased in PCT, and 1 case (12.5%) increased in D-dimer. Of the 2 patients examined by chest digital radiography (DR), one DR finding was not typical and the other one suggested increased bilateral lung markings. Six patients were examined by HRCT, of whom four (50%) showed multiple ground glass opacities on both lobes and two (25%) showed multiple ground glass opacities only on the right lobe; none of the 6 imaging findings suggested pleural effusion. Six patients were discharged from hospital after being cured and 1 patient still underwent treatment. 【Conclusion】 Most of these 8 patients had COVID-19 imported from outside the city, and the patients were relatively young with few underlying diseases. Their major symptoms were fever, cough, and expectoration. All of them exhibited abnormal findings in blood routine examinations; half of them suggested increased CRP while a few ones showed abnormal CK and Ddimer values. The imaging manifestations of most patients were multiple ground glass opacities near the peripheral pleura.