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Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiencysyndrome

Qiqi Zhao, Xin Gao, Guangli Yan, Aihua Zhang, Hui Sun, Ying Han, Wenxiu Li, Liang Liu, Xijun Wang

《医学前沿（英文）》 2020年 第14卷 第3期   页码 335-356 doi: 10.1007/s11684-019-0705-9

摘要： Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD’s efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized , and 23 compounds were discovered . A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.

关键词： traditional Chinese medicine     Sijunzi decoction     spleen qi deficiency syndrome     Chinmedomics     quality-marker    

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Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism:

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 319-323 doi: 10.1007/s11684-017-0553-4

摘要：

Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in and lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of and were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in and a short deletion variant c.572_574delAGA in . This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the and gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

关键词： antithrombin deficiency     protein C activity     mutation     variant     venous thromboembolism     anticoagulants    

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》   页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10     mice     motile cilia     mutation     primary ciliary dyskinesia    

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High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome

Heng Fang, Aihua Zhang, Xiaohang Zhou, Jingbo Yu, Qi Song, Xijun Wang

《医学前沿（英文）》 2020年 第14卷 第5期   页码 651-663 doi: 10.1007/s11684-019-0709-5

摘要： High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultra-performance liquid chromatography–tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite “tyramine glucuronide” through its direct effect on the target heme oxygenase 1 . Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome.

关键词： metabolomics     liquid chromatography-mass spectrometry     metabolites     metabolic pathways    

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Prevalence of vitamin D deficiency in girls with idiopathic central precocious puberty

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《医学前沿（英文）》 2018年 第12卷 第2期   页码 174-181 doi: 10.1007/s11684-017-0544-5

摘要：

The relationship between vitamin D deficiency and idiopathic central precocious puberty (ICPP) has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25-hydroxyvitamin D (25[OH]D) levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-off point for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D≥31.8 ng/ml had a lower odds ratio (unadjusted: OR 0.36, 95% CI 0.15 to 0.83, <0.05; height and weight adjusted: OR 0.44, 95% CI 0.18 to 1.08, = 0.072; BMI adjusted: OR 0.36, 95% CI 0.16 to 0.84, <0.05). The ICPP subjects with 25[OH]D deficiency had a higher body mass index (BMI) than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.

关键词： idiopathic central precocious puberty     threshold effects     vitamin D status    

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non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency

《医学前沿（英文）》 doi: 10.1007/s11684-023-1001-2

摘要： Iron deficiency (ID) and ID anemia (IDA) pose significant public health concerns in China. Although iron sucrose (IS) treatment is well-established in the country, ferric carboxymaltose (FCM) offers the advantage of higher doses and fewer infusions. This open label, randomized, controlled, non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCM (maximum of 2 doses, 500 or 1000 mg iron) and IS (up to 11 infusions, 200 mg iron) treatments in subjects with IDA. The primary endpoint was the achievement of hemoglobin (Hb) response (an increase of ≥2 g/dL from baseline) within 8 weeks, whereas secondary endpoints included changes in Hb, transferrin saturation, and serum ferritin levels. Among the 371 randomized subjects, a similar percentage of subjects treated with FCM and IS achieved Hb-response (FCM 99.4%, IS 98.3%), thereby confirming the non-inferiority of FCM compared with IS (difference 1.12 (−2.15, 4.71; 95% confidence interval (CI))). Furthermore, a significantly higher proportion of FCM-treated subjects achieved early Hb-response at Week 2 (FCM 85.2%, IS 73.2%; difference 12.1 (3.31, 20.65; 95% CI)). Additionally, the increase in TSAT and serum ferritin levels from baseline was significantly greater at all time points for FCM-treated subjects. The safety profiles of FCM and IS were comparable, with the exception of transient hypophosphatemia and pyrexia, which are consistent with FCM’s known safety profile. In conclusion, FCM proves to be an efficacious treatment for IDA, providing faster Hb-response and correction of ID with fewer administrations than IS.

关键词： iron deficiency     anemia     intravenous iron     ferric carboxymaltose     iron sucrose     Hb response     early response    

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Atypical manifestations of acute coronary syndrome — throat discomfort: a multi-center observational

《医学前沿（英文）》 2022年 第16卷 第4期   页码 651-658 doi: 10.1007/s11684-021-0859-0

摘要： To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients’ main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2−31.5), 10.9 (95% CI 1.8−66.9), 25.4 (95% CI 3.6−179.9), and 81.2 (95% CI 13.0−506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.

关键词： acute coronary syndrome (ACS)     throat discomfort (TD)     throat pain     cardiology departments     non-cardiologic physicians    

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Aneurysmal dilatation of the aortic sinuses of Valsalva — beyond Marfan syndrome: a single centre experience

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《医学前沿（英文）》 2014年 第8卷 第4期   页码 419-426 doi: 10.1007/s11684-014-0383-6

摘要：

Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature about congenital sinus of Valsalva aneurysms outside this context. For the purpose of this review, we carried out a literature search on aneurysmal dilatation of the sinuses of Valsalva in Marfan syndrome, and compared this with congenital sinus of Valsalva aneurysms, also including data from a case series from our institution. In conclusion, there are differences in management of aortic dilatation in Marfan syndrome and congenital sinus of Valsalva aneurysms. Though less well-recognised, congenital aneurysms are often associated with significant morbidity and mortality and timely intervention is necessary.

关键词： sinus of Valsalva aneurysms     Marfan syndrome     aortic dissection    

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Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

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《医学前沿（英文）》 2018年 第12卷 第2期   页码 224-228 doi: 10.1007/s11684-017-0538-3

摘要：

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

关键词： bronchiolitis obliterans syndrome (BOS)     hematopoietic stem cell transplantation (HSCT)     lung transplantation (LTX)    

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Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

《工程（英文）》 doi: 10.1016/j.eng.2023.06.007

摘要： Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium-induced colitis in vivo. Axin1ΔIEC and Axin1ΔPC mice became more susceptible to dextran sulfate sodium (DSS)-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

关键词： Axin1     Bacteria     Microbiome inflammation     Inflammatory bowel disease     Immunity     Microbiome     Paneth cells     Akkermansia muciniphila     Wnt    

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Genetic basis of adult-onset nephrotic syndrome and focal segmental glomerulosclerosis

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 333-339 doi: 10.1007/s11684-017-0564-1

摘要：

Nephrotic syndrome (NS) is one of the most common glomerular diseases with signs of nephrosis, heavy proteinuria, hypoalbuminemia, and edema. Dysfunction of glomerular filtration barrier causes protein loss through the kidneys. Focal segmental glomerulosclerosis (FSGS) accounts for nearly 20% of NS among children and adults. Adult-onset FSGS/NS is often associated with low response to steroid treatment and immunosuppressive medication and poor renal survival. Several genes involved in NS and FSGS have been identified by linkage analysis and next-generation sequencing. Most of these genes encode proteins and are highly expressed in glomerular podocytes, which play crucial roles in slit-diaphragm signaling, regulation of actin cytoskeleton dynamics and maintenance of podocyte integrity, and cell–matrix interactions. In this review, we focus on the recently identified genes in the adult-onset NS and FSGS and discuss clinical significance of screening of these genes.

关键词： nephrotic syndrome     focal segmental glomerulosclerosis     genetic    

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Cushing’s syndrome during pregnancy caused by adrenal cortical adenoma: a case report and literature

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《医学前沿（英文）》 2015年 第9卷 第3期   页码 380-383 doi: 10.1007/s11684-015-0407-x

摘要：

Cushing’s syndrome (CS) during pregnancy is a rare condition with significant maternal and fetal complications. A case of CS during the third trimester of pregnancy secondary to adrenocortical adenoma was reported. Literature review revealed the disadvantages of different treatments in this period. Besides the conservative treatment, surgery is recommended for CS during the third trimester of pregnancy secondary to adrenal adenoma, if an experienced surgeon is available.

关键词： Cushing’s syndrome     pregnancy     adrenocortical adenoma    

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Differential diagnosis of cervical nerve compression syndrome of the external intervertebral foramen

WANG Jinwu, NI Weifeng, XU Jianguang, ZHU Haibo, GUO Shangchun, ZENG Bingfang, ZHAO Binghui

《医学前沿（英文）》 2007年 第1卷 第2期   页码 177-180 doi: 10.1007/s11684-007-0033-3

摘要： The aim of the present research is to study the mechanism of cervical nerve compression syndrome of the external intervertebral foramen and its differential diagnosis with cervical spondylosis. Diagnostic treatment with muscle relaxant, vasodilator, neurotrophic medicine and celecoxib (COX)-2 inhibitor were performed in 20 patients with cervical nerve compression syndrome of the external intervertebral foramen and 20 patients with cervical spondylosis confirmed by operation. Diagnostic local block therapy was performed additionally in cases showing little effect after diagnostic treatment. All the patients were followed up postoperatively for more than one year. Fifteen cases with cervical nerve compression syndrome of the external intervertebral foramen were healed by the diagnostic treatment. The other five cases had a short-term remission and there was no recurrence after diagnostic local block therapy. Diagnostic treatment led to short-term alleviation of the symptom in 20 cases with cervical spondylosis confirmed by operation, the results of which was far from satisfactory and operation was undertaken finally in all the 20 cases. The etiology of cervical nerve compression syndrome of the external intervertebral foramen lies in the compression of the cervical plexus, brachial plexus and cervical dorsal rami by the tendinous decussating fibers of the scalenus anticus, medius, minimus and the posterior muscles of the neck. Diagnostic treatment was propitious to differentiate cervical nerve compression syndrome of the external intervertebral foramen from cervical spondylosis.

关键词： satisfactory     COX     minimus     operation     compression syndrome    

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Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome: things are not always

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 293-296 doi: 10.1007/s11684-017-0516-9

摘要：

Familial amyloid cardiomyopathy is a challenging condition that mimics many other diseases, particularly in patients with pronounced neurological presentations and unexplained or equivocal cardiac abnormalities. In this case, a 57-year-old man was admitted for outpatient cardiological evaluation of progressive right heart failure and limb paraesthesias. The patient presented with hypertension, chronic Guillain-Barre syndrome, and sick sinus syndrome. Transthoracic echocardiograms showed a thickened ventricular wall and enlarged atrium. Tissue Doppler showed a restrictive filling pattern. Transthyretin (TTR)-associated amyloidosis, which was revealed by abdominal fat-pad biopsy and DNA analysis, explained the concurrence of independent pathological features, including neuropathy and cardiac involvement. Genetic testing identified a G>T mutation in exon 4 of the transthyretin (TTR) gene. This mutation resulted in the alanine-to-serine substitution at amino acid position 117. Moreover, genetic testing confirmed that the patient’s asymptomatic son carried the same amyloidogenic TTR mutation. Given these findings, the diagnosis of familial amyloid cardiomyopathy, which was misdiagnosed as chronic Guillain-Barre syndrome, was proposed.

关键词： transthyretin (TTR) cardiac amyloidosis     sick sinus syndrome     chronic Guillain-Barre syndrome    

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Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 111-119 doi: 10.1007/s11684-016-0446-y

摘要：

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.

关键词： coronavirus     MERS     Middle East respiratory syndrome    

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标题 作者 时间 类型 操作

Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiencysyndrome

Qiqi Zhao, Xin Gao, Guangli Yan, Aihua Zhang, Hui Sun, Ying Han, Wenxiu Li, Liang Liu, Xijun Wang

期刊论文

Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism:

null

期刊论文

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

期刊论文

High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome

Heng Fang, Aihua Zhang, Xiaohang Zhou, Jingbo Yu, Qi Song, Xijun Wang

期刊论文

Prevalence of vitamin D deficiency in girls with idiopathic central precocious puberty

null

期刊论文

non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency

期刊论文

Atypical manifestations of acute coronary syndrome — throat discomfort: a multi-center observational

期刊论文

Aneurysmal dilatation of the aortic sinuses of Valsalva — beyond Marfan syndrome: a single centre experience

null

期刊论文

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

期刊论文

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

期刊论文

Genetic basis of adult-onset nephrotic syndrome and focal segmental glomerulosclerosis

null

期刊论文

Cushing’s syndrome during pregnancy caused by adrenal cortical adenoma: a case report and literature

null

期刊论文

Differential diagnosis of cervical nerve compression syndrome of the external intervertebral foramen

WANG Jinwu, NI Weifeng, XU Jianguang, ZHU Haibo, GUO Shangchun, ZENG Bingfang, ZHAO Binghui

期刊论文

Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome: things are not always

null

期刊论文

Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns

null

期刊论文