Chronic obstructive pulmonary disease （COPD） is a common clinical chronic airway disease with high morbidity， high mortality， a heavy disease burden， and complex mechanisms that have not been fully elucidated. Clinical problems promote the continuous progress of basic research. The establishment and evaluation of animal models is an important way to delve into the pathogenesis and treatment strategies of COPD. On the basis of the etiology， pathogenesis， diagnostic criteria， and syndrome differentiation of COPD in traditional Chinese medicine （TCM） and Western medicine， this paper summarizes the establishment methods and characteristics of existing animal models of COPD and analyzes the fitting degree of the models with the disease characteristics in Western medicine and syndrome characteristics in TCM. The results showed that the animal models of COPD in Western medicine were mainly induced by single factors and compound factors， and the model with the highest fitting degree was established by cigarette smoke combined with lipopolysaccharide and hormone. The model showed a fitting degree of 84% with the disease characteristics in Western medicine and 70% with the syndrome characteristics in TCM， being consistent with the clinical characteristics of COPD induced by multiple factors. Most of the animal models of COPD in TCM were established on the basis of disease models and combined with TCM etiology and pathogenesis characteristics， and prepared by syndrome differentiation. Among them， the model of accumulation of cold and water retention in lung had the highest fitting degree of 92% with the TCM diagnostic criteria. The models of phlegm-heat obstructing lung and phlegm-stasis obstructing lung had the fitting degree of 94% with clinical manifestations in Western medicine and the highest fitting degree with the diagnostic criteria in Western medicine. Different animal models of COPD have their own advantages and disadvantages， and most of them simply replicate the manifestations of COPD at a certain stage， failing to reflect the multiple causes and the dynamic changes of TCM etiology and pathogenesis. Moreover， the syndromes of these models fail to match the clinical syndromes in TCM. Therefore， establishing the animal models reflecting clinical characteristics of COPD in TCM and Western medicine and improving the model evaluation criteria are important contents to promote the overall development of integrated traditional Chinese and western medicine for COPD.

OBJECTIVES: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure. METHODS: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified via PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested. RESULTS: A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells. CONCLUSIONS Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.
Quercetin/pharmacology* ; Myocytes, Cardiac/drug effects* ; Heart Failure/metabolism* ; Apoptosis/drug effects* ; MAP Kinase Signaling System/drug effects* ; Rats ; Animals ; Isoproterenol

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

Objective:To investigate the predictive value of differential distribution of peripheral lymphocyte subsets before and after the first 131I treatment on the therapeutic response to 131I treatment in patients with papillary thyroid cancer (PTC). Methods:A retrospective study was conducted on 46 PTC patients (16 males, 30 females, age 20-77 years) who underwent total thyroidectomy and received 131I treatment between January 2021 and August 2021 in First Hospital of Shanxi Medical University. Peripheral blood lymphocyte subsets (T, B, CD4 + T, CD8 + T, natural killer (NK), helper T (Th)1, Th2, Th17, and regulatory T (Treg) cells) were measured 1-2 d before and 30 d after 131I treatment. Based on serological and imaging evidence, therapeutic response at 6-12 months post- 131I therapy was categorized as either excellent response (ER) or non-excellent response (NER). Differences of preablative stimulated thyroglobulin (psTg) and clinical baseline characteristics between two groups were assessed by using independent-sample t test, paired t test, or Mann-Whitney U test. Predictive value of lymphocyte subsets before and after 131I treatment for therapeutic response was assessed through logistic regression analysis, ROC curve analysis, and decision curve analysis (DCA). Results:In ER group ( n=33) and NER group ( n=13), most lymphocyte subsets showed different degrees of reduction 30 d after 131I treatment compared to before 131I treatment, such as T, B, CD4 + T and Th1 cells in ER group, as well as T, B, CD4 + T, Th1, Th2, Th17, and Treg cells in NER group ( t values: 2.41-9.57, all P<0.05). Before 131I treatment, NER group had significantly higher levels of psTg, Th2, Th17, and Treg cells compared to the ER group ( t values: from -3.32 to -2.48, U=29.00, all P<0.05). After 131I treatment, most of lymphocyte subsets in NER group (T, B, CD4 + T, CD8 + T, Th1 and Treg cells) showed higher trend than those in ER group but without statistical significances ( t values: from -1.12 to -0.06, all P>0.05). Th2 cells before 131I treatment (odds ratio ( OR)=25.00, 95% CI: 1.36-459.10, P=0.030) was identified as a risk factor for NER. ROC curve analysis indicated that AUCs of psTg and Th2 cells for predicting therapeutic response were 0.932 and 0.790, respectively, which was 0.958 for the combined psTg and Th2 cells. DCA showed that within the threshold probability range of 10%-60%, the curves for psTg, Th2 cells, and the combined psTg and Th2 cells were all higher than the extreme curve, suggesting good effect. Conclusions:Most lymphocyte subsets decrease to varying degrees, and NER group shows a significant decrease 30 d after 131I treatment. Th2 cells may be a risk factor for poor response to 131I treatment, providing a certain value in predicting the therapeutic response to 131I treatment.

Objective: Narrative exposure therapy (NET) has been used in various contexts for the treatment of the effects of trauma, with promising results in clinical trials. However, its effects on anxiety and depression are still unclear. The present study is a systematic review and meta-analysis of the effects of NET on depression and anxiety. Methods: The Embase, Cumulative Index of Nursing and Allied Health Literature, PubMed, Web of Science core collection, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and Wangfang databases were searched from the earliest records to March 2023. Two researchers independently screened the literature, extracted data, evaluated the risk of bias, and cross-checked the data. Meta-analysis was performed using the program RevMan 5.3. Results: Eleven randomized controlled trials with a total of 754 participants were included in the study. The results showed that NET reduced both the depression (standard mean difference [SMD]=-0.51, 95% confidence interval [CI] -0.73–-0.29, p<0.00001) and anxiety (SMD=-0.65, 95% CI -1.13–-0.18, p=0.007) scores of the patients. Furthermore, NET was found to alleviate negative emotions associated with guilt (mean difference [MD]=-3.60, 95% CI -5.52–-1.68, p=0.0005) and negative change (MD=-5.80, 95% CI -9.76–-1.83, p=0.004). Conclusion This analysis showed that NET can alleviate depression and anxiety. It may thus be used in clinical settings to alleviate patients’ negative feelings and aid their overall recovery.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Objective     To analyze the clinical characteristics of the Guang’an Omicron epidemic and summarize the management experiences and practices in pandemic prevention and control of major infectious diseases. Methods     Retrospective analysis was performed on patients infected with coronavirus disease (COVID-19), afterwards treated and observed in the isolation ward of Guang’an People’s Hospital and the shelter of Guang’an City from May 9 to June 26, 2022. The characteristics of patients at different age stages and the related factors affecting the severity, re-positive and negative conversion was analyzed. Results     Finally 1 278 patients were collected, including 508 males and 770 females, with an average age of 41.3±22.6 years. Among them, 1 054 patients were asymptomatic carriers. The overall severe rate was 0.86%, the severe rate of the high-risk group was 3.06%. The median negative conversion time was 10.0 days and re-positive rate was 7.36%. Patients aged>60 years were 2.589 times more likely to have a longer negative conversion time than those aged≤60 years (95%CI 1.921-3.489, P<0.001). Conclusion     The clinical characteristics of Guang’an COVID-19 epidemic are mainly that the elderly with high risk factors are more likely to develop severe cases, have longer clearance time, and re-positve is more likely to occur.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Objective:To describe the treatment strategies in children with septic shock in China.Methods:A questionnaire was prepared and 368 pediatric intensivists from the Pediatric Critical Care Physician Branch of Chinese Medical Doctor Association were surveyed about the treatment of pediatric septic shock from April to June 2017.Results:Surveys were received from 87.2%(68/78) institutions and 368 questionnaires (response-rate 45.1%) were included.59.2% and 77.7% of the respondents chose debridement surgery and fluid drainage as source control intervention.Antibiotics were used within 1 hour of shock in 90.8% of respondents.98.4% of respondents chose normal saline, 72.3% of respondents chosen albumin, and 53.8% of respondents chosen plasma for fluid resuscitation.When no venous access was available during shock resuscitation, 57.1% of respondents preferred intraosseous access.79.3% and 83.2% of the respondents used the adjuvant therapy such as glucocorticoids and intravenous immunoglobulin.96.7%, 85.3% and 22.0% of respondents were likely to provide oxygen and mechanical ventilation, continuous renal replacement, and extracorporeal membrane oxygenation as organ support, respectively.Additionally, 322 (88.7%), 188 (51.1%), and 85 (23.1%) respondents chose the "best advice" options to simulated clinical cases of fluid resuscitation, inotropic agents, and vasoactive agents, respectively.In the simulated cases of vasoactive drugs and inotropic drugs, 69.3% and 24.2% of the respondents chose fluid resuscitation strategy, respectively.In cases of fluid resuscitation, 49.7% (183/368) of respondents reported performing fluid responsiveness and volume status assessment, and instruments used in the assessment included bedside echocardiography[39.4% (145/368)], bioreactance[10.3% (38/368)], transpulmonary thermodilution devices[6.3% (23/368)]. Pediatricians who received advanced life support courses for children ( P=0.006) and intensive care specialist training center training ( P=0.002) were more likely to choose the " best recommendation" option than those who did not attend the training. Conclusion:The current status of pediatric septic shock treatment strategies in China are active source control intervention, antibiotic use and organs support, and increased awareness of non-invasive hemodynamic monitoring.However, there may be excessive fluid infusion and inappropriate use of plasma, glucocorticoids and intravenous immunoglobulin.Different training and continuing education may improve rational treatment strategies.