Objective:Investigate the characteristics of hospitalized patients infected with parvovirus B19 (B19V) and the potential impact of B19V on disease progression and clinical outcomes in patients.Methods:The subjects of this observational retrospective study were 62 hospitalized patients who tested positive for B19V among 3 129 inpatients who visited Peking University People′s Hospital between April 1, 2022, and August 31, 2023, and underwent metagenomic next-generation sequencing (mNGS) for pathogens. Patient data regarding pathogen detection, clinical characteristics, and outcomes were collected, along with other laboratory test results, to assess hospitalization duration, incidence of mixed infections during hospitalization, and clinical outcomes within 30 days. The chi-square test was utilized to analyze differences in patient mortality rates and other relevant factors.Results:B19V infection waspobserved in patients with hematological disorders and solid organ transplant recipients (79.03%, 49/62). Additionally, B19V frequently coexists with other pathogens (40/62), with the highest rates of mixed infections involving human herpesvirus 6, cytomegalovirus, and Epstein-Barr virus, having 20, 9, and 8 cases respectively. The most common site of B19V detection is peripheral blood (χ 2=0.000 3, P<0.001), although it can also be detected in other bodily fluid samples. The 30 day mortality rate among B19V infected patients was 19.35% (12/62) 10 out of 12 deceased patients had concurrent mixed infections with other pathogens. Moreover, patients with mixed B19V infections exhibited a higher mortality rate compared to those with B19V infection alone (χ 2=4.546, P=0.033). Comparative analysis of 24 patients who underwent multiple mNGS tests revealed that patients with chronic B19V infection (12 cases) had a higher mortality rate compared to those with transient B19V infection (12 cases) (χ 2=12, P<0.001). Conclusions:Parvovirus B19 (B19V) infection is more commonly observed in patients with hematological disorders and solid organ transplant recipients, often coexisting with other pathogens. The mortality rate within 30 days of B19V infection is elevated, particularly when accompanied by concurrent mixed infections with other pathogens. Moreover, patients with chronic and persistent B19V infection face an increased risk of mortality.

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Objective: To analyze the death among children under 5 years of age in Huzhou City, Zhejiang Province from 2012 and 2021, so as to provide insights into reduction of mortality among children. Methods: The mortality surveillance data among children under 5 years of age in Huzhou City from 2012 to 2021 were collected from Children Death Report Cards and Surveillance Report among Children under 5 Years of Age, including gender, place of residence, date of death and death diagnosis. The trends in mortality and cause of death were analyzed among children under 5 years of age in Huzhou City from 2012 to 2021. Results: A total of 1 262 deaths occurred among children under 5 years of age in Huzhou City from 2012 to 2021, with mean annual mortality of 4.39‰, and the mortality appeared a tendency towards a decline (χ2trend=132.695, P<0.001). A total of 899 infants died, with mean annual mortality of 3.13‰, and 363 children at ages of 1 to <5 years died, with mean annual mortality of 1.26‰. The mortality appeared a tendency towards a decline among both infants (χ2trend=117.778, P<0.001) and children at ages of 1 to <5 years (χ2trend=19.201, P<0.001). A total of 724 local children died, with mean annual mortality of 3.33‰, and there were 538 deaths among floating children, with mean annual mortality of 7.65‰. The mortality appeared a tendency towards a decline among both local (χ2trend=43.728, P<0.001) and floating children (χ2trend=94.038, P<0.001). The five most common causes of death included preterm birth or low birth weight (207 deaths, 16.40%), drowning (155 deaths, 12.28%), accidental asphyxia (138 deaths, 10.94%), other congenital abnormalities (126 deaths, 9.98%), and congenital heart diseases (113 deaths, 8.95%). Conclusions The mortality appeared a tendency towards a decline among children under 5 years of age in Huzhou City from 2012 to 2021, and preterm birth or low birth weight was the predominant cause of death.

【Objective】 To explore the causes and management of nephrostomy catheter following percutaneous nephrostolithotomy (PCNL) entering the inferior vena cava. 【Methods】 A retrospective analysis was performed on the management of two cases of nephrostomy catheter entering the inferior vena cava. The causes, changes of minimally invasive treatment and prevention plans were discussed. 【Results】 Two patients underwent digital subtraction angiography (DSA) to restore the nephrostomy tube to the renal pelvis collecting system. No renal vein rupture or bleeding occurred during the operation, and the patients’ vital signs were stable. Nephrostomy tube was removed successfully after operation. The wound healing was good, and there was no secondary hemorrhage such as perirenal hematoma. The prognosis was good. 【Conclusion】 Although intravenous nephrostomy tube misplacement is an uncommon PCNL complication, the consequences are serous. One-step retraction displacement of nephrostomy tube to the renal collecting system can effectively manage nephrostomy catheter entering the inferior vena cava.

Objective:To evaluate the clinical performance of direct antimicrobial susceptibility test in blood culture-positive broth, and to provide a basis for optimizing the antibiotic use strategy in clinical bloodstream infection.Methods:A retrospective analysis was conducted on 780 blood culture-positive samples collected in Peking University People′s Hospital from May 2017 to December 2021. The direct antimicrobial susceptibility test was performed by disk diffusion method on blood culture-positive broth. The antimicrobial susceptibility breakpoints were in accordance with Clinical and Laboratory Standards Institute (CLSI) M100 S32 edition document.Results:In this study, a total of 331 strains of Gram-negative bacteria (139 strains of Escherichia coli, 79 strains of Klebsiella pneumoniae, 35 strains of Pseudomonas aeruginosa, 21 strains of Acinetobacter baumannii) and 396 strains of Gram-positive cocci (25 strains of Staphylococcus aureus, 316 strains of coagulase-negative staphylococci, 47 strains of Enterococcussp.) were collected, after excluding 53 cases with two or more isolates. Compared with the routine antimicrobial susceptibility test (AST), the rates of category agreement (CA), major error (ME), and very major error (VME) of Gram-negative bacteria were 86.0% (1368/1 591), 8.7% (139/1 591), and 0.5% (8/1 591), respectively. On the other hand, the CA%, ME%, and VME% of Gram-positive cocci were 89.2% (960/1 076), 7.5% (81/1 076), and 1% (11/1 076), respectively. Regarding the individual antimicrobial agents, the CA% of Escherichia coli was 16/17 for imipenem, 90.1% (109/121) for meropenem, and 70.8% (85/120) for cefepime. For Klebsiella pneumoniae, the CA% of was 10/13 for imipenem, 80.9% (55/68) for meropenem, and 80.3% (53/66) for cefepime. The CA% of meropenem in Pseudomonas aeruginosa and Acinetobacter baumannii were 96.0% (24/25) and 16/16. The CA% of linezolid and cefoxitin in Staphylococcus aureus were 100% (25/25) and 100% (24/24), respectively. The CA% of linezolid, cefoxitin and gentamicin in coagulase-negative staphylococci were 98.9% (269/272), 94.5% (277/293) and 71.6% (194/271) respectively. Finally, for Enterococcus sp., the CA% of vancomycin and ampicillin were 91.5% (43/47) and 94.7% (36/38), respectively. Conclusion:Compared with the conventional AST, the blood culture-positive broth direct AST exhibited high category agreement and low error rates for both Gram-negative bacteria and Gram-positive cocci, which can serve a rapid alternative for AST in cases of clinical bloodstream infection.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To predict the pathogens of bloodstream infection (BSI) in hematopoietic stem cell transplantation (HSCT) patients by plasma microbial cell-free DNA (mcfDNA) sequencing with and without additional amplification.Methods:A total of 978 HSCT patients were enrolled in Peking University People′s Hospital from March to July 2021, and the 7 428 blood samples were prospectively collected from pretransplant conditioning period to 4 months after transplantation. The plasma samples were separated and then cryopreserved. According to blood culture results and whether there were plasma samples before BSI onset, twenty-eight HSCT patients with positive blood culture (39 plasma samples within 1-8 days before BSI onset) and 9 HSCT patients with negative blood culture (9 plasma samples) were filtered. The 39 samples were performed with mcfDNA additional and non-additional amplification sequencing, and the 9 samples were only performed with additional amplification sequencing. With the blood culture results as the gold standard, the consistency between the sequencing and the blood culture results was observed. Student t test and Wilcoxon test were used for statistical analysis. Results:Without additional amplification sequencing, only 7 samples sequencing results were consistent with the blood culture results, and the total pathogen detection rate was 17.95% (7/39). The rates within 3 days and 4-8 days were 23.81% (5/21) and 2/18, respectively. The main pathogenic type detected was gram-negative bacteria (5/7). With additional amplification sequencing, the total pathogen detection rate was 59.26% (16/27) and the rate within 3 days was 8/13. The number of gram-positive bacteria detected was elevated (13/16) and the number of additional microorganisms in additional amplification sequencing was increased significantly ( P=0.001 0), compared with non-additional amplification sequencing. Moreover, additional sequencing analysis of 9 samples from patients with negative culture result showed that no pathogen was detected in six samples, and the common Torque teno virus in HSCT patients was detected in only three samples. Conclusion:The pathogen detection rate of plasma mcfDNA additional amplification sequencing was better than that of non-additional amplification sequencing in HSCT patients before BSI onset, especially in the first three days, which has the potential to predict BSI pathogens.

Objective:To evaluate whether the time to positive (TTP), handling time after positive alarm and turnaround time (TAT) of bacteremia blood culture can be shortened by optimizing blood culture workflow.Methods:This study was conducted retrospectively. Positive blood culture samples collected from Peking University People′s Hospital from January 1, 2014 to June 30, 2021 were analyzed in stages. In the traditional process stage of this study (2014), 502 bottles of positive blood culture samples were included in the analysis. In the first stage of process optimization (2016), the working time of staff was increased to 22:00, and 976 positive blood culture specimens were included in the analysis. In the second stage of process optimization (2018), the rapid identification process of MALDI-TOF MS was added, and a total of 1 029 bottles of positive blood culture samples were included. In the third stage of process optimization (2020) with the introduction of the new VIRTUO BACT/ALERT system. The difference of TTP, handling time after positive alarm and TAT of whole process in different stages of traditional process and process optimization were compared. All data were statistically significant when P<0.05 using rank-sum test. Results:In the traditional process stage (2014), the median quartile time of handling time after positive alarm was 55.70 (47.35, 68.45) h. In the first stage of process optimization (2016), the median quartile time of handling time after positive alarm was 47.25 (33.88, 59.96) h, and the handling time after positive alarm in the first stage of process optimization was significantly shorter than that in the traditional process stage ( Z=?10.734, P<0.001). In the second stage of process optimization (2018), the median quartile time for handling time after positive alarm was 47.18(36.41, 59.40) h, and 12.18% of the preliminary identification results of Gram-negative bacilli before 17:00 could be reported to the clinic before audit. In the third stage of process optimization (2020), the median quartile of TTP and TAT were 39.56 (21.52, 62.65) h and 78.16(64.68, 99.72) h respectively in the original BACT/ALERT 3D system. The new VIRTUO BACT/ALERT system had a median quartile of 37.03(21.08, 58.22) h for TTP and 73.41(62.88, 89.48) h for TAT. VIRTUO BACT/ALERT 3D had a significantly shorter TTP than BACT/ALERT 3D ( Z=?2.273, P=0.023), the TAT of VIRTUO BACT/ALERT system was significantly shorter than that of BACT/ALERT 3D system ( Z=?4.040, P<0.001). Conclusion:By improving the blood culture process of microbiology laboratory in many aspects and measures, the processing time of blood culture in each stage can be shortened and clinical benefits can be obtained.

With the popularization of ureteroscopy, ureteral avulsion has become a common complication of urological surgery in recent years. In the study, we reviewed the clinical management of 2 patients who underwent emergency ureterostomy and selective operation of ileoureteral substitution, emergency repair and selective operation of Boari-flap ureteroneocystostomy respectively. After 22 and 17 months of follow-up, no ureter stricture were found, and hydronephrosis were relieved compared with preoperative in both.

Objective: To propose the concept of a novel regional control and prevention (RCP) system for the outbreak of COVID-19 infectious disease, design an emergency epidemic prevention information system based on the existing network architecture and information system in the region, and a remote intelligent medical consultation and remote office platform, research and develop the technology of risk assessment and early warning for people in the region, and improve the regions’prevention and control ability facing emergency of major infectious diseases. Methods: Taking colleges, affiliated (teaching) hospitals, and cloud applications as typical RCP regional units, the existing local area network interaction methods between the cloud and universities and affiliated (teaching) hospitals are established to realize remote work in the network environment, remote medical imaging, psychological and ethical consultation and interaction; applying multi-agent propagation model based on complex network, combining Global Positioning System (GPS), Radio Frequency Identification (RFID), and electronic fence technology, to realize the risk classification and early warning of units and personnel in the area. Results: In the RCP, a system architecture combining campus network, affiliated (teaching) hospital intranet, and the Internet is used. Dynamic connection is made using distributed technology and cloud storage. The data buffer mechanism of the intermediary database in the network realized telemedicine consultation and telecommuting. Relying on the platform, multi-agent propagation model based on complex network and cellular automaton model are used to realize the score and early warning of population exposure risk in the region by using GPS, RFID and electronic fence technology. Conclusions In the epidemic phase of major infectious diseases, the construction of RCP can improve the response speed of wartime epidemic prevention, provide reasonable data-based warnings and risk ratings, and reduce the exposure risk of susceptible people. The design and development of RCP is a systematic project that needs to combine regional structural and functional characteristics, and the foundation of the early informatization work in the region and the level of the emergency development team determine the development progress, maintenance, and actual application effects. It is recommended to establish a peacetime and wartime combined RCP mode and incorporate it into the government's disease control system to improve the national and regional level of prevention and control of major infectious diseases.