In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVES: To investigate the mechanism through which pinostrobin (PSB) alleviates dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomized into control group, DSS model group, and PSB intervention (30, 60, and 120 mg/kg) groups. Colitis severity of the mice was assessed by examining body weight changes, disease activity index (DAI), colon length, and histopathology. The expressions of tight junction proteins ZO-1 and claudin-1 in the colon tissues were examined using immunofluorescence staining, and macrophage infiltration and polarization were analyzed with flow cytometry. ELISA and RT-qPCR were used for detecting the expressions of inflammatory factors (TNF‑α and IL-6) and chemokines (CCL₂, CXCL₁₀, and CX₃CL₁) in the colon tissues, and PI3K/AKT phosphorylation levels were analyzed with Western blotting. In cultured Caco-2 and RAW264.7 cells, the effect of PSB on CCL₂-mediated macrophage migration was assessed using Transwell assay. Network pharmacology analysis was performed to predict the key pathways that mediate the therapeutic effect of PSB. RESULTS: In DSS-induced mouse models, PSB at 60 mg/kg optimally alleviated colitis, shown by reduced weight loss and DAI scores and increased colon length. PSB treatment significantly upregulated ZO-1 and claudin-1 expressions in the colon tissues, inhibited colonic macrophage infiltration, and promoted the shift of macrophage polarization from M1 to M2 type. In cultured intestinal epithelial cells, PSB significantly inhibited PI3K/AKT phosphorylation and suppressed chemokine CCL₂ expression. PSB treatment obviously blocked CCL₂-mediated macrophage migration of RAW264.7 cells, which could be reversed by exogenous CCL₂. Network pharmacology analysis and rescue experiments confirmed PI3K/AKT and CCL₂ signaling as the core targets of PSB. CONCLUSIONS PSB alleviates DSS-induced colitis in mice by targeting intestinal epithelial PI3K/AKT signaling, reducing CCL₂ secretion, and blocking macrophage chemotaxis and migration, highlighting the potential of PSB as a novel natural compound for treatment of inflammatory bowel disease.
Animals ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Colitis/drug therapy* ; Dextran Sulfate ; Proto-Oncogene Proteins c-akt/metabolism* ; Macrophages ; Chemokine CCL2/metabolism* ; Humans ; Signal Transduction/drug effects* ; Caco-2 Cells ; RAW 264.7 Cells ; Epithelial Cells/drug effects* ; Intestinal Mucosa/metabolism*

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

40 patients with choronic periodontitis underwent periodontal basic treatment were randomly divided into 2 groups(n=20).The patients in control group used special toothpaste and toothbrush to brush their teeth after meals,those in the experimental group brushed their teeth with special toothpaste and toothbrush in the morning,evening and after meals,and wore personalized film pressing trays containing cymene care solution while sleeping at night.Gingival bleeding,periodontal pocket depth and attachment loss were ob-served after 4,6 and 10 weeks respectively.The personalized tray combined with cymbidium reduced the depth of periodontal pocket(P＜0.05)and the rate of probing bleeding sites(P＜0.05)more effectively,and showed no statistical significance in the change of attachment loss(P＜0.05).Cymene care solution is effective in the improvement of periodontal health.

Objective To deeply understand the anatomical basis of temporomandibular joint disorders,and explore and master the pathological characteristics of anterior displacement of temporomandibular joint disc through cadaveric dissection and 3D printing technology.Methods By dissecting the temporomandibular joints of 40 head and neck specimens,the bilateral structures of the temporomandibular joints were measured to obtain condyle and articular disc data.3D modeling was carried out using 3ds Max software and printed out a model of temporomandibular joint.The pathological model of the anterior disc displacement with reduction(ADDwR)was simulated by adjusting the opening degree,the position of the articular disk,and the position of the condyle of the model.Results The precise data of the right and left temporomandibular joint discs and condyle were successfully obtained by dissection and measurement.The thickness of the anterior band of left temporomandibular joint discs was(2.02±0.57)mm,the thickness of the middle band was(1.46±0.33)mm,the thickness of the posterior band was(3.00±0.46)mm,the anterior-posterior diameter was(9.60±0.72)mm,and the internal-external diameter was(17.73±0.84)mm.While the thickness of the anterior band of right temporomandibular joint discs was(1.84±0.35)mm,and the thickness of the middle band was(1.43±0.28)mm,the thickness of posterior band was(3.08±0.49)mm,the anterior-posterior diameter was(9.30±0.88)mm,and the internal-external diameter was(17.38±1.10)mm.The internal-external diameter of the left temporomandibular joint condyle was(18.97±0.41)mm,and the anterior-posterior diameter was(8.56±0.43)mm;the internal-external diameter of the right temporomandibular joint condyle was(18.86±0.75)mm,and the anterior-posterior diameter was(8.40±0.30)mm.The standard temporomandibular joint model was printed out by the measured data.The model was utilized to simulate the physiological state of temporomandibular joint under normal conditions,as well as the three pathological states of closed mouth,closed mouth to open mouth,and open mouth in the case of ADDwR.Conclusion The temporomandibular joint model can more intuitively present the changes of anatomical structure in reversible temporoman-dibular joint disorders,which is helpful for understanding and mastering the different classification of this disease.

Objective To analyze the status and gene subtype distribution of human papillomavirus(HPV)infec-tion in male patients in dermatology outpatient department,provide reference for the prevention and treatment of male HPV infection.Methods Male patients who visited and conducted HPV detection in the dermatology outpa-tient department of a hospital from January 2022 to March 2023 were retrospectively surveyed.Patients were divi-ded into five groups:viral warts group,dermatitis and rash group,urinary tract infection group,balanoposthitis group,and asymptomatic group.Relationship between genotype distribution and patient age,clinical diagnosis,and symptom types was statistically analyzed.Results A total of 1 035 male patients underwent HPV detection,out of which 567 were positive,with a positive detection rate of 54.78％.286,164,6,109,and 470 cases were from viral warts,dermatitis and rash,urinary tract infection,balanoposthitis,and asymptomatic group,respectively.21 sub-types of HPV were detected,with the top three subtypes being type 6(17.97％),11(12.37％),and 52(8.70％).The positive rate of single type HPV infection was 29.86％,accounting for 54.50％.Positive rates of infection,low-risk infection,and multiple mixed infection in different age groups were compared,differences were all statisti-cally significant(all P＜0.05).The positive infection rate in the age group of＜20 years old was higher than that in the age groups of 20-＜30,30-＜40,and 40-＜50 years old,differences were all statistically significant(all P＜0.05).Among the positive patients,199 cases(35.10％)had no clinical symptoms,while 368(64.90％)had clinical symptoms,mainly manifested as viral warts(40.74％,n=231).In viral warts group,HPV-positive pa-tients were mainly of low-risk type,accounting for 80.95％;In balanoposthitis group,HPV-positive patients were mainly of high-risk type,accounting for 84.78％;In asymptomatic group,HPV-positive patients were mainly infected with high-risk types,accounting for 86.43％.Conclusion HPV infection in male outpatient department of derma-tology is mainly single type infection.The clinical diagnosis of low-risk infection is mainly viral warts,while high-risk in-fection is mainly manifested as balanoposthitis.In asymptomatic group,positive infections are mainly of high-risk type.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.