Discussion on the mechanism of Danggui Sini decoction in treating diabetic foot based on network pharmacology and molecular docking and verification of the curative effect by meta-analysis.

Objective: The main active components and mechanism of Danggui Sini decoction (DSD) in treating diabetic foot (DF) were studied and verified by network pharmacology and molecular docking. Evidence-based medicine was used to prove its efficacy. Methods: The TCMSP systematic pharmacology platform screened out DSD's practical components and targets-screening disease targets in GeneCards database, using Cytoscape 3.7.2 to draw DSD-active ingredient-target network diagram, and drawing the protein interaction network diagram through STRING database. The Metascape platform was used to analyze the GO function enrichment and KEGG signal pathway. The molecular docking experiment was carried out by using Auto Dock vina 4.2. The related literature on DSD in treating DF in China Zhiwang, Wanfang, Weipu, and China Biomedical Literature Database was searched. The literature was screened, data was extracted, and quality was evaluated according to the inclusion and exclusion criteria. Then, a meta-analysis was performed using RevMan 5.3 software. Results: A total of 256 targets of all effective components of DSD were obtained. Among 1,272 disease targets, there are 113 common targets. The GO analysis received 6,179 entries, and the KEGG pathway enrichment analysis found 251 related pathways. The molecular docking results of the main targets of diabetic foot and the active substances of DSD all showed a high docking activity. The meta-analysis included six literature, all of which were randomized controlled experiments. The quality grade of the literature was C, and the results showed that the total effective rate of clinical efficacy in the experimental group was significantly higher than that in the control group. Conclusions: DSD may treat DF by participating in biological processes such as cell proliferation regulation, inflammatory reaction, oxidative stress reaction, and promotion of angiogenesis. DSD treats DF through AKT1, TP53, IL6, TNF, VEGFA, and other targets. DSD plays a role in treating DF mainly through the AGE-RAGE signaling pathway and PI3K-AKT signaling pathway. The molecular docking results of AKT1, TP53, IL-6, TNF, and VEGFA with the active substances of DSD show that they all have a high docking activity; among them, VEGFA has a higher docking activity. Compared with conventional treatment, DSD has a high effective rate, short wound healing time, large wound healing area, and high ABI index.

Synthesis of a high-iron fly-ash-based Na-X molecular sieve and its application in the adsorption of low concentration of CO2.

In addressing the environmental challenges posed by the accumulation of fly ash (FA), efforts have been geared towards its high-value utilization. By the use of high-iron FA as a raw material, a high-iron fly-ash-based Na-X molecular sieve was successfully synthesized by hydrothermal method. We combined pretreatment methods such as high-temperature calcination, acid leaching and alkali fusion activation. The as-synthesized product was used for the adsorption of a low concentration of CO2, and the adsorption data were fitted by a physical model. The changes in iron content in pretreatment and molecular sieve synthesis were revealed by SEM-mapping, UV-Raman and UV-Vis. The results showed that the pretreatment process reduces the iron content from 32.3% to 13.3%, and converts the inactive phases to active phases, with n (SiO2/Al2O3) = 4.94. The activated product was transformed further to a Na-X molecular sieve using a hydrothermal method. The product has a single crystal phase and octahedral crystal structure. Its specific surface area was 646.634 m2 g-1, and micropores were distributed between 0.46 nm and 0.71 nm, with a mesoporous phase of 4.6 nm. When used to adsorb a low concentration of CO2, the Na-X molecular sieve has a high adsorption capacity of 3.70 mmol g-1, which reaches 95.11% that of the commercial Na-X molecular sieve. The adsorption breakthrough time and adsorption capacity decreased with an increase in temperature. The adsorption kinetics were consistent with the Bangham model for surface pore adsorption and Weber-Morris model for internal diffusion. During the synthesis process, iron was converted from highly dispersed iron oxide to four-coordinated framework iron. Thus, this paper paves a path for the high-quality transformation and utilization of high-iron fly-ash.

Linear Strain Sensors via a Spatial Heteromodulus Tricontinuous Structure Design for High-Resolution Recording of Snoring Breath.

Porous conductive elastomer composites are very attractive for designing flexible and air-permeable mechanical sensors for healthcare, while it is challenging to achieve a linear and sensitive electromechanical response over a wide strain range for high-resolution recording of physiological activities and body motions. Here, a scalable strategy is developed to construct porous elastomer composites with a bamboo-shaped heteromodulus microstructure in the pores for the fabrication of linear stretchable strain sensors. Such a spatial heteromodulus microstructure is fabricated via phase separation and selective location of high-modulus phase during melt compounding of elastomers and thermoplastics, together with green etching of the water-soluble plastic in the tricontinuous elastomer composites. The bamboo-shaped heteromodulus microstructure is constructed on the pore struts via the fracture of a high-modulus polymer self-assembled on the pore surface and relaxation recovery of the elastomer matrix after prestretching, which blocks the propagation of cut-through microcracks upon stretching. The composites with super low resistance after in situ growth of silver nanoparticles sustain up to 110% tensile strain with a linear and sensitive electromechanical response, demonstrating potential applications in discriminating respiration status and monitoring snoring breath. This work unveils a new approach to fabricate high-performance air-permeable strain sensors in a simple and scalable way.

Highly expressed RPLP2 inhibits ferroptosis to promote hepatocellular carcinoma progression and predicts poor prognosis.

BACKGROUND: RPLP2, an integral part of ribosomal stalk, plays an important role in the tumorigenesis of various cancers. However, its specific effect on HCC remains elusive. METHODS: TCGA, GTEx, HCCDB, HPA, UALCAN, MethSurv, TISIDB, K-M plotter, FerrDb, RNAactDrug, STRING, Cytoscape and R studio were conducted for bioinformatics analysis. RPLP2 expression level in HCC was verified by IHC and western blot. IHC was used to demonstrate the immune cell infiltration. Functional experiments including CCK8, transwell and colony formation assays, and nude mice xenograft model were performed for in vitro and in vivo validation. Western blot, IHC, CCK8 assay and detection of GSH and lipid ROS were adopted to determine the effect of RPLP2 on the ferroptosis of HCC cells. RESULTS: Here, we demonstrate that elevated level of RPLP2 is strongly associated with advanced clinicopathologic features, and predicts poor prognosis of HCC patients. Additionally, DNA methylation level of RPLP2 decreases in HCC, and significantly correlates with patients outcome. Moreover, high RPLP2 expression level is linked closely to the unfavorable immune infiltration. Most importantly, RPLP2 positively associates with ferroptosis suppressor GPX4, and inhibition of RPLP2 could lead to the acceleration of ferroptosis to suppress tumor progression of HCC. Last, drug sensitivity analysis predicts many drugs that potentially target RPLP2. CONCLUSION: Together, our study reveals previous unrecognized role of RPLP2 in HCC, and provides new regulatory mechanism of ferroptosis, indicating RPLP2 may be a novel therapeutic target for HCC.

Research on an Intelligent Mining Complete System of a Fully Mechanized Mining Face in Thin Coal Seam.

The mining environment of thin coal seam working faces is generally harsh, the labor intensity is high, and the production efficiency is low. Previous studies have shown that thin coal seam mining finds it difficult to follow machines, does not have complete sets of equipment, has a low degree of automation, and has difficult system co-control, which easily causes production safety accidents. In order to effectively solve the problems existing in thin coal seam mining, Binhu Coal Mine has established intelligent fully mechanized mining and actively explored automatic coal cutting, automatic support following, and intelligent control. The combination of an SAC electro-hydraulic control system and SAP pumping station control system has been applied in 16,108 intelligent fully mechanized coal mining faces, which realizes the automatic following of underground support and the control of adjacent support, partition support, and group operation; the automatic coal cutting of the shearer is realized by editing the automatic coal-cutting state of the shearer and adjusting the automatic parameters. A centralized control center is set up, which realizes the remote control and one-button start-stop of working face equipment. Through a comparative analysis of 16,108 intelligent fully mechanized mining faces and traditional fully mechanized mining faces, it is found that intelligent fully mechanized mining faces have obvious advantages in terms of equipment maintenance, equipment operation mode, and working face efficiency, which improve the equipment and technical mining level of thin coal seam. The application of intelligent mining in Binhu Coal Mine has a great and far-reaching impact on the development of thin coal seam mining technology in China.

Analysis of the efficacy and factors influencing survival of adjuvant radiotherapy for stage II-III biliary tract carcinoma.

BACKGROUND: To determine the efficacy of adjuvant radiotherapy for stage II-III biliary tract carcinoma. METHODS: We retrospectively analyzed the data of 37 patients who underwent radical resection of biliary tract carcinomas at the Affiliated Hospital of Inner Mongolia Medical University between 2016 and 2020. We analyzed survival differences between patients who did (n = 17) and did not (n = 20) receive postoperative adjuvant radiotherapy by using Kaplan-Meier analysis. The log-rank test and Cox univariate analysis were used. The Cox proportional risk regression model was used for the multifactorial analysis of factors influencing prognosis. RESULTS: The median survival time (28.9 vs. 14.5 months) and the 1-year (82.40% vs. 55.0%) and 2-year survival rates (58.8% vs. 25.0%) were significantly higher among patients who received adjuvant radiotherapy than among those who did not (χ2 = 6.381, p = 0.012). Multifactorial analysis showed that pathological tumor type (p = 0.004), disease stage (p = 0.021), and adjuvant radiotherapy (p = 0.001) were independent prognostic factors in biliary tract carcinoma. Subgroup analyses showed that compared to no radiotherapy, adjuvant radiotherapy significantly improved median survival time in patients with stage III disease (21.6 vs. 12.7 months; p = 0.017), positive margins (28.9 vs. 10.5 months; p = 0.012), and T3 or T4 tumors (26.8 vs. 16.8 months; p = 0.037). CONCLUSION: Adjuvant radiotherapy significantly improved the survival of patients with biliary tract carcinoma, and is recommended especially for patients with stage III disease, positive surgical margins, or ≥ T3.

Study of the mechanical characteristics of coal-serial sandstone after high temperature treatment under true triaxial loading.

In this study, a series of true triaxial loading tests were carried out on coal-measure sandstone after high temperature treatment by using a self-developed true triaxial test system combined with acoustic emission (AE) monitoring, and the mass loss, deformation characteristics and loss failure mode of sandstone before and after heat treatment were systematically studied. It is found that the true triaxial mechanical properties of sandstone after high temperature treatment are closely related to temperature, and the peak strength, maximum principal strain, volume strain, minimum fracture angle and elastic modulus, which all showed bimodal changes, and 800 °C is the threshold temperature of the first four parameters. The transition temperature of the elastic modulus is 400 °C. It is found that the test results of true triaxial high temperature sandstone are in good agreement with the existing true triaxial theory and test results. The failure forms of the samples at different temperatures show inverted "Y" or inverted "N" shapes. Shear failure occurs when the temperature is below 400 °C, and shear-tension failure occurs when the temperature is above 600 °C. At the same time, it is found that the AE signal has four periods, namely the quiet period, growth period, explosion period and decline period. The number of AE events corresponds to the deviatoric stress interval well. Experimental study of the mechanical properties of sandstone under the coupling effect of high temperature and true triaxial stress has guiding significance for the parameter selection and safety evaluation of roof sandstone in underground coal gasification.

The ubiquitin-specific protease 5 mediated deubiquitination of LSH links metabolic regulation of ferroptosis to hepatocellular carcinoma progression.

Epigenetic regulators and posttranslational modifications of proteins play important roles in various kinds of cancer cell death, including ferroptosis, a non-apoptotic form of cell death. However, the interplay of chromatin modifiers and deubiquitinase (DUB) in ferroptosis remains unclear. Here, we found that ubiquitin-specific protease 5 (USP5) is regarded as a bona fide DUB of lymphoid-specific helicase (LSH), a DNA methylation repressor, in hepatocellular carcinoma (HCC). Functional studies reveal that USP5 interacts with LSH and stabilizes LSH by a deubiquitylation activity-dependent process. Furthermore, the USP5-mediated deubiquitination of LSH facilitates the tumorigenesis of HCC by upregulating solute carrier family 7 member 11 (SLC7A11) to suppress ferroptosis of liver cancer cells. Moreover, the USP5 inhibitor degrasyn inhibits DUB activities of USP5 to LSH to suppress the progression of HCC. Additionally, USP5 and LSH are positively correlated and both are overexpressed and linked to poor prognosis in HCC patients. Together, our findings show that USP5 interacts with LSH directly and enhances LSH protein stability through deubiquitination, which, in turn, promotes the development of HCC by suppressing ferroptosis of liver cancer cells, suggesting that USP5 may be a potential therapeutic target for HCC.

A pan-cancer analysis of the role of USP5 in human cancers.

Posttranslational modifications (PTM) such as acetylation, deubiquitination, and phosphorylation of proteins, play important roles in various kinds of cancer progression. Ubiquitin-specific proteinase 5 (USP5), a unique member of deubiquitinating enzymes (DUBs) which recognizes unanchored polyubiquitin specifically, could regulate the stability of many tumorigenesis-associated proteins to influence cancer initiation and progression. However, the diverse biological significance of USP5 in pan-cancer has not been systematically and comprehensively studied. Here, we explored the role of USP5 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, and we also acquired and analyzed data via various software and web platforms such as R, GEPIA2.0, HPA, TISIDB, cBioPortal, UALCAN, TIMER 2.0, CancerSEA and BioGRID. USP5 expression was high in most cancers and differed significantly in different molecular and immune subtypes of cancers. In addition, USP5 had certain diagnostic value in multiple cancers, and high expression of USP5 generally predicted poor prognosis for cancer patients. We also found that the most frequent genetic alterations type of USP5 was mutation, and the DNA methylation level of USP5 decreased in various cancers. Furthermore, USP5 expression correlated with cancer-associated fibroblasts (CAFs), endothelial cells (EC) and genetic markers of immunodulators in cancers. Moreover, the result from single cell sequencing showed that USP5 could regulate several tumor biological behaviors such as apoptosis, DNA damage and metastasis. Gene enrichment analysis indicated "spliceosome" and "RNA splicing" may be the critical mechanism for USP5 to involve in cancer. Taken together, our study elucidates the biological significance of USP5 in the diagnosis, prognosis and immune in human pan-cancer.

Si-integrated lanthanide-doped ferroelectrics for a photomemory based on a photochromic reaction.

We describe a Si-integrated photochromic photomemory based on lanthanide-doped ferroelectric Na0.5Bi2.5Nb2O9:Er3+ (NBN:Er) thin films. We show that upconversion emission can be effectively modulated by up to 78% through the photochromic reaction. The coupling between lanthanide upconversion emission and the photochromic effect ensures rewritable and nondestructive readout characteristics. Moreover, integrating photochromic thin films with Si would benefit from its compatibility with the mature complementary metal-oxide semiconductor (CMOS) technique. These results demonstrate the opportunity to develop more compact photochromic photomemories and related photonic devices.

Mutations and expressions of breast cancer 1/2 in lung cancer.

BACKGROUND: Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) tumor suppressor genes play crucial roles in DNA repair and regulation of transcription. Mutations in these genes are closely associated with the occurrence of cancers. However, the mutation status of BRCA gene in central south Chinese lung cancer patients remains unclear, and its expression levels in lung cancer also need to be further explored. METHODS: In this study, we use next-generation sequencing (NGS) technology to analyze the BRCA genes mutations in 462 central south Chinese lung cancer patients. Public databases including cBioportal, Catalogue Of Somatic Mutations In Cancer (COSMIC), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Expression Profiling Interactive Analysis (GEPIA) are also applied to explore the expression level and mutation status of BRCA in lung cancer patients and their relationships with the prognosis. RESULTS: We found that the mutation rate of BRCA1/2 in central south Chinese lung cancer patients is 4.3% and 6.5% respectively, and missense mutations account for the majority in both BRCA1/2, which are similar to the international status of BRCA1/2 from public databases. In addition, 45 novel mutations of BRCA1/2 in lung cancer are reported in this study. Furthermore, we find that the BRCA2 mutations are negatively correlated with overall survival rate in lung cancer using cBioportal. Last, we demonstrate that both of the mRNA and protein levels of BRCA1/2 are upregulated in lung cancer, and the elevated mRNA expression levels are positively linked with poor prognosis. CONCLUSION: In general, our study better complements knowledge of the BRCA1/2 mutation status in the Chinese lung cancer patients, and firstly reveals the association between BRCA1/2 expression levels and prognosis of lung cancer patients, which may provide great value for the early diagnosis and clinical treatment of lung cancer.

CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Experimental Study on Mechanical and Damage Evolution Characteristics of Coal during True Triaxial Cyclic Loading and Unloading.

Research on the mechanical properties and damage evolution of coal during true triaxial cyclic loading and unloading is of great significance for maintaining the long-term safety and stability of underground engineering structures in coal mines. In this paper, firstly, the deformation, strength and fracturing characteristics of coal during true triaxial loading and true triaxial cyclic loading and unloading were analyzed. Then, the residual strain characteristics, energy distribution and evolution of coal were systematically studied. Additionally, the damage evolution laws of coal during cyclic loading and unloading were quantitatively analyzed from the perspectives of residual strain and energy dissipation, respectively. The damage evolution law based on residual strain showed that when the intermediate principal stress was high, the damage to coal was directional. With the increase in cyclic load, the coal damage variables in the directions of σ1 and σ3 increased exponentially, while that in the direction of σ2 increased quadratically. The damage evolution law based on energy dissipation showed that the coal damage variable increased exponentially with the increase in cyclic load. With the increase in σ2, the increasing speed of coal damage variable decreased first and then increased. The damage variables established based on residual strain and energy dissipation can both reveal the damage deterioration mechanism of coal during true triaxial cyclic loading and unloading, which is of great theoretical and engineering significance for scientifically evaluating the stability of underground coal and rock engineering and preventing the occurrence of major geological disasters.

GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer.

In the treatment of most malignancies, radiotherapy plays a significant role. However, the resistance of cancer cells to ionizing radiation (IR) is the main reason for the failure of radiotherapy, which causes tumor recurrence and metastasis. In this study, we confirmed that GPR162, an orphan receptor in the G-protein-coupled receptor family, acted as a novel radiotherapy sensitizer by interacting with the stimulator of interferon genes (STING), which targeted DNA damage responses, activated IRF3, accelerated the activation of type I interferon system, promoted the expression of chemokines including CXCL10 and CXCL4, and inhibited the occurrence and development of tumors. Interestingly, the activation of STING by overexpression of GPR162 was independent of the classical pathway of cGAS. STING inhibitors could resist the antitumor effect of overexpression of GPR162 in IR-induced mouse models. In addition, most solid tumors showed low expression of GPR162. And the higher expression of GPR162 indicated a better prognosis in patients with lung adenocarcinoma, liver cancer, breast cancer, etc. In summary, these results suggested that GPR162 may serve as a potential sensitizer of radiotherapy by promoting radiotherapy-induced STING-IFN production and increasing the expression of chemokines including CXCL10 and CXCL4 in DNA damage response, providing an alternative strategy for improving cancer radiotherapy.

Boosting thermoelectric performance of HfSe2 monolayer by selectivity chemical adsorption.

In this work, a strategy to boosting thermoelectric (TE) performance of 2D materials is explored. We find that, appropriate chemical adsorption of atoms can effectively increase the TE performance of HfSe2 monolayer. Our results show that the adsorption of Ni atom on HfSe2 monolayer (Ni-HfSe2) can improve the optimal power factor PF and ZT at 300 K, increased by more than ∼67% and ∼340%, respectively. The PF and ZT of Ni-HfSe2 at 300 K can reach 85.06 mW m-1 K-2 and 3.09, respectively. The detailed study reveal that the adsorption of Ni atom can induce additional conductional channels of electrons, enhance the coupling of acoustic-optical phonons and the phonon anharmonicity, resulting in an obvious increment of electrical conductivity (increased by more than ∼89%) in n-type doped system and an ultralow phonon thermal conductivity (1.17 W/mK at 300 K). The high electrical conductivity and ultralow phonon thermal conductivity results in the significant increments of PF and ZT. Our study also shows that, Ni-HfSe2 is a thermal, dynamic and mechanical stable structure, which can be employed in TE application. Our research indicates that selectivity chemical adsorption is a promising way to increase TE performance of 2D materials.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.

The progress and challenges of circRNA for diabetic foot ulcers: A mini-review.

Since the Human Genome Project was successfully completed, humanity has entered a post-genome era, and the second-generation sequencing technology has gradually progressed and become more accurate. Meanwhile, circRNAs plays a crucial role in the regulation of diseases and potential clinical applications has gradually attracted the attention of physicians. However, the mechanisms of circRNAs regulation at the cellular and molecular level of diabetic foot ulcer (DFU) is still not well-understood. With the deepening of research, there have been many recent studies conducted to explore the effect of circRNAs on DFU. In this mini-review, we discuss the potential role of circRNAs as therapeutic targets and diagnostic markers for DFU in order to gain a better understanding of the molecular mechanisms that underlie the development of DFU and to establish a theoretical basis for accurate treatment and effective prevention.

Efficacy and safety of tibial cortex transverse transport for diabetic foot: A protocol for systematic review and meta-analysis.

INTRODUCTION: Diabetic foot (DF) is one of the most serious chronic complications of diabetes. In recent years, the use of the tibial cortex transverse transport (TTT) technique has enabled great progress in microcirculation reconstruction and achievement of good outcomes in DF treatment. The objective of this systematic review protocol is to evaluate the efficacy and safety of TTT for DF. METHODS: Literature search was conducted using the Cochrane Library, Embase, PubMed, Web of Science, China Science Technology Journal Database (VIP), Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), and Chinese Biomedical Literature Service System (CBM) from inception until March, 1st 2022. In addition, our reviewers will retrieve dissertations, grey literature, systematic reviews, and reference lists of the relevant studies. Randomized controlled trials (RCTs) which compared the TTT for DF with conventional treatment will be included. Our reviewers will perform subgroup analysis, sensitivity analysis, and publication bias analysis to evaluate the heterogeneity and robustness. RevMan 5.3 software and Stata V.16.0 software will be used to analyze the available data. ETHICS AND DISSEMINATION: Ethical approval was not required because this protocol neither collected private information, nor involved animal experiments. The research was disseminated by academic journals or related meetings. PROSPERO REGISTRATION NUMBER: CRD42021279717.