Objective:To explore the clinical characteristics of children with septic shock and analyze the drug resistance of blood culture positive bacteria.Methods:The clinical data,positive blood culture strains and drug sensitivity results of 127 children with septic shock admitted to the Department of Intensive Care Medicine of Hunan Children's Hospital from September 2015 to August 2021 were retrospectively analyzed.Results:A total of 134 strains of bacteria or fungi were isolated from the blood culture samples of 127 children with septic shock,and gram-negative strains were the main ones,accounting for 67.16% (90/134).Haemophilus influenzae and Escherichia coli were the main gram-negative bacteria,accounting for 38.81% (52/134) and 20.15% (27/134)，respectively,while Streptococcus pneumoniae was the main gram-positive bacteria,accounting for 8.21% (11/134),and Candida albicans was the main fungus,accounting for 10.45% (14/134).The number of white blood cells,the levels of serum C-reactive protein,procalcitonin,venous blood sugar and arterial blood lactic acid in patients were all significantly higher than normal values,and the white blood cells count and neutrophil percentage in gram-positive bacterial infections were significantly higher than those with gram-negative bacterial infections and fungal infections( P<0.05).Procalcitonin increased most obviously when infected by gram-negative bacteria,and the difference was statistically significant ( P<0.05).Gram-positive strains were sensitive to vancomycin,teicoplanin,and linezolid,but only 50% of Streptococcus pneumoniae were sensitive to penicillin.Gram-negative strains had relatively high drug resistance,among which Klebsiella pneumoniae were only highly resistant to imipenem,cilastatin and levofloxacin,reaching 50%.Haemophilus influenzae was resistant to cephalosporins and β-amides enzyme antibiotic,and the drug sensitivity rate of lactamase antibiotics was high,with a resistance rate of 50% only to ampicillin,cefuroxime,amikacin,and compound sulfamethoxazole.There were not many fungal strains,and most antifungal drugs were effective against blood culture-positive fungi. Conclusion:The main pathogens of infection in children with septic shock are gram-negative bacteria,and have high resistance to general antibiotics.We should pay attention to their drug resistance when using antibiotics empirically.

Objective:To investigate the predictive value of sputum heparin binding protein(HBP) in sepsis related acute respiratory distress syndrome(ARDS).Methods:This study was a prospective case-control study.A total of 134 children with sepsis who were admitted in PICU at Hunan Children′s Hospital from January 2020 to November 2021 were included, including 63 children who had completed fiberoptic bronchoscopy.The 63 children were divided into sepsis without ARDS group, sepsis with mild ARDS group, and sepsis with moderate to severe ARDS group according to the presence and severity of ARDS.Sputum was collected and HBP was detected in all children with sepsis when they were admitted to the hospital.The alveolar lavage fluid within 72 hours of admission was reserved for HBP.The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)- α were detected, and the blood biochemistry, pulmonary imaging, pediatric critical case score and other data within 72 hours were collected.Results:(1) Among 63 children with fiberoptic bronchoscopy, 29 were in sepsis without ARDS group, 18 were in the sepsis with mild ARDS group, and 16 were in the sepsis with moderate to severe ARDS group.There was no significant difference in the pediatric critical case score and the location of primary infection focus among the three groups at admission.The primary infection focus was respiratory system in 36 cases, whose sputum HBP level was (42.1±9.8) ng/mL, and 27 children with other systems infection, whose sputum HBP level was (37.8±10.8) ng/mL, there was no significant difference between two groups ( t=1.65, P=0.104). (2) There were significant differences in sputum HBP, alveolar lavage fluid HBP, IL-6 and TNF-α levels among sepsis with mild ARDS group, sepsis with moderate and severe ARDS group and sepsis without ARDS group ( P<0.05). The sputum HBP of 34 children with sepsis combined with ARDS was positively correlated with alveolar lavage fluid HBP, IL-6, TNF-α levels and lung injury score, and negatively correlated with SpO 2/FiO 2 ( P<0.05). (3)Among the 34 children with sepsis combined with ARDS, the sputum HBP concentration of children with invasive ventilation was significantly higher than that of children with non-invasive ventilation ( P<0.05). The sputum HBP concentration in children with three or more organ damage was significantly higher than that of children with two or less organ damage ( P<0.05). The sputum HBP concentration of dead children was higher than that of surviving children ( P<0.05). (4) The area under curve of sputum HBP for predicting ARDS was 0.772 (95% CI: 0.655~0.889). When the cut-off point value of sputum HBP was 27.9 mU/L, whose sensitivity and specificity were 70.6% and 79.3%, respectively.The area under curve of sputum HBP for predicting moderate and severe ARDS was 0.793 (95% CI: 0.661~0.926). When the cut-off point value of sputum HBP was 51.55 mU/L, whose sensitivity and specificity were 81.3% and 76.6%, respectively. Conclusion:Sputum HBP is elevated in children with sepsis and ARDS, which is related with the severity of the disease.Sputum HBP has a good predictive value for the diagnosis and severity of children with sepsis and ARDS, and can be used as a clinically effective and convenient evaluation index for children with sepsis related ARDS.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39⁺CD73⁺ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A_2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6C^hi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF⁺CD4⁺ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

Objective:To investigate the clinical features of pertussis in children and analyze the risk factors of severe pertussis.Methods:The clinical data of 248 children with pertussis hospitalized in Hunan Children′s Hospital from March 2018 to March 2022 were analyzed retrospectively.According to the age at admission, the patients were divided into two groups: ≤3 months and > 3 months.According to the patient′s condition, they were classified into ordinary group and severe group.According to the pathogens detected, the children were divided into single infection group and mixed infection group.The independent sample t-test, chi- square test were used to analyze the clinical indexes of the infants in above groups. Results:(1)Of 248 hospitalized children with pertussis, 204 cases (82.2%) were less than 1 year old, 92 cases (37.0%) had contact with a coughing family member before, and 169 cases (68.1%) were unvaccinated.Among 248 children, 193 cases (77.8%) had an elevated white blood cell count, and 145 cases (58.4%) had mixed infections.The most common pathogen was respiratory syncytial virus [29/248(11.6%)]. About 173 cases (69.7%) had concurrent pneumonia, and 35 cases (14.1%) had pulmonary consolidation.(2)Compared with the group > 3 months of age, more patients in the group ≤3 months of age had contact with a coughing family member before, and suffered from cyanosis, dyspnea, respiratory failure, heart failure and pertussis encephalopathy ( χ2=4.612, 20.810, 7.882, 16.617, 13.740, 7.846, all P<0.05). The proportions of patients in the group ≤3 months of age required intensive care unit(ICU) hospitalization and mechanical ventilation were higher than those in the group > 3 months of age ( χ2=14.810, 21.436, all P<0.05). The mortality of the group ≤3 months of age was higher than that of the group >3 months of age ( χ2=12.016, P<0.05). Children ≤3 months of age had a higher WBC level [(27.83±27.70)×10 9/L vs.(23.34±15.28)×10 9/L, t=22.244, P<0.001], longer duration of spasmodic cough [(16.56±9.33) d vs.(15.06±6.16) d, t=10.145, P=0.002] and longer hospitalization time [(11.47±10.48) d vs.(9.48±4.80) d, t=20.050, P<0.001] than those >3 months of age.(3)Compared with the ordinary group, a higher proportion of children in the severe pertussis group were under 3 months old, and had not been vaccinated against pertussis vaccine ( χ2=14.803, 4.475, all P<0.05). The ratio of patients with dyspnea, an lymphocyte count/neutral cell(LC/NC) ratio <1, mixed infections, lung consolidation and pleural effusion in the severe pertussis group was higher than that in the ordinary group ( χ2=116.940, 43.625, 13.253, 106.370, 11.874, all P<0.05). The patients in the severe pertussis group had a higher WBC [(61.66±29.63)×10 9/L vs.(18.83±10.00)×10 9/L, t=112.580, P<0.001] and a lower LC (0.494±0.186 vs.0.676±0.132, t=13.752, P<0.001) than those in the ordinary group.(4)Compared with the single infection group, the proportions of children with fever, dyspnea, fine moist lung rales, an LC/NC ratio <1, and lung consolidation were higher in the mixed infection group ( χ2=8.909, 6.804, 7.563, 8.420, 12.458, all P<0.05). More children in the mixed infection group required ICU hospitalization and mechanical ventilation than those in the single infection group ( χ2=11.677, 7.397, all P<0.05). The mixed infection group had higher respiratory failure and death rates than the single infection group ( χ2=7.980, 4.267, all P<0.05). Compared with the single infection group, the mixed infection group had a higher WBC level [(27.73±24.13)×10 9/L vs.(21.25±14.65)×10 9/L, t=13.318, P<0.001], longer hospitalization time [(11.593±9.010) d vs.(8.339±4.047) d, t=17.283, P<0.001], and a smaller LC ratio (0.626±0.165 vs.0.684±0.132, t=7.997, P=0.005). (5) Logistic regression analysis showed that age ≤3 months, peak WBC and dyspnea were risk factors of severe pertussis. Conclusions:Hospitalized pertussis children are prone to pneumonia and pulmonary consolidation.Patients aged ≤3 months with a large WBC and dyspnea easily develop into severe pertussis.Monitoring blood routine is helpful for judging the severity of the disease.Mixed infections increase the incidence of complications and can impair the treatment effect.

Objective : To explore the characteristics of impaired attention network function in chronic insomnia pa- tients． Methods : Polysomnography ( PSG) ，sleep scale ，attention network test ( ANT) and neuropsychological cognitive scale were used to evaluate the sleep quality，attention network function and cognitive function of 73 pa- tients with chronic insomnia and 65 healthy subjects. Results : Compared with normal control group，the scores of pittsburgh sleep quality index(PSQI) and insomnia severity index (ISI) in the chronic insomnia group increased， total sleep time reduced，sleep latency prolonged，sleep efficiency decreased，wake after sleep onset and arousal index increased，the proportion of non-rapid eye movement sleep stage 1 increased，the proportion of non-rapid eye movement sleep 3 and the proportion of rapid eye movement sleep decreased，and differences were statistically sig- nificant (all P＜0．05) ．In the attention network test，the efficiency of executive control network decreased in the chronic insomnia group，and the difference was statistically significant (all P＜0. 05) ．In neuropsychological tests， patients in the chronic insomnia group had spent more time on the Stroop color word test-word and trail making test- B．Correlation analysis showed that executive control function was associated with decreased non-rapid eye move- ment sleep stage 3 andincreased PSQI scores in chronic insomnia group． Conclusion Chronic insomnia patients have a certain degree of cognitive impairment，mainly executive control network impairment，which is associated with slow-wave sleep reduction.

Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.

目的：分析Claudin-2蛋白在食管鳞癌（esophageal squamous cell carcinomas，ESCC）组织中的表达及其与患者临床病理特征、5年生存率的关系，探索其对ESCC细胞KYSE450的增殖、迁移和侵袭的影响。方法：选取河南省肿瘤医院2010至2013年间初治的ESCC患者手术切除肿瘤组织52例及其中20例对应的癌旁组织标本，采用免疫组化和WB法检测Claudin-2的表达并分析其与患者临床病理特征和5年生存率的关系。WB法检测ESCC细胞（KYSE450、KYSE150、KYSE510、KYSE140）和人永生化食管上皮细胞SHEE中Claudin-2的表达，构建Claudin-2 shRNA慢病毒载体并转染KYSE450细胞构建敲低Claudin-2表达的细胞系，进一步通过克隆形成实验、细胞划痕实验及Transwell实验检测敲低Claudin-2对KYSE450细胞增殖、迁移和侵袭的影响。结果：ESCC组织中Claudin-2阳性率显著高于癌旁组织（P<0.05），ESCC组织中Claudin-2的表达与淋巴结转移有关（P<0.05）。Claudin-2表达阳性患者5年生存率显著低于阴性者（P<0.05）。成功构建敲低Claudin-2表达的KYSE450细胞系。sh-Claudin-2组细胞的克隆形成数、伤口愈合率和侵袭细胞数均显著低于sh-NT组和对照组（P<0.05）。结论：ESCC组织中Claudin-2的表达高于癌旁组织，且与患者5年生存率呈负相关，Claudin-2能够增强KYSE450细胞的增殖、迁移和侵袭能力。

Objective:To investigate the effect of long-term application of prostaglandin analog drops on bulbar conjunctival thickness in rabbits.Methods:Twenty-four healthy New Zealand white rabbits were randomly divided into latanoprost group, carteolol group and blank control group using the random number table method, with 8 rabbits in each group.The left eyes of rabbits were taken as experimental eyes.The rabbits in the latanoprost group and carteolol group were given latanoprost eye drops or carteolol eye drops once a day for 2 months according to grouping.The bulbar conjunctival thickness of left eyes of the latanoprost group and carteolol group were measured by optical coherence tomography (OCT) at baseline and two months after administration, respectively.The conjunctival tissue of the three groups were extracted to investigate the protein and mRNA expression level of matrix metalloproteinases-1 (MMP-1) and MMP-3 by Western blot and real-time fluorescence quantitative polymerase chain reaction (PCR). The study protocol was approved by an Ethics Committee of Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (No.2017-0014). The use and care of the experimental animals complied with the ARVO Statement.Results:In the latanoprost group, the conjunctival thickness was significantly reduced from baseline (178.88±5.23)μm to (124.19±11.29)μm at 2 months after administration ( P<0.01). In the carteolol group, there existed no significant difference in the conjunctival thickness between baseline (184.94±11.85)μm and (183.31±8.71)μm at 2 months after administration ( P>0.05). The conjunctival thickness at 2 months after administration of the latanoprost group was significantly thinner than that of the carteolol group ( P<0.01). The protein and mRNA expression levels of MMP-1 and MMP-3 in conjunctival tissue of the latanoprost group were significantly higher than those of the blank control group and carteolol group (all at P<0.01). Conclusions:The long-term topical use of prostaglandin analog drops can significantly reduce the bulbar conjunctival thickness in rabbits.The mechanism may be related to the elevated expression levels of MMP-1 and MMP-3 in the bulbar conjunctival tissue.

Objective:To explore the application effect of modified early cardiac rehabilitation in patients with acute myocardial infarction after percutaneous coronary intervention (PCI) .Methods:Using the convenient sampling method, a total of 193 patients who were diagnosed with acute ST-segment elevation myocardial infarction and underwent PCI in Huabei Petroleum Administration Bureau General Hospital were selected as research objects from January 2018 to January 2020. They were randomly divided into the observation group (97 cases) and the control group (96 cases) . Patients in the control group received routine nursing, while the observation group received modified early cardiac rehabilitation nursing. The Barthel Index, 6-Minute Walk Test (6MWT) and the MOS Item Short from Health Survey (SF-36) were used to compare the effects of interventions.Results:After intervention, the distance of 6MWT in the observation group was longer than that in the control group, and the score of Barthel Index in the observation group was higher than that in the control group, and the differences were statistically significant ( P<0.05) . After 6 months of follow-up, scores of general health, social function, emotional function, physiological function and mental health in SF-36 of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Modified early cardiac rehabilitation is beneficial to improve the activity of daily living, increase exercise tolerance and improve quality of life of patients with acute myocardial infarction after PCI.