OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Perimenopausal anxiety and depression state fall under the categories of"visceral agitation"and"perimenopausal syndrome"in traditional Chinese medicine(TCM).Grounded in the theory of"Yang transforms qi,yin shapes form",this study posits that the pathogenesis of this condition is complex,often presenting with concurrent deficiency and excess syndromes,and is closely associated with yang deficiency-induced stagnation and qi stagnation leading to mental decline.The pathological mechanism is summarized as yang deficiency being the root and qi stagnation the manifestation.This article proposes a"yang-oriented treatment"approach for perimenopausal anxiety-depression disorders,employing a stepwise integrated acupuncture protocol termed"One Needling,Two Moxibustion,Three Consolidation":"One Needling"prioritizes regulating qi flow via acupuncture to soothe the liver and harmonize the spirit;"Two Moxibustion"utilizes refined moxibustion to warm yang,resolve stagnation,and activate yang circulation;"Three Consolidation"combines bloodletting therapy to remove stasis and regenerate tissues with intradermal needle embedding to stimulate yang and regulate visceral functions.This synergistic protocol aims to nourish the heart-mind,awaken the orifices of consciousness,alleviate perimenopausal anxiety and depressive symptoms,and consolidate therapeutic efficacy.

ObjectiveTo evaluate the effectiveness of Gandou decoction （GDD） by analyzing theclinical efficacy of GDD combined with speech training on the treatment of dysarthria with endoretention of damp-heat in Wilson's disease （WD）， so as to provide more clinical data and theoretical support for the selection of appropriate treatment schemes for WD patients with dysarthria with endoretention of damp-heat. MethodA total of 60 eligible WD patients with dysarthria with endoretention of damp-heat were selected and divided into a control group and a treatment group according to the random grouping method， with 30 cases in each group. The control group was treated with speech training + sodium dimercaptopropanesulfonate （DMPS）， and the treatment group was combined with GDD on the basis of the control group， with eight days as a course of treatment for 32 days. The total clinical effectiveness rate （Goldstein clinical classification）， dysarthria grading assessment from China Rehabilitation Research Center， TCM syndrome scores， 24-hour urine copper content， and modified Frenchay dysarthria rating scale scores of the two groups were compared before and after treatment. ResultAfter treatment， the total effective rate of the observation group was 90.0% （27/30）， and that of the control group was 70.0% （21/30）. The total effective rate of the observation group was significantly higher than that of the control group （Z=-1.986，P<0.05）. After treatment， the modified Frenchay dysarthria score， dysarthria grading assessment from China Rehabilitation Research Center， and 24-h urine copper in the two groups were significantly increased （P<0.05， P<0.01）， and the TCM syndrome score was significantly decreased （P<0.01）. Compared with the control group after treatment， except for the respiratory and jaw score， the modified Frenchay dysarthria score of the observation group was significantly increased （P<0.05， P<0.01）. The dysarthria grading from China Rehabilitation Research Center and 24-h urine copper content were significantly increased （P<0.01）， and the observation group had better efficacy. During the study period， there were no serious adverse reactions such as fever， rash， oral and eyelid mucosal swelling， exfoliative dermatitis， vomiting， diarrhea， or allergic shock during copper excretion treatment of DPMS and oral administration of GDD. ConclusionGDD combined with speech training can improve the symptoms and efficacy of WD patients with dysarthria with endoretention of damp-heat and enhance the patients' living standard to a certain extent， which can be widely used in clinics.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.

Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.

Objective To explore whether adiponectin receptor 1/2(AdipoR1/R2)mediates berberine to alleviate renal lipid toxicity in mice with diabetic kidney disease.Methods C57BLKS/J db/db mice and db/m mice were selected and divided into 4 groups,with 8 in each group.db/db mice and db/m mice were given berberine(150 mg·kg-1·d-)or placebo by gavage for 12 weeks,respectively.After intervention,blood glucose,blood lipids,urinary microalbumin/creatinine ratio and urinary albumin excretion rate were determined.Kidney tissues were taken for pathological examination,and oil red O staining,immunohistochemistry,ELISA and Western blotting were used to examine lipid deposition,AdipoRl/R2 expression and fibrosis markers expressions,etc.,respectively.The human glomerular endothelial cell line(HGEC)was used to verify the role of AdipoR1/R2 in berberine alleviating renal lipid toxicity.Results After berberine intervention,the body weight,blood glucose,lipids,proteinuria,renal lipid deposition,and renal pathological changes decreased in db/db mice(P＜0.05);the expressions of AdipoR1 and AdipoR2 increased,expressions of TGF-β1 and Col-Ⅳ decreased,and the expressions of PPAR-α and p-AMPK increased in kidney tissue of db/db mice(P＜0.05).In high-fat cultured HGEC cells treated with berberine-treated db/db mouse serum,the expressions of TGF-β1 and Col-Ⅳ decreased,while the expressions of PPAR-α and p-AMPK increased(P＜0.05);after AdipoR1/R2 on HGEC cells were silenced,the expressions of TGF-β1 and Col-Ⅳ increased,while the expressions of PPAR-α and p-AMPK decreased(P＜0.05).Conclusions Berberine can reduce renal lipid toxicity in diabetic nephropathy mice,and adiponectin receptor may mediate this effect of berberine.

Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.

Objective To develop and test the reliability and validity of the Intrinsic Capacity Assessment Scale for the Older People,so as to provide an effective tool for the assessment of the intrinsic capacity of the aged.Methods Based on the International Classification of Functioning,Disability and Health(ICF)as the theoretical framework,the initial version of The Intrinsic Capacity Assessment Scale for the Older People was developed through literature analysis,Delphi expert consultation and pre-survey.From July to September 2023,650 old people were selected by convenience sampling method to conduct a survey,and 20 old people were surveyed after 2 weeks again to test the reliability and validity of the scale.Results The effective questionnaire recovery rates of the 2 rounds of expert correspondence were 92.3％and 91.7％;the expert authority coefficients were 0.83 and 0.86;the mean importance scores of items were 2.04-3.79 and 3.50-3.82,and the full score ratios were 4.2％-83.3％and 54.6％-86.4％,respectively.The coefficients of variation were 0.11-0.42 and 0.11-0.23,respectively.A total of 5 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 68.327％.The results of confirmatory factor analysis showed that the fit indexes were x2/df=1.908,RMSEA=0.054,CFI=0.931,IFI=0.932,TLI=0.922,indicating a good fit.The Cronbach's α coefficient of the scale was 0.944;the split half reliability was 0.806;the retest reliability was 0.933.The content validity index of item level was 0.82-1.00,and the content validity index of scale level was 0.91.The Intrinsic Capacity Assessment Scale for the Older People included 35 items in 5 dimensions:movement,vitality,sensation,cognition and psychology.Conclusion The Intrinsic Capacity Assessment Scale for the Older People has good reliability and validity,and it can be used as a reliable tool to evaluate the intrinsic capacity level of the aged.