ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

Bronchial asthma （abbreviated as asthma） is one of the common chronic airway inflammatory diseases in the respiratory system， which is difficult to cure. Airway mucus hypersecretion （AMH） is an important factor leading to acute asthma attacks. Traditional Chinese medicine （TCM） possesses therapeutic advantages characterized by multiple pathways， multiple targets， and multiple links， and its mechanism of action in intervening in AMH has gradually drawn attention. TCM can effectively alleviate the symptoms of patients by intervening in asthma through methods such as eliminating phlegm and eliminating fluid retention. This review finds that the pathogenesis of asthma-associated AMH is correlated with decreased mucociliary clearance function and enhanced mucus secretion function； single TCM （such as Platycodon grandiflorum）， effective components of TCM （such as pinellia polysaccharides）， and compound prescriptions （mainly heat-clearing and phlegm-resolving prescriptions， etc.） can improve asthma-associated AMH by regulating the PI3K/Akt and JAK/STAT signaling pathways， inhibiting airway inflammatory responses， oxidative stress， and recovering the water-salt ratio of the mucus layer itself.

Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.

ObjectiveTo explore the dynamic evolution law of syndrome elements in different stages of chronic obstructive pulmonary disease （COPD）. MethodThe clinical questionnaire of COPD was formulated，and the clinical data of 303 patients with COPD in the acute exacerbation stage，risk window stage，and stable stage in the First Affiliated Hospital of Henan University of Chinese Medicine from June 2019 to December 2020 were dynamically collected. The Clinical Investigation and Research Database on the Evolution of Syndrome Elements of COPD was established，with syndrome elements as nodes and complex relationships between syndrome elements and syndrome elements in different stages as edges. With the help of Pycharm （JetBrains PyCharm Edition 2018.2.3） development tool，python programming was used to preprocess the data and perform complex network modeling. The complex network of different stages of COPD was constructed to analyze the evolution law of syndrome factors in different stages. ResultA total of 303 patients with COPD were included and finished. Eleven syndrome elements were extracted in the acute exacerbation stage，10 syndrome elements were extracted in the risk window stage，and 8 syndrome elements were extracted in the stable stage. According to the complex network centrality and edge weight of disease syndrome elements，it was found that the core nodes of disease syndrome elements in the network from the acute exacerbation stage to the stable stage were phlegm，heat，and Qi deficiency，Qi deficiency，phlegm，and dampness，and Qi deficiency，Yin deficiency，and blood stasis. ConclusionFrom the acute exacerbation stage to the stable stage，the disease syndrome elements change from excess to deficiency，and phlegm heat gradually changes into phlegm dampness，and gradually weakens or disappears. Qi deficiency runs through the whole process of the disease and turns into both qi and yin deficiency with blood stasis.

Objective To investigate the value of neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width-to-lymphocyte ratio (RLR), and lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of early small hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods A retrospective analysis was performed for 132 patients newly diagnosed with early HCC who underwent RFA in Tianjin Second People's Hospital from September 2011 to December 2020. Preoperative data were collected and the patients were followed up to observe recurrence and overall survival (OS). The X-tile tool was used to determine the optimal cut-off values of NLR, RLR, and LMR based on 5-year survival rate and recurrence-free survival (RFS) rate, and then the patients were divided into N-R-L 0 group with 92 patients, N-R-L 1 group with 29 patients, and N-R-L 2 group with 11 patients. The chi-square test was used for comparison of categorical data between the three groups. The Kaplan-Meier method was used to plot the survival curve, and the log-rank test was used to compare RFS and OS rates between groups. The factors with statistical significance in the log-rank test were included in the multivariate Cox regression analysis to determine the risk factors for RFS and OS rates. Results There were significant differences in Child-Pugh class and albumin between the N-R-L 0, N-R-L 1, and N-R-L 2 groups ( χ 2 2=10.992 and 5.699, both P < 0.05). The 1-, 3-, and 5-year OS rates of the three groups were 100%/96.3%/90.7%, 96.6%/60.4%/41.3%, and 81.8%/46.8%/15.6%, respectively ( χ 2 =38.46, P < 0.000 1), and the 1-, 3-, and 5-year RFS rates of the three groups were 76.9%/52.5%/33.3%, 42.9%/13.1%/0, and 11.1%/0/0, respectively ( χ 2 =35.345, P < 0.000 1). The multivariate Cox regression analysis showed that tumor diameter ≥ 2 cm (hazard ratio[ HR ]=2.10, 95% confidence interval[ CI ]: 1.28-3.43, P =0.003; HR =3.67, 95% CI : 1.58-8.52, P =0.002), N-R-L score of 1 point ( HR =3.14, 95% CI : 1.81-5.46, P < 0.000 1; HR =8.27, 95% CI : 3.15-21.71, P < 0.000 1), and N-R-L score of 2 points ( HR =2.61, 95% CI : 1.06-6.42, P =0.037; HR =14.59, 95% CI : 3.96-53.78, P < 0.000 1) were independent predictive factors for RFS and OS. Conclusion N-R-L, a systemic inflammatory response marker composed of NLR, RLR, and LMR, is an independent risk factor for recurrence and survival of early small HCC after RFA, and it can be used as a useful noninvasive biomarker in combination with tumor features to predict the recurrence and survival of early HCC after RFA.

Objective To investigate the value of the hepatocellular carcinoma (HCC) risk model REAL-B score in predicting the risk of HCC in chronic hepatitis B (CHB) patients receiving antiviral therapy in comparison with mPAGE-B, aMAP and PAGE-B scores. Methods A retrospective analysis was performed for the clinical data of 1160 CHB patients who received entecavir or tenofovir treatment for more than 1 year from January 2013 to December 2015 in Tianjin Second Peolple's Hospital, and the events of HCC were recorded. The area under the ROC curve (AUC) was used to evaluate the value of REAL-B, mPAGE-B, aMAP, and PAGE-B scores in predicting HCC. The Kaplan-Meier method was used to evaluate the cumulative incidence rate of HCC at different time points, and the log-rank test was used to compare the incidence rate of HCC between the groups with different scores. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results Among the 1160 CHB patients, 108 (9.8%) progressed to HCC within a median follow-up time of 5.3 (5.0-6.3) years. REAL-B score had an AUC of 0.848 (95% confidence interval [ CI ]: 0.816-0.880) in predicting the onset of HCC within 5 years, followed by aMAP score (AUC=0.823, 95% CI : 0.786-0.860), mPAGE-B score (AUC=0.822, 95% CI : 0.788-0.857), and PAGE-B scores (AUC=0.780, 95% CI : 0.736-0.824). The 5-year cumulative incidence rate of HCC was 0.8% in the low-risk group (with a REAL-B score of 0-3 points), which was significantly lower than the incidence rate of 11.8% in the medium-risk group (with a REAL-B score of 4-7 points) and 35.6% with the high-risk group (with a REAL-B score of 8-13 points) ( P < 0.05). In the low-risk group, REAL-B score had a negative predictive value of 100% and 99.67%, respectively, in predicting HCC within 3 and 5 years. Conclusion REAL-B score accurately predicts the risk of HCC in CHB patients receiving antiviral therapy, with a better predictive value than the other risk models within 3 years of antiviral therapy.

Objective:To explore the clinical features of decompensated liver cirrhosis patients with acute kidney injury (AKI) progressing to chronic kidney disease (CKD) and its impact on prognosis.Methods:From January 2015 to July 2019, at Tianjin Second People′s Hospital, the general data and laboratory test results of 346 hospitalized patients with decompensated liver cirrhosis were retrospectively analyzed. The patients were followed up for 12 months. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors of AKI and CKD. Kaplan-Meier method was used for survival analysis. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:A total of 128 patients with decompensated liver cirrhosis developed AKI, and 25 of them developed into CKD. Univariate analysis showed that age, hypertension, complications of liver cirrhosis infection, ascites and hepatic encephalopathy, acute-on-chronic liver failure, Child-Turcotte-Pugh score of liver function, baseline serum creatinine, post-admission serum creatinine, serum sodium, white blood cell count, total cholesterol, triglyceride, high-density lipoprotein, total bilirubin, albumin, international normalized ratio (INR) and prothrombin time activity were risk factors of AKI in patients with decompensated liver cirrhosis ( t=3.822, χ2=12.534, 26.761, 5.035, 3.894 and 26.101, U=7 004.500, 9 132.500, 5 925.000, 10 144.000, 10 717.500, 10 827.000, 10 912.000, 5 741.500, 10 017.000, 10 187.500, 11 680.500 and 11 321.500, all P<0.05). The risk factors of AKI progressing to CKD in decompensated liver cirrhosis included the etiology of liver cirrhosis, hypertension, baseline serum creatinine, serum creatinine at the time of diagnosis of AKI, total cholesterol, INR, AKI etiology and AKI classification ( χ2=13.153 and 9.144, U=353.000, 337.000, 576.500 and 481.000, χ2=9.501 and 17.801, all P<0.05). The results of multivariate logistic regression analysis showed that the independent risk factors of AKI progressing to CKD in decompensated liver cirrhosis included baseline serum creatinine (odds ratio ( OR)=1.066, 95% confidence interval ( CI) 1.020 to 1.114, P=0.005) and AKI classification ( OR=6.086, 95% CI 1.828 to 20.260, P=0.003). The Kaplan-Meier survival curve showing that after following up for 12 months, the survival rate of patients with decompensated liver cirrhosis patients who progressed to CKD from AKI was lower than that of patients who did not developed into CKD (52.0%, 13/25 vs. 86.4%, 51/59), and the difference was statistically significant ( χ2=11.482, P=0.001). Conclusion:The transition from AKI into CKD is common in patients with liver cirrhosis, which affects the clinical prognosis and reduces the survival rate.

Objective:In the context of COVID-19 pandemic, the epidemic severities, non-pharmaceutical intervention intensities, individual behavior patterns and vaccination coverage vary with countries in the world. China has experienced a long period without indigenous cases, unfortunately, multi local outbreaks caused by imported cases and other factors have been reported, posing great challenges to COVID-19 prevention and control in China. Thus it is necessary to explore the mechanisms of the re-emerged COVID-19 epidemics and their differences.Methods:Based on susceptible exposed infectious recovered (SEIR) epidemic dynamics model, we developed a set of novel evolution equations which can describe the dynamic processes of integrated influence of interventions, vaccination coverage and individual behavior changes on the re-emergency of COVID-19 epidemic. We developed methods to calculate the optimal intervention intensity and vaccination rate at which the size of susceptible population can be reduced to less than threshold for the re-emergency of COVID-19 epidemic.Results:If strong interventions or super interventions are lifted too early, even a small cause can lead to the re-emergence of COVID-19 epidemic at different degrees. Moreover, the stronger the early control measures lifted are, the more severe the epidemic is. The individual behavior changes for the susceptibility to the epidemic and the enhancement or lifting of prevention and control measures are key factors to influence the incidence the multi outbreaks of COVID-19. The optimist early intervention measures and timely optimization of vaccination can not only prevent the re-emergency of COVID-19 epidemic, but also effectively lower the peak of the first wave of the epidemic and delay its arrival.Conclusion:The study revealed that factors for the re-emergence of COVID-19 epidemics included the intensity and lifting of interventions, the change of individual behavior to the response of the epidemic, external incentives and the transmissibility of COVID-19.

Objective:To evaluate the effect and safety of adjustable closed loop(ACL) in the treatment of short bowel syndrome (SBS).Methods:From January 2017 to December 2017, the clinical data of 2 cases with ostomy in continuity after surgery in Children's Hospital Affiliated to Xi'an Jiaotong University were analyzed.The age was 1 and 3 months, both were females, and preservation of intestinal tube length were 65 cm and 60 cm respectively.They were all diagnosed SBS with a lot of stool like water.Self-made ACL was installed to maintain SBS.The blood circulation of stoma, weight, BMI, defecating, abdomen, nutrition status changes, nursing convenience, intestinal infection susceptibility were observed.Results:There was no necrosis in stoma, and the overall condition was improved, and no significant increase in abdominal distension.ACL used in babies with ostomy in continuity could improve the anus stool, weight, nursing convenience.Conclusion:ACL installed in baby with SBS could contribute to intestinal management, and is easy to install.

Objective To investigate the predictive value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for invasiveness of hilar cholangiocarcinoma (HC).Methods The retrospective casecontrol study was conducted.The clinicopathological data of 65 HC patients who were admitted to the Sun Yat-sen Memorial Hospital from January 2012 to November 2017 were collected.Patients received DW MRI before treatment,and 2 senior imaging doctors analyzed imaging data and measured the apparent diffusion coefficient (ADC) for the primary lesions of HC.Observation indicators:(1) MRI situations of HC;(2) relationship between ADC and clinicopathological factors;(3) receiver operator characteristic (ROC) curve analysis;(4) treatment and follow-up situations.According to patients' conditions,treatment plans were done within 2 weeks after MRI and patients underwent radical resection of HC.Follow-up using telephone interview was performed to detect tumor recurrence up to December 2017.Measurement data with normal distribution were represented as (x)±s,and comparisons between group and among group were respectively analyzed using the t test and one-way ANOVA.Spearman's rank correlation was performed to analyze the relationship between ADC and clinicopathological factors.ROC curves assessed the diagnostic efficiency of ADC.Results (1) MRI situations of HC:MRI and magnetic resonanced cholangio-pancreatography (MRCP) in 65 patients showed varying degrees of soft rattan-like dilations of intrahepatic bile ducts and truncation signs of bile tracts in hepatic port.Of 65 patients,tumors in 23,7 and 35 patients were respectively pedunculated type,polypoid type and infiltrating type.The pedunculated-type lesions of 23 patients presented as low signal on T1WI and slightly high signal on T2WI;after enhanced scans of MRI,pedunculated-type lesions of 7 patients demonstrated moderate homogenous enhancement in 3 patients,ring-like enhancement with internal liquefaction necrosis in 10 patients and moderate heterogeneous enhancement in 10 patients,respectively.The polypoid-type lesions presented as low signal on T1WI and high signal on T2WI,and moderate homogenous enhancement by enhanced scans of MRI.There were varying degrees of bile duct wall thickness and irregular nodules in the infiltrating-type lesions of 35 patients,showing moderate enhancement by enhanced scans of MRI.All the lesions of 65 patients using DW MRI demonstrated restricted diffusion,showing a clear boundary between lesions and normal surrounding bile ducts or liver tissues;heterogeneous enhancement lesions by MRI scans presented as heterogeneously high signal on DWI and heterogeneously low signal on ADC map,and necrotic area of lesions showed low signal on DWI;homogenous enhancement by MRI scans presented as homogenously high signal on DWI and homogenously low signal on ADC map.(2) Relationship between ADC and clinicopathological factors:ADC was respectively (1.382±0.165)× 10-3 mm2/s,(1.343±0.138)× 10-3 mm2/s,(1.291-±0.226)×10-3 mm2/s,(1.111±0.243)×10-3 mm2/s in stage Ⅰ,Ⅱ,Ⅲ and Ⅳ (TNM staging) and (1.441± 0.355) × 10-3 mm2/s,(1.226 ± 0.177) × 10-3 mm2/s,(1.061 ± 0.228) × 10-3 mm2/s in highdifferentiated,moderate-differentiated and low-differentiated tumors (pathological grading) and (1.403±0.176)× 10-3 mm2/s,(1.121±0.238)× 10-3 mm2/s in Ki-67 score ≤ 10％ and ＞ 10％ and (1.115±0.241)× 10-3 mm2/s,(1.347±0.174)× 10-3 mm2/s in HC patients with and without lymph node metastasis,with statistically significant differences in the above indicators (F =4.158,9.866,t =11.607,13.464,P＜0.05).Results of Spearman's rank correlation analysis showed that ADC had a negative correlation with TNM staging,pathological grading and Ki-67 score (r=-0.532,-0.522,-0.409,P＜0.05).(3) ROC curve analysis:using 1.225×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of stage Ⅰ-Ⅱ HC and stage Ⅲ-Ⅳ HC were 70.5％ and 81.0％,and area under ROC curve was 0.705 (95％CI:0.62-0.84,P＜0.05).Using 1.100×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lowdifferentiated HC and moderate-and high-differentiated HC were 88.2％ and 64.3％,and area under ROC curve was 0.814 [95％ confidence interval (CI):0.69-0.90,P＜0.05].Using 1.243×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of Ki-67 score ≤ 10％ and ＞ 10％ were 66.7％ and 75.0％,and area under ROC curve was 0.783 (95％CI:0.62-0.90,P＜0.05).Using 1.222×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lymph node metastasis were 91.3％ and 71.4％,and area under ROC curve was 0.873 (95％CI:0.76-0.94,P＜0.05).(4) Treatment and followup situations:65 patients underwent successful radical resection of HC.Thirty-three patients were followed up for 1-24 months.Of 33 patients,5 had tumor recurrence within 6 months postoperatively,including 4 with ADC ＜ 1.100× 10-3 mm2/s,13 had tumor recurrence after 6 months postoperatively,and 15 didn't have tumor recurrence or metastasis,including 1 with ADC ＜ 1.100× 10-3 mm2/s.Conclusions There are different ADC in differentTNM staging,pathological grading,Ki-67 score and with or without lymph node metastasis of HC.ADC of DWMRI can be used as a preoperative imaging predictor for invasiveness of HC.