NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation.

The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. henryi. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways.

Morphology-Tailored Hydroxyapatite Nanocarrier for Rhizosphere-Targeted Phosphorus Delivery.

High hydrophilicity and soil fixation collectively hamper the delivery of phosphorus (P) released from conventional chemical phosphorus fertilizers (CPFs) to plant rhizosphere for efficient uptake. Here, a phosphorus nutrient nanocarrier (PNC) based on morphology-tailored nanohydroxyapatite (HAP) is constructed. By virtue of kinetic control of building blocks with designed calcium phosphate intermediates, rod-like and hexagonal prism-like PNCs are synthesized, both having satisfactory hydrophobicity (water contact angle of 105.4- 132.9°) and zeta potential (-17.43 to -58.4 mV at pH range from 3 to 13). Greenhouse experiments demonstrate that the P contents increase by up to 183% in maize rhizosphere and up to 16% in maize biomass when compared to the CPF. Due to the water potential gradient driven by photosynthesis and transpiration, both PNCs are stably transported to maize rhizosphere, and they are capable to counteract soil fixation prior to uptake by plant roots. Within the synergies of the HAP morphological characteristics and triggered phosphate starvation response, root anatomy confirms that two pathways are elucidated to enhance plant P replenishment from the PNCs. Together with structure tunability and facile synthesis, our results offer a new nanodelivery prototype to accommodate plant physiological traits by tailoring the morphology of HAP.

Botany, traditional usages, phytochemistry, pharmaceutical analysis, and pharmacology of Eleutherococcus nodiflorus (Dunn) S.Y.Hu: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus nodiflorus (Dunn) S.Y.Hu (Araliaceae), also called Eleutherococcus gracilistylus, Acanthopanax gracilistylus, and Xi-zhu-wu-jia (Wujiapi or Nan Wujiapi) in Chinese, is a widely used traditional Chinese herb with the effects of dispelling pathogenic wind and eliminating dampness, nourishing liver and kidney, diuresis and detumescence, promoting blood circulation for removing blood stasis, and strengthening the bones and tendons according to the theory of Traditional Chinese Medicine (TCM). It has been used as medicine for the treatment of paralysis, arthritis, rheumatism, lameness, body asthenia, fatigue, edema, beriberi, and liver diseases. Meanwhile, E. nodiflorus (EN, thereafter) has ginseng-like activities known as "ginseng-like herb". AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of EN, including taxonomic position, botany, traditional usages, phytochemistry, pharmaceutical analysis, pharmacology and toxicology. Among them, phytochemical and pharmacological studies are mainly focused. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Web of Science, PubMed, Google Scholar, Baidu Scholar, SciFinder and Chinese national knowledge infrastructure (CNKI). Monographs and Chinese pharmacopeia were also utilized as references. RESULTS: In the past decade, a great number of phytochemical and pharmaceutical analyses, as well as pharmacological studies on EN have been carried out. Several kinds of chemical compositions have been reported, including essential oil, sesquiterpenes, diterpenes, triterpenes, phenylpropanoids, lignans, caffeoyl quinic acids, flavonoids, steroids, fatty acids, ceramides as well as other compounds, among which, diterpenes and triterpenes were considered to be the most active components. The fingerprint chromatography, qualitative and quantitative analysis were used for the methods of quality control of EN. Considerable pharmacological experiments in vitro and in vivo have demonstrated that EN possessed hypoglycemic, anti-inflammatory, anticancer, anti-ageing, anti-fatigue, immunomodulatory, hepatoprotective, antioxidant, anti-AChE, anti-BuChE, anti-hyaluronidase, and antiobesity activities. CONCLUSIONS: As an important TCM, a large number of investigations have proved that EN and terpenoids isolated from EN have markedly therapeutic efficacy on diabetes, inflammation, and cancer disorders. These research findings provide modern scientific evidence for the traditional uses of EN. Moreover, more novel and active secondary metabolites from EN, as well as the in vivo and clinical in-depth tests are required in the future.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.

Background: Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods: Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results: The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1ß, TNF-α, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1ß, TNF-α, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions: Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.

Corydalis Rhizoma as a model for herb-derived trace metabolites exploration: A cross-mapping strategy involving multiple doses and samples.

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients. However, most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts, making it difficult to achieve comprehensive detection and identification. In this paper, an efficient strategy was proposed: herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted. The fragmentation patterns were summarized from representative standards combining with specific cleavage behaviors to deduce structures of metabolites. Ion abundance plays an important role in compound identification, and high ion abundance can improve identification accuracy. The types of metabolites in different biological samples were very similar, but their ion abundance might be different. Therefore, for trace metabolites in biological samples, we used the following two methods to process: metabolites of high dose herbal extract were analyzed to characterize those of clinical dose herbal extracts in the same biological samples; cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples. Compared with not using this strategy, 44 more metabolites of clinical dose herbal extract were detected. This study improved the depth, breadth, and accuracy of current methods for herb-derived metabolites characterization.

Combination of HDE and BIIB021 efficiently inhibits cell proliferation and induces apoptosis via downregulating hTERT in myelodysplastic syndromes.

Treatment for higher-risk patients with myelodysplastic syndrome (MDS) should aim to modify the disease course by avoiding progression to acute myeloid leukemia and improving survival. When a patient is not eligible for intensive chemotherapy and lacks a donor hematopoietic cell source, or for a patient in a poor economic situation, consideration can be given to the use of Chinese herbal medicine. Numerous plant extracts, such as camptothecin, vinblastine and paclitaxel, have been reported to display antitumor effects, serving as potential therapeutic strategies for cancer. In the present study, the ultra-performance liquid chromatography-tandem mass spectrometry system (Waters Corporation) was used to detect the main chemical components of HDE, CCK-8 assay to detect the effects of HDE and BIIB021 on the proliferation of SKM-1 cells; and designed hTERT-small interfering (si)RNAs to detect the effects of HDE and BIIB021 on SKM-1 cell apoptosis after HTERT gene knockdown. The present study investigated a newly extracted coumarin HDE, the active component in Oldenlandia diffusa Willd, which efficiently inhibited SKM-1 (MDS cell line) proliferation and induced apoptosis, as determined by performing Cell Counting Kit-8 and flow cytometry assays, respectively. The effect of HDE was associated with decreased telomerase activity. Moreover, heat shock protein 90 inhibitor BIIB021 significantly enhanced the antitumor effects of HDE on SKM-1 cells. In addition, SKM-1 cell apoptosis was increased in human telomerase reverse transcriptase (hTERT)-knockdown cells compared with the negative control group. Cell apoptosis in hTERT-knockdown SKM-1 cells was further enhanced following HDE, BIIB021 or combination treatment, as evidenced by increased levels of cleaved caspase 3, cleaved caspase 8 and cleaved poly ADP ribose polymerase. Collectively, the results indicated synergistic antitumor effects of HDE and BIIB021, providing a novel therapeutic combination for higher-risk MDS.

Acanthopanax henryi: Review of Botany, Phytochemistry and Pharmacology.

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Serum metabolic profiling of traditional Chinese medicine syndromes in patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION: The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

A review on traditional usages, chemical constituents and pharmacological activities of periploca forrestii schltr.

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca forrestii Schltr. was listed as a classical medicinal plant in "Miao medicine", which is a branch of traditional Chinese medicine (TCM). According to the theory of TCM, P. forrestii has the efficacy of relaxing tendons and activating collaterals, and dispelling wind and eliminating dampness. Hence, it was often used for the therapy of rheumatoid arthritis and traumatic injury in clinical practice. AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of P. forrestii. The researches on botany, traditional uses, phytochemistry, pharmacology and toxicology of the plant are summarized. We mainly focus on the phytochemical and pharmacological investigations. As a representative class of phytochemicals in P. forrestii, more attention is paid to cardiac glycosides. The insights into potential action of mechanisms and possible future studies on P. forrestii are also discussed. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed and Chinese national knowledge infrastructure. Monographs and Chinese pharmacopoeia were also utilized as references. RESULTS: To date, all kinds of phytochemical constituents have been isolated and identified from this plant including cardiac glycosides, steroids, terpenoids, flavonoids, phenylpropanoids, quinones, organic phenolic acids and others. Among these, cardiac glycosides were considered as the major ingredients and bioactive materials. Modern pharmacological studies demonstrated that the plant possessed extensive bioactivity, such as anti-inflammatory and analgesic effects, immunosuppressive action, wound healing activity, antioxidant, anti-tumor and, cardiotonic properties. CONCLUSIONS: As an important medicinal plant, lots of studies have proved that P. forrestii has significant therapeutical effects, especially on rheumatoid arthritis and traumatic injury. These results provide modern scientific evidence for traditional use and contribute to the development of novel remedies for chronic diseases. However, the exact mechanism of action remains to be elucidated. Furthermore, the long-term in vivo toxicity and clinical efficacy also require in-depth exploration in the future.

Corydalis Rhizoma as a model for herb-derived trace metabolites exploration:A cross-mapping strategy involving multiple doses and samples / 药物分析学报

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from represen-tative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to char-acterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

Efficient recovery of phosphorus in sewage sludge through hydroxylapatite enhancement formation aided by calcium-based additives.

Reclaiming abundant phosphorus from sewage sludge (SS) via pyrolysis for use as a fertilizer has gained increasing attention owing to the rapid depletion of global P reserves. In this study, the enhancement effect of Ca-based additives on sludge P transformation to hydroxylapatite through pyrolysis was systematically investigated. Three Ca-based additives were added in the pyrolysis of SS, and they were found to promote the conversion of sludge P to hydroxylapatite, which is bioavailable to plants. The characterization of the sludge-derived pyrochars indicated that the addition of 10% CaO, 5% Ca(OH)2, or 10% Ca3(PO4)2 facilitated peak hydroxylapatite production. The thermodynamic simulation of the production of hydroxylapatite during pyrolysis showed that these additives increased the enthalpy of the pyrolysis system. Furthermore, the pyrolysis with CaO addition had the lowest enthalpy, thereby suggesting that the addition of CaO during sludge pyrolysis was preferable for recovering sludge P in the form of hydroxylapatite. Moreover, the hydroxylapatite produced with these additives was unstable when the pyrolysis temperature was above 900 °C. The pot experiment demonstrated the feasibility using the sludge-derived pyrochars as P fertilizer for plant growth. Therefore, changing the Ca form and/or Ca/P ratio with the addition of Ca-based additives could be an effective strategy for reclaiming P from SS in the form of hydroxylapatite, and this demonstrates a pathway for global P sustainability by recycling P from P-abundant wastes.

Platelet-Rich Plasma Vs Autologous Blood Vs Corticosteroid Injections in the Treatment of Lateral Epicondylitis: A Systematic Review, Pairwise and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the effectiveness of platelet-rich plasma (PRP), autologous blood (AB), and corticosteroid injections in patients with lateral epicondylitis. TYPE OF STUDY: Network meta-analysis. LITERATURE SURVEY: Randomized controlled trials (RCTs) that compared any two forms of injections among PRP, AB, and corticosteroid for the treatment of lateral epicondylitis were searched from inception to 30 November 2018, on PubMed, Embase, and Cochrane library. METHODOLOGY: Two researchers independently selected and assessed the quality of RCTs with the Cochrane Risk of Bias Tool. All relevant data from the included studies were extracted and heterogeneity was checked by Cochran's Q test and inconsistency statistic (I2 ). Publication bias was evaluated by constructing contour-enhanced funnel plots. Stata 15 software was applied for pairwise meta-analysis and network meta-analysis. To explore the efficacy between different follow-up periods, we considered the duration within 2 months to be short term, whereas 2 months or more was considered long term. SYNTHESIS: Twenty RCTs (n = 1271) were included in this network meta-analysis. According to ranking probabilities, corticosteroid ranked first for visual analog score (VAS) (surface under the cumulative ranking [SUCRA] = 90.7), modified Nirschl score (82.9), maximum grip strength (69.5), modified Mayo score (MMS) (77.9), and Patient-Related Tennis Elbow Evaluation (PRTEE) score (93.3) for the short-term period. For the long-term period, PRP ranked first for VAS (94.3), pressure pain threshold (99.8), Disabilities of Arm Shoulder and Hand (DASH) score (75.2), MMS (88.2), and the PRTEE score (81.8). CONCLUSION: PRP was associated with more improvement in pain intensity and function in the long term than were the comparators. However, in the short term, corticosteroids were associated with the most improvement.