Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Non-pharmaceutical interventions（NPIs）against the COVID-19 restricted the spread of respiratory infectious diseases.After the lifting of NPIs for the COVID-19 pandemic，a resurgence of respiratory syncytial virus（RSV）has been observed in multiple countries and regions globally，exhibiting epidemiological and clinical characteristics distinct from previous RSV epidemic during the pre-COVID-19 era.This resurgence poses new challenges for clinical management of RSV infection.This review elucidates the changes in epidemiological and clinical features of pediatric RSV epidemic after the lifting of NPIs，potential mechanisms underlying these changes，as well as advances in RSV prevention and control，aiming to enhance the understanding of pediatric RSV infection following the lifting of NPIs，and provides reference for further optimization of strategies in the prevention，control，and clinical management of pediatric RSV infection.

Objective:To compare the epidemiological and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection in Kunming among the pre-and post-COVID-19 era, and to establish a prediction model for severe RSV infection in children during the post-COVID-19 period.Methods:This was a retrospective study. Clinical and laboratory data were collected from 959 children hospitalized with RSV infection in the Department of Pulmonary and Critical Care Medicine at Kunming Children′s Hospital during January to December 2019 and January to December 2023. Patients admitted in 2019 were defined as the pre-COVID-19 group, while those admitted in 2023 were classified as the post-COVID-19 group. Epidemiological and clinical characteristics were compared between the two groups. Subsequently, comparison of the clinical severity among the two groups was performed based on propensity score matching (PSM). Furthermore, the subjects in the post-COVID-19 group were divided into severe and non-severe groups based on clinical severity. Chi-square test and Mann-Whitney U test were used for pairwise comparison between groups, and multivariate Logistic regression was applied for the identification of independent risk factors and construction of the prediction model. The receiver operating characteristic (ROC) curve and calibration curve were employed to evaluate the predictive performance of this model. Results:Among the 959 children hospitalized with RSV infection, there were 555 males and 404 females, with an onset age of 15.4 (7.3, 28.5) months. Of which, there were 331 cases in the pre-COVID-19 group and 628 cases in the post-COVID-19 group. The peak period of RSV hospitalization in the post-COVID-19 group were from May to October 2023, and the monthly number of inpatients for each of these months were as follows: 72 cases (11.5%), 98 cases (15.6%), 128 cases (20.4%), 101 cases (16.1%), 65 cases (10.4%), and 61 cases (9.7%), respectively. After PSM for general data, 267 cases were matched in each group. The proportion of wheezing in the post-COVID-19 group was lower than that in the pre-COVID-19 group (109 cases (40.8%) vs. 161 cases (60.3%), χ2=20.26, P<0.001), while the incidences of fever, tachypnea, seizures, severe case, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein and interleukin-6 levels were all higher than those in the pre-COVID-19 group (146 cases (54.7%) vs. 119 cases (44.6%), 117 cases (43.8%) vs. 89 cases (33.3%), 37 cases (13.9%) vs. 14 cases (5.2%), 69 cases (25.8%) vs. 45 cases (16.9%), 3.6 (1.9, 6.4) vs. 2.3 (1.8, 4.6), 9.9 (7.1, 15.2) vs. 7.8 (4.5, 13.9) mg/L, 20.5 (15.7, 30.4) vs. 17.2 (11.0, 26.9) ng/L, χ2=5.46, 6.36, 11.47, 6.42, Z=4.13, 3.06, 2.96, all P<0.05). There were 252 cases and 107 cases with co-infection in the post-and pre-COVID-19 groups, respectively. The proportion of triple and quadruple infection in the post-COVID-19 group was higher than that in the pre-COVID-19 group (59 cases (23.4%) vs. 13 cases (12.1%), 30 cases (11.9%) vs. 5 cases (4.7%), χ2=5.94, 4.46, both P<0.05). Among the 252 cases with co-infection in post-COVID-19 group, the most prevalent pathogens involving in co-infections, in order, were Mycoplasma pneumoniae 56 cases (22.2%), Influenza A virus 53 cases (21.0%), Rhinovirus 48 cases (19.0%), Parainfluenza virus 35 cases (13.9%), and Adenovirus 28 cases (11.1%).The result of multivariate Logistic regression showed that age ( OR=0.70, 95% CI 0.62-0.78, P<0.001), underlying diseases ( OR=10.03, 95% CI 4.10-24.55, P<0.001), premature birth ( OR=6.78, 95% CI 3.53-13.04, P<0.001), NLR ( OR=1.85, 95% CI 1.09-3.15, P=0.023), and co-infection ( OR=1.28, 95% CI 1.18-1.38, P<0.001) were independently associated with the development of severe RSV infection in the post-COVID-19 group. The ROC curve of the prediction model integrating the above five factors indicated an area under the curve of 0.85 (95% CI 0.80-0.89, P<0.001), with an optimal cutoff of 0.21, a sensitivity of 0.83 and a specificity of 0.80. The calibration curve showed that the predicted probability in this model did not differ significantly from the actual probability ( P=0.319). Conclusions:In the post-COVID-19 era in Kunming, the peak in pediatric hospitalizations for RSV infection was from May to October, with declined incidence of wheezing and increased incidence of fever, tachypnea, seizures, severe cases, and rates of triple and quadruple co-infections. Age, underlying diseases, premature birth, NLR, and co-infection were identified as independent risk factors for severe RSV infection in the post-COVID-19 period. In this study, a risk prediction model for severe pediatric RSV infection was established, which had a good predictive performance.

Objective:To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality.Methods:This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results:The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups ( P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×10 9/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases ( OR=0.01, 95% CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) ( OR=3.31, 95% CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) ( OR=1.56, 95% CI 1.05-2.32, P=0.029) and D dimer ( OR=1.49, 95% CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95% CI 0.79-0.94), 0.89 (95% CI 0.84-0.95) and 0.87 (95% CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions:Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

Objective:To analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA).Methods:A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children′s Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up.Results:There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×10 9vs. 2.1 (1.4, 2.8)×10 9/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×10 9vs. 9.5 (4.0, 19.0)×10 9/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×10 9vs. 6 (3, 8)×10 9/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×10 9vs. 6.5 (4.6, 16.8)×10 9/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC ( OR=1.09, 95% CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group ( OR=0.00, 95% CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group ( OR=1.04, 95% CI 1.01-1.07). Conclusions:Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

Acute respiratory distress syndrome(ARDS)is a severe respiratory disease in children and the pathogenesis is not fully defined.It is mainly related to various mechanisms of lung injury such as inflammation and autophagy.In recent years, studies have found that, endoplasmic reticulum stress(ERS)can aggravate lung injury in ARDS, in which protein homeostasis imbalance can induce activation of the unfolded protein response(UPR).The UPR reconstructs homeostasis by mediating transmembrane protein-related signaling pathways, while continuous excessive ERS will promote apoptosis and autophagy.This review summarizes the progress of the signaling pathway of UPR related to lung injury and its inflammatory effect in ARDS.

Objective:To investigate the value of bronchoalveolar lavage fluid (BALF) genechip analysis for the identification of pathogens in children with refractory pneumonia.Methods:A retrospective study of 500 children clinically diagnosed with refractory pneumonia in the Department of Respiratory and Critical Care Medicine, Kunming Children′s Hospital, Kunming Medical University between January 2020 to January 2022 was made.During hospitalization, bronchoscopic examination and bronchoalveolar lavage were performed.BALF was collected and analyzed using genechip technology to detect potential pathogens.At the same time, bacterial culture tests of sputum and BALF samples from the patients were performed. χ2 test was used to compare the positive rates of pathogens detected by different detection methods. Results:Of the 500 children patients, 482 cases (96.4%) were positive of BALF genechip analysis for pathogen identification.There were 71 cases (14.7%) infected with a single pathogen, and 411 cases (85.3%) with 2 or more pathogens.The top 3 bacteria were Streptococcus pneumoniae [117 cases (8.3%)], Haemophilus influenzae [63 cases (4.5%)], and Bordetella pertussis [32 cases (2.3%)]. The patients were mostly infected with respiratory syncytial virus [269 cases (19.1%)], followed by parainfluenza virus [217 cases (15.4%)], and adenovirus [132 cases (9.3%)]. Among the 500 patients, 116 cases (23.2%) were positive of BALF genechip analysis for bacteria identification, 47 cases (9.4%) had a positive BALF culture, 43 cases (8.6%) had a positive sputum culture.The bacterial detection rate of BALF genechip analysis was statistically significantly higher than that of BALF culture and sputum culture tests ( χ2=34.90, 39.85; all P<0.001). Conclusions:Most patients with refractory pneumonia have mixed infections.The genechip technology can rapidly and efficiently identify the pathogens, thus providing clinical guidance for anti-infection treatment.

The main target organ of 2019 novel coronavirus(2019-nCoV)was the lung and acute respiratory distress syndrome, a life-threatening condition, could happen in severe cases.The main receptor of 2019-nCoV is angiotensin-converting enzyme 2(ACE2). Other receptors reported included CD147, tyrosine protein kinase receptor UFO, Neuropilin-1, Kidney injury molecule-1, et al.When 2019-nCoV is bound with ACE2, the expression of ACE2 would be down-regulated, which causes an increased angiotensin level and consequent lung injury through downstream signals.In addition, 2019-nCoV infection can induce inflammatory cytokine storm, cause coagulation dysfunction, trigger lung epithelial cell apoptosis, et al, which collaboratively contribute to lung injury.The clinical symptoms of 2019-nCoV infection in children are mild, which is thought due to the advantages of children in innate immune response and the low level of adaptive immune response.The fundamental means to prevent and treat lung injury was inhibiting the proliferation and replication of the 2019-nCoV virus, but so far, there are no specific antiviral drugs found yet.Approaches like recombinant human soluble ACE2 protein, neutralizing antibody against protein S, inhibiting angiotensinⅡ, contradicting inflammation factors, or stem cell infusion may be helpful to prevent and alleviate lung injury.

Purpose: This study aimed to describe the clinical response to five-step systematic therapy (FSST) in the management of plugged ducts and mastitis. FSST was a comprehensive milk stasis dredging treatment, which contained five steps to make the milk out of the plugged duct. Methods: This retrospective study included 922 breastfeeding women, 714 with plugged ducts, and 208 with mastitis who received FSST from June to September 2017. The breast pain score, swelling degree, and range of breast induration were recorded pre-FSST and post-FSST. Results: After a single FSST, pain score and swelling degree were significantly improved (both p < .001) in all cases. After FSST, the mean breast pain relief score was 1.69 ± 0.70, whereas the mean swelling fade away degree was 1.61 ± 0.62. In the subgroup analysis, pain score and swelling degree were significantly improved (both p < .001) in the plugged ducts group and the mastitis group. The score of pain relief in the plugged ducts group was less than that in the mastitis group (1.63 ± 0.68 vs. 1.91 ± 0.70, t = 5.30; p < .001), whereas improvement of swelling fade away was greater in the plugged ducts group than the mastitis group (1.65 ± 0.64 vs. 1.48 ± 0.56, t = 3.49; p = .001). The composition ratio of changes in induration range between the two groups was statistically different (Pearson χ2 = 137.87, p < .001), of which more obvious improvement in the plugged ducts group than the mastitis group (χ2 = 25.65, p < .001). Conclusion FSST can relieve pain, reduce breast swelling and range of induration, and for plugged ducts or mastitis varied degree differently.

Purpose: This study aimed to describe the clinical response to five-step systematic therapy (FSST) in the management of plugged ducts and mastitis. FSST was a comprehensive milk stasis dredging treatment, which contained five steps to make the milk out of the plugged duct. Methods: This retrospective study included 922 breastfeeding women, 714 with plugged ducts, and 208 with mastitis who received FSST from June to September 2017. The breast pain score, swelling degree, and range of breast induration were recorded pre-FSST and post-FSST. Results: After a single FSST, pain score and swelling degree were significantly improved (both p < .001) in all cases. After FSST, the mean breast pain relief score was 1.69 ± 0.70, whereas the mean swelling fade away degree was 1.61 ± 0.62. In the subgroup analysis, pain score and swelling degree were significantly improved (both p < .001) in the plugged ducts group and the mastitis group. The score of pain relief in the plugged ducts group was less than that in the mastitis group (1.63 ± 0.68 vs. 1.91 ± 0.70, t = 5.30; p < .001), whereas improvement of swelling fade away was greater in the plugged ducts group than the mastitis group (1.65 ± 0.64 vs. 1.48 ± 0.56, t = 3.49; p = .001). The composition ratio of changes in induration range between the two groups was statistically different (Pearson χ2 = 137.87, p < .001), of which more obvious improvement in the plugged ducts group than the mastitis group (χ2 = 25.65, p < .001). Conclusion FSST can relieve pain, reduce breast swelling and range of induration, and for plugged ducts or mastitis varied degree differently.