Some new progress and evidence have been made in the diagnosis and treatment of pediatric acute infectious diarrhea since the publication of the “Chinese clinical practice guidelines for acute infectious diarrhea in children” (2018 edition guidelines). The updated “Chinese clinical practice guidelines for acute infectious diarrhea in children” incorporates new evidence-based recommendations for managing acute infectious diarrhea in the Chinese pediatric population. Building on the 2018 edition guidelines, expert panels reviewed clinical evidence, assessed preliminary recommendations, and conducted open-ended discussions to finalize the updated guidelines. These guidelines are founded on the latest literature and evidence-based practices. A literature review was performed in databases such as PubMed, Cochrane, EMBASE, China Biomedical Database, and the Chinese Journal Full-text Database up to June 2024. The search focused on the terms “acute diarrhea” or “enteritis”, along with “adolescent”, “child”, “pediatric patient”, “baby”, or “infant”. The updated guidelines address various aspects of acute infectious diarrhea, including diagnosis, etiological evaluation, dehydration assessment, fluid therapy, diet therapy, medical therapy, and prevention strategies. The main updates focused on etiological diagnosis and the use of probiotics, racecadotril, zinc, and antibiotics in treating acute infectious diarrhea. The updated guidelines address disputed treatments for acute infectious diarrhea through evidence-based revisions. Standardized etiological evaluations guide management. Probiotics are moderately advised for viral watery diarrhea; racecadotril remains unsupported. Zinc supplementation is recommended for children >6 months in deficient regions. Antibiotics are restricted to cases with dysenteric-like symptoms, suspected cholera with severe dehydration, or comorbidities.

Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail sequences were detected using nested PCR, TA cloning, and Sanger sequencing, and these findings were confirmed by mNGS and amplicon sequencing. The secondary structure was predicted using the Mfold web server. The results indicated that head-to-tail sequences were detected in 42 specimens through TA cloning from 351 specimens positive for HBoV1 DNA, yielding 92 sequences into 32 types and 2 categories. Additionally, head-to-tail sequences were detected in 16 specimens by amplicon sequencing, yielding 60 sequences categorized into 23 types. The 374nt type, detected in 13 specimens, contains variants 374a and 374b, which differ in the unpaired loop regions of the palindrome or complementary reverse sequences, implying a switch of template chains during the replication process. The mNGS results in three specimens confirmed the presence of circular genome in copies below 1%. In conclusion, head-to-tail sequences of HBoV1 were common in children with ARI and were highly diverse in length and sequences. The variants may be generated by the switch of the template chain in the rolling-circle replication model.

A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis‐based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV‐A replaced RSV‐B in July 2021 to become the dominant subtype. Six RSV‐A and eight RSV‐B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.

Our previous surveillance revealed that t203-like G9 (tentatively designated subtype G9-VI) rotaviruses re-emerged in 2010 in Beijing and rapidly prevailed over the G9-III subtype (the most common G9 subtype globally) and previously predominant G genotypes over the following two years. G9-VI belongs to the VP7 evolutionary lineage VI, which includes unusual and sporadic human rotaviruses from China (t203) and Japan. To obtain insight into the epidemiology, evolution, and transmission advantages of G9-VI rotavirus, we performed follow-up surveillance (2014-2017) and whole-genome analysis of 12 representative G9 strains. The results showed that the G9 genotype was predominant (77.4%), with a marked increase in prevalence (previously 43.5%). Within the G9 genotype, subtype G9-VI accounted for the majority (98.3%) of cases. The most prevalent P-genotype was P[8] (93.7%), within which subtype P[8]b was rare (0.7%). Phylogenetically, the G9-VI subtype strains in this study clustered closely with contemporary emerging human rotaviruses from many other countries in VP7 lineage VI, indicating that this subtype is capable of spreading globally. These currently emerging G9-VI rotaviruses formed a distinct monophyletic subcluster when compared to early G9-VI rotaviruses. Furthermore, four specific amino acid substitutions and synonymous codon substitutions were observed in the VP7 genes between the current G9-VI and globally common G9-III rotaviruses. The remaining nine genes of all of the analyzed representative G9 strains, whether G9-VI or G9-III, combined with the P[8]a, P[8]b, or P[6] genotype and exhibited the same Wa-like backbone constellation.

Human adenovirus serotype 31 (HAdV-31) is closely associated with gastroenteritis in children and can cause fatal systemic disseminated diseases in immunocompromised patients. The lack of genomic data for HAdV-31, especially in China, will greatly limit research on its prevention and control. Sequencing and bioinformatics analyses were performed for HAdV-31 strains from diarrheal children in Beijing, China, during 2010–2022. Three capsid protein genes (hexon, penton, and fiber) were obtained in 37 cases, including one in which the whole genome was sequenced. HAdV-31 strains clustered into three distinct clades (I–III) in a phylogenetic tree constructed based on concatenated genes and the whole genome; the endemic strains only gathered into clade II, and most of the reference strains clustered into clade I. Compared with penton and hexon, fiber had a faster evolutionary rate (1.32 × 10−4 substitutions/site/year), an earlier divergence time (1697), lower homology (98.32–100% at the amino acid level), and greater genetic variation (0.0032). Four out of the six predicted positive selection pressure codons were also in the knob of fiber. These results reveal the molecular evolution characteristics and variations of HAdV-31 in Beijing, and fiber may be one of the main evolution driving forces.

Purpose Immune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients. Methods The genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated. Results The highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1β in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1β in the first serum samples from patients with ON1 compared to those with BA9 of subtype B. Conclusions Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.

PurposeTo identify the predictive role of pretreatment skeletal muscle mass index (SMI) for long-term survival of bladder cancer patients. MethodsSeveral databases were searched for studies investigating the relationship between pretreatment SMI and prognosis in bladder cancer. The overall survival (OS) and cancer-specific survival (CSS) were defined as primary and secondary outcomes, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. ResultsNine studies involving 1476 cases were included. The results demonstrated that a lower pretreatment SMI was significantly related to poorer OS (HR = 1.56, 95% CI: 1.33-1.82, P<0.001) and subgroup analysis based on thresholds of SMI revealed similar results. Besides, pretreatment SMI was also obviously related to CSS (HR = 1.75, 95% CI: 1.36-2.25, P<0.001). ConclusionLower pretreatment SMI was associated with worse long-term survival of bladder cancer patients.

Background Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. Methods Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. Results A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched ( P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. Conclusions The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

急性感染性疾病仍然是儿科最常见的疾病。准确和及时地作出病原学诊断对于帮助这类疾病的有效治疗至关重要。基于症候群检测的多重核酸分子检测技术是指使用单一实验同时检测多种可造成相似症状的病原的检测方法。因其敏感性、特异性高并且快速高效在近几年被迅速广泛用于呼吸道、消化道、血流、中枢神经系统及关节感染的实验室病原快速诊断。

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. Conclusion: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged.

Objective:To understand the characters of norovirus infection in children with acute diarrhea in Beijing from 2014 to 2019.Methods:Fecal specimens were collected from children with acute diarrhea visiting the hospital affiliated to the Capital Institute of Pediatrics from April 2014 to December 2019 for norovirus screening by reverse transcription-polymerase chain reaction (RT-PCR). Then RdRp gene and VP1 gene of norovirus (NoV) were amplified and sequenced from positive specimens and then genotyped by Norovirus Genotyping Tool 2.0.Results:Fecal specimens were collected from 2 577 cases with acute diarrhea and tested for NoV RNA in this study, of which 484 cases (18.78%, 484/2 577) were positive for NoV. NoV infection can occur all year round, with obvious seasonal distribution, the epidemic peak is in autumn and winter. There was no gender difference in the detection of NoV ( χ2=1.77, P=0.183). 399 specimens genotyped by VP1 gene with 98.25% (392/399) being GII and GII.4 Sydney as the mainly genotype (52.13%, 208/399), followed by GII.3 (19.8%, 79/399) and GII.2 (18.5%, 74/399). Then 267 specimens also were genotyped by RdRp region, which revealed that the main genotype was GII.P31 (57.3 %, 153/267), followed by GII.P12 (15.36%, 41/267) and GII.P16 (14.98 %, 40/267). Dual-typing revealed that various combination strains, GII.4 Sydney[P31] (53.18%, 142/267) as the major combination, followed by GII.3[P12] and GII.2[P16] (15.36%, 41/267 and 10.49%, 28/267). While GII.3[P12] showed a downward trend, GII.4 Sydney[P16] increased gradually. Conclusions:Norovirus is an important pathogen of acute diarrhea in children in Beijing, from 2014 to 2019, with various prevalent genotypes.

当抗菌药物在20世纪初问世时，医疗卫生界曾认为人类已经赢得了这场与细菌的战争。然而，随着微生物的持续进化，人们很快就发现，微生物能够对几乎所有正在使用的抗菌药物产生抵抗。感染性疾病一直为人类疾病与死亡的重要原因。抗微生物药物耐药性的出现对感染性疾病的病种与发病人数以及医疗费用的增长都产生了巨大的影响。因此，医疗卫生界有必要对常见的细菌感染的抗微生物药物耐药性问题给予极大的关注。

Background Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. Result The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. Conclusions In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.

Background Current diagnostic criteria for cancer cachexia are inconsistent, and arguments still exist about the impact of cachexia on the survival of patients with colorectal cancer. In this study, we aim to investigate the prognostic value of a novel cachexia indicator, the cachexia index (CXI), in patients with colorectal cancer. Methods The CXI was calculated as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio. The cut-off value of CXI was determined by the receiver operating characteristic (ROC) curves and Youden’s index. The major outcomes were major complications, overall survival (OS), and recurrence-free survival (RFS). Results A total of 379 patients (234 men and 145 women) were included. The ROC curves indicated that CXI had a significantly diagnostic capacity for the detection of major complications. Based on Youden’s index, there were 231 and 148 patients in the low and high CXI groups, respectively. Patients in the low CXI group had significantly older age, lower BMI, and a higher percentage of cachexia and TNM stage II+III. Besides, Patients in low CXI group were associated with a significantly higher rate of major complications, blood transfusion, and longer length of stay. Logistic regression analysis indicated that low CXI, cachexia, and coronary heart disease were independent risk factors for the major complications. Kaplan Meier survival curves indicated that patients with high CXI had a significantly more favorable OS than those with low CXI, while no significant difference was found in RFS between the two groups. Besides, there were no significant differences in OS or RFS between patients with and without cachexia. The univariate and multivariate Cox regression analysis indicated that older age, low CXI, and coronary heart disease instead of cachexia were associated with a decreased OS. Conclusion CXI was better than cachexia in predicting OS and could be a useful prognostic indicator in patients with colorectal cancer, and greater attention should be paid to patients with low CXI.

Acute respiratory tract infection is the most common infectious disease in children, which seriously threatens children′s health.Rapid and accurate etiological diagnosis is of great significance for the clinical treatment and control of these diseases.Pathogen nucleic acid test was applied and became the main method of respiratory tract infection diagnosis for its high sensitivity and specificity.To regulate the application of pathogen nucleic acid amplification test in respiratory tract infection in children, improve the diagnosis level, expert consensus on nucleic acid amplification test of respiratory pathogens in children was prepared to guide the application and promote pathogens diagnosis ability.

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Background Human bocavirus 1 (HBoV1), first discovered in 2005, was positive in symptomatic and healthy children and co-detected with other respiratory viruses. It is a long journey to decisively demonstrate the unique viral pathogenic function of acute respiratory tract infection (ARTI) in pediatric patients. Methods Respiratory specimens collected from pediatric patients with ARTI from January 2017 to December 2021 were screened by a capillary electrophoresis-based multiplex PCR (CEMP) assay, then genotyped by PCR and sequencing for HBoV1. For the antigen test, a part of HBoV1 DNA positive nasopharyngeal aspirates (NPAs) was used as an antigen, while a rabbit anti-HBoV1 DR2 specific to HBoV1 was used as an antibody in the indirect-immunofluorescence assay (IFA). Finally, the levels of IgG specific to HBoV1 in acute and convalescent sera selected retrospectively from only HBoV1 DNA-positive patients were evaluated by IFA. Results Among 9,899 specimens, 681 were positive for HBoV1 DNA (6.88%, 681/9899), which included 336 positives only for HBoV1 (49.34%, 336/681) and 345 (50.66%, 345/681) positives also for other pathogens. In the antigen test, there were 37 among 47 NPAs determined as HBoV1 antigen-positive (78.72%, 37/47), including 18 (48.65%, 18/37) positives solely for HBoV1 DNA. Among 4 pediatric patients with both acute and convalescent sera, there was one positive for HBoV1 antigen (D8873) and 2 lack the antigen results (D1474 and D10792), which showed seroconversion with a ≥ 4-fold increase in IgG levels. Conclusions The combination results of nucleic acid, antigen, and serology tests answered that HBoV1 is a genuine pathogen for ARTI in pediatric patients.

To identify the prognostic value of the pretreatment geriatric nutritional risk index (GNRI) in colorectal cancer. Several electronic databases were searched up to March 15, 2022, for relevant studies. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Bess's funnel plot and Egger's test were conducted to detect publication bias, and the trim-and-fill method was performed to identify potentially unpublished papers and their impacts on the overall results. Nine studies from Japan and China involving 3440 participants were enrolled in the current meta-analysis. The pooled results indicated that a low pretreatment GNRI was significantly associated with poorer OS (HR = 2.28, 95% CI: 1.69-3.07, P < 0.001; I2=63.5%, Pheterogeneity=0.005) and DFS (HR = 1.62, 95% CI: 1.35-1.96, P < 0.001; I2=46.4%, Pheterogeneity=0.114). Subgroup analysis stratified by country and treatment showed similar results. Significant publication bias was manifested by the asymmetric Begg's funnel plot and P = 0.012 of Egger's test, but three potentially unpublished studies did not have a significant impact on the overall results. A lower pretreatment GNRI was a novel prognostic risk factor for Japanese and Chinese colorectal cancer patients.