Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.

Imaging examination is a crucial part in diagnosis and treatment of central nervous system infection(CNSI),involving complex imaging sequences and parameters.This consensus was jointly written by multiple CNSI imaging experts in China,aimed to standardize imaging examination of CNSI.

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]

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Dynamic tracking analysis of monoclonal antibodies(mAbs)biotransformation in vivo is crucial,as certain modifications could inactivate the protein and reduce drug efficacy.However,a particular chal-lenge(i.e.immune recognition deficiencies)in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen.To address this limitation,a multi-epitope affinity technology utilizing the metal organic framework(MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region(CDR)mimotope peptide(HH24)and non-CDR mimotope aptamer(CH1S-6T)onto the surface of MOF@Au nanocomposite.Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited signifi-cantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope af-finity technology.Moreover,the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry(LC-QTOF-MS).Therefore,multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb.Particularly,the novel bioanalytical platform can be suc-cessfully used for the tracking analysis of trastuzumab modifications in different biological fluids.Compared to the spiked phosphate buffer(PB)model,faster modification trends were monitored in the spiked serum and patients'sera due to the catalytic effect of plasma proteins and relevant proteases.Differences in peptide modification levels of trastuzumab in patients'sera were also monitored.In summary,the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb,contributing to improved understanding and paving the way for future research and clinical applications.

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin