Diabetic Peripheral Neuropathy （DPN） is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress， inflammation， and mitochondrial dysfunction. These factors are combined to damage nerve fibers， leading to sensory issues， pain， and numbness. Through a coordinated effect， these factors trigger nerve fiber damage and lead to sensory abnormalities， pain and numbness in limbs， and other symptoms， seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability， and further aggravates nerve damage via oxidative stress， mitochondrial dysfunction， autophagy impairment， inflammatory reaction， and other mechanisms， accelerating DPN occurrence and progression. In terms of medical treatment， current methods focus on blood sugar control， pain relief medicine， and microcirculation improvement， while no therapy has been developed based on cellular senescence. In contrast， traditional Chinese medicine （TCM） shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach， as well as syndrome differentiation and treatment， effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients， including puerarin， ginsenosides， and berberine， can reduce inflammation， oxidative stress， and apoptosis via signaling pathway regulation， thereby slowing cellular senescence to alleviate nerve damage. Furthermore， TCM compounds such as Buyang Huanwutang， Taohong Siwutang， and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore， this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence， summarizing the mechanism of DPN and TCM intervention strategies.

This study aims to evaluate the therapeutic effect of Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix(AOF-SR) in a diabetic kidney disease(DKD) mouse model, explore its potential mechanism in regulating the NOD-like receptor protein 3(NLRP3) inflammasome via phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway, and provide new theoretical support for traditional Chinese medicine(TCM) intervention in DKD. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), the active ingredients and potential targets of AOF-SR were screened and its molecular mechanisms were investigated through molecular docking, molecular dynamics simulations, and experimental validation. The db/db mice were randomly divided into four groups: model group, low-dose AOF-SR group, high-dose AOF-SR group, and canagliflozin group. The db/m mice served as normal group. After one week of acclimatization, the mice underwent drug intervention. Starting from one week after treatment, body weight, blood glucose levels, and 24-hour urinary protein(24hUP) were measured every two weeks. After 13 weeks of administration, tissue collection and indicator detection were performed. Blood glucose, 24hUP, urinary microalbumin(mAlb), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were determined. Pathological changes in kidney tissue were observed using hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum IL-1β, IL-18, and caspase-1, while RT-qPCR was employed to measure the mRNA expression levels of IL-1β, IL-18, caspase-1, and NLRP3. Western blot was used to assess the protein expression levels of NLRP3, PI3K, p-Akt, Akt, p-mTOR, and mTOR. Network pharmacology analysis indicated that wogonin, pinocembrin, hancinol, and kaempferol were the core compounds for drug treatment of the disease. Molecular docking and molecular dynamics simulations showed that core compounds, particularly wogonin, could specifically bind to PIK3R1, thereby regulating the PI3K/Akt/mTOR pathway. The experimental results indicated that both low and high doses of AOF-SR and canagliflozin significantly reduced blood glucose, 24hUP, mAlb, Scr, and BUN levels in db/db mice, while improving kidney pathological damage and inflammatory cell infiltration. Moreover, the treatments reduced the mRNA expression levels of caspase-1, IL-1β, and IL-18 in the kidneys of db/db mice, as well as the secretion of these factors in the serum. The drugs also inhibited the mRNA and protein expression levels of NLRP3 in the kidneys of db/db mice and decreased the protein levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, AOF-SR may improve kidney inflammation in DKD mice by regulating the PI3K/Akt/mTOR signaling pathway and inhibiting NLRP3 inflammasome activation.
Animals ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Signal Transduction/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Diabetic Nephropathies/metabolism* ; Inflammasomes/drug effects* ; Male ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mice, Inbred C57BL

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To compare clinical effect of Ludloff operation on the clinical efficacy of patients with hallux valgus combined with hammertoe of the second toe. METHODS: The clinical data of 66 patients with hallux valgus treated with Ludloff surgery from July 2015 to July 2022 were retrospectively analyzed. According to exclusion criteria, 33 patients with hallux valgus combined with hammertoe were finally included as case group, and 33 patients with simple hallux valgus were paired as control group. There were 11 males and 22 females in case group, aged from 24 to 62 years old with an average of (33.6±12.7) years old;body mass index (BMI) ranged from 19 to 25 kg·m^-2 with an average of(21.7±3.1) kg·m^-2;17 patients on the left side and 16 patients on the right side;hallux valgus angle (HVA) ranged from 25° to 47° with an average of (36.3±10.2) °;the intermetatarsal angle (IMA) ranged from 13° to 21° with an average of (16.9±3.2) °. There were 12 males and 21 females in control group, aged from 22 to 61 years old with an average of (32.2±10.9) years old;BMI ranged from 18 to 26 kg·m^-2 with an average of (22.0±4.2) kg·m^-2;15 patients on the left side and 18 patients on the right side;HVA ranged from 26° to 46° with an average of (37.2±9.3) °;IMA ranged from 12° to 21° with an average of (17.3±4.7) °. HVA, IMA, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores and visual analogue scale (VAS) were compared at 3, 6 and 12 months after operation between two groups. RESULTS: Both groups were completed 1 year postoperative follow-up. Postoperative cutaneous margin necrosis occurred in 2 patients of case group and incision rupture occurred in 1 patient of control group. There was no significant difference between two groups (χ²=0.058, P>0.05). Both groups were achieved bone union at stageⅠat 12 weeks after opertaion, and no recurrence of bunion was observed during follow-up. Three months after operation, AOFAS forefoot function score of case group was (73.4±8.6), which was lower than that of control group (82.1±10.3), and the difference was statistically significant (P<0.05). There were no significant differences in HVA, IMA, AOFAS and VAS between two groups at 6 and 12 months after operation (P>0.05). CONCLUSION Ludloff surgery for the treatment of bunions with malleform toe of the second toe is slow in the early postoperative functional recovery, but it did not affect the long-term clinical outcome of the patients.
Humans ; Hallux Valgus/physiopathology* ; Male ; Female ; Middle Aged ; Adult ; Retrospective Studies ; Hammer Toe Syndrome/physiopathology* ; Young Adult

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To investigate the impact of limonin(LIM)on the necrotic apoptosis of myocardial cells in rats with myocardial infarction(MI)by regulating the receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway.Methods:A total of 60 Sprague-Dawley rats were randomly divided into sham-operation group(Sham group),MI model group(Model group),low-dose LIM group(LIM-L group,25 mg/kg LIM),high-dose LIM group(LIM-H group,50 mg/kg LIM),and high-dose LIM+RIP1 inhibitor Nec-1 group(LIM-H+Nec-1 group,50 mg/kg LIM+0.6 mg/kg Nec-1),with 12 rats in each group.A rat model of MI was established by ligation of the coronary artery.The changes of cardiac func-tion were examined for each group;HE staining was used to observe the pathological changes of myocardial tissue;the 2,3,5-triphen-yltetrazolium chloride-Evans blue method was used to measure myocardial infarct area;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was used to observe the necrotic apoptosis of myocardial cells;quantitative real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins associated with the RIP1/RIP3/MLKL signaling pathway and the expression of apoptosis-related proteins.Results:Compared with the Sham group,the Model group had significant re-ductions in left ventricular ejection fraction,left ventricular systolic pressure,and the expression level of B-cell lymphoma-2(Bcl-2)in myocardial tissue(all P<0.001)and significant increases in left ventricular end-systolic volume,left ventricular end-diastolic pres-sure,left ventricular end-diastolic volume,myocardial infarct area,cell apoptosis rate,the mRNA and protein expression levels of RIP1,RIP3,and MLKL in myocardial tissue,and the protein expression levels of Bcl-2 associated X protein and cysteinyl aspartate-specific proteinase 3 in myocardial tissue(all P<0.001),as well as swelling and disordered arrangement of myocardial cells with ne-crosis and massive inflammatory cell infiltration on HE pathological sections.Compared with the Model group,the LIM-H group showed reverse changes in the above indicators(RIP1 mRNA:P=0.002,RIP3 mRNA:P=0.008,and the other indexes P were all<0.001),with alleviations of myocardial histopathological injury and inflammatory cell infiltration.Nec-1 promoted the effect of LIM in alleviating the necrotic apoptosis of myocardial cells in MI rats.Conclusion:LIM may alleviate the necrotic apoptosis of myocardial cells in MI rats by downregulating the RIP1/RIP3/MLKL signaling pathway.

The faithful segregation of genetic material to daughter cells is a fundamental biological process and a prerequisite for autonomous construction of robustly self-replicating artificial cells.Artificial cells are mimic cell structures with part or whole functions of normal cells.The complexity of eukaryotic chromosome segregation machinery has limited its applications in the field of synthetic biology.In contrast,the plasmid segregation machineries employed by prokaryotes are relatively simple and can provide valuable approaches for the bottom-up construction of complex artificial cells.This review aimed to comprehensively analyze the origin species and working mechanism of three bacterial plasmid segregation systems,namely ParABS,ParMRC,and TubZRC systems.The current researches on plasmid segregation both in bacterial and artificial cellular systems were summarized,and the future directions of this field were also proposed.

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin