Recent approaches for the synthesis of heterocycles from amidines via a metal catalyzed C-H functionalization reaction.

Transition metal catalyzed C-H bond activation has become one of the most important tools for constructing new chemical bonds. Introducing directing groups to the substrates is the key to a successful reaction, these directing groups can also be further transformed in the reaction. Amidines with their unique structure and reactivity are ideal substrates for transition metal-catalyzed C-H transformations. This review describes the major advances and mechanistic investigations of the C-H activation/annulation tandem reactions of amidines until early 2024, focusing on metal-catalyzed C-H activation of amidines with unsaturated compounds, such as alkynes, ketone, vinylene carbonate, cyclopropanols and their derivatives. Meanwhile this manuscript also explores the reaction of amidines with different carbene precursors, for example diazo compounds, azide, triazoles, pyriodotriazoles, and sulfoxonium ylides as well as their own C-H bond activation/cyclization reactions. A bright outlook is provided at the end of the manuscript.

Progress in the Regulation of Immune Cells in the Tumor Microenvironment by Bioactive Compounds of Traditional Chinese Medicine.

The tumor microenvironment (TME) can aid tumor cells in evading surveillance and clearance by immune cells, creating an internal environment conducive to tumor cell growth. Consequently, there is a growing focus on researching anti-tumor immunity through the regulation of immune cells within the TME. Various bioactive compounds in traditional Chinese medicine (TCM) are known to alter the immune balance by modulating the activity of immune cells in the TME. In turn, this enhances the body's immune response, thus promoting the effective elimination of tumor cells. This study aims to consolidate recent findings on the regulatory effects of bioactive compounds from TCM on immune cells within the TME. The bioactive compounds of TCM regulate the TME by modulating macrophages, dendritic cells, natural killer cells and T lymphocytes and their immune checkpoints. TCM has a long history of having been used in clinical practice in China. Chinese medicine contains various chemical constituents, including alkaloids, polysaccharides, saponins and flavonoids. These components activate various immune cells, thereby improving systemic functions and maintaining overall health. In this review, recent progress in relation to bioactive compounds derived from TCM will be covered, including TCM alkaloids, polysaccharides, saponins and flavonoids. This study provides a basis for further in-depth research and development in the field of anti-tumor immunomodulation using bioactive compounds from TCM.

Single Cell Phenotypic Analysis for Cancer Stem Cell Identification by Dual-Isotope ICP-QMS.

Single cell phenotypic analysis is significant for clinical diagnosis, treatment, and prognosis of cancer. Accurate differentiation of cancer stem cell (CSC) subpopulations from a large number of cancer cells may become a cancer surveillance tool and provide important implications for the development of new CSC-targeted therapy strategies. Herein, we report a new approach based on dual-isotope inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) for single cell phenotypic analysis. High-throughput single cell sampling was achieved by a spiral channel microfluidic chip for cell focusing and alignment, and single cell analysis was performed with time-resolved ICP-QMS by identifying the highly specific probes. This enables the monitoring of two surface protein markers (EpCAM and MUC1) of three cell types, i.e., HeLa, MCF-7, and HepG2, at single cell level. The analysis of breast cancer stem cells further confirmed its capability in distinguishing rare cell phenotypes. The present study provides promising possibilities for adopting ICP-QMS in biomedical investigations in terms of cell typing, stemness identification of tumor cells, and cell heterogeneity analysis.

Two-Dimensional Multi-parameter Cytometry Platform for Single-Cell Analysis.

A 2D flow cytometry platform, known as CytoLM Plus, was developed for multi-parameter single-cell analysis. Single particles or cells after hydrodynamic alignment in a microfluidic unit undergo first-dimension fluorescence and side scattering dual-channel optical detection. They were thereafter immediately directed to ICP-MS by connecting the microfluidic unit with a high-efficiency nebulizer to facilitate the second-dimension ICP-MS detection. Flow cytometry measurements of fluorescent microspheres evaluated the performance of CytoLM Plus for optical detection. 6434 fluorescence bursts were observed with a valid signal proportion as high as 99.7%. After signal unification and gating analysis, 6067 sets of single-particle signals were obtained with 6.6 and 6.2% deviations for fluorescence burst area and height, respectively. This is fairly comparable with that achieved by a commercial flow cytometer. Afterward, CytoLM Plus was evaluated by 2D flow cytometry measurement of Ag+-incubated and AO-stained MCF-7 cells. A program for 2D single-cell signal unification was developed based on the algorithm of screening in lag time window. In the present case, a lag time window of -4.2 ± 0.09 s was determined by cross-correlation analysis and two-parameter optimization, which efficiently unified the concurrent single-cell signals from fluorescence, side scattering, and ICP-MS. A total of 495 sets of concurrent 2D signals were screened out, and the statistical analysis of these single-cell signals ensured 2D multi-parameter single-cell analysis and data elucidation.

Experimental evidence that cuckoos choose host nests following an egg matching strategy.

The arms race between brood parasites and their hosts provides a classic model to study coevolution. Hosts often reject the parasitic egg, and brood parasites should therefore select host nests in which the colour of the eggs best matches that of their own. Although this hypothesis has received some support, direct experimental evidence is still lacking. Here, we report on a study of Daurian redstarts, which show a distinct egg-colour dimorphism, with females laying either blue or pink eggs. Redstarts are often parasitized by common cuckoos, which lay light blue eggs. First, we showed that cuckoo eggs were more similar in spectral reflectance to the blue than to the pink redstart egg morph. Second, we report that the natural parasitism rate was higher in blue than in pink host clutches. Third, we performed a field experiment in which we presented a dummy clutch of each colour morph adjacent to active redstart nests. In this set-up, cuckoos almost always chose to parasitize a blue clutch. Our results demonstrate that cuckoos actively choose redstart nests in which the egg colour matches the colour of their own eggs. Our study thus provides direct experimental evidence in support of the egg matching hypothesis.

The C2 H2 -type zinc finger transcription factor OSIC1 positively regulates stomatal closure under osmotic stress in poplar.

Salt and drought impair plant osmotic homeostasis and greatly limit plant growth and development. Plants decrease stomatal aperture to reduce water loss and maintain osmotic homeostasis, leading to improved stress tolerance. Herein, we identified the C2 H2 transcription factor gene OSMOTIC STRESS INDUCED C2 H2 1 (OSIC1) from Populus alba var. pyramidalis to be induced by salt, drought, polyethylene glycol 6000 (PEG6000) and abscisic acid (ABA). Overexpression of OSIC1 conferred transgenic poplar more tolerance to high salinity, drought and PEG6000 treatment by reducing stomatal aperture, while its mutant generated by the CRISPR/Cas9 system showed the opposite phenotype. Furthermore, OSIC1 directly up-regulates PalCuAOζ in vitro and in vivo, encoding a copper-containing polyamine oxidase, to enhance H2 O2 accumulation in guard cells and thus modulates stomatal closure when stresses occur. Additionally, ABA-, drought- and salt-induced PalMPK3 phosphorylates OSIC1 to increase its transcriptional activity to PalCuAOζ. This regulation of OSIC1 at the transcriptional and protein levels guarantees rapid stomatal closure when poplar responds to osmotic stress. Our results revealed a novel transcriptional regulatory mechanism of H2 O2 production in guard cells mediated by the OSIC1-PalCuAOζ module. These findings deepen our understanding of how perennial woody plants, like poplar, respond to osmotic stress caused by salt and drought and provide potential targets for breeding.

Genomic divergence between two sister Medicago species triggered by the quaternary climatic oscillations on the Qinghai-Tibet plateau and northern China.

Speciation is a central topic in evolutionary biology. However, how genomic divergence originates and accumulates in the face of gene flow during ecological adaptation remains poorly understood. Closely related species that have adapted to distinct environments but inhabit some overlapping ranges provide an ideal system to evaluate this issue. Here, we combine population genomics and species distribution models (SDMs) to examine genomic divergences between two sister plant species, Medicago ruthenica and M. archiducis-nicolai, that occur in northern China and the northeast Qinghai-Tibet Plateau, respectively, with overlapping distributions in the border of the two regions. M. ruthenica and M. archiducis-nicolai are well-delimited based on population genomic data, although hybrids exist in sympatric sampling locations. Coalescent simulations and SDMs suggest that the two species diverged from each other in the Quaternary but have been in continuous contact with gene flow occurring between the two species since then. We also discovered positive selection signatures associated with genes both outside and within genomic islands in both species that are probably involved in adaptations to arid and high-altitude environments. Our findings provide insights into how natural selection and climatic changes in the Quaternary initiated and maintained interspecific divergence of these two sister species.

Prevalence and risk factors of tuberculosis among people living with HIV/AIDS in China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.

Predictive value of coronary artery computed tomography-derived fractional flow reserve for cardiovascular events in patients with coronary artery disease.

BACKGROUND: Coronary computed tomography-derived fractional flow reserve (FFR-CT) assesses whether coronary artery lesions will result in myocardial ischemia. This study aimed to evaluate the predictive value of FFR-CT for cardiovascular events in patients with coronary artery disease (CAD). METHODS: Data were collected retrospectively from patients with CAD who underwent FFR-CT at our hospital from January 2020 to February 2022 (1-year average follow-up). Patients were divided into ischemic (FFR-CT ≤ 0.80) and non-ischemic (FFR-CT > 0.80) groups. The incidence of endpoint events (cardiac death, acute myocardial infarction, unplanned revascularization, unstable angina, and stable angina) was calculated. The FFR-CT value was correlated with endpoint events using Cox regression models and Kaplan-Meier survival curves. RESULTS: We recruited 134 patients (93 [69.4%] and 41 [30.6%] patients in the ischemic and non-ischemic groups, respectively). The ischemic group had a higher proportion of men, patients with type 2 diabetes and hypertension, and patients taking antiplatelet drugs and ß­blockers than did the non-ischemic group (all p < 0.05), whereas other parameters were comparable. Multivariate Cox regression analysis revealed no significant differences in cardiac death, acute myocardial infarction, unplanned revascularization, and unstable angina between the groups. The incidence of stable angina events (hazard ratio: 3.092, 95% confidence interval: 1.362-7.022, p = 0.007) was significantly higher in the ischemic group. Kaplan-Meier survival analysis revealed a significant difference in event-free survival for stable angina between the groups (p = 0.002). CONCLUSION: In patients with CAD, FFR-CT showed an independent predictive value for stable angina within 1 year of examination.

Clinical impact of posterior wall isolation in catheter ablation for persistent atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The clinical outcomes of pulmonary venous isolation alone for persistent atrial fibrillation (PerAF) remain unclear. Adjuvant posterior wall isolation (PWI) has become a potential supplementary strategy for improving the outcome of PerAF ablation. This meta-analysis aimed to evaluate the effect of PWI added to catheter ablation for PerAF. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of PerAF ablation with and without PWI. The efficacy outcomes were recurrence of atrial arrhythmia (AA), atrial fibrillation (AF), and atrial tachycardia (AT), and the safety outcome was adverse events. RESULTS: In total, eight studies with 1428 patients were included in the pooled analyses. The results showed that PWI significantly reduced the recurrence of AA (RR = 0.69, 95% CI = 0.55-0.87, p = .002, I2  = 63%) and AF (RR = 0.57, 95% CI = 0.40-0.80, p = .001, I2  = 70%). AT recurrence (RR = 0.92, 95% CI = 0.67-1.27, p = .63, I2  = 42%) and adverse events (RR = 1.11, 95% CI = 0.67-1.84, p = .70, I2  = 0%) were comparable between the two groups. In the sub-analyses, the efficacy of PWI in reducing AA recurrence was consistent in patients who underwent cryoablation or debulking ablation. CONCLUSION: PWI effectively decreased AA recurrence after PerAF ablation without increasing the risk of AT or procedure-related complications. However, more randomized studies are needed to confirm these results.

[A heart sound classification method based on complete ensemble empirical modal decomposition with adaptive noise permutation entropy and support vector machine].

Heart sound signal is a kind of physiological signal with nonlinear and nonstationary features. In order to improve the accuracy and efficiency of the phonocardiogram (PCG) classification, a new method was proposed by means of support vector machine (SVM) in which the complete ensemble empirical modal decomposition with adaptive noise (CEEMDAN) permutation entropy was as the eigenvector of heart sound signal. Firstly, the PCG was decomposed by CEEMDAN into a number of intrinsic mode functions (IMFs) from high to low frequency. Secondly, the IMFs were sifted according to the correlation coefficient, energy factor and signal-to-noise ratio. Then the instantaneous frequency was extracted by Hilbert transform, and its permutation entropy was constituted into eigenvector. Finally, the accuracy of the method was verified by using a hundred PCG samples selected from the 2016 PhysioNet/CinC Challenge. The results showed that the accuracy rate of the proposed method could reach up to 87%. In comparison with the traditional EMD and EEMD permutation entropy methods, the accuracy rate was increased by 18%-24%, which demonstrates the efficiency of the proposed method.

Photoprotection by mitochondrial alternative pathway is enhanced at heat but disabled at chilling.

The mitochondrial alternative pathway (AP) represents an important photoprotective mechanism for the chloroplast, but the temperature sensitivity of its photoprotective role is unknown. In this study, using the aox1a Arabidopsis mutant, the photoprotective role of the AP was verified under various temperatures, and the mechanism underlying the temperature sensitivity of the AP's photoprotective role was clarified. It was observed that the photoprotective role of the AP increased with rising temperature but was absent at low temperature. The photoprotective role of the AP was severely reduced under non-photorespiratory conditions. Disturbance of the AP inhibited the conversion of glycine to serine in mitochondria, which may restrain upstream photorespiratory metabolism and aggravate photoinhibition. With rising temperatures, photorespiration accelerated and the restraint of photorespiration caused by disturbance of the AP also increased, determining the temperature sensitivity of the AP's photoprotective role. We also verified that not only the AP but also the cytochrome pathway in mitochondria contributes to photoprotection by maintaining photorespiration.

Cyclometalated Ru(II) ß-carboline complexes induce cell cycle arrest and apoptosis in human HeLa cervical cancer cells via suppressing ERK and Akt signaling.

Two new cyclometalated Ru(II)-ß-carboline complexes, [Ru(dmb)2(Cl-Ph-ßC)](PF6) (dmb = 4,4'-dimethyl-2,2'-bipyridine; Cl-Ph-ßC = Cl-phenyl-9H-pyrido[3,4-b]indole; RußC-3) and [Ru(bpy)2(Cl-Ph-ßC)](PF6) (bpy = 2,2'-bipyridine; RußC-4) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC50 values of 3.2 ± 0.4 µM (RußC-3) and 4.1 ± 0.6 µM (RußC-4), which were considerably lower than that of non-cyclometalated Ru(II)-ß-carboline complex [Ru(bpy)2(1-Py-ßC)] (PF6)2 (61.2 ± 3.9 µM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RußC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RußC-3-induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RußC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs.

ω-3 DPA Protected Neurons from Neuroinflammation by Balancing Microglia M1/M2 Polarizations through Inhibiting NF-κB/MAPK p38 Signaling and Activating Neuron-BDNF-PI3K/AKT Pathways.

Microglia M1 phenotype causes HPA axis hyperactivity, neurotransmitter dysfunction, and production of proinflammatory mediators and oxidants, which may contribute to the etiology of depression and neurodegenerative diseases. Eicosapentaenoic acid (EPA) may counteract neuroinflammation by increasing n-3 docosapentaenoic acid (DPA). However, the cellular and molecular mechanisms of DPA, as well as whether it can exert antineuroinflammatory and neuroprotective effects, are unknown. The present study first evaluated DPA's antineuroinflammatory effects in lipopolysaccharide (LPS)-activated BV2 microglia. The results showed that 50 µM DPA significantly decreased BV2 cell viability after 100 ng/mL LPS stimulation, which was associated with significant downregulation of microglia M1 phenotype markers and proinflammatory cytokines but upregulation of M2 markers and anti-inflammatory cytokine. Then, DPA inhibited the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65 pathways, which results were similar to the effects of NF-κB inhibitor, a positive control. Second, BV2 cell supernatant was cultured with differentiated SH-SY5Y neurons. The results showed that the supernatant from LPS-activated BV2 cells significantly decreased SH-SY5Y cell viability and brain-derived neurotrophic factor (BDNF), TrkB, p-AKT, and PI3K expression, which were significantly reversed by DPA pretreatment. Furthermore, DPA neuroprotection was abrogated by BDNF-SiRNA. Therefore, n-3 DPA may protect neurons from neuroinflammation-induced damage by balancing microglia M1 and M2 polarizations, inhibiting microglia-NF-κB and MAPK p38 while activating neuron-BDNF/TrkB-PI3K/AKT pathways.

miR-133a-3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer.

Although many methods and new therapeutic drugs have been developed, the overall survival rate and long-term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this study, we investigated the effects of microRNA miR-133a-3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells. The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR-133a-3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3'-UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets.

Deep Dehalogenation of Florfenicol Using Crystalline CoP Nanosheet Arrays on a Ti Plate via Direct Cathodic Reduction and Atomic H.

Efficient elimination of antibacterial activity of halogenated antibiotics by dehalogenation pretreatment is desired for a biochemical treatment process. In this study, crystalline cobalt phosphide nanosheet arrays on a Ti plate (C-CoP/Ti) are fabricated by a simple electrodeposition and phosphorization process. The crystalline structure greatly promotes atomic hydrogen (H*) generation. Moreover, the nanosheet arrays can provide abundant active sites and accelerate electron transfer and mass transport. As a result, the dehalogenation rate of florfenicol (FLO, an emerging organic pollutant) on C-CoP/Ti is 11.1, 2.97, and 13.6 times higher than that on amorphous CoP/Ti, Pd/Ti, and bare Ti, respectively. The C-CoP/Ti electrode achieves 97.4% dehalogenation of FLO (20 mg L-1) within 30 min at -1.2 V (vs Ag/AgCl). Nearly 100% of Cl and 20% of F are broken away within 120 min, showing the highest electrocatalytic defluorination efficiency reported so far. Both experimental results and theoretical calculations reveal that the dehalogenation of FLO on C-CoP/Ti is synergistically accomplished via direct reduction of electron transfer and indirect reduction of H*. This study develops a highly efficient non-noble metal electrode material for dehalogenation of halogenated organic compounds.

Borate Inorganic Cross-Linked Durable Graphene Oxide Membrane Preparation and Membrane Fouling Control.

Graphene oxide (GO) membranes have the potential to be next-generation membranes. However, the GO layer easily swells in water and risks shedding during the long-term filtration. Organic GO interlayer organic cross-linking agent was not resistant to oxidation, which limits the application scope of GO membrane. In this study, an inorganic cross-linked GO membrane was prepared via the reaction of sodium tetraborate and GO hydroxyl groups, and a -B-O-C- cross-linking bond was detected by X-ray photoelectron spectroscopy (XPS). Additionally, a new atomic force microscope scratch method to evaluate the cross-linking force of a nanoscale GO layer was proposed. It showed that the critical destructive load of the inorganic cross-linked GO membrane increased from 8 to 80 nN, which was a 10-fold increase from that of the nonlinked sample. During the NaOH/sodium dodecyl sulfate (SDS) destructive wash tests, morphology, flux and retention rate of inorganic cross-linked GO remained stable while the comparative membranes showed significant destruction. At the same time, based on the better oxidation resistance, organic membrane fouling was effectively controlled by the introduction of trace ·OH radicals. This study provides a new perspective for GO membrane preparation, interlayer cross-linking force testing and membrane fouling control.

Compressive Force Spectroscopy: From Living Cells to Single Proteins.

One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these "tensile" force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.

Review of systematic reviews and Meta-analyses investigating Traditional Chinese Medicine treatment for type 2 diabetes mellitus.

OBJECTIVE: To conduct a review of the systematic reviews and meta-analyses on the Traditional Chinese Medicine (TCM) treatment of type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Cochrane, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang, and other databases from database inception to May 2014 for systematic reviews and meta-analyses on TCM treatment of T2DM. Manuscripts were read by two investigators if they met the inclusion criteria, and data were extracted. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used to classify research quality, and the evidence quality was graded by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eighteen systematic reviews and meta-analyses were considered. Fifteen analyzed the efficacy of Chinese herbal medicines, and three investigated the efficacy of acupuncture. AMSTAR evaluation ranged from 3-10, and re-evaluation of the main results implied that treatment of T2DM with TCM has certain advantages when compared with conventional Western medicine. However, the evidence quality was generally low. CONCLUSION: This work shows favorable evidence for the clinical treatment of TCM on T2DM. However, it is recommended that evidence-based decisions are made based on clinical trials because of the GRADE scores of the studies. To achieve higher quality of clinical research, clinical research on TCM requires specific and suitable research methods. Further trials may increase the quality of evidence to evaluate the clinical efficacy of TCM for T2DM.