AIM:To investigate the role of serum high-sensitivity C-reactive protein(hsCRP)in the pathogenesis and progression of diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM).METHODS:A nested case-control study was conducted involving 187 T2DM patients(187 eyes)who attended at Eye Center, Beijing Tongren Hospital, Capital Medical University from June 2017 to October 2024. Patients were categorized into three groups: the diabetes mellitus(DM)group, non-proliferative DR(NPDR)group, and proliferative DR(PDR)group. Baseline information was collected, including age, sex, duration of DM, and duration of hypertension. All patients underwent fasting biochemical tests and comprehensive ophthalmic examinations.RESULTS: A positive correlation was observed between hsCRP and fasting blood glucose(FBG; P=0.004)and glycated hemoglobin A1c(HbA1c; P=0.048)by Spearman's rank correlation coefficient analysis. After adjusting for confounding factors, multivariable Logistic regression identified hsCRP as a significant risk factor for DR(OR=2.67, 95% CI: 1.19-5.96, P=0.017). CONCLUSION:Serum hsCRP is positively correlated with FBG and HbA1c and can serve as an important predictor of the severity of DR.

OBJECTIVES: To investigate the protective effects and underlying mechanisms of Gynostemma pentaphyllum (GP)ethanol extract on motor dysfunction in a mouse model of Parkinson's disease (PD). METHODS: Eighty C57BL/6 male mice were randomly divided into five groups: control group, model group, levodopa group (positive control group), low-dose GP group, and high-dose GP group, with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata of the mice. Two weeks after 6-hydroxydopamine, positive control group received intraperitoneal injection of levodopa 10 mg·kg^－1·d^－1, while low-dose GP and high-dose GP groups received GP extract 100 or 200 mg·kg^－1·d^－1 orally for three weeks. After a 3-week-treatment, the effects of GP on motor dysfunction in 6-hydroxydopamine-induced PD were assessed using open field and CatWalk gait tests, while the effects on muscle strength were evaluated by forelimb grip strength. Immunofluorescence staining was used to detect the number of tyrosine hydroxylase (TH) positive neurons. The levels of dopamine and serotonin in the midbrain were determined by enzyme-linked immunosorbent assay. In addition, Western blotting was performed to detect the expression of mitogen-activated protein kinase (MAPK) family proteins such as p-extracellular signal-regulated kinase (ERK)1/2, p-p38 and p-c-Jun N-terminal kinase (JNK)1/2, and mitochondrial apoptosis pathway proteins such as B-cell lymphoma (Bcl)-2, Bcl-2 associated X protein (Bax), and cleaved-cysteine aspartic acid specific protease (caspase)-3. RESULTS: Behavioral experiments showed that GP significantly improved the spontaneous activity and motor coordination of PD mice (P<0.05). The forelimb grip strength was also increased by GP treatment (P<0.05), compared to the PD model group. In addition, compared with the model group, the number of TH-positive neurons in substantia nigra pars reticulata region, the levels of dopamine and serotonin in midbrain and the expression of p-ERK1/2 were significantly increased by GP treatment (all P<0.05), whereas the expression of p-p38 and p-JNK1/2, the ratio of Bax/Bcl-2 and cleaved-caspase-3/caspase-3 were significantly decreased (all P<0.05). CONCLUSIONS The results indicate that GP might increase dopamine and serotonin levels in the midbrain and promote the survival of dopaminergic neurons in substantia nigra pars reticulata by regulating the expression of phosphorylation of MAPK family proteins and the expression of mitochondrial apoptosis-related proteins, thereby ameliorating motor deficits in PD mice.
Animals ; Mice ; Male ; Gynostemma/chemistry* ; Mice, Inbred C57BL ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Parkinson Disease/metabolism* ; Disease Models, Animal ; Neurons/pathology*

OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Objective:To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients.Methods:We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison.Results:The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM ( P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM ( P=0.035) . Conclusion:This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

Objective To explore the application low of stimulation parameters of transcutaneous electrical acupoint stimulation(TEAS)and transcranial direct current stimulation(tDCS)for post-stroke movement disorders based on data mining.Methods The relevant clinical research literature was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed and Web of Science from January 2000 to May 2023.A database was set up after quality assessment.Frequency analysis,association rules and complex network analysis were used to explore the application law of core acupoints and electrical stimulation parameters.Results A total of 79 articles were included and 128 groups of data were contained.For TEAS,the core acupoints included Waiguan(TE5),Shousanli(LI10),Zusanli(ST36),Hegu(LI4),Neiguan(PC6),Yanglingquan(GB34),etc.,while the most commonly used acupoint combinations of upper limb and lower limb were Shousanli(LI10)-Waiguan(TE5)and Yanglingquan(GB34)-Zusanli(ST36).Among the electrical stimulation parameters of TEAS,the frequencies used vary widely,and 100 Hz was most commonly used,while 2 Hz TEAS was also mainly used for stimulating acupoints located on upper limbs in the treatment of flaccid paralysis.The application of other electrical stimulation parameters was relatively consistent.The bidirectional symmetrical square-wave with 200-250 μs pulse-width was used in majority of studies.The stimulus intensity was mostly determined by patient tolerance.For tDCS,stimulation electrodes were often positioned on the projection of the primary M1,and the safe stimulus intensity was mostly set as 1 to 2 mA.Conclusion In the treatment of post-stroke movement disorders,appropriate acupoints and electrical stimulation parameters of TEAS should be determined on the muscle strength and muscle tension of stroke patients at different stages after stroke,particularly the selection of electric stimulating frequency.

Objective:To develop and evaluate metal artifact removal systems (MARSs) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images.Methods:A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05).Results:Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0 mm, 1.5 mm, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively ( F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively ( F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 ( F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 ( F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 ( F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 ( F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARSs. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions:Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

Objective:To develop and evaluate metal artifact removal systems (MARS) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images.Methods:A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05).Results:Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0, 1.5, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively ( F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively ( F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 ( F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 ( F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 ( F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 ( F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARS. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions:Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Objective:To evaluate the efficacy and safety of treating allogeneic hematopoietic stem cell transplantation (allo-HSCT) with azacitidine plus BUCY2 as a conditioning regimen for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).Method:From January 1, 2022 to July 15, 2023, a retrospective study was conducted for the relevant clinical data of 26 AML-MDS patients undergoing allo-HSCT with azacitidine plus BUCY2 as a conditioning regimen at Wuhan Union Hospital. There were 15 males and 11 females. For haploidentical transplantation, rabbit anti-human thymocyte immunoglobulin (ATG) was added. And tacrolimus + mycophenolale mofetil + recombinant humanized anti-CD25 monoclonal antibody injection (Xenopax) ± methotrexate were utilized for preventing GVHD. For human leukocyte antigen matched transplantation, cyclosporin A + methotrexate + Xenopax were employed for preventing GVHD. Incidence timing, severity, incidence rate of acute/chronic graft versus host disease (a/cGVHD), granulocyte/platelet engraftment time, infection type, overall survival and relapse date were recorded.Result:Granulocyte engraftment was attained with a median engraftment time of 12 (9~18) day and platelet engraftment with a median engraftment time of 16 (13~34) day. The incidence of acute graft-versus-host disease (aGVHD) was 63.14% (95% CI: 60.90%~65.37%), the incidence of grade Ⅲ aGVHD 6 (95% CI: 11.39%~13.23%) and the median onset time of aGVHD 49 (11~93) day post-transplantation. The incidence of chronic graft-versus-host disease (cGVHD) was 52.68% (95% CI: 49.23%~56.13%) and the incidence of moderate-severe cGVHD 11.43% (95% CI: 10.20%~12.66%). Infections were caused by cytomegalovirus (CMV) viremia (7 cases), bacteria (3 cases) and fungus (4 cases). Until the last follow-up, 23 recipients achieved relapse-free survival and continued MRD negativity. Death occurred due to recurrence (2 cases) and GVHD plus severe infection (1 case). Cumulative incidence of relapse (CIR) was 10.20% (95% CI: 9.21%~11.18%), 1-year overall survival (OS) 83.50% (95% CI: 67.90%~100%), GVHD/relapse-free survival (GRFS) 70.30% (95% CI: 52.30%~94.30%) and non-relapse mortality (NRM) 5.02% (95% CI: 4.53%-5.52%). Conclusion:Using azacitidine plus BUCY2 as a conditioning regimen, OS of allo-HSCT for AML-MDS is higher than that of traditional regimen. The risks of III-IV aGVHD, relapse and infection are safe and controllable.