Oxidative stress is a pivotal factor in the onset and progression of diabetic kidney disease （DKD）， and it plays an essential role in the prevention and treatment of DKD. The "Gaozhuo" pathogenesis posits that DKD is characterized by the invasion of Gaozhuo and damage to the kidney collaterals， with the underlying cause being the insufficiency of spleen Qi and the internal formation of Gaozhuo， which provides valuable guidance on oxidative stress. The insufficiency of spleen Qi and the internal formation of Gaozhuo represent a dynamic， evolving process. Gaozhuo invades the kidney collaterals， impairs kidney Qi， and progressively leads to the congealing and stagnation of Gaozhuo and blood， ultimately resulting in the failure of both the spleen and kidneys. The damage caused by Gaozhuo to the kidney collaterals and kidney Qi is analogous to the organ and functional damage of the kidneys induced by excessive reactive oxygen species and oxidative stress. Damage to the kidney collaterals means organic injuries to the glomeruli， renal tubules， and renal interstitium， and the depletion of kidney Qi refers to damage to glomerular filtration and renal tubular reabsorption. The congealing and stagnation of Gaozhuo and blood in the kidney collaterals is similar to oxidative stress-induced thickening of the glomerular basement membrane and fibrosis. The interaction between spleen and kidney Qi deficiency and the congealing and stagnation of Gaozhuo and blood creates a vicious cycle that exacerbates the condition， ultimately evolving into the failure of both the spleen and kidneys. The failure of the spleen and kidneys is analogous to renal failure， and its extreme manifestation is end-stage renal disease and uremia. The treatment of oxidative stress in DKD with traditional Chinese medicine （TCM） is based on the principles of strengthening the spleen and tonifying the kidneys， and dispelling turbidity and removing blood stasis. According to the syndrome type， it is recommended to use methods such as strengthening the spleen and tonifying Qi while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling dampness and removing turbidity， strengthening the spleen and tonifying the kidneys while dispelling turbidity and removing blood stasis， or consolidating the spleen and kidneys while clearing away turbidity and blood stasis.

Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Retinal microcirculatory disorder is a key factor in the occurrence and development of diabetic retinopathy （DR）， and also an important link in the prevention and treatment of DR. The theory of "Gaozhuo" holds that the microcirculatory disorder in DR is based on the deficiency of spleen Qi and is characterized by the obstruction caused by "Gaozhuo" and blood stasis. The deficiency of spleen Qi is an essential precondition for the endogenous formation and accumulation of Gaozhuo， while Gaozhuo invasion is the direct cause of microcirculatory disorders in DR. The deficiency of spleen Qi and the endogenous formation of Gaozhuo mean the process in which glucose metabolism dysfunction induces an excessive production of inflammatory factors and lipid metabolites. The obstruction caused by "Gaozhuo" and blood stasis is the direct pathogenesis of microcirculatory disorders in DR， encompassing two stages： Gaozhuo obstruction and turbidity and stasis stagnation. Gaozhuo obstruction and turbidity and stasis stagnation represent the process in which inflammatory factors and lipid metabolites damage the retinal microcirculation and induce thrombosis， thus mediating microcirculatory disorders. Turbidity and stasis stagnation and blood extravasation outside the vessels reveal the progression to microvascular rupture and hemorrhage resulting from the microcirculatory disorders. According to the pathogenesis evolution of the theory of "Gaozhuo"， microcirculatory disorders in DR can be divided into deficiency of spleen Qi with Gaozhuo obstruction， deficiency of spleen Qi with turbidity and stasis stagnation， and turbidity and stasis stagnation with blood extravasation outside the vessels. Clinically， treatment principles should focus on strengthening the spleen and benefiting Qi， resolving turbidity， and dispersing stasis. Different syndrome patterns should be addressed with tailored therapies， such as enhancing the spleen and benefiting Qi while regulating Qi and reducing turbidity， strengthening the spleen and benefiting Qi while resolving turbidity and dispelling stasis， and strengthening the spleen and resolving turbidity while removing stasis and stopping bleeding. Representative prescriptions include modified Wendantang， modified Buyang Huanwutang， modified Danggui Buxuetang， Zhuixue Mingmu decoction， Tangmuqing， Shengqing Jiangzhuo Tongluo Mingmu prescription， Danhong Huayu decoction， and Yiqi Yangyin Huoxue Lishui formula.

Non-alcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）， and hepatic stellate cell （HSC） activation is the key link in the progression of NAFLD to liver fibrosis. According to the theory of "Gaozhuo"， spleen deficiency and Qi stagnation， along with Gaozhuo invasion， are the causes of NAFLD progression to liver fibrosis， which reveals the pathogenesis essence of HSC activation in traditional Chinese medicine （TCM）. Among them， spleen deficiency and Qi stagnation are the root causes of the endogenous formation of Gaozhuo. Spleen deficiency indicates the insulin sensitivity decrease and glucose metabolism disorders， and Qi stagnation means the dysregulation of hepatic glucose and lipid metabolism， which creates the preconditions for HSC activation. Gaozhuo invasion is the direct cause of HSC activation， including three stages： Internal retention of Gaozhuo， turbidity and stasis stagnation， and toxic stasis and consolidation. Internal retention of Gaozhuo refers to the abnormal metabolism and deposition of hepatic lipids， as well as the microcirculatory disorders. Turbidity and stasis stagnation is the process by which lipotoxicity stimulates the transformation of HSC into myofibroblast （MFB）， and toxic stasis and consolidation represent the secretion of a large amount of extracellular matrix （ECM） by MFB to promote the fibrosis. According to the theory of Gaozhuo and the activation process of HSC， syndromes for T2DM combined with NAFLD can be classified into spleen deficiency and Qi stagnation with internal retention of Gaozhuo， spleen Qi deficiency with turbidity and stasis stagnation， and spleen Qi deficiency with toxic stasis and consolidation. Clinically， the treatment principle is to strengthen the spleen and promote Qi， resolve turbidity， and eliminate blood stasis. Both TCM compounds and monomers can effectively inhibit the HSC activation. TCM compounds can be classified into categories for regulating spleen and harmonizing liver， resolving turbidity and removing stasis， and detoxifying and removing stasis. They mainly work by improving lipid metabolism， reducing lipid accumulation in the liver， alleviating inflammatory and oxidative stress responses， inhibiting the activation and proliferation of HSC， and reducing ECM deposition， thereby delaying the progression of liver fibrosis.

ObjectiveTo study the mechanism of Huanglian Jiedutang （HLJDT） in treating mice with atherosclerosis （AS） by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group， and 50 ApoE^-/- mice were randomly divided into five groups： model group， low-dose group of HLJDT， medium-dose group of HLJDT， high-dose group of HLJDT， and atorvastatin （ATV） group. ApoE^-/- mice were fed a high-fat diet for eight weeks to establish the AS model， and at the 9th week， they were given normal saline， low， medium， and high doses of HLJDT （3.9， 7.8， 15.6 g·kg^-1·d^-1）， and atorvastatin calcium tablets （0.01 g·kg^-1·d^-1）， respectively， for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） in blood fat were measured by the automatic biochemical analyzer， and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase （SOD） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The content of reduced glutathione （GSH） in serum was detected by the microplate method， and that of malondialdehyde （MDA） in serum was detected by the TBA method. The protein expression of nuclear factor E₂-associated factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway was detected by Western blot. ResultsCompared with those of the normal group， the contents of TC， LDL-C， TG， HDL-C， and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased （P<0.01）， while the expression levels of SOD and GSH in serum， as well as Nrf2， solute carrier family 7 member 11 （SLC7A11）， and GPX4 in aorta were significantly decreased （P<0.01）. Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta， volume atrophy， mitochondrial crista reduction， or a loose and disorganized form. Compared with those in the model group， the aortic vascular plaque deposition was significantly decreased in the low-dose， medium-dose， and high-dose groups of HLJDT and ATV group， and the contents of serum TC， LDL-C， TG， and MDA in serum were significantly decreased （P<0.05， P<0.01）. The contents of serum SOD and GSH and the expression levels of Nrf2， SLC7A11， and GPX4 in the aorta were increased （P<0.05， P<0.01）， and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased， and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition， decrease blood lipid and MDA expression， increase SOD and GSH expression， and ameliorate the pathological changes of ferroptosis， the mechanism of which is related to the Nrf2/GPX4 signaling pathway.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome