A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

SARS-CoV-2 has posed a significant threat to a subset of the patient population.The occurrence of hematological malignancies and tumor treatment can lead to immunosuppression in patients,which significantly increases the risk of serious complications,severe incidence and mortality after SARS-CoV-2 infection.The treatment of a patient with follicular lymphoma infected with SARS-CoV-2 was described in detail.The patient remained positive for RT-PCR tests during the hospitalization for nearly 90 days.After undergoing 5 rounds of antiviral treatment,along with glucocorticoid anti-inflammatory therapy,low-molecular-weight heparin for anticoagulation,antibiotics for infection control,and respiratory support through the use of a ventilator,the patient eventually obtained negative result of the RT-PCR test.Subsequently,the patient was successfully weaned from mechanical ventilation and discharged.By summarizing the treatment process of this case,we hoped to provide reference and experience for future clinical diagnosis and treatment.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.
Acute Disease ; Burkitt Lymphoma ; Child ; Gene Deletion ; Humans ; Ikaros Transcription Factor/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.
Artificial Intelligence ; Electroencephalography/methods* ; Epilepsy/diagnosis* ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/diagnosis* ; Intensive Care Units, Neonatal ; Multicenter Studies as Topic ; Prospective Studies ; Randomized Controlled Trials as Topic ; Seizures/drug therapy*

Objective:To investigate the effect of usage of transthoracic echocardiography(TTE) on the prognosis of patients after acute kidney injury (AKI) in intensive care unit (ICU).Methods:The clinical data of patients with AKI in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ v1.4) database was collected retrospectively, and the patients were divided into TTE group (with TTE within 24 hours of AKI diagnosis) and No-TTE group (without TTE examination or first TTE examination was more than 24 hours after AKI diagnosis). Propensity score matching (PSM) was utilized to balance the baseline variables between the two groups and Cox regression analysis was used to evaluate the independent risk factors for 28-day all-cause mortality (the primary outcome). Moreover, after PSM, the effects of TTE usage on the second outcomes (including the volumes of intravenous fluid and urine output in the first, second and third 24-hour after the diagnosis of AKI; the total number of mechanical ventilation-free days, renal replacement therapy-free days and vasopressor-free days within 28 days after ICU admission; use of diuretics after the diagnosis of AKI; reduction in serum creatinine within 48 hours after the diagnosis of AKI; and the length of ICU stay and hospital stay) were also evaluated.Results:Among 23 945 eligible AKI patients, 3 365 patients (14.1%) patients received TTE within 24 hours after the diagnosis of AKI and finally there were 3 361 patients in TTE group and No-TTE group included in this study after PSM based on the ratio of 1∶1. After PSM, all variables in the two groups were well balanced (standardized mean difference<0.1, respectively). Before and after PSM, patients in TTE group had lower 28-day all-cause mortality compared with patients in No-TTE group (10.76% vs 13.04%, χ2=13.535, P<0.001; 10.65% vs 18.80%, χ2=88.932, P<0.001), and Kaplan-Meier survival curves also revealed that patients in the TTE group had higher cumulative survival rate compared with patients in No-TTE group (Log-rank χ2=15.438, P<0.001; Log-rank χ2=75.360, P<0.001, respectively). Multivariate Cox regression analysis showed that TTE was an independent influencing factor for 28-day all-cause mortality before and after PSM ( HR=0.80, 95% CI 0.73-0.89, P<0.001; HR=0.58, 95% CI 0.51-0.65, P<0.001). And all subgroup analyses showed the similar results. Compared with patients in the No-TTE group, patients in the TTE group had higher volume of intravenous fluid on the first day and the second day after the diagnosis of AKI (both P<0.01). Patients in the TTE group had higher volume of urine output on the first day and the third day after the diagnosis of AKI (both P<0.01). The patients in the TTE group had a significantly lower duration of vasopressor-free and mechanical ventilation-free (both P<0.01). The usage of diuretic was significantly higher in the TTE group compared with that in the No-TTE group (54.1% vs 44.2%, χ2=65.609, P<0.001). With respect to serum creatinine, the reduction in serum creatinine within 48 hours after the diagnosis of AKI was higher in the TTE group than that in the No-TTE group [36.6(23.0, 97.2) μmol/L vs 30.1(14.2, 61.9) μmol/L, Z=-9.549, P<0.001]. Moreover, TTE group had shorter ICU stay than that in the No-TTE group [5.03(3.40, 8.90) d vs 5.37(3.77, 10.00) d, Z=-6.589, P<0.001]. There were no significant difference between the two groups in other secondary outcomes (all P>0.05). Conclusions:Timely TTE utilization after AKI incident is associated with better clinical outcomes for ICU patients.

Objective:To preliminarily establish the multidisciplinary cooperative vaccination management model for pediatric patients with hematological and oncological diseases, and to explore its feasibility.Methods:In this prospective study a total of 150 children with hematological and oncological diseases visited immunization clinic of Shanghai Children′s Medical Center from March 2017 to August 2018 were enrolled in this study. After establishing the multidisciplinary team, designing vaccination plan, staff training, implementation and quality control, a multidisciplinary immunization clinic was set up and the vaccination plan were implemented. The implementation rate of vaccination immunization, the HBsAb level and serum hepatitis B surface antibody (HBsAb) level before and after treatment, the HBsAb level and serum immunoglobulin G antibody (IgG) levels of measles, mumps, rubella (MMR) before and 6 months after immunization, the vaccine-related adverse reactions were assessed prospectively. Chi-square test or Fisher exact test was used to compare the differences of antibody level.Results:A total of 124 cases had been vaccinated as planned, with a coverage rate of 82.7%. Among these cases, the difference of HBsAb positive rate before and after treatment was significant (62.9% (78/124) vs.13.7% (17/124), χ2= 63.489, P<0.01). In 64 cases that completed three doses of hepatitis B immunization, there was a significant difference in HBsAb positive rate before and 6 months after immunization (6.3% (4/64) vs. 98.4% (63/64), P<0.01). In 40 cases that completed MMR immunization, the IgG antibody positive rate for measles (22.5% (9/40) vs. 82.5% (33/40), χ2 =31.746, P<0.01), mumps (22.5% (9/40) vs.82.5% (33/40), χ2 =28.872, P<0.01), rubella (25.0% (10/40) vs.62.5% (25/40), χ2 =11.429, P<0.01) before and 6 months after immunization were significantly different. Of the 421 doses of immunization, 25 (5.9%) doses reported controlled systemic or local adverse event. Conclusions:The immunization of pediatric patients with hematological and oncological diseases is of great importance. The newly-developed multidisciplinary cooperation immunization model for Chinese children with hematological and oncological diseases is feasible, and the immunization protocol is safe and has a certain effect.