ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Objective To observe the clinical efficacy of uterine-sparing U-shaped reconstruction surgery in the treatment of diffuse uterine adenomyosis.Methods A total of 48 patients with diffuse uterine adenomyosis underwent surgical treatment from October 2019 to September 2022.All the patients underwent a modified lesion resection procedure via sagittal plane incision of the uterine corpus,enabling direct visualization for U-shaped excision of adenomyotic foci within the myometrium,followed by endometrial cavity reconstruction and uterine remodeling.The dysmenorrhea score,menstrual volume score,serum CA125,and uterine volume were assessed at 1,6,and 12 months postoperatively.Results All the 48 patients underwent surgery successfully.The average surgery time was(115.7±13.6)min,the average intraoperative blood loss was(109.4±30.9)ml,and the total length of hospital stay was(8.6±1.7)d.At 1,6,and 12 months after surgery,the dysmenorrhea score,menstrual volume score,serum CA125 levels,and uterine volume were significantly lower as compared to the pre-operative values(all P=0.000).The hemoglobin level at 1 month after surgery was significantly higher than that before surgery(P=0.000).No symptomatic or ultrasonic recurrences were observed in all the 48 cases.Two cases got unexpected pregnancy after surgery.Conclusions Uterine-sparing U-shaped reconstruction surgery is a safe and effective treatment for diffuse uterine adenomyosis.It does not require special instruments,and is simple and easy to perform.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To observe the clinical efficacy of uterine-sparing U-shaped reconstruction surgery in the treatment of diffuse uterine adenomyosis.Methods A total of 48 patients with diffuse uterine adenomyosis underwent surgical treatment from October 2019 to September 2022.All the patients underwent a modified lesion resection procedure via sagittal plane incision of the uterine corpus,enabling direct visualization for U-shaped excision of adenomyotic foci within the myometrium,followed by endometrial cavity reconstruction and uterine remodeling.The dysmenorrhea score,menstrual volume score,serum CA125,and uterine volume were assessed at 1,6,and 12 months postoperatively.Results All the 48 patients underwent surgery successfully.The average surgery time was(115.7±13.6)min,the average intraoperative blood loss was(109.4±30.9)ml,and the total length of hospital stay was(8.6±1.7)d.At 1,6,and 12 months after surgery,the dysmenorrhea score,menstrual volume score,serum CA125 levels,and uterine volume were significantly lower as compared to the pre-operative values(all P=0.000).The hemoglobin level at 1 month after surgery was significantly higher than that before surgery(P=0.000).No symptomatic or ultrasonic recurrences were observed in all the 48 cases.Two cases got unexpected pregnancy after surgery.Conclusions Uterine-sparing U-shaped reconstruction surgery is a safe and effective treatment for diffuse uterine adenomyosis.It does not require special instruments,and is simple and easy to perform.

Purpose: We aimed to determine whether intra-anal cryotherapy reduces postoperative pain in patients undergoing hemorrhoidectomy. Methods: This randomized controlled trial was conducted from January 2023 to August 2024. Patients with symptomatic grade III hemorrhoids were randomized 1:1 to receive either 1 minute of intra-anal cryotherapy or standard postoperative care. Because cryotherapy was applied before reversal of general anesthesia, patients were blinded to treatment allocation. The primary outcome was pain at rest on postoperative day (POD) 1. Secondary outcomes included pain after defecation, time to return to work or non-work activities, 30-day complications, and compliance with analgesia. Pain was measured using the visual analog scale. Results: A total of 50 patients were randomized (25 per group). All 50 were included in the analysis. Baseline clinicodemographic characteristics were comparable between groups. The primary outcome, POD 1 pain at rest, did not demonstrate superiority of cryotherapy compared with standard care (median 3.0 vs. 4.0, P=0.062). However, the POD 1 pain score after defecation was significantly lower with cryotherapy than without (3.0 vs. 4.0, P=0.046). On POD 2, median pain scores at rest and after defecation were both significantly lower in the cryotherapy cohort (at rest: 2.0 vs. 4.0, P=0.043; after defecation: 2.0 vs. 5.0, P=0.001). Conclusion Intra-anal cryotherapy significantly reduces pain after defecation in the early postoperative period following surgery for grade III hemorrhoids. Its therapeutic efficacy, ease of application, and safety support consideration for routine use.Trial registration ClinicalTrials.gov identifier: NCT06005727

Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.

Objective To explore the clinical efficacy of Jianpi Shuyan Decoction(mainly composed of Astragali Radix,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Angelicae Sinensis Radix,Pinelliae Rhizoma Praeparatum,Cortex Magnoliae Officinalis,Bombyx Batryticatus,and Platycodonis Radix)combined with thumbtack needling therapy(treated with thumbtack-type needle for subcutaneous embedding)in the treatment of chronic sore throat,i.e.,chronic pharyngitis,of spleen-qi weakness type.Methods Sixty-eight patients with chronic pharyngitis of spleen-qi weakness type were randomly divided into the control group and the trial group,with 34 patients in each group.The two groups were given buccal use of Cydiodine Buccal Tablets,and additionally,the trial group was treated with Jianpi Shuyan Decoction combined with thumbtack needling therapy at the six acupoints for pharyngeal disease,i.e.,Futu(LI18),Yamen(GV15),Lianquan(CV23),Tiantu(CV22),Lieque(LU7),and Zhaohai(KI6).Seven days constituted one course of treatment,and the two groups were treated for a total of two courses of treatment.One month and three months after the completion of treatment,the long-term follow-up of the patients was carried out.Before and after the treatment,the changes in visual analogue scale(VAS)score of the illness,inflammatory indicators of C-reactive protein(CRP)and interleukin 2(IL-2),and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed.Moreover,the clinical efficacy,recurrence rate and clinical safety of the two groups were evaluated.Results(1)During the study,2 patients in each of the two groups fell off,and finally 32 patients in each group completed the whole course of treatment.(2)After 2 weeks of treatment,the total effective rate of the trial group was 90.63%(29/32),and that of the control group was 75.00%(24/32).The total effective rate(tested by chi-square test)and overall efficacy(tested by rank sum test)of the trial group were significantly superior to those of the control group(P＜0.05).(2)After 2 weeks of treatment,the VAS score of the illness in the two groups was improved compared with that before treatment(P＜0.05),and the improvement of the VAS scores in the trial group was significantly superior to that in the control group(P＜0.05).(3)After 2 weeks of treatment,the levels of serum inflammatory indicators of CRP and IL-2 in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of serum CRP and IL-2 levels in the trial group was significantly superior to that in the control group(P＜0.05).(4)After 2 weeks of treatment and one month and three months after the completion of treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P＜0.05),but the scores in the two groups one month after the completion of treatment did not differ from those three months after the completion of treatment(P＞0.05).The intergroup comparison showed that the decrease of the scores in the trial group was significantly superior to that in the control group after two weeks of treatment and one month and three months after the completion of treatment(P＜0.05).(5)During the treatment,there were no obvious adverse reactions occurring in the two groups and there were no obvious abnormalities in the safety indexes of blood routine test and liver and kidney function,with high safety.(6)The results of long-term follow-up showed that the recurrence rate of the trial group was 9.38%(3/32)and that of the control group was 18.75%(6/32),and the difference between the two groups was statistically significant(P＜0.05).With the consideration of the changes of TCM syndrome scores in the two groups,it is indicated that the long-term efficacy of the trial group was significantly superior to that of the control group.Conclusion On the basis of buccal use of Cydiodine Buccal Tablets,the application of Jianpi Shuyan Decoction combined with thumbtack needling therapy at the six acupoints for pharyngeal disease exerts certain effectin the treatment of patients with chronic pharyngitis of spleen-qi weakness type.The combined therapy is more effective on relieving clinical symptoms,inhibiting inflammatory response and maintaining long-term efficacy than Cydiodine Buccal Tablets alone.