OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Objective:To evaluate the relationship between lung injury induced by cardiopulmonary bypass (CPB) and acetyltransferase p300 (p300) in rats.Methods:Eighteen SPF healthy adult male Sprague-Dawley rats, aged 12-16 weeks, weighing 350-450 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (S group), CPB group, and CPB+ left lung ischemia-reperfusion (I/R) group (CPB+ IR group). CPB group was connected to CPB pipeline for cardiopulmonary bypass. The lung I/R injury model was prepared by clamping the left lung hilum for 45 min followed by opening during CPB, 30 min later CPB was terminated, and mechanical ventilation was continuously performed for 1.5 h before ending the experiment in CPB+ IR group. Arterial blood gas analysis was performed and oxygenation index (OI) and respiratory index (RI) were calculated before CPB, at 10 min after opening the lung hilum, and immediately after the end of experiment. The bronchoalveolar lavage fluid (BALF) and left lung tissues were collected immediately after the end of experiment for determination of the concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in BALF and total protein in BALF and concentrations of IL-17 in lung tissues (by enzyme-linked immunosorbent assay), expression of p300, phosphorylated p300 (p-p300), and acetylated histone H3 (AC-H3) in lung tissues (by Western blot) and expression of p-p300 (using immunohistochemical staining) and for microscopic examination of the pathological changes of lung tissues (under the light microscope) which were scored. Results:Compared with S group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB and CPB+ IR groups ( P<0.05). Compared with CPB group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB+ IR group ( P<0.05). Conclusions:The mechanism by which CPB induces lung injury may be related to up-regulation of the expression of p300 and enhancement of activity of p300 in lung tissues and increased release of inflammatory factors in rats.

Objective To establish a method to simultaneously determinate cobalt, nickel, arsenic, molybdenum, silver, cadmium and lead in blood and urine using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). Methods The blood samples were diluted 20 times with a mixed solution of nitric acid (0.10% V/V) and Triton X-100 (0.02% V/V). The urine samples were diluted 10 times with nitric acid (1.00% V/V). Yttrium-89, rhodium-103, and lutetium-175 were used as internal standards to decrease matrix interference, and either On-Mass mode or Mass-Shift mode was used to decrease mass spectrometry interference, with detection by ICP-MS/MS. Results The linear ranges of the seven elements were 0.100-10.000 μg/L, with the correlation coefficient >0.999 9. The detection limits for the seven elements in the blood and urine were 0.003-0.021 and 0.003-0.031 μg/L, respectively, and the minimum quantification limits were 0.009-0.064 and 0.009-0.094 μg/L, respectively. The recovery rates were 96.64%-102.90% and 96.34%-104.50% for the blood and urine, respectively. The within-run relative standard deviations (RSDs) were 0.32%-2.33% and 0.25%-2.31%, and the between-run RSDs were 1.07%-3.81% and 1.30%-3.62% for blood and urine, respectively. The samples were stable at 4 ℃ for at least 14 days. Conclusion ICP-MS/MS is a simple, sensitive, and accurate method for rapid detection of seven heavy metal elements in the blood and urine of occupational hazard-exposed workers.

Objective To investigate the clinical characteristics of 16 patients with connective tissue diseases associated interstitial lung disease(CTD-ILD)complicated with lung cancer,and to improve the cognition of the disease.Methods Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer,who were admitted to our center,were retrospectively analyzed,including general conditions,clinical characteristics,auxiliary examinations,pathological classification of lung cancer,TNM type,treatment and clinical outcome.Results Among the 16 CTD-ILD patients with lung cancer,there were 12 males and 4 females.The mean age at diagnosis of CTD-ILD was(64.7±9.2)years,and the mean age at diagnosis of lung cancer was(66.6±8.7)years.Lung occupying space on imaging(62.5%)was the most common initial symptom in lung cancer patients,followed by cough and phlegm(12.5%)and chest pain(12.5%).Of patients with lung cancer,adenocarcinoma(8 cases,50.0%)was the most common pathological type,followed by small cell lung cancer(4 cases,25.0%).The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases(50.0%),with a median time of 36.0(11.3,57.0)months,followed by 7 cases(43.8%)of CTD-ILD diagnosed with lung cancer at the same time.The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case(6.3%).The most common TNM stage for lung cancer was stage Ⅳ(9 cases,56.25%).Sixteen patients were followed up from 1 to 64 months,with a median of 8.5(1.5,14.3)months.Eleven patients(68.8%)died,including 8 patients(72.7%)died of infection and 3 patients(27.3%)died of end-stage lung cancer.Conclusion For CTD-ILD patients,close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis.

Objective:To investigate the clinical characteristics and treatment strategies of patients with connective tissue disease (CTD) related lymphatic duct obstruction.Methods:The clinical data, laboratory tests results, imaging data, and treatment of CTD patients associated with lymphatic vessel obstruction were retrospectively collected from January 2008 to December 2020 at Beijing Shijitan Hospital. Lymphatic duct obstruction was confirmed by thoracic duct ultrasound or thoracic duct MRI or lymphoscintigraphy or direct lymphangiography. SLE and RA patients were matched with gender and age in a 1∶2 ratio, and SLE and RA patients without lymphatic reflux disorder admitted at the same time were randomly selected as the control group. When comparing the data between the two groups, t-test or rank sum test was used to test continuous variables, and chi-square test or Fisher′s exact probability method was used to test categorical variables. Results:Forty-four patients with CTD complicated with thoracic duct obstruction were included, with a male-to-female ratio of 7∶37, including 14 cases of rheumatoid arthritis (RA), 21 cases of systemic lupus erythematosus (SLE), 8 cases of primary Sjogren's syndrome (pSS), and 1 case of systemic sclerosis (SSc). The onset age of CTD ranged from 14 to 68 years, the mean age was (37±15) years and the median duration of CTD was 66 (range 1~480) months. The median age at the onset of lymphatic duct obstruction such as limb edema or thoracoabdominal effusion was (42±17) years, and the median duration of lymphatic duct obstruction symptoms was 12 (range 3~480) months. 59%(26/44) of patients were diagnosed with CTD followed by the diagnosis of thoracic duct obstruction, and 41%(18/44) of patients had lymphatic duct obstruction symptoms as the initial presentation of CTD. Thoracic duct-related imaging was performed in 44 patients and showed thoracic duct obstruction (64%, 28/44), thoracic duct malformation or variation (36%, 16/44), limb lymphatic reflux disorder (34%, 15/44), and small bowel lymphatic duct dilatation or intestinal protein loss (18%, 8/44), respectively. Compared with the control group, among these patients, patients with RA complicated with lymphatic involvement had a younger onset age [(34±14)years old vs. (44±13)years old, t=-2.15, P=0.037)] and longer RA course [(17±11)months vs. (7±7)months, t=3.38, P=0.002] and presented with limb swelling (12/14). While compared with the control group, SLE patients complicated with lymphatic duct obstruction presented with celiac multi-plasmatic effusion (20/21), more patients presented with multiple serous cavity effusion [95%(20/21) vs. 62%(25/42), χ2=7.63, P=0.006], but the prevalence of lupus nephritis [(60%(12/21) vs. 86%(36/42), χ2=4.87, P=0.027] and lupus encephalopathy [0%(0/21) vs. 16.7%(17/42), χ2=6.11, P=0.013] was lower. 27% (12/44) of patients improved with aggressive glucocorticoids combined with immunosuppressive therapy, 54%(24/44) of patients were performed with lymphatic duct reconstruction surgery on top of medical treatment, 5 patients were lost of follow-up, and 2 patients deceased. Conclusion:CTD patients may develop lymphatic duct obstruction during the disease course, while lymphatic duct obstruction can also be the initial presentation of CTD. Rheumatologists and surgeons should be alert to this rare situation. Young women with refractory polyserositis or lymphedema should be examined for the possibility of combined CTD. Lymphatic duct obstruction may be associated with long-term chronic inflammation in CTD. Glucocorticoids combined with immunosuppressive agents and surgery can be used to treat lymphatic duct obstruction in patients with CTD.

Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy(DCM).Methods The technology platform of Chinese medicine system pharmacology(TCMSP)and the small molecule drug target prediction(Swiss Target Prediction)platform were used to excavate the active components of Scutellariae Radix and the target of its response.DCM related disease gene targets were screened using GeneCards,Disgene,UniPort and OMIM databases,and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram.Cytoscape 3.9.1 software was a-dopted to visualize the key target network.Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM,and draw pathway maps through the KEGG database.H9c2 and AC16 cardio-myocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group,35 mmol/L D-glucose as the high glucose group,and 10 μmol/L Baicalin was used for intervention.The levels of TGF-β1,collagen Ⅰ(COL Ⅰ)and collagen Ⅲ(CO LⅢ)mRNA were detected by RT-qPCR,and the expression of Smad2/3,p-Smad2/3,COL Ⅰ and COL Ⅲprotein were detected by Western blot,TGF-β1 level in supernatant was assessed by ELISA.Results Through the a-bove platform,a total of 33 effective ingredients including Baicalin,441 core targets,and 1 884 DCM disease genes were retrieved,150 core genes for treating DCM with Scutellariae Radix were obtained.The drug-disease interacted genes such as TGF-β1,TP53,MMP-9 and IL-6 were obtained through String PPI,KEGG signaling pathways such as MAPK and PI3K/Akt were enriched.In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1,COL Ⅰ and COL Ⅲ mRNA levels,p-Smad2/3,COL Ⅰ and COL Ⅲ protein levels,and signifi-cantly increased the content of TGF-β1 in the supernatant,while Baicalin weakened its expression.Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets,among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective: To explore the epidemic characteristics of injury related deaths in children and adolescents aged 1-24 years old in China from 2010 to 2020, so as to provide a basis for the formulation of policies and measures related to the control of injuries and deaths among children and adolescents. Methods: The data were sourced from the China Death Cause Monitoring Dataset from 2010 to 2020. Annual percentage change (APC) and average annual percentage change (AAPC) of injury deaths in China in this age group during the period 2010 to 2020 were analyzed by Join point regression. Results: From 2010 to 2020, the standardized death rate of injury showed a decreasing trend (AAPC=-6.90%, t =4.58, P <0.01). The standardized death rates of male and rural injuries showed an overall downward trend, with AAPC rates of -8.37% and -7.79%( t =11.87, 10.34, P <0.01). An increasing trend was observed in the 20-24 year-old age group during 2010-2018 (APC=18.11%, t =6.50, P <0.01). The death rate from injuries was higher in males than females, and higher in rural areas compared with urban areas ( χ 2=16 483.64, 3 268.65 , P <0.01). A downward trend was observed in accidental falls and suicide, the overall standardized mortality rate of traffic accidents, accidental poisoning, fire, drowning, homicide and other injuries (AAPC=-10.22%, -6.21%, -7.50%, -7.94%, -9.01% , -10.97%, t =16.23, 7.29, 2.53, 9.32, 7.88, 4.58, P <0.05). Conclusion From 2010 to 2020, the overall injury standardized mortality rate in the 1-24 year-old age group shows a decreasing trend, but it remains at a relatively high level. Prevention efforts should be continuously strengthened, especially for urban areas, and should focus on women and those aged 20-24 years old, as well as accidental falls and suicide prevention.

Objective:To improve the understanding of patients with connective tissue diseases(CTD) associated with lung cancer.Methods:The clinical manifestations of in-patients diagnosed as CTD associated with lung cancer in our center from January 2011 to May 2022 were retrospectively analyzed,including demographic information,pathological classification of lung cancer,TNM stage,the time sequence of the diagnosis of CTD and lung cancer, treatment and clinical outcomes. The mean±standard deviation was used for the numeric variables and the number of cases (%) was used in the counting data. Fifty patients were cofirmed to have squamous cell carcinoma, adenocarcinoma and small-cell carcinoma group. Chi-square test was used to compare the differences between groups.Results:Fifty-six patients with CTD were complicated with lung cancer, of whom 27 were male, and 29 were female. The age of CTD at diagnosis was (58±15) years. The age of lung cancer at diagnosis was (69±10) years. Of patients with CTD, rheumatoid arthritis was the most common type of rheumatic disease, followed by polymyositis/dermatomyositis, systemic sclerosis and systemic lupus erythematosus. Of patients with CTD, 24 cases (42.9%) had interstitial pulmonary disease. Of patients with lung cancer, mass ( n=26, 46.4%) was the most common initial presentation, followed by cough and expectoration ( n=19, 33.8%). Non small cell lung cancer, the most common pathological type, was found in 47 cases (83.9%), followed by small cell lung cancer in 6 cases(10.7%). Stage Ⅳ was the most common stage in 36 cases(65.5%) by TNM staging. The diagnosis of CTD was earlier than that of lung cancer in 42 cases (42/56), with an median of 90 (45, 244) months, ranged between 7 months and 50 years. The diagnosis of lung cancer was earlier than that of CTD in 2 cases (2/56), with the interval of 7 and 15 months respecticely. Twelve cases (12/56) were diagnosed with CTD at the same time, and the interval between CTD and lung cancer was within 6 months. Fifty-five patients were followed up with an median of 10 (2, 24) months. In 15 patients (26.8%) with stable conditions, stageⅠ( n=10, 66.7%) cancer was the most common stage, followed by stage Ⅱ( n=2, 13.3%). Thirty-seven patients (66.1%) died of end stage lung cancer ( n=21, 56.8%) or infection ( n=16, 43.2%). The most lethal was stage Ⅳ ( n=32, 86.5%) lung cancer. There were significant differences in sex [male 9 cases (90.0%), 13 cases (38.2%) vs 4 cases (66.7%), χ2=8.88, P=0.012], smoking [8 cases (80.0%), 11 cases (32.4%) vs 4 cases (66.7%), χ2=8.24, P=0.016] and TNM stage [stage I for 0 case (0), 12 cases(35.3%) vs 0 case (0), stage Ⅱ-Ⅲ for 4 cases (40.0%), 3 cases (8.8%) vs 0 cases (0), stage Ⅳ for 6 cases (60.0%), 19 cases (55.9%) vs 6 cases (100%), χ2=13.58, P=0.009] among squamous cell carcinoma, adenocarcinoma and small-cell carcinoma groups. Conclusion:The prognosis of patients with CTD complicated with lung cancer is poor and the mortality rate is high. Therefore, close follow-up and regularly imaging are necessary for CTD patients.

Objective:To improve the understanding of the relationship between lymphedema and retroperitoneal fibrosis (RPF).Methods:Four cases with lymphedema and RPF in Beijing Shijitan Hospital Capital Medical University were reported. The diagnosis and treatment were analyzed and discussed.Results:All four patients had lymphedema onset and imaging showed suspicious RPF. One case of non-Hodgkin's lymphoma was confirmed by lymph node biopsy. The malignant lesions were excluded in the other two cases by pathology or positron emission tomography (PET)/computerized tomography (CT). They were proved to be idiopathic retroperitoneal fibrosis after treatment with glucocorticoid combined immunosuppressive agents. Another case was systemic amyloidosis mimicking retroperitoneal fibrosis.Conclusion:Lymphatic involvement in RPF is relatively rare, and the possibility of RPF should be considered when patients develop lymphedema. Even if the initial diagnosis is RPF, we should be wary of tumors or other diseases. Imaging examination should be performed, and tissue biopsy should be used if necessary, so as to facilitate early diagnosis and treatment and improve the prognosis of patients.