ObjectiveTo investigate the potential mechanism of Yiqi Yangyin Huoxue Formula （益气养阴活血方， YYHF） in the treatment of membranous nephropathy （MN） based on the NOX4-mediated stromal cell-derived factor-1α（SDF-1α）/CXC chemokine receptor 4 （CXCR4） signaling pathway. MethodsA total of 42 male SD rats were randomly divided into blank group （n=6） and modeling group （n=36）. The modeling rats were given a single injection of sheep antirat Fx1A （6 ml/kg） serum into the tail vein to establish MN model. Thirty-six rats with successful modeling were further divided into model group （normal saline， 10 ml/kg）， benazepril group （10 mg·kg^-1·d^-1）， the medium-dose YYHF group （11.0 g·kg^-1·d^-1） and high-dose YYHF group （22.0 g·kg^-1·d^-1）， with 9 rats in each group. All groups received daily intragastric administration for 6 consecutive weeks. During the experimental period， the general condition of rats in each group was observed. After gavage administration finished， a fully automated biochemical analyzer was used to measure the 24-hour urine total protein （24 h-UTP） and serum biochemical parameters， including albumin （ALB）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， serum creatinine （SCr）， total cholesterol （TC）， and triglyceride （TG）. Hematoxylin-eosin （HE） staining and periodic acid-silver metheramine （PASM） staining were used to observe the histopathological changes of renal tissues in each group of rats. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were detected by ELISA. The protein expression levels of NOX4， SDF-1α， CXCR4， Nrf2， nuclear factor kappa B subunit p65 （NF-κB p65） and podocyte slit diaphragm protein nephrin in rat renal tissues were detected by Western Blotting. The mRNA expressions of NOX4， SDF-1α， CXCR4， Nrf2， NF-κB p65 and Nephrin in renal tissues were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultsCompared to the blank group， rats in the model group exhibited typical features of MN， including lethargy， reduced activity， dull and coarse fur， marked edema， and massive proteinuria. Compared to the model group， these abnormal conditions were improved to varying degrees in all treatment groups. The high-dose YYHF group showed a level of improvement comparable to that of the benazepril group， with overall recovery superior to that of the medium-dose YYHF group. Compared to the blank group， the model group showed increased levels of 24 h-UTP， BUN， SCr， TC and TG， decreased level of ALB， increased levels of MDA and protein and mRNA expressions of NOX4， SDF-1α， CXCR4 and NF-κB p65 in renal tissue， along with decreased levels of SOD and protein and mRNA expressions of Nrf2， Nephrin （P＜0.01）， accompanied by severe renal pathological damage. Compared to the model group， the benazepril and the medium- and high-dose YYHF groups showed significant improvements in the above indicators （P＜0.01）， along with alleviation of renal pathological injury. The 24 h-UTP level in the high-dose YYHF group was lower than that in the medium-dose group （P＜0.01）， while no statistically significant difference was observed among the other treatment groups （P＞0.01）. ConclusionYYHF may alleviate oxidative stress and inflammatory responses by down-regulating the expression of NOX4 and inhibiting the SDF-1α/CXCR4-Nrf2 signaling pathway， thereby improving podocyte damage and protecting renal function.

Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer (BC) by using two-sample Mendelian randomization (MR). Methods This study employed a two-sample MR analysis, with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−) from the BCAC Consortium as the outcome variables. For causal inference, inverse variance weighting (IVW) was employed as the primary analytical method, alongside multiple consistency validation approaches, including MR-Egger, weighted median, weighted mode, simple mode, and Bayesian weighted Mendelian randomization. Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality. Results Significant causal associations were identified for specific immune cell phenotypes across subtypes. In HR+ BC, the HER2+ subtype was associated with seven immunophenotypes (five protective and two risk increasing), whereas the HER2− subtype was associated with eight immunophenotypes (four protective and four risk increasing). In HR− BC, the HER2+ subtype was associated with five immunophenotypes (one protective and four risk increasing), and the HER2− subtype (triple-negative BC) was associated with seven immunophenotypes (six protective and one risk-increasing). CD28+CD45RA−CD8+ T cells and naive CD8+ T cells have a bidirectional causal relationship with HR+/HER2+ breast cancer, Whereas the expression of CD8 on CD39+CD8+ cells also has a bidirectional relationship with HR+/HER2− breast cancer. Furthermore, CD4−CD8− NKT cells exhibited opposing effect directions in HER2+ versus HER2− subtypes. Conclusion From a genetic perspective, this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC, revealing heterogeneity in immune regulation.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.

Objective To explore the mechanism of IgA nephropathy(IgAN)caused by multi-glycosides of Tripterygium wilfordii(GTW)through the regulation of Silent information regulatory factor 1(SIRT 1)/nuclear transcription factor E2-related factor 2(Nrf 2)/antioxidant enzyme heme oxygenase 1(HO-1)signaling pathway.Methods Forty-five male SD rats were selected and randomly divided into two groups:the blank group(n=9)and the model group(n=36).In addition to the blank group,the BSA+CCl4+LPS group was used.At the end of 12 weeks,two rats were randomly selected for verification,and the model was successfully established.The 34 model rats were randomly divided into 3 groups:the model group(n=10),prednisone group(n=12),and GTW group(n=12).Urine,blood and kidney tissues were harvested 4 weeks after drug administration.Urinary erythrocyte number,24-h urinary protein quantification(24 h-UTP),alanine transaminase(ALT),serum albumin(ALB),urea nitrogen(BUN),and blood creatinine(SCr)were performed for each group;the protein expression of SIRT1,Nrf2,HO-1 and PINK1 was detected by Western blotting analysis;real-time polymerase chain reaction(RT-PCR)detection of SIRT1,Nrf2,HO-1 and PINK1 mRNA expression in rat kidney tissue;and detection of IgA deposition in the renal mesangial area by immunofluorescence.Kidney histopathological changes were observed in all the rats by hematoxylin-eosin(HE)staining.Results The results compared with those in the blank group,the urinary red blood cell count and 24 h-UTP,ALT,BUN,and SCr levels were significantly greater(P<0.01);The ALB level was significantly lower(P<0.01);renal tissue SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly lower(P<0.01);IgA deposition in the mesentery was obvious;renal pathological damage was severe;and the difference was statistically significant. Compared with those in the model group,urinary red blood cell counts and 24 h-UTP,ALT,BUN,and SCr levels in the prednisone and GTW groups were significantly lower (P<0.01);ALB levels were significantly greater (P<0.01);SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly greater (P<0.01);IgA deposition in the mesangial area was reduced,and renal pathology was improved,with statistically significant difference. Conclusions GTW may alleviate oxidative stress injury,protect renal function,and improve renal injury by activating the SIRT 1/Nrf 2/HO-1 signaling pathway.

Objective To explore the mechanism of IgA nephropathy(IgAN)caused by multi-glycosides of Tripterygium wilfordii(GTW)through the regulation of Silent information regulatory factor 1(SIRT 1)/nuclear transcription factor E2-related factor 2(Nrf 2)/antioxidant enzyme heme oxygenase 1(HO-1)signaling pathway.Methods Forty-five male SD rats were selected and randomly divided into two groups:the blank group(n=9)and the model group(n=36).In addition to the blank group,the BSA+CCl4+LPS group was used.At the end of 12 weeks,two rats were randomly selected for verification,and the model was successfully established.The 34 model rats were randomly divided into 3 groups:the model group(n=10),prednisone group(n=12),and GTW group(n=12).Urine,blood and kidney tissues were harvested 4 weeks after drug administration.Urinary erythrocyte number,24-h urinary protein quantification(24 h-UTP),alanine transaminase(ALT),serum albumin(ALB),urea nitrogen(BUN),and blood creatinine(SCr)were performed for each group;the protein expression of SIRT1,Nrf2,HO-1 and PINK1 was detected by Western blotting analysis;real-time polymerase chain reaction(RT-PCR)detection of SIRT1,Nrf2,HO-1 and PINK1 mRNA expression in rat kidney tissue;and detection of IgA deposition in the renal mesangial area by immunofluorescence.Kidney histopathological changes were observed in all the rats by hematoxylin-eosin(HE)staining.Results The results compared with those in the blank group,the urinary red blood cell count and 24 h-UTP,ALT,BUN,and SCr levels were significantly greater(P<0.01);The ALB level was significantly lower(P<0.01);renal tissue SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly lower(P<0.01);IgA deposition in the mesentery was obvious;renal pathological damage was severe;and the difference was statistically significant. Compared with those in the model group,urinary red blood cell counts and 24 h-UTP,ALT,BUN,and SCr levels in the prednisone and GTW groups were significantly lower (P<0.01);ALB levels were significantly greater (P<0.01);SIRT1,Nrf2,HO-1,PINK1 protein and mRNA expression were significantly greater (P<0.01);IgA deposition in the mesangial area was reduced,and renal pathology was improved,with statistically significant difference. Conclusions GTW may alleviate oxidative stress injury,protect renal function,and improve renal injury by activating the SIRT 1/Nrf 2/HO-1 signaling pathway.

OBJECTIVE To investigate the renal protective effect and mechanism of Shenbining granule on IgA nephropathy （IgAN） rats by regulating the CXC chemokine motif ligand 12 （CXCL12）/CXC chemokine receptor 4 （CXCR4）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS A total of 60 rats were randomly assigned into blank group （n＝12） and modeling group （n＝48）. IgAN model of modeling group was induced by using bovine serum albumin， carbon tetrachloride and lipopolysaccharide， followed by model validation. Ultimately， a total of 55 rats （9 in the blank group， 46 in the modeling group） were included in the subsequent study. The rats in the modeling group were randomly divided into model group （n＝10）， prednisone acetate group [positive control group， 6.25 mg/（kg·d）， n＝12]， Shenbining granule low- and high-dose groups [4.17， 8.33 g/（kg·d）， n＝12]. They were given relevant medicine/distilled water intragastrically， once a day， for 4 consecutive weeks. After the last medication， biochemical indicators in the urine and serum of rats were measured， and pathological morphological changes in the renal tissues of rats were observed. IgA deposition in the renal tissues， as well as the mRNA expression levels of CXCL12， CXCR4 and STAT3， and the protein expression levels of CXCL12， CXCR4， STAT3 and phosphorylated STAT3 （p-STAT3） were detected. Additionally， the level of interleukin-6 （IL-6） in the renal tissue was measured. RESULTS Compared with the model group， the low-dose and high-dose Shenbining granule groups showed significantly decreased urinary red blood cell count， 24 h total urinary protein， blood urea nitrogen， serum creatinine， and alanine amino-transferase， along with increased Alb levels （P＜0.05）. Pathological damage in the renal tissues was alleviated， with reduced IgA deposition in the mesangial region （P＜0.05）； protein and mRNA expressions of CXCL12， CXCR4 and STAT3， as well as phosphorylation level of STAT3 protein and the IL-6 level， were significantly decreased in renal tissue （P＜0.05）. CONCLUSIONS Shenbining granule may exert its renal protective effects in IgAN rats by inhibiting the activation of the CXCL12/ CXCR4/STAT3 signaling pathway， downregulating the expression of inflammatory factors such as IL-6， alleviating renal inflammation， and thereby improving renal pathological damage.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus