1.Drug discovery of sclerostin inhibitors.
Sifan YU ; Dijie LI ; Ning ZHANG ; Shuaijian NI ; Meiheng SUN ; Luyao WANG ; Huan XIAO ; Dingdong LIU ; Jin LIU ; Yuanyuan YU ; Zongkang ZHANG ; Samuel Tin Yui YEUNG ; Shu ZHANG ; Aiping LU ; Zhenlin ZHANG ; Baoting ZHANG ; Ge ZHANG
Acta Pharmaceutica Sinica B 2022;12(5):2150-2170
Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
2.A comparison between endoscopic CO2 laser cauterization and open neck surgery in the treatment of congenital piriform fistula.
Shu Ling HUANG ; Liang Si CHEN ; Mi Mi XU ; Xi Xiang GONG ; Bei ZHANG ; Lu LIANG ; Xiao Li SHENG ; Jian Dong ZHAN ; Xiao Ning LUO ; Zhong Ming LU ; Si Yi ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(6):619-625
Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO2 laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO2 laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.
Carbon Dioxide
;
Cautery
;
Endoscopy
;
Female
;
Fistula/surgery*
;
Humans
;
Lasers, Gas/therapeutic use*
;
Male
;
Pyriform Sinus/surgery*
;
Retrospective Studies
;
Treatment Outcome
3.24-hour observation of patients after intrathecal morphine for lower segment caesarean section – Is it overrated? A prospective observational study
Thiruselvi Subramaniam ; Shu Ning Kong ; Shi Ting Tee ; Muhammad Faiz Bin Ismai ; Joanne Sue James ; Hamitra Gandhi
International e-Journal of Science, Medicine and Education 2021;15(3):37-45
Background:
Side effects of intra-thecal (IT) morphine in lower caesarean section (LSCS) can be dangerous hence they are co-managed by the anesthesia pain team for a minimum of 24 hours. The aim of this study was to identify the side effects and consider the possibility of earlier discharge from the pain team to the parent team.
Methods:
A prospective observational study was conducted on 323 patients who received IT morphine for LSCS. An interviewer-centered questionnaire was used to obtain data on the side effects.
Results:
Side effects were experienced by 80% (n=259) of the patients, and none developed respiratory depression. Side effects occurred in first 6 hours in 94% (n=244) of the patients, 5% (n=13) within 6 to 12 hours and 1% (n=2) within 12 to 24 hours. Pruritus was the most common side effect (88%; n=227) and 93% (n=210) experienced it within the first 6 hours. Nausea and vomiting occurred in 54% (n=139) of the patients with side effects and 70% (n=97) of them experienced them within the first 6 hours. Kruskal-Wallis H test showed that Malays experienced more side effects, χ2(2) = 3.363, p = 0.004. No difference in pain scores was noted between races at 0-6 hours and 12-24 hours. However, Indians had higher scores at 6-12 hours (χ2(1) =4.31, p = 0.031).
Conclusion
The most common side effect was pruritus, then nausea and vomiting with no respiratory depression. Most occurred in the first 12 hours suggesting possibility of earlier discharge by the pain team to the parent team. However, further research is needed as guidelines suggest 24 hours, fearing respiratory depression. Side effects in Malays and increased pain perception among Indians need exploration.
Caesarean Section
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Drug-Related Side Effects and Adverse Reactions
;
Send to: Racial Groups
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Respiratory Insufficiency
4.Exploring Anti-inflammation Mechanism of Pien Tze Huang via Regulating of Microglia Polarization
Hai-yang SHU ; Dan-cai FAN ; Ning ZHAO ; Cheng LYU ; Ai-ping LYU ; Xiao-juan HE
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(5):48-53
Objective::To investigate the anti-inflammation mechanism of Pien Tze Huang (PTH) via regulating microglia polarization. Method::The experiment was divided into five groups, Blank, M1[lipopolysaccharide (LPS) 100 μg·L-1+ interferon-
5.The effect of suppressive oligodeoxynucleotides on interferon-γ and phosphorylation of signal transducers and activators of transcription 4 expression of silica-induced pulmonary inflammation in mice.
Peng LEI ; Hai-xia KONG ; Jing-shu ZHANG ; Ning HE ; Shi-xin WANG ; Ya-guang WENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2013;31(7):522-525
OBJECTIVETo investigate the protective effect of suppressive oligodeoxynucleotides (Sup ODN) on interferon-γ (IFN-γ) and signal transducers and activators of transcription (pSTAT4) expression of Silica-induced pulmonary inflammation in Mice.
METHODSSixty Balb/c mice were randomly divided into 4 groups, normal control group, silicious group, suppressive oligodeoxynucleotides (Sup ODN) group, control oligodeoxynucleotides (Con ODN) group. Except the normal control group injected normal saline, the rest groups were induced by the intratracheal instillation of 0.1 ml (5 g/L) of sterilized silica suspension. Sup ODN group and Con ODN group were treated by i.p. injection of 0.3 ml (1mg/mL) of suppressive or control ODN 3 h before silica administration. After 7 days, the animals were killed and levels of IFN-γ were detected by ELISA. The pathologic changes in lung tissues of mice were observed with HE staining. Expressions of IFN-γ and pSTAT4 in lung tissue were detected with immunohistochemistry and quantified by Image-Pro Plus 7.0.
RESULTSHE staining showed that the lung tissue of silicious group were damaged seriously than Sup ODN group. Compared with the normal control group (serum: (280.1±41.3) pg/ml, lung tissue: (0.249±0.373), IFN-γ increased in silicious group (serum: (886.3±81.7) pg/ml, lung tissue: (0.270±0.300) (P < 0.05). Compared with the normal control group and Con ODN group [(894.5±91.6) pg/ml], IFN-γ in the serum of Sup ODN group decreased significantly (P < 0.01). Compared with the silicious group , IFN-γ in lung tissue decreased in Sup ODN group (0.241±0.250) (P < 0.05). Compared with the normal control group (0.279±0.353), pSTAT4 in lung tissue increased significantly in silicious group (0.313±0.231) (P < 0.01). Compared with the silicious group, pSTAT4 in lung tissue decreased significantly in Sup ODN group (0.269±0.523) (P < 0.01).
CONCLUSIONSup ODN attained protective effect on Silica treated mice by suppressing expression of IFN-γ and pSTAT4.
Animals ; Female ; Inflammation ; metabolism ; Interferon-gamma ; metabolism ; Lung ; drug effects ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Oligodeoxyribonucleotides ; pharmacology ; Phosphorylation ; STAT4 Transcription Factor ; metabolism ; Silicon Dioxide ; toxicity
6.Assessment of coronary stent lumen visibility and patency by dual-source computed tomographic angiography.
Lian-yan KONG ; Dong LIU ; Yi-ning WANG ; Lan SONG ; Zhu-hua ZHANG ; Zheng-yu JIN ; Shu-yang ZHANG ; Bing JI
Acta Academiae Medicinae Sinicae 2010;32(6):601-606
OBJECTIVETo assess the in-stent lumen visibility and image quality of coronary stents by dual-source computed tomography (DSCT) coronary angiography, and the diagnostic accuracy of DSCT in the detection of coronary in-stent restenosis.
METHODSDSCT was performed at 147 stents in 78 patients at an interval of (21.8?22.2) months after coronary stent implantation. Axial multi-planar reconstruction of the stents and curved-planar reconstruction through the median of the stents were evaluated for stent image quality on a 5-point scale, and the stent lumen diameters were detected. Thirty out of these 78 patients underwent conventional coronary angiography within one month after CT angiography. The patency of 60 stents were independently evaluated by two blinded readers.
RESULTSImage quality was good to excellent on average score (1.6?0.6) . Stent image quality score was correlated with stent diameter, stent location, and heart rate. All stents were assessable in lumen visibility with an average visible lumen diameter percentage of (72.2?12.2) %. Visible lumen diameter percentage was correlated with stent diameter and stent location. For the stents with calcified plaques, the visible lumen diameter percentage at the calcified site was significantly lower than that at the non-calcified site (P<0.001) . Compared with the conventional coronary angiography, 12 out of 14 in-stent stenoses were correctly detected. The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of in-stent stenosis was 85.7%, 95.7%, 85.7%, and 95.7%, respectively. For stents whose diameter >0.275cm, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. The agreement between CT findings and coronary angiography results was 93.3%, and it was correlated with stent diameter and heart rate.
CONCLUSIONSUsing a DSCT, coronary stent lumen is partially visible and the image quality is high. Stent diameter and location can influence the stent lumen visibility and image quality. DSCT has a high diagnostic accuracy for the detection of in-stent restenosis and may be a valuable modality for the follow-up of coronary artery stent patency."
Aged ; Coronary Angiography ; methods ; Coronary Restenosis ; diagnostic imaging ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Stents ; Tomography, X-Ray Computed ; methods ; Vascular Patency
7.Assessment of coronary stents by 64-slice computed tomography: in-stent lumen visibility and patency.
Ling-Yan KONG ; Zheng-Yu JIN ; Shu-Yang ZHANG ; Zhu-Hua ZHANG ; Yi-Ning WANG ; Lan SONG ; Xiao-Na ZHANG ; Yun-Qing ZHANG
Chinese Medical Sciences Journal 2009;24(3):156-160
OBJECTIVETo assess lumen visibility of coronary stents by 64-slice computed tomography (CT) coronary angiography, and determine the value of 64-slice CT in non-invasive detecting of in-stent restenosis after coronary artery stent implantation.
METHODSTotally, 60 patients (54 males, aged 57.0+/-12.7 years) and 105 stents were investigated by 64-slice CT at a mean interval of 20.0+/-16.6 months after coronary stents implantation. Axial multi-planar reconstruction images of the stents and curved-planar reconstruction images through the median of the stents were reconstructed for evaluating stent image quality on a 5-point scale (1=excellent, 5=non-assessable), and stent lumen diameter was detected. Conventional coronary angiography was performed in 18 patients, and 32 stents were evaluated.
RESULTSImage quality was good to excellent on average (score 1.71+/-0.76). Stent image quality score was correlated to heart rate (r=0.281, P<0.01) and stent diameter (r=-0.480, P<0.001). All the stents were assessable in lumen visibility with an average visible lumen diameter percentage of 60.7%+/-13.6%. Visible lumen diameter percentage was correlated to heart rate (r=-0.193, P<0.05), stent diameter (r=0.403, P<0.001), and stent image quality score (r=-0.500, P<0.001). Visible lumen diameter percentage also varied depending on the stent type. In comparison with the conventional coronary angiography, 4 of 6 in-stent stenoses were correctly detected. The sensitivity and specificity for the detection of in-stent stenosis were 66.7% and 84.6%, respectively.
CONCLUSIONSUsing a 64-slice CT, the stent lumen is partly visible in most of the stents. And 64-slice CT may be useful in the assessment of stent patency.
Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Stenosis ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Radiographic Image Interpretation, Computer-Assisted ; Retrospective Studies ; Tomography, X-Ray Computed
8.Assessment of global left ventricular function by 64-slice spiral CT in patients with old myocardial infarction.
Lan SONG ; Zhu-Hua ZHANG ; Yi-Ning WANG ; Ling-Yan KONG ; Lu ZHOU ; Shu-Yang ZHANG ; Feng FENG ; Li-Ren ZHANG ; Zheng-Yu JIN
Acta Academiae Medicinae Sinicae 2009;31(2):221-226
OBJECTIVETo investigate the clinical value of 64-slice spiral CT (64SCT) in assessing global left ventricular function in patients with old myocardial infarction (OMI), with magnetic resonance imaging (MRI) as the reference standard.
METHODSA total of 28 patients (23 men and 5 women) with OMI underwent contrast-enhanced 64SCT with retrospective electrocardiographic-gating, MRI, and transthoracic echocardiography (Echo). The data sets of 64SCT and MRI were reconstructed at both end-diastole and end-systole to measure left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejective fraction (EF), and myocardial mass at end-diastole (MM). The data acquired with 64SCT and Echo were compared with the results obtained on MRI as the standard of reference respectively.
RESULTSThe parameters of global left ventricular function obtained with 64SCT were significantly correlated with the MRI data (r = 0.788-0.976, P < 0.001). EDV, ESV, SV, EF, and MM were slightly overestimated by 64SCT compared with MRI; however, there was no significant difference among the measurements. 64SCT was in good agreement with MRI. For the EDV, ESV, SV, and EF, the limits of agreement with Echo were significantly larger than with 64SCT compared with MRI (P < 0.05). The sensitivity, specificity, and accuracy of 64SCT to identify EF value less than 50% were 84.6%, 100% and 92.9%, respectively, whereas those of Echo were 61.5%, 66.7% and 64.3%, respectively. The accuracy of 64SCT was significantly higher than that of Echo (P < 0.01). There was a significantly larger overestimation of EDV, ESV, and SV with Echo than with 64SCT compared with MRI (P < 0.05), whereas EF was not significantly different.
CONCLUSIONSA strong correlation between 64SCT and MRI is found for all parameters. 64SCT agrees well with MRI, and allows more reliable and accurate evaluation of global left ventricular function in patients with OMI than Echo compared with MRI.
Adult ; Aged ; Echocardiography ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; physiopathology ; Tomography, Spiral Computed ; methods ; Ventricular Function, Left ; physiology
9.Diagnostic value of dual-source CT coronary angiography on the detection of coronary artery disease with myocardial perfusion defect.
Yi-Ning WANG ; Ling-Yan KONG ; Zhu-Hua ZHANG ; Li-Bo CHEN ; Lan SONG ; Shu-Yang ZHANG ; Qi MIAO ; Zheng-Yu JIN
Acta Academiae Medicinae Sinicae 2009;31(2):160-165
OBJECTIVETo determine the accuracy of dual-source CT (DSCT) coronary angiography (CAG) for the diagnosis of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT), by using SPECT and conventional CAG as the reference standard.
METHODSThirty-five patients with suspected or known CAD underwent both DSCT coronary angiography and MPI (using exercise or adenosine stress-rest protocol) with technetium-99m sestamibi SPECT. All the patients were beta-blockers-naïve before DSCT scan. The DSCT CAG studies were classified as having no stenosis, non-obstructive (< 50% luminal narrowing) stenosis, or obstructive (> or = 50% luminal narrowing) stenosis. MPI examinations were classified as showing normal or abnormal (reversible and/or fixed defects). A comparative regional analysis of coronary stenosis on DSCT versus myocardial perfusion on SPECT was made. In a subset of 20 patients, CAG was performed as a reference standard for CT angiography.
RESULTSOn the basis of the DSCT data, 98.4% of coronary segments were assessable. Twenty-seven branches were classified as having no stenosis, among which 85% had normal MPI. Nine branches showed non-obstructive stenosis and 69 branches showed at least one obstructive lesion. Only 50 (64%) branches with an abnormal DSCT had abnormal MPI; even in branches with obstructive stenosis on DSCT, 23 (33%) still had a normal MPI. By receiver operating characteristic curve analysis, at the optimal cutoff value of 58% stenosis, the sensitivity and specificity of DSCT to detect myocardial perfusion defect as defined by SPECT were 85% and 65%. In the subgroup compared with CAG, the sensitivity and specificity of DSCT to identify obstructive stenosis were 93% and 96%.
CONCLUSIONSDSCT and SPECT provide mutually complementary information on CAD. CT angiography can help rule out functionally relevant CAD, but has poor capability in predicting ischemia. DSCT provides high-quality diagnostic image without heartbeat controlling and has a high accuracy in detecting obstructive stenosis.
Aged ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia ; diagnostic imaging ; Technetium Tc 99m Sestamibi ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed
10.Coronary angiography with dual source computed tomography: initial experience.
Zhu-hua ZHANG ; Zheng-yu JIN ; Shu-yang ZHANG ; Song-bai LIN ; Dong-jing LI ; Ling-yan KONG ; Yi-ning WANG ; Lan SONG ; Yun WANG ; Wen-min ZHAO ; Wen-bin MOU ; Li-ren ZHANG ; Wen-ling ZHU ; Qi MIAO ; Qi FANG
Chinese Medical Sciences Journal 2007;22(4):205-210
OBJECTIVETo explore the scan technique and image quality of coronary angiography with dual source computed tomography (CT) without oral metoprolol preparation.
METHODSPlain and enhanced dual source CT coronary angiography without oral metoprolol preparation was prospectively performed in 600 patients. Calcium scoring with plain scan images as well as multi-planar reconstruction (MPR), maximum intensity projection (MIP), and volume rendering technique (VRT) reconstruction with enhanced scan images were performed in all cases. The scan technique and post-reconstruction experience was summarized. The image quality was classified as 1 to 4 points, and coronary segments classified according to the American Heart Association standards were evaluated.
RESULTSThe average calcium score of the 600 cases was 213.6 +/- 298.7 (0-3,216.5). The average heart rate of the enhanced scan was 82.1 +/- 16.2 (47-139) bpm. The post-reconstruction methods with which coronary segments could be shown as best as possible consisted of single phase reconstruction method, two or more phases supplemented method, and electrocardiogram editing method. Altogether 8,457 coronary segments were evaluated, among which 97.2% were evaluated as point 1, 1.7% point 2, 0.5% point 3, and 0.6% point 4. The coronary segments in 261 cases were completely normal, while 360 segments were diagnosed with < 50% stenosis and 625 segments with > or = 50% stenosis.
CONCLUSIONSExcellent coronary artery image can be obtained with dual source CT in patients with any heart rate without oral metoprolol preparation. Heart rate is not a major source of the artifact, coronary segments can be well shown with single or multiple-phase reconstruction method.
Adult ; Coronary Angiography ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; methods


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