OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo investigate the expression characteristics of serum HBV RNA in patients with low-level viremia （LLV） and its value in the diagnosis of LLV. MethodsA total of 402 chronic hepatitis B （CHB） patients who attended Affiliated Hospital of Zunyi Medical University from December 2023 to May 2025 were enrolled， and according to their viral load， they were divided into complete virologic response （CVR） group （190 patients with HBV DNA <20 IU/mL） and LLV group （212 patients with an HBV DNA level of ≥20 IU/mL and <2 000 IU/mL）. The two groups were analyzed in terms of age， sex， disease type， serum HBV RNA， HBeAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and total bilirubin （TBil）， and according to HBeAg status， the patients in the LLV group were further divided into HBeAg-negative group with 140 patients and HBeAg-positive group with 72 patients. The chi-square test was used for comparison of categorical data between two groups， and the Mann-Whitney U test was used for comparison of continuous data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for LLV in CHB patients， and a Spearman’s rank correlation analysis was used to analyze the correlation of HBV RNA with HBV DNA， ALT， AST， and TBil in the LLV group. The receiver operating characteristic （ROC） curve was plotted to evaluate the efficacy of HBV RNA in the diagnosis of LLV. ResultsCompared with the CVR group， the LLV group had a significantly higher serum level of HBV RNA ［3 （1　—　5） log₁₀ copies/mL vs 2 （1　—　3） log₁₀ copies/mL， Z=-2.346， P=0.019］ and a significantly higher proportion of patients with hepatitis B cirrhosis （31.13% vs 22.11%， χ²=4.155， P=0.042） or hepatocellular carcinoma （9.91% vs 4.74%， χ²=3.876， P=0.049）. The multivariate Logistic regression analysis showed that HBV RNA （odds ratio=1.163， 95% confidence interval： 1.058　—　1.278， P=0.002） was an independent risk factor for the onset of LLV in CHB patients. Among the patients with LLV， HBeAg-positive patients had a significantly higher level of HBV RNA than HBeAg-negative patients ［6 （4　—　7） log₁₀ copies/mL vs 2 （1　—　3） log₁₀ copies/mL， Z=-9.962， P<0.001］. The correlation analysis showed that HBV RNA level had no significant correlation with HBV DNA， ALT， AST， or TBil in the patients with LLV （all P>0.05）. The ROC curve analysis showed that HBV RNA had an AUC of 0.567 for the diagnosis of LLV （P=0.021）， with an optimal cut-off value of 4.5 log₁₀ copies/mL， a sensitivity of 30.7%， and a specificity of 85.8%. ConclusionSerum HBV RNA level is an independent risk factor for the development of LLV in CHB patients， and there is a significant increase in the expression of HBV RNA in HBeAg-positive patients. Therefore， it may serve as a potential biomarker for clinical risk assessment.

ObjectiveTo investigate the anti‑pancreatic fibrosis mechanism of Klotho‑derived peptide 7 （KL7） by observing its effect on a mouse model of chronic pancreatitis （CP） induced by cerulean， and to provide a basis for clinical medication. MethodsA total of 40 male BALB/c mice were randomly divided into control group， model group， low-dose KL7 group （2 mg/kg）， and high-dose KL7 group （4 mg/kg）， with 10 mice in each group. All mice except those in the control group were given intraperitoneal injection of cerulean （50 μg/kg） 6 times a day at an interval of 1 hour， twice a week for 4 consecutive weeks to establish a model of CP. The mice in the low-dose KL7 group and the high-dose KL7 group were treated with different doses of KL7 once a day for 4 consecutive weeks. In vivo imaging was used to observe the accumulation of KL7 in the pancreas； molecular docking was used to detect the binding of KL7 to transforming growth factor-β type Ⅱ receptor （TβRⅡ）； the mice were measured in terms of body weight and pancreatic weight； HE staining was used to observe the pathological changes of pancreatic tissue； Masson staining was used to observe the degree of pancreatic fibrosis； immunohistochemical staining was used to measure the expression of α-smooth muscle actin （α-SMA） and type Ⅰ collagen （COL1A1）； Western blotting was used to measure the protein expression levels of α-SMA， TβRII， and phosphorylated small mothers against decapentaplegic homolog 2/3 （p-Smad2/3） in pancreatic tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups. ResultsKL7 was significantly enriched in the pancreatic tissue of CP mice， and there was a strong binding activity between KL7 and TβRⅡ. Compared with the control group， the model group had significant reductions in pancreatic mass and relative pancreatic mass （P<0.000 1）， with disordered structure of pancreatic tissue， an increase in inflammatory cell infiltration， and significant increases in fibrosis degree， the positive areas of α-SMA and COL1A1 （P<0.000 1）， and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.05）. Compared with the model group， the high-dose KL7 group had significant increases in pancreatic mass and relative pancreatic mass （P<0.01）， with alleviation of structural damage of pancreatic tissue and inflammatory cell infiltration， a significant reduction in fibrosis degree， and significant reductions in the positive areas of α-SMA and COL1A1 （P<0.001） and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.01）. ConclusionKL7 has a significant targeted therapeutic effect on pancreatic fibrosis in CP mice through specific binding of KL7 to TβRⅡ， thereby inhibiting the activation of the TGF-β/Smad signaling pathway.

Premature ovarian insufficiency （POI） is a reproductive endocrine disorder that severely affects female reproductive health. However， there remains a lack of clinically effective and safe therapeutic options to restore ovarian function. Traditional Chinese medicine （TCM）， with its advantages of multi-component and multi-target holistic regulation， has shown unique potential in the prevention and treatment of POI. Among TCM monomers， curcumin， resveratrol， and icariin exert antioxidant， anti-inflammatory， and anti-ovarian granulosa cell apoptosis effects by regulating signaling pathways such as nuclear factor-erythroid 2-related factor 2/heme oxygenase-1， phosphoinositide 3-kinase/protein kinase B， and mitogen-activated protein kinase. Single TCM herbs， including American ginseng， Cuscutae Semen， and Cistanches Herba， can regulate sex hormone levels， and alleviate ovarian oxidative stress and immune damage. TCM compound formulas such as Yijing decoction， Siwu decoction， Zuogui pill， and Kuntai capsule modulate multiple signaling pathways， including vascular endothelial growth factor/vascular endothelial growth factor receptor-2， phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin， and silence information regulator 1/p53， thereby promoting angiogenesis， inhibiting mitochondrial apoptosis， and regulating autophagy and ferroptosis， which ultimately delay follicular atresia and improve ovarian reserve function. Further studies are suggested to apply artificial intelligence to deeply explore the underlying mechanisms and carry out high-quality clinical trials， so as to promote the standardized application of TCM in the prevention and treatment of POI.

Rheumatoid arthritis （RA） is an autoimmune disease characterized by chronic synovial inflammation and joint destruction， with a complex pathogenesis. Macrophage polarization plays a pivotal role in disease progression. Recent studies demonstrate that microRNA （miRNA）， as critical post-transcriptional regulators， can participate in the inflammatory response process by regulating the polarization state of macrophages， thereby aggravating RA joint damage. This review summarizes the mechanism of action of various miRNA in regulating macrophage polarization， and emphasizes their potential therapeutic value in RA.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

Breast milk is the optimal natural food for newborns. However， some newborns cannot receive maternal breast milk due to reasons such as mother-infant separation or insufficient lactation. The establishment of human milk banks （HMB） can effectively address these issues， thereby increasing the breastfeeding rate among hospitalized newborns and improving their quality of survival. However， HMB in China is still in the development and improvement stage. Its implementation involves a series of ethical issues， such as informed consent， privacy protection， economic incentives， quality and safety， and fair resource distribution， which hinder HMB’s widespread promotion. Therefore， discussing the ethical dilemmas faced by the widespread establishment of HMB in China’s hospitals and analyzing coping strategies are crucial for improving the breastfeeding rate of newborns. This paper deeply analyzed and sorted out the ethical issues and challenges currently faced by HMB in China， and proposed corresponding strategies， including “ensuring informed consent and voluntary participation of both donors and recipients，” “protecting the privacy of donors and recipients，” “establishing an ethics-based moral incentive and social support system，” “strictly controlling quality and safety issues”， and “developing fair and rational policies，” aiming to provide a reference solution for addressing ethical concerns in the establishment and operation of HMB.

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

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

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*