Objective:To explore the clinical features, risks of recurrence and prognosis of neuroblastoma (NB) with intraspinal extension in children, and to perform a long-term follow-up to monitor their health problems.Methods:Clinical data of 22 children with NB with intraspinal extension treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2007 to December 2019 were retrospectively analyzed, including gender, age at diagnosis, clinical stage, and risks of recurrence.They were divided into non-recurrent group and recurrent group, and the survival was analyzed by Kaplan-Meier method.Results:(1)Fifteen(68.2%) children had motor nervous symptoms as the initial symptoms, including lower limb pain, weakness, and limited mobility, and 10(45.5%) showed moderate-to-severe nervous compression.(2)Neuronal enolase(NSE) (<200 μg/L), lactate dehydrogenase(LDH) (≤500 U/L) and vanillylmandelic acid(VMA) were in the normal range in most of children in the non-recurrence group, and a single site was involved.(3)Tumor lesions were not completely resected in the majority of children in the recurrent group, and their NSE (≥200 μg/L), LDH (>500 U/L) and VMA (more than 3 times higher) were abnormally higher, or suffered multisite pyramidal metastasis.(4)The median survival time (MST) was 119.4 months for children in the non-recurrent group, while it was only 25.3 months for those in the recurrent group.The 3-year overall survival (OS) rate was (95.5±6.4)% for the non-recurrent group, compared to only (20.0±17.9)% for children in the recurrent group ( χ2=9.387, P=0.002). Likewise, the 3-year event-free survival (EFS) rate for children in the non-recurrent group was (94.1±5.7)%, whereas it was only (20.0±17.9)% for children in the recurrent group( χ2=29.700, P<0.001). (5)Eleven of 22 children had long-term health problems, especially motor nerve function defects and scoliosis. Conclusions:Motor neurological, and moderate-to-severe neurological compression predominates are the main symptoms of NB children with intraspinal extension at the initial diagnosis.Patients who exhibit intradural tumor remnants, higher NSE, LDH, or VMA levels, and intradural extension with multiple sites of cone metastases are prone to recurrence.Once relapsed, the prognosis is extremely poor.The prognosis of NB with intraspinal extension in children is related to the severity of the initial neurological impairment, the duration of tumor compression, and the treatment regimen.Early diagnosis and intervention may reduce the risk of long-term health problems in children.

Objective:To investigate the effect of gallic acid on the morphology, proliferation and cell cycle of keloid fibroblasts, as well as on collagen contraction and the transforming growth factor-β (TGF-β) /Sma- and Mad-related proteins (Smads) signaling pathway, and to explore the role and mechanisms of action of gallic acid in the treatment of keloids.Methods:From August to December 2022, 3 keloid tissue samples were collected from 3 patients with clinically and pathologically confirmed keloids after surgery in the Department of Dermatologic Surgery, Wuhan No.1 Hospital. Primary fibroblasts were isolated and cultured by using the tissue culture method, and 3- to 8-passage fibroblasts were used for subsequent experiments. Cultured keloid fibroblasts were divided into 4 groups: low-, medium- and high-dose gallic acid groups treated with 0.025, 0.05 and 0.1 mg/ml gallic acid respectively, and a control group cultured with Dulbecco′s modified Eagle′s medium (DMEM) containing 10% fetal calf serum. After 24-, 48-, and 72-hour treatment, cellular proliferative activity was evaluated by cell counting kit 8 (CCK8) assay, and collagen contraction by using a three-dimensional culture method. After 24-hour treatment in the above groups, pictures were taken using a differential interference inverted fluorescence microscope, and changes in the cell cycle were analyzed by flow cytometry. Some keloid fibroblasts were divided into 2 groups: an experimental group (high-dose gallic acid group) treated with 0.1 mg/ml gallic acid, and a control group cultured with DMEM containing 10% fetal calf serum. After 24-hour treatment, enzyme-linked immunosorbent assay (ELISA) was performed to determine the changes in supernatant concentrations of TGF-β1, TGF-β2, and TGF-β3 in the two groups, real-time fluorescence-based quantitative PCR to detect the relative mRNA expression levels of TGF-β1, TGF-β2, TGF-β3, Smad2, Smad3, Smad4, and α-smooth muscle actin (α-SMA). Statistical analysis was carried out using t test, one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Compared with the control group, the gallic acid groups showed gradual changes in the shape of keloid fibroblasts under the microscope as the dose of gallic acid increased, including gradually shrinking cell bodies, enlarged intercellular spaces, cell atrophy, increased number of apoptotic cells, etc. CCK8 assay showed that the cellular proliferative activity changed significantly as the dose of gallic acid increased and the treatment time was prolonged ( Fgroup = 78.31, P < 0.001; Ftime = 4.17, P = 0.037), and the proliferative activity of keloid fibroblasts was significantly lower in the high-dose gallic acid group than in the control group at 24, 48, and 72 hours (all P < 0.05). The three-dimensional culture showed that different degrees of collagen contraction occurred in all groups over time, marked collagen contraction was observed in the control group, and a lower degree of collagen contraction in the gallic acid groups; the collagen contraction indices were significantly lower in the medium- and high-dose gallic acid groups than in the control group at 24, 48, and 72 hours (all P < 0.05). Flow cytometry showed that the cell apoptosis rates were significantly higher in the low-, medium- and high-dose gallic acid groups (38.68% ± 3.05%, 41.82% ± 2.19%, 43.56% ± 3.58%, respectively) than in the control group (12.58% ± 1.56%, all P < 0.001) after 24-hour treatment; compared with the control group, the medium- and high-dose gallic acid groups showed significantly decreased proportions of cells in the G0/G1 phase (both P < 0.01), but significantly increased proportions of cells in the S phase and G2/M phase (all P < 0.05). ELISA revealed that the TGF-β1 concentration was significantly lower in the high-dose gallic acid group (758.58 ± 31.42 pg/ml) than in the control group (1 081.30 ± 44.72 pg/ml, t = 11.81, P<0.001), there was no significant difference in the TGF-β2 concentration between the high-dose gallic acid group (71.05 ± 7.40 pg/ml) and the control group (76.43 ± 6.51 pg/ml, t = 1.09, P = 0.317), while the TGF-β3 concentration was significantly higher in the high-dose gallic acid group (5.70 ± 3.87 pg/ml) than in the control group (0.00 ± 0.00 pg/ml, t = 2.94, P = 0.026). As real-time fluorescence-based quantitative PCR revealed, the high-dose gallic acid group showed significantly decreased mRNA expression levels of TGF-β1, Smad2, Smad3, Smad4, and α-SMA (all P < 0.05), but significantly increased mRNA expression level of TGF-β3 ( t = 6.78, P = 0.002) compared with the control group; however, there was no significant difference in the TGF-β2 mRNA expression level between the above two groups ( t = 0.05, P = 0.962) . Conclusion:Gallic acid could change the cell cycle, inhibit the proliferative activity, promote apoptosis and change the shape of keloid fibroblasts, and thus inhibit scar formation and contraction, which may be related to the inhibition of TGF-β/Smads signaling pathway.

ObjectiveTo analyze the epidemiological characteristics of varicella in Yangpu District， Shanghai from 2005 to 2022， predict the trend of varicella in Yangpu District in 2023， and provide evidence for prevention and control of varicella outbreaks. MethodsInformation of varicella cases reported in Yangpu District from 2005 to 2022 was obtained from the China Information System for Disease Control and Prevention. Descriptive statistics was used to characterize the varicella epidemiology. An autoregressive integrated moving average （ARIMA） model was established by using the number of cases per month from 2005 to2022 to predict the trend of varicella epidemics in Yangpu District in 2023. The varicella incidence in 2022 was used to evaluate the fitness of the ARIMA model. ResultsFrom January 2005 to December 2021， a total of 11 527 cases of varicella were reported in Yangpu District， Shanghai. After excluding duplicates and clinical diagnoses， 11 413 cases were included into the analysis. The annual average incidence rate was 51.87/10⁵， the age of onset was mainly under 20 years old （66.5%）， and the occupation was mainly students （49.7%）. The ARIMA （1，1，0）×（0，1，1）₁₂ model was constructed and showed a good fitness while using monthly reported varicella cases in 2022 for model fitting. It was predicted that 1 089 cases of varicella would be reported in Yangpu District in 2023. ConclusionIt is predicted that varicella cases in Yangpu District will increase in 2023. It is recommended to continue promoting delayed varicella vaccination to maintain a high level of vaccination rate. Before the peak of the epidemic， health education regarding varicella should be strengthened， and measures for epidemic prevention and control should be reinforced to prevent varicella outbreaks.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy

The development of high-throughput sequencing techniques enabled a deeper and more comprehensive understanding of environmental microbiology. Specifically, the third-generation sequencing techniques represented by nanopore sequencing have greatly promoted the development of environmental microbiology research due to its advantages such as long sequencing reads, fast sequencing speed, real-time monitoring of sequencing data, and convenient machine carrying, as well as no GC bias and no PCR amplification requirement. This review briefly summarized the technical principle and characteristics of nanopore sequencing, followed by discussing the application of nanopore sequencing techniques in the amplicon sequencing, metagenome sequencing and whole genome sequencing of environmental microorganisms. The advantages and challenges of nanopore sequencing in the application of environmental microbiology research were also analyzed.
Environmental Microbiology ; High-Throughput Nucleotide Sequencing ; Metagenome ; Nanopore Sequencing ; Nanopores

ObjectiveTo determine the scores of patients with a confirmed diagnosis of drug-induced liver injury （DILI） using Roussel Uclaf Causality Assessment Method （RUCAM）， Maria ＆ Victorino assessment scale， and Revised Electronic Causality Assessment Method （RECAM）， to compare the accuracy of the three scales in diagnosis， and to investigate their clinical significance in the diagnosis of DILI. MethodsA total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled， with liver biopsy results supporting DILI and a clear history of medication. Clinical data were collected from all subjects， and the above causality assessment scales were used for scoring. The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales， and the weighted kappa coefficient was used to analyze the consistency between the three scales. ResultsFor all patients with DILI enrolled， RECAM had the highest accuracy， with a significant difference compared with RUCAM （χ²=5.667，P=0.017）. RUCAM and RECAM had moderate consistency in diagnosis （κw=0.469）， while RECAM and Maria ＆ Victorino scale had poor consistency （κw=0.156）. For the patients with acute DILI， RECAM， RUCAM， and Maria ＆ Victorino scales had a diagnostic inconsistency rate of 3.7%， 11.1%， and 42.6%， respectively； for the patients with hepatocellular type DILI， the three scales of a diagnostic inconsistency rate of 8.9%， 21.4%， and 62.5%， respectively； for the patients with cholestasis type or mixed type DILI， the three scales of a diagnostic inconsistency rate of 10.0%， 22.5%， and 47.5%， respectively. ConclusionThe use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate， and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis （cholestasis type DILI and mixed type DILI）， the use of RECAM and RUCAM scales can also improve diagnostic rate. The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.