Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To construct and validate a nomogram prediction model for the high-risk human papilloma-virus(HPV)infection and its natural clearance in professional women.Methods Women with regular professions,who underwent professional medical examination and were confirmed with high-risk HPV infection without cervical cancer and cervical epithelial neoplasia in a hospital from March 2020 to March 2021 were studied.Patients were di-vided into the model group and the validation group in a 7:3 ratio.The model group were subdivided into the natural clearance group and the persistent infection group based on follow-up results.The general information,reproduc-tive-related treatment,sexual partner-related information,and examination results of the two groups of patients were compared.Potential factors for natural clearance of high-risk HPV infection in professional women were screened out by LASSO regression.Independent influencing factors were screened out with multivariate logistic re-gression.Based on multivariate logistic regression results,a nomogram prediction model was constructed and valida-ted using R programming language.Results A total of 329 cases were included,230 in the model group and 99 in the validation group.There was no statistically significant difference in general information between the two groups of patients(all P＞0.05).Among the 230 high-risk HPV infection patients in the model group,165 turned negative at the end of follow-up,with a natural clearance rate of 71.74％.Based on LASSO regression analysis,multivariate logistic regression analysis showed that age,contraceptive method,number of sexual partners,excessive foreskin of sexual partners,initial viral load,HPV infection type,and reproductive tract inflammation were independent influ-encing factors for the natural clearance of high-risk HPV infection in professional women(all P＜0.05).The re-ceiver operating characteristic(ROC)curve analysis showed that the areas under the curve(AUC)of natural clea-rance of high-risk HPV infection in professional women in the model group and validation group were 0.834(95％CI:0.776-0.893)and 0.817(95％CI:0.755-0.879),respectively.H-L goodness-of-fit test result showed that the difference between the nomogram model and the ideal model was not statistically significant(P＞0.05).The cali-bration curve results showed that the predicted curves of the model group and validation group were basically fit with the standard curve,indicating a high predictive accuracy of the model.The decision curve analysis results of the model group showed that when the probability threshold of natural clearance of high-risk HPV infection in profes-sional women predicted by the nomogram model was 0.15-0.95,the net benefit rate of patients was＞0.Conclusion The natural clearance rate of high-risk HPV infection in professional women is high,mainly influenced by factors such as age,contraceptive method,and number of sexual partners.The nomogram model constructed in this study has high accuracy and discrimination in predicting the natural clearance rate of high-risk HPV infection in profes-sional women.

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy

Objective:To summarize the clinical features and gene variations in children with Townes-Brocks syndrome (TBS).Methods:The clinical data of a female infant diagnosed with TBS caused by human spalt-like transcription factor 1 ( SALL1) gene mutation in Gansu Maternal and Child Health Hospital in May 2022 were analyzed retrospectively. Relevant articles up to July 2022 were retrieved from several databases including CNKI, VIP, Wanfang, Chinese Medical Journal Network and PubMed with the terms of " SALL1 gene" and "Townes-Brocks syndrome". Patients diagnosed with TBS caused by SALL1 gene mutation were retrieved and the clinical phenotype-genotype correlations in patients with TBS caused by frameshift mutation in SALL1 gene were analyzed and summarized. Descriptive statistical analysis was applied. Results:(1) Clinical data: The index patient was a 40-day-old girl exhibiting major clinical manifestations of polycystic kidney dysplasia, congenital external ear deformity, preaxial polydactyly and recto-perineal fistula. Whole exome sequencing and Sanger sequencing revealed a heterozygous variation of c.420delC (p.S141fs*42) in the SALL1 gene, while the same gene was found to be wild type in her parents and sister. The variant was predicted to be pathogenic (PVS1+PS2+PM2). (2) Literature review retrieved 161 cases of TBS, of which 71 were attributable to a frameshift mutation in SALL1 gene. Clinical phenotypes of the 71 cases and the index case were summarized. TBS was mainly characterized by external ear, hand and anal deformities, sometimes accompanied by hearing loss, abnormal kidney development and foot deformity. A small number of affected cases presented with rare clinical phenotypes such as abnormal eyes, hypothyroidism and abnormal development. At present, the human gene mutation database records 110 variations in the SALL1 gene, with a majority located in exon 2. The most common mutation type was frameshift variation, accounting for 52%, followed by missense variation and nonsense variation. Conclusion:TBS should be considered in children with ear, hand and anal malformations, accompanied by renal dysfunction and hearing loss, and genetic testing is recommended for timely diagnosis.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

OBJECTIVE: To explore the genetic etiology of a child with Pitt-Hopkins syndrome. METHODS: A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy. RESULTS: The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant. CONCLUSION The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.
Child ; Female ; Humans ; Male ; Pregnancy ; Intellectual Disability/genetics* ; Mosaicism ; Mothers ; Mutation ; Parents ; Transcription Factor 4/genetics*

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

ObjectiveTo explore the effects of metformin （Met） on amyloid-β （Aβ） in AD cell model M146L and the underlying mechanism. MethodsMTT assay was performed to determine the optimal concentration of Met. Western blotting was performed to measure the protein levels of Aβ₄₂， amyloid precursor protein （APP） ， β-site APP-cleaving enzyme （BACE）and proteolytic enzymes including insulin-degrading enzyme （IDE）， neprilysin （NEP）， and light chain 3 Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ）； Immunofluorescence was performed to visualize how Aβ₄₂ peptides and IDE were affected by Met. Western blotting was performed to test levels of IDE and Aβ₄₂ after treatment of Met and Bacitracin （Bac）， a special inhibitor of IDE. ResultsIn this study， we showed that the levels of Aβ₄₂ were down-regulated by the Met treatment （P<0.05）. No effect was observed on the expression of APP and BACE， both of which are related to the production of Aβ， after Met treatment in M146L cells （P＞0.05）. Furthermore， levels of proteolytic enzymes including IDE， NEP， and LC3Ⅱ/Ⅰ levels were markedly decreased in the M146L cells compared to the CHO cells （P<0.05） ， and only the level of IDE was reversed after the Met treatment for 24 h （P<0.05）. Importantly， Met-mediated Aβ₄₂ degradation in M146L cells was completely blocked by the Bac （P<0.05）. ConclusionsThis study clarifies the ameliorating effect of Met on the abnormal accumulation of Aβ₄₂ in M146L cells， and that the underlying mechanism is mediated by the increased expression of IDE in the Aβ degradation pathway， providing an experimental basis for the T2DM drug metformin as a potential therapeutic target for AD.

ObjectiveTo investigate the effect of the M2 microglia marker Arginase1 （Arg1） knockdown on cognitive function in APP/PS1 transgenic mouse model of Alzheimer's disease （AD）. MethodsArginase1 genetically engineered mice were used and divided into C57BL/6 control group （WT）， Arginase1 low expression group （Arg1^+/-）， Alzheimer's disease mouse model group （APP/PS1）， Arginase1， APP/PS1 transgenic mice Arginase1 low expression group （Arg1^+/-； APP/PS1）. We used open field test （OFT） to assess the autonomous activity and adaptive capacity of mice； morris water maze experiment （MWM） to evaluate learning and memory function of mice； thioflavine-S staining to observe the brain amyloid β-protein （Aβ） deposition in mice； immunofluorescence staining to detect the expression of microglia markers ionized calcium-binding adaptor molecule 1 （Iba1）， transmembrane protein 119 （Tmem119） and lysosomal protein （CD68）； Elisa to determine Aβ_1-40 and Aβ_1-42 expression in hippocampal and cortical tissues； and protein immunoblot （Western blot） to measure the expression of amyloid precursor protein （APP）， beta-site APP-cleaving enzyme （BACE）， enkephalinase （NEP）， and interleukin-1β （IL-1β）. ResultsCompared with APP/PS1 group， Arg1^+/-； APP/PS1 group showed significantly increased duration and frequency in central area （P<0.00 1）； significantly reduced escape latency （P<0.001）， significantly increased dwell time， path length in the target quadrant and times of crossing the platform （all P<0.05）； significant decrease of Aβ deposition in the hippocampus （P<0.000 1） and significant increased expression of CD68 by microglia in the hippocampal region （P=0.039 2， P=0.000 3）； decreased levels of Aβ_1-40， Aβ_1-42， APP， IL-1β and increased expression of NEP protein （P<0.000 1）. No significant difference in BACE protein expression （P=0.497 7） was found. ConclusionDown-regulation of Arg1 may promote microglia activation in the brain， up-regulate the level of Aβ-degrading enzyme NEP， reduce Aβ deposition and neuroinflammation in the brain， thus improve the spatial learning capacity of APP/PS1 mouse model of AD.