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.

OBJECTIVE To evaluate the comprehensive quality of Houttuynia cordata from different producing areas. METHODS Using total flavonoids， water-soluble extract， moisture， total ash and acid-insoluble ash as indicators， the entropy weight method was used to objectively weigh each indicator， and the relative correlation degree （r）i calculated by grey correlation method was used as a measure to comprehensively evaluate the quality of H. cordata. RESULTS The weights of total flavonoids， total ash， moisture， acid-insoluble ash， and water-soluble extract were 0.295 5， 0.227 3， 0.188 7， 0.145 1， and 0.143 4， respectively. The weights of total flavonoids and total ash were relatively large. The ri of 30 batches of H. cordata ranged from 0.233 2 to 0.673 9； the average ri of samples from Quanzhou County and Ziyuan County of Guangxi Zhuang Autonomous Region were the highest， which were 0.638 3 and 0.598 7， respectively， followed by samples from Lingchuan County of Guangxi Zhuang Autonomous Region （0.556 1） and Jianshui County of Yunnan Province （0.452 8）. The quality of medicinal materials produced in the above producing areas was generally good and stable. CONCLUSIONS Entropy weight method combined with the grey correlation method can be used to comprehensively evaluate the quality of H. cordata. The overall quality of H. cordata produced in Quanzhou County of Guangxi Zhuang Autonomous Region is the best.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models.MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo.Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.

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 establish the metho d for the concentration det ermination of foretinib derivative LWK- 126 in liver microsomes，and to study its metabolism stability in liver microsomes of rats ，Beagle dogs and human. METHODS ：In the in vitro incubation system of liver microsomes ，LWK-126 was dissolved in liver microsomal incubation systems of rats ，Beagle dog and human initiated by reduced nicotinamide adenine dinucleotide phosphate solution. After incubation in water at 37 ℃ for 0，5，10，20， 30 and 60 min，the reaction was terminated with acetonitrile containing internal standard （1 μg/mL tolbutamide）. UPLC-MS/MS method was applied to determine the concentration of LWK- 126 in the incubation systems. The determination was performed on Waters BEH C 18 column with mobile phase consisted of water （containing 0.1％ formic acid ）-acetonitrile（containing 0.1％ formic acid）by gradient elution at the flow rate of 0.4 mL/min. The column temperature was 30 ℃，and the sample size was 2 μL. The mass spectral analysis was performed in a positive electrospray ionization mode ，and the full MS experiment was run with the selective reaction monitoring mode with a scanning range of m/z 50→1 200. Taking the concentration of LWK- 126 at 0 min as reference，the remaining percentage and the enzyme kinetic parameters were calculated. RESULTS ：The linear range of LWK- 126 was 0.05-15 μg/mL（R 2＝0.999 2）；the lower limit of quantification was 0.05 μg/mL，and the lowest detection limit was 0.01 μg/mL. The precision，accuracy，extraction recovery and matrix effect all met the analysis requirements of biological samples. The remaining percentage of LWK- 126 in liver microsomes of human ，rats and Beagle dogs for 60 min were （33.17±4.52）％，（3.14± 6.73）％，（1.38±5.85）％；t1/2 of them were 33.15，11.76，5.62 min；the clearance rates were 38.45，118.81，245.76 μL（/ min·mg）， respectively. CONCLUSIONS ：The method for the content ； determination of LWK- 126 in liver microsomes is established successfully. The order of metabolic stability of LWK- 126 in 〔2016〕4015） liver microsomes of different species is human ＞rats＞Beagle dogs.

OBJECTIVE：To establish the method for determining protein binding rate of dipeptidyl peptidase- 4 inhibitor LGT- 6 in different species of plasma ，and to compare their difference. METHODS ：By equilibrium dialysis ，LGT-6（3，30，300，3 000 nmol/L）was equilibrated in rat ，monkey and human plasma （i. e. internal dialysis solution ）for 48 h，using phosphate buffer as the external dialysis solution. The concentration of LGT- 6 in internal and external dialysis solution was determined by UPLC-MS/MS using tolbutamide as internal standard ，and the plasma protein binding rate was calculated. The determination was performed on ACQUITY UPLC HSS T 3 column with water （containing 0.01％ formic acid ）-acetonitrile（containing 0.01％ formic acid ）as mobile phase at the flow rate of 0.6 mL/min. The column temperature was 40 ℃，and the sample size was 2 μL. The ion source was electrospray ion source ，and the multiple ion monitoring mode was used to carry out positive ionization scanning. The ion pairs for quantitative analysis were m/z 487.0→434.3（LGT-6），m/z 271.1→172.0（internal standard ），respectively. RESULTS ：At the concentrations of 3，30，300，and 3 000 nmol/L，the protein binding rates of LGT- 6 in rat plasma were （96.25±0.97）％，（84.16± 1.24）％，（78.25±0.61）％，（66.63±0.95）％；the protein protein binding rates in monkey plasma were （98.54±0.58）％，（87.27± 1.01）％，（79.35±0.86）％，（66.69±0.54）％；the protein binding rates in human plasma were （99.40±1.03）％，（84.48± 1.15）％，（77.62±0.77）％，（66.93±0.48）％. At the same concentration ，the protein binding rates of LGT- 6 in rat ，monkey and human plasma had no significant difference （P＞0.05）. In the same species of plasma ，there were significant differences in the plasma protein binding rates of different concentration of LGT-6 among those groups （P＜0.05），and it decreased with 才〔2016〕4015） the increase of drug concentration. CONCLUSIONS ： The method for the determination of plasma protein binding rate of LGT-6 is successfully established. The data revealed that the protein binding rate of LGT- 6 is concentration-dependent ， there was no obvious spec ies difference on protein binding rates of LGT- 6 in rat ，monkey and human plasma under the same concentration.

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 study the predictive value of magnetic resonance imaging (MRI),positron emission computed tomography (PET)and PET/MRI coregistration in intractable epilepsy of children.Methods A retrospec-tively analysis was performed based on the surgery data at the Department of Children Epilepsy Center of Peking Univer-sity First Hospital from September 2015 to March 2016.The clinical data,surgery and follow－up study data,interictal and ictal electroencephalogram,MRI,PET and PET/MRI coregistration data were collected.By comparison with the epi-leptogenic zone designed by pre－surgical workup,the accuracy of MRI,PET and PET/MRI coregistration in detecting lesion was assessed.In the patients who had no seizure during≥1 year follow－up,their sensitivity,specificity,positive predictive value,negative predictive value of MRI,PET and PET/MRI coregistration were calculated.Results (1)A total of 62 patients underwent surgery,30 boys and 32 girls. The average age on epilepsy onset was 2. 50 years (2 days－11.70 years),and average age on surgery was 5.10 years old(0.75－15.60 years old).(2)Surgical treat-ment of 62 cases included the resection of the focal or lobar (32 cases,51.6%),and the multilobar (16 cases, 25. 8%).Hemispherotomy was done in 14 cases (22.6%).During ≥1 year follow－up,seizure outcome was Engel class Ⅰ in 57 cases (91.9%)out of the 62 patients,Engel classⅡto Engel classⅣin 1 case,3 cases,and 1 case, respectively.(3)Referred to epileptogenic zone designed by presurgical workup,MRI represented 64.5%(40/62 ca-ses)results with accordance,PET and PET/MRI coregistration was 72.5%(45/62 cases)and 85.5%(53/62 cases), respectively,and the difference was significant(χ2＝7.25,P＝0.03).(4)Based on the patients of Engel class Ⅰ, their sensitivity and specificity were 66.7%,60.0% in MRI,75.4%,60.0% in PET %,and 85.9%,80.0% in PET/MRI coregistration,respectively.(5)There were 11 ＂non－lesion＂ cases of all focal cortical dysplasia in patholo-gy,and subtle structural abnormalities were de tected in 9 cases by reviewing MRI.Conclusions PET/MRI coregistra-tion can improve lesion detection of intractable epilepsy in children.

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.