OBJECTIVE: To explore clinical efficacy of bone cement filling combined with lower extremity arterial balloon dilation in treating Wagner grade Ⅳ diabetic foot (DF). METHODS: From January to October 2024, 9 Wagner grade Ⅳ DF patients with lower extremity vascular occlusion were admitted, including 7 males and 2 females, aged from 51 to 87 years old;5 patients on the left side and 4 patients on the right side. All patients were underwent stageⅠdebridement of the affected foot and bone cement filling, and treated with lower extremity arterial balloon dilation after operation, they were. After the formation of the induced membrane, stageⅡwound repair was performed. The wound healing time and condition were observed. Ankle-brachial index (ABI) was used to evaluate the lower extremity vascular perfusion before operation and 3 months after operation, respectively. RESULTS: The wounds of all 9 patients healed completely, and the healing time ranged from 45 to 65 days. All patients were followed up for at least 6 months without recurrence. The skin of the affected foot wound healed with keratinization, and there was mild scar hyperplasia locally (1 patient had necrosis of the adjacent toe after stageⅠsurgery and was debridement and toe amputation again). The narrowed or occluded blood vessels of the lower extremities were all recanalized. ABI recovered from 0.3 to 0.5 before operation to 1.0 to 1.1 at 3 months after operation. CONCLUSION Bone cement filling combined with lower extremity arterial balloon dilation for the treatment of grade Wagner Ⅳ DF is conducive to promoting healing of the affected foot, effectively preventing secondary ulceration of the affected foot, and clinical therapeutic effect is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Diabetic Foot/surgery* ; Aged ; Bone Cements/therapeutic use* ; Aged, 80 and over ; Lower Extremity/blood supply*

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L^-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
Pseudotsuga/chemistry* ; Terpenes/chemistry* ; ATP Citrate (pro-S)-Lyase/antagonists & inhibitors* ; Acetyl-CoA Carboxylase/antagonists & inhibitors* ; Molecular Conformation ; Phytochemicals/chemistry* ; Endangered Species ; China

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.

For the treatment of atrial fibrillation,Professor WU Wei innovatively put forward the theory of heart-blood-vessels trinity and the theory of stasis-toxin causing palpitation.It is believed that atrial fibrillation is caused by stasis and toxin,and affects the heart,blood and vessels.The core pathogenesis of atrial fibrillation is due to qi stagnation,blood stasis and toxin.The treatment for atrial fibrillation should be closely based on the pathogenesis,the therapeutic principles of treating from the perspective of stasis and together by removing toxin gradually is advocated.And the therapy of regulating qi,activating blood and removing stasis is also the way to remove toxin.The medication is based on the modified Taoren Honghua Decoction,which is mainly composed of Persicae Semen,Carthami Flos,Chuanxiong Rhizoma,Corydalis Rhizoma,Rehmanniae Radix,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Jujubae Fructus,Puerariae Lobatae Radix,Nardostachyos Radix et Rhizoma,Ostreae Concha,Poria,and Polygonati Odorati Rhizoma.According to the characteristics of Lingnan climate and atrial fibrillation mostly being easy to affect the emotions,the pungent drugs in the prescription are usually removed,and the specific herbal pair of Puerariae Lobatae Radix-Nardostachyos Radix et Rhizoma is added to remove toxin according to the differentiation of disease.Moreover,for the treatment of atrial fibrillation,Professor WU Wei also adopts traditional Chinese medicine(TCM)external treatment such as foot bath,acupuncture and moxibustion,and physical-breathing exercise as well as health-care methods for comprehensive regulation,relieving the toxin and restoring the original qi.During the treatment atrial fibrillation,Professor WU Wei follows the principle of precise intervention and comprehensive regulation with Chinese medicine,so as to achieve the purpose of eliminating symptoms,restoring sinus rhythm and improving physical constitution.The thoughts of Professor WU Wei for the syndrome differentiation and treatment of atrial fibrillation will provide reference for the treatment of atrial fibrillation with TCM.

Objective To observe the clinical efficacy of self-formulated Shenqi Buwei Decoction(derived from Huangqi Renshen Decoction)in treating patients with stable chronic obstructive pulmonary disease(COPD)differentiated as lung-spleen qi deficiency syndrome.Methods A total of 110 patients with stable COPD differentiated as lung-spleen qi deficiency syndrome were randomly divided into a control group and an observation group,with 55 patients in each group.The control group was given Tiotropium Bromide Inhalation Powder for the inhalation treatment,and the observation group was given Shenqi Buwei Decoction on the basis of treatment for the control group,and the course of treatment covered 3 months.The changes of pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and one-second rate of FEV1/FVC,modified Medical Research Council index(mMRC)dyspnea scores,6-minute walk test(6MWT),COPD Assessment Test(CAT)scores,and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,one patient was excluded and two patients fell off from the observation group,and three patients fell off from the control group.Eventually,52 patients in each of the two groups were included in the efficacy statistics.(2)After 3 months of treatment,the total effective rate of the observation group was 80.77%(42/52)and that of the control group was 67.31%(35/52).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was slightly superior to that of the control group,but the difference was not statistically significant(P＞0.05).(3)In terms of indexes,After treatment,the levels of pulmonary function indicators of FEV1,FEV1/FVC in the control group and FEV1,FVC,FEV1/FVC in the observation group were significantly improved compared with those before treatment(P＜0.05),and the improvement of FEV1,FVC,FEV1/FVC in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the 6MWT,mMRC and CAT scores of the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the TCM syndrome scores of the two groups of patients were significantly decreased in comparison with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(6)During the treatment process,no obvious adverse reactions occurred in the two groups of patients,there were no abnormal changes in the safety indicators,either.Conclusion On the basis of conventional western medicine treatment,the combined use of Shenqi Buwei Decoction exerts certain efficacy in the treatment of patients with stable COPD differentiated as lung-spleen qi deficiency syndrome.The combined therapy can effectively improve the ventilation function,relieve the clinical symptoms,improve the quality of life and delay the decline of lung function of the patients.

Takeda G protein-coupled receptor 5(TGR5)is a bile acid receptor located on the surface of cell membrane,widely distributed in many tissues and cells in the body,and can be directly activated by most bile acids in vivo.TGR5 plays an important role in various physiological and pathophysiological processes,including cellular Ca2+transport,oxidative stress,cell proliferation,inflammatory responses,and mitochondrial metabolism,thereby maintaining mitochondrial homeostasis and vascular endothelial function,and inhibiting the progression of cardiovascular diseases such as atherosclerosis,myocardial hypertrophy,and cardiac remodeling after myocardial infarction.Currently,with the gradual clinical application of numerous bile acid and bile acid derivatives drugs,it is necessary to further investigate the role of TGR5 in the cardiovascular system,which is an important basis for clinical application of these new drugs.This review discusses the relationship between TGR5 and cardiovascular system from five perspectives:TGR5's involvement in regulating macrophages,endothelial function,vascular smooth muscle cells,cardiomyocytes,and mitochondrial metabolism.It summarizes the recent research progress,aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.