ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

OBJECTIVE To investigate the absorption characteristics and tissue distribution of silybin （Sy） nanocrystals prepared by two methods in different intestinal segments of rats. METHODS Sy nanocrystals （i.e. Sy-NS-G and Sy-NS-F） with comparable particle sizes were prepared using high-pressure homogenization and anti-solvent precipitation methods， respectively. Rats were randomly divided into three groups： Sy raw drug group， Sy-NS-G group， and Sy-NS-F group. Each group was further divided into three subgroups with low， medium， and high （60， 120， 180 μg/mL） mass concentrations （calculated based on Sy）， with 3 rats in each subgroup. The absorption rate constant （Ka） and apparent absorption coefficient （Papp） of Sy raw drug， Sy-NS-G and Sy-NS-F in different intestinal segments were investigated by using the in vivo one-way intestinal perfusion experiment. Additionally， the rats were divided into three groups: Sy raw drug group， Sy-NS-G group， and Sy-NS-F group， with 20 rats in each group. Rats in each group were administered a single intragastric dose of 50 mg/kg （calculated based on Sy）. They were sacrificed at 0.3， 1， 4， 10， and 24 hours post-administration respectively， to investigate the tissue distribution of Sy raw drug， Sy- NS-G， and Sy-NS-F in the heart， liver， spleen， lungs， kidneys， brain and intestines. RESULTS In duodenum and jejunum， the Ka and Papp of the nanocrystals prepared by the two methods remained unchanged with the increase of Sy concentration， and there was no significant difference （P＞0.05）； the absorption of Sy-NS-F in the duodenum was greater than that of Sy-NS-G； the absorption sites of Sy-NS-G and Sy raw drug were mainly in the ileum， while those of Sy-NS-F were mainly in the duodenum and ileum. The concentrations of Sy-NS-G and Sy-NS-F in different tissues of rats were different； Sy-NS-G peaked in most tissues at 1 h， and the distribution concentration was as follows： intestine＞spleen＞heart＞lungs＞liver≈brain＞kidneys. Sy-NS-F reached its peak at 1 h， and the distribution concentration was in the order of intestine＞spleen＞kidney＞lung＞heart≈liver＞brain. CONCLUSIONS The absorption mode of Sy nanocrystals in the duodenum and ileum is mainly passive diffusion. In the duodenum， the absorption of Sy-NS-F is greater than that of Sy-NS-G； there are significant differences in the tissue distribution of Sy-NS-G and Sy-NS-F in rats.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Objective To investigate the clinical efficacy of microecological agents combined with dietary fiber in the treatment of chronic obstructive pulmonary disease(COPD)and its impacts on intestinal flora and inflammatory factors in patients.Methods A total of 80 patients with acute exacerbation of COPD were enrolled and randomly divided into dietary fiber group and combination group,with 40 patients in each group.The dietary fiber group received dietary fiber intervention,while the combination group received microecological agents combined with dietary fiber intervention.Nutrient intake,body mass index(BMI),nutritional indicators[albumin(ALB),hemoglobin(Hb),prealbumin(PA)],inflammatory markers[procalcitonin(PCT),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)],intestinal mucosal barrier function[diamine oxidase(DAO),intestinal fatty acid-binding protein(I-FABP),D-lactic acid(D-LA)],and intestinal bacterial counts were compared between the two groups.Results After intervention,BMI and total calorie,intake of fat,carbohydrate,and protein were higher in both groups compared with before intervention,and were higher in the combination group than in the dietary fiber group(P＜0.05).After inter-vention,ALB,Hb,and PA levels were higher in both groups compared with before intervention,and were higher in the combination group than in the dietary fiber group(P＜0.05).After inter-vention,PCT,CRP,and TNF-α levels were lower in both groups compared with before interven-tion,and were lower in the combination group than in the dietary fiber group(P＜0.05).After in-tervention,D-LA levels were higher,and the DAO and I-FABP levels were lower in both groups compared with before intervention(P＜0.05).D-LA levels were higher,while DAO and I-FABP levels were lower in the combination group compared with the dietary fiber group(P＜0.05).After intervention,the number of Escherichia coli and Enterococci were lower in the combination group than in the dietary fiber group,while the number of Lactobacilli,Bifidobacteria,and Bacteroides were high-er(P＜0.05).There were no statistically significant differences in the total incidence of adverse re-actions or edema status after intervention between the two groups(P＞0.05).Conclusion Micro-ecological agents combined with dietary fiber exhibit significant efficacy in the treatment of COPD,which can stabilize the intestinal microbial community,reduce inflammatory responses,and improve nutritional status.

Objective To analyze serum prolactin(PRL)levels during pregnancy in healthy single pregnant women of childbearing age in Suzhou,and to establish and verify the reference interval of serum PRL.Methods From January to March,2022,the data of pregnant women with healthy single pregnancy at child-bearing age were collected and prospectively followed up until delivery.According to the gestational age,the subjects were divided into early pregnancy group(less than 14 weeks),middle pregnancy group(14-27+6 weeks)and late pregnancy group(≥28 weeks).PRL was determined by Soling LIAISON XL automatic chemi-luminescence immunoassay and LIAISON? prolactin.After eliminating outliers,the medical reference interval of serum PRL during pregnancy was established by percentile method(P2.5-P97.5).In addition,20 samples of healthy single pregnant women of childbearing age were randomly collected in early,middle and late pregnancy to verify the established reference interval.When no more than two PRL measurements in each group exceeded the established reference interval,they were considered validated.Results A total of 170 participants were included in the early pregnancy group,229 participants in the middle pregnancy group and 130 participants in the late pregnancy group.There were significant differences in serum PRL levels in pregnant women at different stages of pregnancy.With the increase of gestational age,serum PRL level increased.The reference intervals of serum PRL in early,middle and late pregnancy were 477-4270 mIU/L,1060-6574 mIU/L and 3497-18 274 mIU/L,respectively.All the established reference intervals were verified.Conclusion This study has established the reference interval of serum PRL during pregnancy of healthy single pregnant women of childbear-ing age in Suzhou area,to provide help for clinical rational application of this index,and further reference for the prevention of pregnancy-related diseases.

Objective:To investigate the risk factors of skin adverse events associated with immune checkpoint inhibitor (ICI) therapy in patients with urologic neoplasms, and establish a predictive model.Methods:A single-center retrospective case-control study enrolled 91 advanced urologic neoplasms patients who received ICI therapy at the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2025. Patients were divided into the skin lesion group ( n=44) and the control group ( n=47). Patients in the skin lesion group experienced related skin adverse events during ICI treatment, while patients in the control group did not experience such events during ICI treatment. The general data and laboratory indicators were compared between the two groups. The normally distributed measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; the non-normally distributed measurement data were expressed as the median (interquartile range) [ M ( Q1, Q3)], and the Kruskal-Wallis test was used for comparison between groups. The count data were expressed as the number of cases and percentages, and the Chi-test was used for comparison between groups. First, a univariate analysis was conducted on the influencing factors of skin adverse events in patients with urologic neoplasms after ICI treatment. Then, the indicators with statistically significant differences in the univariate analysis were further included in the multivariate Logistic regression model to screen the independent risk factors for predicting skin adverse events. The R software was used to incorporate the factors with significant differences from multivariate analysis into the prediction model and construct a Nomogram. The calibration curve was utilized to evaluate the consistency between predicted values and actual observed results. Meanwhile, the discrimination of the model was verified by the receiver operating characteristic (ROC) curve and the area under the curve (AUC), so as to comprehensively verify the reliability and clinical application value of the prediction model. Results:The results of univariate analysis showed that there were statistically significant differences between the skin lesion group and the control group in terms of the proportion of other immune responses, serum albumin level, absolute eosinophil count, and C-reactive protein (CRP) levels ( P<0.05). These factors were included in multivariate Logistic regression, which identified elevated absolute eosinophil count and elevated CRP as the independent risk factors for related skin adverse events in patients with urologic neoplasms after ICI treatment. A predictive nomogram was built based on these factors. The calibration curve showed high consistency between predicted and actual probabilities, and ROC analysis confirmed the combined model had high predictive value (AUC=0.883, P<0.001). Conclusions:Elevated absolute eosinophil count and elevated CRP level are independent predictors of immune-related skin adverse events in urologic neoplasms patients after ICI treatment. The prediction model constructed based on these two factors facilitates early clinical screening and identification of high-risk patients.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*