Severe community-acquired pneumonia(SCAP) is one of the leading causes of death in children.Early identification of risk factors in children with SCAP,accurate assessment of disease conditions and reduction of mortality in children with SCAP are important tasks at present.The death risk factors of SCAP in children are affected by many factors,which are different among countries,regions and families.At present,the relevant prospective studies and retrospective studies are not comprehensive.This review summarized the literatures on the risk factors of SCAP death in children at home and abroad in recent years,to provide the basis for the diagnosis of childhood SCAP.

Objective:To investigate the predictive value of heparin binding protein(HBP) combined with pediatric sequential organ failure assessment(pSOFA) in children with sepsis.Methods:Children with sepsis admitted to PICU of Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2021 to June 2022 were selected as study group,while those who underwent elective surgery for inguinal hernia and assessment of precocious puberty and short stature during the same period were selected as control group.All children with sepsis were divided into sepsis group and septic shock group according to their severity as well as survival group and death group according to prognosis.The study group was monitored for HBP on the 1st,3rd,and 7th day of admission,while the control group was monitored for HBP on the 1st day of admission.Patients in the sepsis group received pSOFA scores immediately after admission.The laboratory results and HBP concentrations were compared between groups，and a joint model was established in combination with pSOFA to observe its predictive performance in sepsis prognosis.Results:A total of 50 children with sepsis were included in study group，including 45 children with sepsis and five children with septic shock.There were 27 males and 23 females，aged 1 month～13 years（median age two years）.There were 7 deaths in this study，including two patients with sepsis and five patients with septic shock.The HBP concentration in the study group was significantly higher than that in the control group on the 1st day，and the HBP concentration in the group gradually decreased with the prolongation of hospital stay.The concentration of HBP on the first day of septic shock group was higher than that of sepsis group，and the difference was statistically significant（ P<0.001）.The concentration of HBP on the 1st day in the sepsis death group was significantly higher than that in the sepsis survival group（ P=0.023）.The receivor operator characteristic curve analysis showed that HBP and pSOFA had good predictive value for the death of children with sepsis，and the joint model of HBP and pSOFA（75.1×pSOFA-0.1×HBP）had the best predictive performance for the death of children with sepsis，but there was no significant difference with the pSOFA. Conclusion:The HBP level significantly increases in children with sepsis，and gradually decreases with the length of hospital stay，and HBP has great value in predicting the outcome of death in children with sepsis，and the combination of pSOFA could improve its predictive ability of death,but not better than pSOFA.

Objective:To analyze the epidemiological characteristics of Mycoplasma pneumoniae ( Mp) infection in hospitalized children with community-acquired pneumonia in Hunan Province and to provide a theoretical basis for clinical diagnosis and treatment. Methods:The epidemiological characteristics of Mp infection in children hospitalized for community-acquired pneumonia in the Children′s Medical Center of the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People′s Hospital) from January 1, 2013 to December 31, 2021 were retrospectively analyzed. Results:A total of 55 681 children with community-acquired pneumonia were enrolled during the study period, of whom 27.24% (15 170/55 681) were tested positive for Mp. The positive rate was lower in boys than in girls (23.39% vs 33.39%, χ 2=665.998, P<0.001). The positive rate of Mp infection increased with age with the highest rate in children who were 5-14 years old (67.92%) and the lowest in infants less than one year old (6.38%). The detection rates of Mp infection varied between years with the highest rate in 2019 (38.31%). The positive rates of Mp infection during the COVID-19 epidemic in 2020-2021 were similar to those in 2013-2018. Among the children hospitalized for community-acquired pneumonia, the detection rate of Mp was significantly higher in summer and autumn than in winter and spring (χ 2=648.753, P<0.001), with the highest detection rate reaching to 56.91% in the summer of 2019. In contrast, the detection rates of Mp in the spring and summer of 2020 were 15.60% and 17.44%, respectively, being the lowest detection rates ever for spring and summer, while the detection rates in the autumn and winter rebounded (31.22% and 28.48%). During the Mp epidemic in 2019, the age at onset, the proportion of severe pneumonia and the cost of treatment were higher as compared with those in other years. In 2020, the number of cases positive for Mp was the lowest on record, as was the proportion of severe pneumonia and admission rate to PICU ( P<0.001). Conclusions:In hospitalized children with community-acquired pneumonia, there were gender, age and season differences in Mp infection. In the summer of 2019, there was a Mp epidemic in Hunan Province, which increased the proportion of severe pneumonia and the cost of treatment. After the outbreak of COVID-19, the rate of Mp infection dropped significantly in the spring of in 2020 as well as in the summer, but rebounded in the autumn and winter. This might be due to the strict restrictive measures taken early during the COVID-19 pandemic that effectively controlled the spread of Mp.

Community-acquired pneumonia(CAP) is one of the leading causes of death in children under 5 years of age.Early identification and clarification of its severity and appropriate therapeutic measures can improve survival, but there are limitations in the existing laboratory indices applied to diagnose CAP.Therefore, it is still necessary to find new and highly specific biomarkers that can identify the etiology and predict the severity of the disease before it worsens in children, and provides a basis for more effective therapeutic measures.Metabolomics provides a new way to search for biomarkers and pathogenesis through qualitative and quantitative analysis of metabolite changes in biological samples.This review summarized the latest research progress on metabolomics in childhood CAP, hoping to provide ideas for the early diagnosis and treatment of childhood CAP.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

Objective:To summarize the clinical characteristics of children with Mycoplasma pneumoniae pneumonia(MPP) complicated with pleural effusion, and explore the effect of mixed adenovirus infection on children with MPP complicated with pleural effusion.Methods:The clinical data of children with MPP complicated with pleural effusion diagnosed in Children′s Medical Center at the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People′s Hospital) from January 2013 to December 2019 were collected.MPP cases were divided into single infection group and mixed infection group according to whether mixing adenovirus infection.The clinical characteristics were compared between two groups.Results:A total of 180 children with MPP complicated with pleural effusion were included, the male to female ratio was 1.22∶1 (99/81), the age was 66.13 (44.35, 83.98) months, and the most common cases were children over 5 years old (55.56%). The length of hospitalization was 9.00 (7.00, 12.00) days.Fever (93.33%) and cough (98.33%) were the most common clinical manifestations, and mild increases in C-reactive protein, erythrocyte sedimentation rate and D-dimer were the most common laboratory results.Among included children, right pleural effusion was the most common (54.44%), bilateral pleural effusion accounted for 26.67%, and left pleural effusion accounted for 18.89%.Compared with single infection group, the mixed infection group had a longer hospital stay, a higher proportion of oxygen intake, a higher proportion of gamma globulin use, and a higher value of lactate dehydrogenase and aspartate aminotransferase.The results of multivariate Logistic regression analysis showed that compared with single infection group, although the mixed infection group had a higher proportion of gamma globulin use (36.54% vs.10.93%, P<0.05), the length of hospital stay, clinical manifestations, laboratory examination, chest CT and fiberoptic bronchoscopy showed no statistically significant difference between two groups. Conclusion:MPP complicated with pleural effusion is more common in children over 5 years old, especially in the right side.Mild increases of C-reactive protein, erythrocyte sedimentation rate, and D-dimer are more common.The clinical features of MPP complicated with pleural effusion are similar between mixed adenovirus infection group and single infection group.

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%, P < 0.001) and relapse-free survival (RFS) rate (88.9% vs. 63.4%, P = 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498-9.562) and RFS rate (HR = 3.296; 95% CI, 1.279-8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P < 0.001), and their combination provided a higher predictive accuracy (AUC = 0.730; 95% CI, 0.654-0.805). In conclusion, our results suggest that TLS is an independent positive prognostic factor for OSCC patients. These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.

[Objective]To investigate the effect of Donepezil on dysgnosia in patients with mild-moderate general paralysis of the insane(GPI).[Methods]Forty-seven patients with GPI were assigned into study group(n=24)or control group(n=23). All these patients were treated with a large dose of penicillin for 2 weeks and then with Benzathine for 3 weeks. And the Donepezil admin-istered to patients in study group.The mini-mental state examination(MMSE)and the clinical dementia rating(CDR)were scored as the measurement of efficiency.[Result]The scores of the MMSE and CDR were not statistically different between the two groups at baseline and 4 weeks after treatment,and both were increased 12 weeks after treatment(P<0.05),especially in study group as com-pared with those in control group(P < 0.05).[Conclusion]Donepezil as an adjunctive therapy may be effective for dysgnosia in patients with mild-moderate GPI. Donepezil is also safe and well tolerated.

Background: Aberrant Bcl-2 transcription is closely related with nodal diffuse large B-cell lymphoma (DLBCL), however, the relationship between Bcl-2 and primary gastrointestinal DLBCL (PGI-DLBCL) was not fully studied.Aims: To investigate the relationship between Bcl-2 gene amplification and protein expression and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL.Methods: Clinical data was collected from 136 PGI-DLBCL patients receiving surgical treatment, and a telephone interview was conducted for survival information.Bcl-2 gene amplification and protein expression in tumor tissue were determined by fluorescence in situ hybridization and immuno-histochemistry, respectively, and relationships between Bcl-2 and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL were analyzed.Results: Among 136 PGI-DLBCL patients, 33 (24.3%) showing gene amplification and 90 (66.2%) showing protein expression of Bcl-2;gene amplification was correlated with primary tumor location, Ann Arbor stage, serum lactate dehydrogenase level, B symptom and International Prognostic Index (IPI) score (P<0.05), while protein expression was correlated with primary tumor location and immunophenotype (P<0.05).5-year overall survival (OS) in patients positive for Bcl-2 gene amplification and patients with non-GCB immunophenotype and positive for Bcl-2 protein expression were inferior to those negative ones (41.5%vs.71.5%, P<0.05;54.6% vs.84.6%, P<0.05).In Bcl-2 gene amplification or protein expression positive patients, 5-year OS of CHOP chemotherapy was inferior to that of rituximab combined with CHOP chemotherapy (48.6%vs.80.3%, P<0.05;66.4%vs.83.4%, P<0.05).Conclusions: Detection of Bcl-2 gene amplification is useful for prediction of prognosis in PGI-DLBCL.Both patients with Bcl-2 gene amplification and non-GCB patients with Bcl-2 protein expression have a poorer prognosis.Rituximab may improve the prognosis in patients with Bcl-2 gene amplification or protein expression.

AIM: To explore the role of P2X7 receptor in inhibition of lipopolysaccharide (LPS)-stimulated BV-2 cell activation by minocycline .METHODS:BV-2 cells were divided into 5 groups:control group, LPS group, LPS+0.1 μmol/L Mino group, LPS+1 μmol/L Mino group and LPS+10 μmol/L Mino group.The expression of P2X7 re-ceptor was determined by real-time PCR and Western blotting .The levels of TNF-αand IL-1βin the microglia culture su-pernatants were measured by ELISA .The morphological changes of the cells were also observed .RESULTS: After ex-posed to LPS, the expression of P2X7 receptor increased in BV-2 cells at mRNA and protein levels .The concentrations of TNF-αand IL-1βin the microglia culture supernatants also increased .Meanwhile, 0.1~10μmol/L minocycline inhibited those changes in a dose-dependent manner .CONCLUSION:Minocycline inhibits the activation of microglia .The mecha-nism may be related to the P2X7 receptor.