5-Fluorouracil resistance due to sphingosine kinase 2 overexpression in colorectal cancer is associated with myeloid-derived suppressor cell-mediated immunosuppressive effects.

PURPOSE: Colorectal cancer (CRC) is one of the top five cancer-related causes of mortality globally. Acquired resistance has hindered the effectiveness of 5-fluorouracil (5-FU), the main chemotherapeutic drug used to treat CRC. Sphingosine kinase 2 (SphK2) may be a cancer treatment target and involved in 5-FU resistance. METHODS: Cell growth was examined using MTT and clone formation assays for SphK2 expression. To identify immune cells in mice, flow cytometry was performed. West blotting demonstrated alterations in cell division and inflammation-related proteins. SphK2 levels and inflammation-related variables were studied using Elisa. RESULTS: Due to SphK2 overexpression, immunosuppression, and 5-FU resistance are caused by the development of myeloid-derived suppressor cells (MDSCs) subsequent to IL-6/STAT3 activation and alterations in the arginase (ARG-1) protein. After therapy, the combination of SphK2 inhibitors and 5-FU can effectively suppress MDSCs while increasing CD4+ and CD8+ T cell infiltration into the tumor microenvironment, lowering tumor burden, and exhibiting a therapeutic impact on CRC. CONCLUSIONS: Our findings suggest that 5-FU treatment combined with simultaneous Spkh2 inhibition by ABC294640 has anti-tumor synergistic effects by influencing multiple effects on tumor cells, T cells, and MDSCs, potentially improving the poor prognosis of colorectal cancer patients.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited. Objective: A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition. Methods: Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'. Results: A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-ß and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using 18F-FDG PET, however, more data is needed. Conclusions: GLP-1 RA therapy did not alter amyloid-ß and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.

C3d Immunohistochemical Staining on Paraffin-Embedded Tissue for Diagnosis of Pemphigus.

CONTEXT.­: Pemphigus is an autoimmune blister disease that causes blisters on the skin and mucosal surfaces. Direct immunofluorescence (DIF) testing is critical for the clinical diagnosis of pemphigus. However, it is limited to fresh tissue specimens and fluorescence microscopy. OBJECTIVE.­: To assess the value of C3d immunohistochemistry (IHC) on paraffin-embedded skin tissue for the diagnosis of pemphigus by comparing C3d-IHC results to DIF and enzyme-linked immunosorbent assay testing in pemphigus and other blister-related skin diseases. DESIGN.­: C3d-IHC assays were retrospectively performed on paraffin-embedded skin tissue sections from 115 patients (63 with pemphigus and 52 controls). Both the case group and the control group underwent the same protocol, and cases with C3d position in the peripheral spinous layer were considered as positive samples. RESULTS.­: C3d-IHC and DIF testing had similar performance for pemphigus diagnosis, with a sensitivity of 71.0% (95% CI, 51.8%-85.1%) and 77.4% (95% CI, 58.5%-89.7%), specificity of 96.4% (95% CI, 79.8%-99.8%) and 100% (95% CI, 85.0%-100%), positive predictive value of 95.7% (95% CI, 76.0%-99.8%) and 100% (95% CI, 82.8%-100%), and a negative predictive value of 75.0% (95% CI, 57.5%-87.3%) and 80.0% (95% CI, 62.5%-90.9%), respectively. CONCLUSIONS.­: Our study indicated that C3d-IHC results for paraffin-fixed tissues were not significantly different from DIF results for the diagnosis of pemphigus. The C3d-IHC assay has the potential for routine diagnosis of pemphigus, especially in the absence of fresh-frozen tissue.

Secretory quality control constrains functional selection-associated protein structure innovation.

Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.

Monomeric C-reactive protein level is associated with osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and secondary bone hyperplasia. C-reactive protein (CRP) is an acute-phase protein that is widely used as a marker of inflammation. Elevated plasma levels of CRP are commonly observed in patients with OA during the acute phase. Current evidence indicates that CRP dissociating into a monomeric form (mCRP) is the main functional conformation at inflammatory loci. However, it remains unclear whether mCRP is associated with OA and whether mCRP can be used as a biomarker for its pathogenesis. In the present study, the concentration of CRP, mCRP and anti-mCRP autoantibody were detected by performing ELISA. The levels of plasma CRP, mCRP and anti-mCRP autoantibody between healthy subjects and patients with OA were compared. The results revealed that plasma mCRP was strongly associated with OA, while mCRP autoantibodies exhibited little correlation with this condition. Additionally, it was identified that the plasma mCRP levels in Kellgren-Lawrence (KL) grade 4 patients were significantly higher than in those with KL grade 3. Thus, it was revealed in the present study that plasma level of mCRP is associated with OA, which may directly reflect the disease degree of patients. Therefore, mCRP may be a potential indicator that can be used to monitor the disease activity and evaluate the efficiency of OA therapy.

C-Reactive Protein Protects Against Acetaminophen-Induced Liver Injury by Preventing Complement Overactivation.

BACKGROUND AND AIMS: C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). METHODS: The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post-AILI induction in wild-type mice. RESULTS: CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus-mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. CONCLUSION: Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

Mechanism of allergic rhinitis treated by Centipeda minima from different geographic areas.

CONTEXT: The coriander plant Centipeda minima (L.) A. Braun et Aschers (Compositae) is used for the treatment of allergic rhinitis. OBJECTIVE: Analyze the difference of the C. minima volatile oil from 7 geographic areas and its therapeutic effect on allergic rhinitis. MATERIALS AND METHODS: The volatile oils from different geographic areas were extracted and analyzed, the protein and biological pathway for the treatment of allergic rhinitis were predicted by network pharmacology. Established three groups of Sprague-Dawley rat allergic rhinitis models (n = 10). The treatment group was given 100 µL/nostril of 0.1% C. minima volatile oil, the blank and model groups were given the same amount of normal saline. After 15 days, serum inflammatory factors were detected by ELISA. Nasal mucosa tissues were examined by hematoxylineosin staining and immunuhistrochemistry. RESULTS: There are differences in the content of volatile oil in the seven geographic areas. Experiments showed that the concentration of TNF-α in the serum of the administration group decreased from 63.66 ± 2.06 to 51.01 ± 4.10 (pg/mL), IL-4 decreased from 41.90 ± 3.90 to 28.68 ± 3.39 (pg/mL), IgE decreased from 22.18 ± 1.40 to 17.59 ± 1.60 (pg/mL), IL-2 increased from 314.14 ± 10.32 to 355.90 ± 10.01(pg/mL). Immunohistochemistry showed that compared with the model group, the PTGS2 and MAPK3 proteins in the administration group were significantly reduced. DISCUSSION AND CONCLUSIONS: C. minima volatile oil is a multi-target and multi-pathway in the treatment of allergic rhinitis, which provides a new research basis and reference for the treatment of allergic rhinitis.

Desmoplastic Melanoma: A Clinicopathological Analysis of Three Cases in the Chinese Population.

PURPOSE: To investigate the clinicopathological characteristics and immunophenotype of desmoplastic melanoma (DM) in the Chinese population. PATIENTS AND METHODS: We report three cases of DM diagnosed by the Pathology Department of Shanghai Dermatology Hospital. We describe the clinical and pathological characteristics of the three cases and examine molecular markers used in the diagnosis of DM. Finally, we summarize the current literature in the DM field. RESULTS: Clinically, lesions in the three DM patients were characterized by non-pigmented nodules or papules. Microscopically, we observed an abundance of fibrous interstitium mixed with spindle cells exhibiting various degrees of atypia. Occasionally, these structures exhibited changes in lentigo maligna at the epidermal junction, accompanied by the presence of lymphoid follicular structures and neurophilic behavior. Diagnosis of DM was confirmed by immunohistochemical staining, which revealed high expression levels of S-100 and SOX-10. Melanocyte markers were focally positive or negative. Unlike DMs from other populations, our three patients were negative for WT-1 and P53. All three cases received surgical resection, which is the preferred treatment for DM, and none of the patients experienced recurrence. CONCLUSION: DM in these Chinese patients was similar to that observed in other DM populations in terms of immunophenotype and clinical and histological features. A notable absence in p53 staining was observed in the three cases reported here, suggesting that p53 negativity should not exclude the diagnosis of DM in the Chinese population.

Diagnostic efficacy of different pathologic methods for assessing tissue obtained by endoscopic ultrasound-guided fine needle aspiration: a prospective study.

AIMS: The best method for processing specimens by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has not been standardized and varies considerably between medical centers. The purpose of this study is to explore whether a combination of histologic and cytologic methods can increase the diagnostic efficacy of EUS-FNA in solid lesions around the digestive tract. METHODS: We recruited 52 patients (65 cases total) with solid lesions around the digestive tract who underwent EUS-FNA as performed by the same endoscopic physician from December 2016 to January 2018. All the EUS-FNA specimens were processed by conventional smear cytology (CS), liquid-based cytology (LBC), cell block (CB), and histopathology. All the pathologic results were tracked to investigate the diagnostic value of the methods. RESULTS: Fifty-three malignant lesions and 12 benign lesions were analyzed. The diagnostic accuracy levels of the CS, LBC, CB, and histopathology were 96.9%, 89.2%, 91.9%, and 48.1%, respectively. CS had a higher diagnostic accuracy than CB (P < 0.05) and LBC (P < 0.05). The cytologic methods had a significantly higher diagnostic accuracy than histopathology (P < 0.05). The combined diagnostic accuracy of all the methods was 100%. The diagnostic sensitivities of the CS, LBC, CB and histopathology were 96.2%, 86.8%, 90.4%, and 37.2%, respectively, and the diagnostic specificity of each of the four methods was 100%. CONCLUSIONS: Different pathological methods can compensate for one another, substantially improving the overall positive detection rate of EUS-FNA. Combining cytology and histology can contribute additional diagnostic efficacy to EUS-FNA in solid lesions around the digestive tract.

Vasohibin 1, a clinically relevant biomarker, contributes to pre-eclampsia.

BACKGROUND: Pre-eclampsia is a leading health threat for pregnant women which is characterised by hypertension and proteinuria. The detailed mechanism is elusive and no effective therapy is available. Predictive biomarkers are needed for accurate diagnosis. Vasohibin-1 (VASH1) is an intrinsic inhibitor of angiogenesis induced by angiogenic factors in endothelial cells. This study aimed to evaluate the role of VASH1 as a useful biomarker for pre-eclampsia. METHODS: VASH1 level was examined by ELISA and immunoblotting assay in the serum and placental samples from healthy pregnant women and pre-eclampsia patients. Cellular assay was performed to assess cell migration and invasion with different levels of VASH1. The level of VASH1 was measured under different oxygen conditions by qPCR. RESULTS: VASH1 was highly expressed in the serum and placenta of pre-eclampsia patients. Overexpression of VASH1 led to attenuated cell migration and invasion ability and reduced levels of matrix metallopeptidase 2 and 9. VASH1 was significantly induced in primary human trophoblast cells and placental explants under hypoxic condition in hypoxia-inducible factor 1 alpha-dependent manner. CONCLUSION: Our study suggested that VASH1 could be used as a potentially novel biomarker for pre-eclampsia and its level may positively correlate with the disease status.

Action mechanism of Roman chamomile in the treatment of anxiety disorder based on network pharmacology.

Anxiety disorder is a common psychiatric disease. Roman chamomile as medicine or tea has long been used as a mild tranquilizer to reduce anxiety, but the mechanism is unclear. This research is based on network pharmacology combined with database mining to find the ingredients, action pathways and key targets of Roman chamomile for the treatment of anxiety. About 126 common targets related to chamomile and anxiety were obtained, and these targets were involved in 56 KEGG pathways. GEO screened LRRK2 as a key protein, and molecular docking showed that the protein could stably bind to drug components. Roman chamomile has the characteristics of multi-target and multi-pathway in the treatment of anxiety disorder. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as neuroactive ligand-receptor interaction, serotonin synapse, and cAMP signaling pathway. LRRK2 may be an important gene for Roman chamomile in the treatment of anxiety disorder. PRACTICAL APPLICATIONS: Roman chamomile is well known for its use in medicine and tea making. It contains many nutrients, which can relieve people's anxiety, help sleep, antibacterial and anti-inflammatory. In this article, through network pharmacology combined with Gene Expression Omnibus data mining and molecular docking, the target and mechanism of Roman chamomile in the treatment of anxiety were discussed, and its efficacy was verified by model animals, which not only clarified its mechanism at the systematic level, but also proved to be effective at the biological level. It provides a reference for the further development and utilization of Roman chamomile.

Corrigendum: Monomeric C-Reactive Protein Binds and Neutralizes Receptor Activator of NF-κB Ligand-Induced Osteoclast Differentiation.

[This corrects the article DOI: 10.3389/fimmu.2018.00234.].

Preparation and quality evaluation of a volatile oil microemulsion from Flos magnoliae and Centipeda minima.

In order to improve the water solubility of the volatile oils extracted from Flos magnoliae (FM) and Centipeda minima (CM), they were prepared as a microemulsion (ME), which were then used in the development of an FM and CM volatile oil ME for the treatment of allergic rhinitis (AR). ME was prepared by phase inversion emulsification, and the prescription factors such as emulsifier, co­emulsifier, oil phase, Km, which represents the ratio of the mass of emulsifier to that of the co­emulsifier, and preparation factors such as temperature affecting the formation of the ME were selected according to the formation area of ME in a pseudo­ternary phase diagram. The quality of the ME was evaluated based on its appearance, particle size, Zeta potential and stability. The content of eucalyptol in ME was determined by gas chromatography­mass spectrometry (GC­MS). The cumulative permeability of the ME within 24 h was measured with a transdermal diffusion tester. The results revealed that the best formula for preparation of the ME was as follows: Castor oil polyoxyethylene ether (EL­40) was the emulsifier; the co­emulsifier was anhydrous ethanol; the Km was 2:1; the mixed phase of volatile oil and isopropyl myristate with mass ratio of 1:1 was used as oil phase; and the preparation temperature was 25˚C. The content of eucalyptol in the ME was 2.57 mg/g, and the cumulative permeability of the ME in 24 h was significantly increased compared with that of the reference oil solution. The appearance of the ME was uniform, and the solution was transparent. In conclusion, compared with traditional preparations, FM and CM volatile oil ME is a novel, improved and more effective preparation for the treatment of AR.

Paeoniflorin attenuates gestational diabetes via Akt/mTOR pathway in a rat model.

BACKGROUND: Gestational diabetes mellitus (GDM) is a type of diabetes associated with pregnancy and may impose risks on both mother and fetus. Akt paeoniflorin was shown to have anti-inflammatory and anti-hyperglycemia properties and has a potential ability to suppress mammalian target of rapamycin (mTOR) signaling. The current study aimed to study the effect of paeoniflorin on GDM maternal, fetal, and placental characteristics in vivo. METHODS: Streptozotocin (STZ)-induced gestational diabetes rat model was used in our study. The expression levels of phosphorylation (p-) and total protein expression levels of protein kinase B (Akt), mTOR, serum/glucocorticoid regulated kinase 1 (SGK1), and eIF4E-binding protein 1 (4E-BP1) in the placenta were determined by Western blot assay. The blood glucose, insulin, and leptin levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that placental Akt/mTOR signaling was substantially upregulated in GDM patients compared with healthy donors. Paeoniflorin administration alleviates the dysregulation of blood glucose, leptin, and insulin levels in both maternal and fetal GDM rats. Paeoniflorin treatment suppressed the overactivation of Akt/mTOR signaling in placental tissues. More importantly, administration of paeoniflorin was beneficial for normalization of fetal size and body weight in the GDM rats. CONCLUSION: Our study suggested that application of paeoniflorin may serve as a potential therapeutical strategy for patients with GDM.

Network pharmacology exploration reveals a common mechanism in the treatment of cardio-cerebrovascular disease with Salvia miltiorrhiza Burge. and Carthamus tinctorius L.

BACKGROUND: This study aimed to identify the key genes and KEGG pathways in Carthamus tinctorius L. (Safflower) and Salvia miltiorrhiza Burge. (Salvia) for the treatment of cardio-cerebrovascular disease, and to explore their potential molecular mechanisms. METHODS: Compounds and targets in Safflower and Salvia were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We obtained targets of myocardial infarction (MI) and cerebral infarction (CI) data from Therapeutic Target Database (TTD), Drugbank and DisGeNET datasets. The network of Safflower, Salvia, CI and MI was established and then executing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the functional characteristics were performed. The Chinese herbal prescription and target for CI and MI were obtained by searching in the database. Finally, the main pathways of Salvia and Safflower in Chinese patent medicines were analyzed. The MCAO model was established in rats, and compatibility of salvia with safflower was experimentally verified. RESULTS: We obtained a total of 247 genes targeted by 52 compounds from Safflower and 119 genes targeted by 48 compounds from Salvia. In total, we identified 299 known therapeutic targets for the treatment of CI and 960 targets for the treatment MI. There are 23 common targets for Salvia, Safflower, MI, and CI. A total of 85 KEGG pathways were also enriched and intersected with the pathway of proprietary Chinese medicine to yield 25 main pathways. Safflower and Salvia have the best therapeutic effect in MCAO. CONCLUSION: We identified gene lists for Safflower and Salvia in CI and MI. Bioinformatics and interaction analyses may provide new insight into the treatment of cardio-cerebrovascular diseases with Safflower and Salvia.

Stable Rhodium (IV) Oxide for Alkaline Hydrogen Evolution Reaction.

Water electrolysis in alkaline electrolyte is an attractive way toward clean hydrogen energy via the hydrogen evolution reaction (HER), whereas the sluggish water dissociation impedes the following hydrogen evolution. Noble metal oxides possess promising capability for catalyzing water dissociation and hydrogen evolution; however, they are never utilized for the HER due to the instability under the reductive potential. Here it is shown that compressive strain can stabilize RhO2 clusters and promote their catalytic activity. To this end, a strawberry-like structure with RhO2 clusters embedded in the surface layer of Rh nanoparticles is engineered, in which the incompatibility between the oxide cluster and the metal substrate causes intensive compressive strain. As such, RhO2 clusters remain stable at a reduction potential up to -0.3 V versus reversible hydrogen electrode and present an alkaline HER activity superior to commercial Pt/C.

A Study on the Mechanism of Lavender in the Treatment of Insomnia Based on Network Pharmacology.

AIMS AND OBJECTIVE: The common disease of insomnia has complex and diverse clinical manifestations. Lavender represents an effective treatment of insomnia, but the molecular mechanism underlying the effectiveness of this treatment is not clear. The purpose of this study is to investigate the active components, target proteins and molecular pathways of lavender in the treatment of insomnia, thus explaining its possible mechanism. MATERIALS AND METHODS: Firstly, 54 active components of lavender were identified by gas chromatography-mass spectrometry (GC-MS). The target protein of lavender was predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and the target protein of insomnia was predicted by the DisGeNET and DrugBank databases. Then, the "component-target-disease" network diagram was constructed using the Cytoscape 3.7.1 software. KEGG and GO enrichments were analyzed using the R statistical language. Finally, the key target proteins were verified by collecting and verifying the target protein GEO data using the Discovery Studio 3.5 molecular docking verification software. RESULTS: 906 target proteins of lavender were predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and 182 insomnia target proteins were predicted by the DisGeNET and DrugBank databases. The results of GO enrichment analysis showed that it included the reaction process of ammonium ion, the regulation of the membrane potential and the secretion of catecholamine, while the results of KEGG enrichment included the calcium signaling pathway, serotonin synapse, morphine addiction and many more. Finally, using the Discovery Studio3.5 molecular docking verification software, it was verified that the key target proteins are ADRB1 and HLA-DRB1. CONCLUSION: The components in the lavender essential oil include the Ethyl 2-(5-methyl-5-vinyltetrahydrofuran- 2-yl)propan-2-ylcarbonate (0.774); 5-Oxatricyclo[8.2.0.04,6]dodecane, 4,12,12-trimethyl- 9-methylene-, (1R,4R,6R,10S)-(0.147); P-Cymen-7-ol (0.063); .alpha-Humulenem (0.317); Acetic acid, hexyl ester (1.374); etc. The role lavender plays in the treatment of insomnia might be accomplished through the regulation of the key targets ADRB1 and HLA-DRB1.

Randomized Controlled Trials of Tianma Gouteng Decoction Combined with Nifedipine in the Treatment of Primary Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertension is a primary risk factor for cardiovascular disease (CVD). Tianma Gouteng decoction (TGD), originating from Zabingzhengzhixinyi, has been used for thousands of years in China to treat hypertension, giddiness, and migraine. This updated meta-analysis aimed at assessing the efficacy and safety of TGD combined with nifedipine in the treatment of primary hypertension. METHODS: Related research published prior to September 1, 2019, was found in electronic databases without language limitations. Fourteen studies were selected and analyzed for specified criteria, including the quality of the studies. All outcomes were recorded exhaustive. Data management and analysis were performed using RevMan 5.3 software. RESULTS: A total of 1,537 (769 cases in the experimental group and 768 cases in the control group) patients were enrolled. The total efficacy rate was improved significantly for the combination of nifedipine with TGD compared to nifedipine treatment alone (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (P < 0.00001) when two studies (shicaihong 2017 and xiaoyugao 2017) were removed. And the results of DBP showed no heterogeneity (I 2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (P < 0.00001) when two studies (shicaihong 2017 and xiaoyugao 2017) were removed. And the results of DBP showed no heterogeneity (. CONCLUSION: The combination of TGD and nifedipine has a better effect in the treatment of hypertension, including blood pressure lowering and patients' TCMs improving. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results.