1.Parabacteroides distasonis promotes liver regeneration by increasing β-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.
Manlan GUO ; Xiaowen JIANG ; Hui OUYANG ; Xianglong ZHANG ; Shuaishuai ZHANG ; Peng WANG ; Guofang BI ; Ting WU ; Wenhong ZHOU ; Fengting LIANG ; Xiao YANG ; Shicheng FAN ; Jian-Hong FANG ; Peng CHEN ; Huichang BI
Acta Pharmaceutica Sinica B 2025;15(3):1430-1446
The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.
2.Pharmacokinetic study of the complication of Ephedra sinica and Prunus armeniaca in bronchial asthma model rats
Linlin CHEN ; Jingen XIE ; Xuecheng FAN ; Qian RAO ; Tianyi YANG ; Jiayu TIAN ; Xiong XIAO ; Wenjun GAO ; Wenhong LI
China Pharmacy 2024;35(13):1588-1593
OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group, model group, E. sinica group (12 g/kg, calculated by raw drug, similarly hereinafter), P. armeniaca group (6 g/kg) and E. sinica-P. armeniaca drug-pair group (12 g/kg of E. sinica+6 g/kg of P. armeniaca), with 6 rats in each group. Except for the blank group, the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate, once a day, for 7 d. One hour before modeling every time, rats in each group were gavaged with the corresponding drug/normal saline, once a day, for 7 d. After the final administration and provocation of asthma, blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated (with geranylgeranyl as the internal standard), and the mass concentrations of ephedrine/pseudoephedrine, methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group, cmax and AUC0-21.33 h (or AUC0-10.67 h) of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group, while CLZ/F and VZ/F were significantly increased (P<0.05 or P<0.01); tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened (P< 0.05).Compared with P. armeniaca group, the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened, and CLZ/F was significantly increased (P<0.01); the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened, and the AUC0-10.67 h, CLZ/F, and VZ/F were significantly increased (P<0.01). CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids, thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.
3.Echocardiographic evaluation on infants with pulmonary atresia and intact ventricular septum:Surgical decision and post operation right ventricle development
Jing YANG ; Wenhong DING ; Qiang WANG ; Bin LI ; Yongtao WU ; Yuekun SUN ; Zhenbo HU
Chinese Journal of Medical Imaging Technology 2024;40(11):1672-1676
Objective To observe value of echocardiographic evaluation on infants with pulmonary atresia and intact ventricular septum(PA/IVS)for surgical decision and post operation right ventricle(RV)development.Methods Forty-six PA/IVS infants who underwent pulmonary valve(PV)annuloplasty(group A,n=25),PV annuloplasty and RV outflow tract reconstruction with/without additional systemic-to-pulmonary artery shunt(group B,n=15),and systemic-to-pulmonary artery shunt and atrial septal enlargement(group C,n=6)were retrospectively enrolled.Status of RV developments were compared among groups before operation as well as 1 and 6 months after operation.Results The presentation age in group B was younger than,while in group C was older than that in group A(both P<0.05).Before operation,tricuspid valve(TV)annulus diameter,TV annulus Z-score and TV/mitral valve(MV)annulus ratio in groups B and C were both smaller than those in group A(all P<0.05),whereas RV/left ventricle(LV)longitudinal diameter ratio in group B was larger and PV annulus Z-score in group C was smaller than those in group A(both P<0.05).Meanwhile,preoperative PV annulus Z-score and RV/LV longitudinal diameter ratio in group B were both larger than those in group C(both P<0.05).One month after operations,TV annulus diameter,TV annulus Z-score and TV/MV annulus ratio in group B and C,as well as PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group A(all P<0.05),while PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group B(all P<0.05).Six months after operations,no significant difference of TV annulus diameter,PV annulus diameter,PV annulus Z-score,TV/MV annulus ratio nor RV/LV longitudinal diameter ratio was found between group A and B(all P>0.05),but the above indexes in group C were all lower than those in group A and B(all P<0.05).Besides,no significant difference of TV annulus Z-score was found between group A and B(P>0.05),which were lower in group C than in group A(P<0.05).Conclusion Echocardiographic evaluation on PA/IVS infants was helpful to establishment of forward blood flow from RV to pulmonary arteries in time,hence promoting RV development.
4.Visualization of research trends and hotspots in the field of end tuberculosis based on VOSviewer
Shijia GE ; Jibin XIN ; Yang LI ; Jun YING ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2024;42(7):409-415
Objective:To analyze the research literature related to end tuberculosis (TB) using bibliometric methods, so as to provide researchers with insights into current research trends and hotspots in this field.Methods:A search was conducted using the Web of Science core collection data base on March 5, 2024. The research was limited to articles and reviews published between 2014 and 2023. The results were visualized with VOSviewer, and an analysis was performed on the involved national, international research cooperation networks and keyword clustering.Results:A total of 1 092 articles related to end TB research were retrieved and screened, with a total citation counts of 14 871 and an average citation counts of 13.62 per article. The United States of America had the highest number of publications (328 articles, 30.04%), while China ranked seventh (100 articles, 9.16%). International scientific collaboration network analysis indicated that countries primarily included the United Kindom, the United States of America, Switzerland, South Africa, the Netherlands, Australia, and India, which had formed close cooperation in the field of end TB research. Keyword clustering analysis suggested that current research hotspots in end TB field included cost analysis related to TB, management of latent TB individuals, strategies for TB prevention and control, key technologies in TB elimination, and TB epidemiology and associated risk factors.Conclusions:Over the past decade, the number of publications and citations in the field of end TB is relatively high. International research collaboration has been extensive, and the research content covers multiple dimensions, including the management and cost analysis of different disease stages, technological innovations, considerations for comprehensive control strategy, and epidemiology.
5.Clinical analysis of maternal autoantibody-mediated complete left bundle branch block in 9 children
Xiaoli WANG ; Fang YANG ; Ling HAN ; Wenhong DING ; Xinxin GUO ; Xinyu LIN ; Shengwei CHEN
Chinese Journal of Pediatrics 2024;62(9):872-876
Objective:To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies.Methods:A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results:Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions:Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.
6.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
7.Study on influencing factors associated with the analysis of 226Ra gamma spectra
Qiang ZHOU ; Jing ZHANG ; Baolu YANG ; Wenhong LI ; Zeshu LI ; Fei TUO
Chinese Journal of Radiological Medicine and Protection 2023;43(2):112-117
Objective:To measure the influencing factors associated with the analysis of 226Ra gamma spectra in order to obtain more acurate and precise measuring result on a basis of further optimizing the gamma spectrometry method for 226Ra activity. Methods:A laboratory-based HPGe gamma spectrometer was used to carry out the studies on tracking measurement of sample sealing time, measurement of background fluctuation with lead shielding, analytical method, and selection of characteristic gamma ray energy peak of its daughter nuclides in 226Ra measurement. Results:After the sample was sealed for 12 d, the decay products of 226Ra- 222Rn basically reached equilibrium. The day and night fluctuations of 222Rn in the shielded lead room were obvious but had no obvious regularity. The way of filling nitrogen into the shielded lead room could reduce or avoid the influence of background fluctuations. For 31 soil samples measured after 23 days of sealing, the result of using the efficiency curve method showed that the 226Ra result calculated from the 351.9 keV energy peak were generally higher than the 609.3 keV energy peak, and the higher ratio ranged from 8.0% to 20.7%. The result of relative comparison method showed that the deviation ratio of the two peaks ranged from -4.1 % to 10.3 %. Conclusions:It is recommended to consider the uncertainty attributed from decay equilibrium about 4 % of measured at 12 d after the sample is sealed. When filling nitrogen through the shielded lead chamber to avoid background fluctuations, attention must be paid to the matching relationship between the volume of the lead chamber and the nitrogen filling flow. When the efficiency curve method is used to analyze the activity of 226Ra, the 214Bi ( 609.3 keV ) energy peak has the effect of cascade coincidence addition, so 214Bi(609.3 keV) energy peak should be avoided. When the relative comparison method is used to analyze the activity of 226Ra, both two energy peaks of 214Pb ( 351.9 keV ) and 214Bi ( 609.3 keV ) can be used.
8.The norm of the Physical Activity afterschool Questionnaire for Preschooler (P-PAQ) in urban areas of China
Chinese Journal of School Health 2023;44(9):1328-1332
Objective:
To establish the norm of the Physical Activity afterschool Questionnaire for Preschooler(P-PAQ) in urban areas of China, so as to provide a basis for graded guidance from the family perspective and to improve children s physical activity levels.
Methods:
From October 2020 to January 2021, 6 267 children aged 3-6 years old were recruited from 40 kindergartens in eight cities across six major administrative regions by stratified cluster sampling, and the P-PAQ initially developed by the researchers of this study were completed by the primary caregivers. The questionnaire was administered to collect data relating to the amount of physical activity undertaken by the preschoolers, and the norm was determined by quartiles. Data relating to parental concepts of sports and parental behavior were assessed by calculating mean scores in order to establish the norm.
Results:
Among preschoolers in urban areas, the M(P 25 ,P 75 ) of total physical activity time (min/day), moderate-to-vigorous physical activity time (min/day), outdoor time (min/day) and screen time (min/day) on school days outside kindergarten and on weekends were 84 (54,120), 22 (8,40), 12 (0,24) and 18 (6,30), and 170 (115,240), 60 (30,95), 90 (35,120) and 30 (20,60), respectively. When the score of parents sports concept and behavior (total score of 40) were≥34, 29-<34, 24-<29, <24, it was defined as four levels about above medium, medium, lower medium and lower, respectively. And for two dimensions,when the score of parental sports concept were ≥19, 17-<19, 15-<17, <15,and the score of parental behaviors were ≥16, 12-<16, 8-<12, <8, it was defined as four levels about upper medium, medium, lower medium and lower, respectively.
Conclusion
The norm of extracurricular activities among preschool children in Chinese cities has good representativeness and appropriate threshold values, which could provide a valuable reference for early assessment, as well as guidance in relation to out-of-school physical activity behaviors among children aged 3-6 years old.
9.Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection.
Jin LI ; Wenhong FAN ; Jianxiong MA ; Wei ZHOU ; Xinxin PANG ; Cungui TIAN ; Guohui YANG ; Yan WANG ; Na ZHAO
Journal of Biomedical Engineering 2023;40(2):320-326
In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.
Radiopharmaceuticals
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Injections
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Hand
10.Clinical characteristics and pregnancy outcomes of pregnant women with left ventricular non-compaction
Huanying WANG ; Zhaoliang BAO ; Dong YANG ; Yanna LI ; Lan BU ; Wenhong DING ; Jun ZHANG
Chinese Journal of Obstetrics and Gynecology 2022;57(5):332-338
Objective:To investigate the clinical characteristics and pregnancy outcomes in pregnant women with left ventricular non-compaction (LVNC).Methods:The clinical data of seven pregnant women with LVNC from January 2011 to December 2021 in Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed, including age, gestational age of symptom first occured, LVNC history, clinical symptoms, New York Heart Association (NYHA) cardiac function class, echocardiography, blood brain natriuretic peptide (BNP), treatment and the maternal and fetal outcomes.Results:Five cases were diagnosed before pregnancy, of which there were three women with medication; one case diagnosed in the month of pregnancy; one case diagnosed at 36 weeks of gestation. NYHA cardiac function was grade Ⅰ in four cases and grade Ⅱ in three cases before or during the first trimester of pregnancy. Of the five pregnant women who underwent echocardiography, there were one case of left ventricular insufficiency, three cases of mild left ventricular dysfunction and one case of normal left ventricular function before or during the first trimester of pregnancy. Of the five pregnant women to the second and third trimester of pregnancy, there were one case of grade Ⅳ, one case of grade Ⅲ, two cases of grade Ⅱ-Ⅲ and one case of grade Ⅱ in NYHA class ; three cases of left ventricular insufficiency, two cases of normal left ventricular function by echocardiography four cases had cardiac symptoms at 15-24 weeks of gestation and were treated with medication. In four cases, blood BNP increased to 214-1 197 ng/L during pregnancy, and were 89-106 ng/L after termination of pregnancy. There were 4 cases with arrhythmia. Indications for termination of pregnancy: LVNC complicated with heart failure in two cases, LVNC complicated with decreased cardiac function and threatened preterm birth in one case, complicated with pregnancy at full term in two cases, LVNC complicated with severe pulmonary hypertension in one case, and left ventricular dysfunction in one case. Cesarean section in four cases in the third-trimester, in one case in the second-trimester, and forceps curettage in two cases were taken. Two full-term infants,two preterm infants were born without LVNC.Conclusions:Women diagnosed with LVNC and low left ventricular ejection fraction before pregnancy are more prone to decreased cardiac function during pregnancy. Carrying out pregnancy risk assessment and strengthening the multi-disciplinary team management of high risk factors in pregnancy are conducive to achieve good pregnancy outcomes.


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