The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

OBJECTIVE To establish a method to detect the blood concentration of ibrutinib and apply it to the clinic. METHODS Using zanubrutinib as internal standard， the concentration of ibrutinib was detected by high performance liquid chromatography （HPLC） after plasma samples were processed by solid-phase extraction. The separation was performed on an Agilent 5 TC-C18（2） column with acetonitrile-0.5% potassium dihydrogen phosphate solution （43∶57， V/V） as the mobile phase at a flow rate of 1 mL/min， a detection wavelength of 260 nm， a column temperature of 40 ℃ ， a sample size of 20 μL， and a run time of 25 min. The concentration of ibrutinib was measured in the plasma of 9 patients with non-Hodgkin’s lymphoma 2 h after drug administration on the 30th day by the above method. RESULTS The linear range of the assayed mass concentration of ibrutinib was 10-500 ng/mL （R 2＝0.998 9）， the lower limit of quantification was 10 ng/mL， and the RSDs of the intra-batch and inter-batch precision tests were not higher than 12.77%. The recoveries of the extraction were 74.80% and 97.70%， with both RSDs＜2.90%， and the RSDs of the stability tests were not higher than 7.10%. The peak plasma concentrations of 9 patients were 15.341-279.628 ng/mL. CONCLUSIONS The established HPLC method is simple and rapid， and can be used for the determination of ibrutinib concentration in plasma samples.

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Objective:To construct a droplet digital PCR (ddPCR) for quantification of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine.Methods:The genome of SARS-CoV-2 BA.1 strain was used as the target gene. A set of primer and probe was designed based on the conserved sequence of spike protein, and the ddPCR for quantification of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine was established. The linearity, accuracy, specificity, repeatability and durability of the method were verified.Results:The optimal annealing temperature for ddPCR was 63℃. When the number of virus particles was in the range of 5×10 5-2×10 7 VP/ml, the linearity and the recovery rate of the method were good; the specificity of the probe and primer was good; the coefficient of variation (CV) values of the repeatability and the intermediate precision were within 10%; the CV value of the durability was within 15%. When comparing ddPCR with qPCR, the CV values were all within 10%. Conclusions:The established ddPCR had high sensitivity, good stability and strong specificity, suggesting that it could be used for the quantitative detection of virus particles in recombinant adenovirus-vectored SARS-CoV-2 vaccine.

Objective To investigate the effect of Ⅲ-type phosphatidylinositide 3 kinase (PI3K) pathway adjusting autophagy on brain damage mechanism after cardiopulmonary resuscitation (CPR) and hypothermia treatment.Methods The asphyxia induce cardiac arrest-CPR model was reproduced on healthy male Sprague-Dawley (SD) rats.Sixty rats after restoration of spontaneous circulation (ROSC) were randomly divided into normothermia group,therapeutic hypothermia group and PI3K inhibitor 3-methyl adenine (3-MA) pretreatment group,differentiated by 24 hours and 48 hours after ROSC.Each group had 10 rats at each time point.The anal temperature in the normothermia group was maintained at (37.0 ± 0.2) ℃,and the rats in the hypothermia group were given cooling treatment immediately after ROSC,and the target rectal temperature was 32-34 ℃.In the 3-MA pretreatment group,10 mmol/L 3-MA 5 μL was injected into the ventricle 20 minutes before asphyxia,and other groups were given the same amount of normal saline.Ten rats without CPR were included in Sham group only received anesthesia and catheterization.The rats were sacrificed at 24 hours and 48 hours after ROSC respectively,and the brain tissues were harvested,the brain water content (BWC) was measured by dry-wet weight method.Western Blot was used to determine the autophagy related proteins Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3),apoptosis related proteins Bcl-2 and caspase-3,and the Ⅲ-type PI3K pathway proteins Vps34 and Atgl4.Ultrastructural changes in brain tissue were observed with transmission electron microscope.Neurological deficit scores (NDS) was obtained in each group at 48 hours after ROSC.Results Compared with Sham group,the cortex at 24 hours after ROSC in normothermic group showed obvious edema,apeptosis and autophagy began to appear under transmission electron microscope,and the expressions of autophagy,apoptosis and Ⅲ-type PI3K-related proteins in brain tissue were significantly increased in a time-dependent manner,and the neurological function at 48 hours after ROSC was significantly damaged.After hypothermia intervention,brain edema of rats was significantly reduced,no obvious apoptosis was found,but autophagy was increased,the expressions of autophagy-related proteins Vps34,Atg14 and Ⅲ-type PI3K-related proteins Beclin-1 and LC3 at 48 hours after ROSC were further higher than those of normothermic group (Vps34/GAPDH:0.25±0.03 vs.0.15±0.04,Atg14/GAPDH:0.12±0.03 vs.0.05±0.04,Beclin-1/GAPDH:0.060±0.002 vs.0.018±0.002,LC3-Ⅱ/GAPDH:0.160±0.010 vs.0.050± 0.010,all P ＜ 0.05),the expressions of apoptosis related proteins Bcl-2 and caspase-3 were significantly lowered (Bcl-2/GAPDH:0.05±0.03 vs.0.20±0.04,caspase-3/GAPDH:0.050±0.002 vs.0.140±0.015,both P ＜ 0.05),neurological function was significantly improved (NDS:157±85 vs.343± 198,P ＜ 0.05).Pretreatment with 3-MA inhibited the protective effect of hypothermia on brain tissues.The expressions of Vps34,Atg14,Beclin-1 and LC3 in brain tissues at 48 hours after ROSC in 3-MA pretreatment group was significantly lower than those in the hypothennia group (Vps34/GAPDH:0.18±0.03 vs.0.25±0.03,Atg44/GAPDH:0.07±0.04 vs.0.12±0.03,Beclin-1/GAPDH:0.015±0.003 vs.0.060±0.002,LC3-Ⅱ/GAPDH:0.045±0.030 vs.0.160±0.010,all P ＜ 0.05),the expressions of Bcl-2 and caspase-3 were significantly increased (Bcl-2/GAPDH:0.15±0.04 vs.0.05±0.03,caspase-3/GAPDH:0.120±0.015 vs.0.050±0.002,both P ＜ 0.05),and NDS score was significantly increased (341±208 vs.157±85,P ＜ 0.05).Conclusion Hypothermia treatment reduced brain edema and ameliorated brain function after CPR,which might be related to increase autophagy and inhibit apoptosis adjustment by activating Ⅲ-type PI3K pathway.

Objective To investigate the clinical features, diagnosis, treatment and outcome of patients with Takayasu arteritis associated pulmonary hypertension (TA-PH). Methods Patients diagnosed as TA-PH in Shanghai Pulmonary hospital from 2008 to 2017 were retrospectively reviewed and followed up. Baseline characteristics including hemodynamics were collected. Data were summarized as mean ± standard deviation or frequency (％). Survival analyses were performed using the Kaplan-Meier method. Results Thirteen TA-PH patients (10 female, aged 39±11 years old) were included. The duration from symptoms onset to diagnosis was 2 months to 50 years, and ten patients were diagnosed TA and PH at the same time. Shortness of breath was the most common clinical manifestation (12 cases), followed by chest pain and tightness (8 cases) and palpitation (6 cases). All patients had a moderated WHO functional class and 8 patients were in active phase. Vessel wall thickening, lumen narrowing, occlusion and/or dilation were found in CT pulmonary angiography and angiography. Mean pulmonary arterial pressure (48.0±14.0) mmHg and pulmonary vascular resistant (7.59±4.21) Wood U were increased. All patients received PH-specific therapies, and patients at active status took glucocorticoid. Stentimplantation in pulmonary artery was performed in 4 patients. Three patients died during the follow-up. Conclusions Patients with TA are at risk of PH, and PH can be the first manifestation of TA, which suggest that PH should be screened regularly in patients with TA and shortness of breath. The prognosis of TA-PH is poor. PH-specific therapies and vascular reconstruction therapy may be effective, but need further investigation.

Inflammatory bowel disease(IBD)is a chronic non-specific intestinal inflammatory disease,including ulcerative colitis(UC)and Crohn's disease(CD). Changing lifestyle can improve patients'symptoms to a certain extent and enhance the efficacy of drugs. The anti-inflammatory effect of exercise in IBD has been confirmed,but its specific mechanism is not clear. This article reviewed the advances in study on the anti-inflammatory effect of exercise on IBD.

Objective To explore the characteristics and survival of connective tissue disease (CTD) patients with both of pulmonary arterial hypertension (PAH) arnd interstitial lung disease (ILD),and to compare with CTD patients with isolated PAH.Methods All adult CTD patients who visited one of the three referral centers in China with a diagnosis of PAH confirmed by right heart catheterization from July 2006 to May 2011 were enrolled.They were then divided into two groups (ILD with and without-ILD group) based on chest CT and then the comparison of baseline characteristics and survival at the endpoint of follow up were made between the two groups.T test,Mann-Whitney U test,x2 test,Kaplan-Meier survival analysis and Cox regression analysis were used for statistical analyses.Results One hundred and twenty-six patients were recruited into the study.Patients with ILD (n=27) were older than those without ILD (n=99).Lung function results including FVC [(75±18)％ vs (83±13)％,t=2.212,P=0.037] and DLCO [(54±22)％ vs (68±20)％,t=2.392,P=0.019] in ILD group were significantly wose than those without-ILD group.Although some important hemodynamic parameters such as mean pulmonary arterial pressure and pulmonary vascular resistance were better in the ILD group than the without-ILD group,Kaplan-Meier analysis showed that the short term survival of ILD group was significantly worse than that of the without-ILD group (72.7％ versus 94.7％ at 1 year and 63.6％ versus 81.1％ at 3 year,P=0.047).In ILD group,Cox regression analysis showed that SvO2 was the only independent factor for the short term survival [HR=0.19,95％CI (0.04,0.83),P=0.027],and Kaplan-Meier analysis showed patients with SvO2＜60％ had significantly lower short term survival than patients with SvO2 ≥60％ (1 and 2 year survival were 60.0％ and 40.0％ versus 92.9％ and 77.4％ respectively,P=0.002).Conclusion Patients with both PAH and ILD is a special subtype in CTD.Although with the superiority of hemodynamics,these patients have significantly worse survival than CTD patients with isolated PAH.Low SvO2 is the independent risk factor for the short term mortality in patients of CTD complicated by both PAH and ILD.More attention should be paid to these patients and the management strategy should be investigated further.

Objective To evaluate the effects of therapeutic hypothermia on both neurological status and survival rate in patients after cardiac arrest.Methods The data were searched from MEDLINE,PubMed,EMBASE,Cochrane Library,Wanfang database,CNKI and CBM.The randomized and controlled trials were selected for evaluating the main outcomes of neurological status and survival rate in patients after cardiac arrest.Meta-analysis was carried out by using Review Manger 5.0 software.The results were expressed in risk ratio (RR) for dichotomous outcomes data with 95％ confidence intervals (CI),and P ＜ 0.05 was considered to be significant.Results Eight randomized controlled clinical trials with a total of 1 512 patients met our inclusion criteria.The overall risk ratio of favorable neurological status was 1.34 (95％ CI:1.01-1.78,P ＜0.05) and of survival rate was 1.09 (95％ CI:0.98-1.20,P ＞0.05) with therapeutic hypothermia compared with controls,however,when the applications of conventional cooling trials were analyzed,the risk ratio was 1.51 (95％ CI:1.22-1.87,P ＜0.01) and 1.36 (95％CI:1.13 -1.63,P ＜ 0.01),respectively.Conclusions Patients treated with therapeutic hypothermia after cardiac arrest had more favorable neurological status compared with the controls.There was no benefit of therapeutic hypothermia to survival rate identified.Compare with conventional cooling methods,the therapeutic hypothermia could improve neurological status and survival rate in patients after cardiac arrest.