This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

The paper introduces Professor FAN Gangqi's clinical experience in treatment of migraine. Regarding the syndrome/pattern differentiation of TCM, a four-approach framework is established, identifying the nature of illness, analyzing the syndrome/pattern and pathogenesis, determining the stage of illness, and identifying body constitution. In treatment, the principle of treatment is determined in line with syndrome/pattern differentiation, so as to ensure the therapeutic effect by means of "four dimensions". The acupuncture regimens are formulated in terms of the illness stages, "strong needling stimulation in acute stage for analgesia, and needle retaining in chronic stage for long-term effect". "Focusing on neuovascular pathway" is the effective approach to treatment of migraine with acupuncture and moxiubstion. The clinical holistic model by combining acupuncture with medication is advocated because that "the single acupuncture is weak in therapeutic effect, but with medication combined, the effect is enhanced". The different acupuncture techniques are provided comprehensively in treatment of migraine such as horizontal and row-like needling, collateral needling at Taiyang (EX-HN5), acupuncture at Sankong (Yuyao [EX-HN4], Sibai [ST2] and Jiachengjiang [Extra]), acupoint injection at Tianyou (TE16) and Renying (ST9), and acupoint embedding therapy at Fengchi (GB20).
Humans ; Migraine Disorders/diagnosis* ; Acupuncture Therapy ; Moxibustion ; Acupuncture Points ; Female ; Male ; Adult

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

Diabetic kidney disease （DKD） is one of the main causes of chronic kidney disease. Both traditional Chinese medicine （TCM） and western medicine have their own advantages in the prevention and treatment of DKD， but there are also many difficulties. By analysis of the difficulties faced by TCM and western medicine in the differentiation and treatment of DKD， based on the theory of "miniature masses in the renal collaterals"， combined with long-term clinical practice， "internal heat leading to mass" is proposed as the core pathogenesis of DKD. Therefore， a trinity model of "disease-syndrome-symptom" for differentiation and treatment of DKD based on the core pathogenesis has been proposed. This model highlights the status of the core pathogenesis of "internal heat leading to mass" in DKD， and conducts a three-dimensional identification from the perspectives of disease， syndrome and symptom， so as to inspire clinical practice.

Objective To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics(RG)technology,in combination with chemotherapy drug,gemcitabine(GEM),against pancreatic cancer cells.Methods The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study.The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay.CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses[multiplicities of infection(MOI):0,0.1,1.0,3.0]on the survival rate of pancreatic cancer cell lines(Panc02,PANC-1,SW1990,BxPC-3)and normal pancreatic ductal epithelial cells(HPDE6-C7)after treatment for 24,48 or 72 h.Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice(6 weeks old)were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group.PBS(100 μL/animal)or OvFlu-GM-CSF virus(1× 107PFU/100 μL)was given to the mice of the corresponding groups through intratumoral injection,while GEM(100 mg/kg)was injected intraperitoneally,once per 3 days,for totally 9 times.Changes in tumor volume and survival rate were monitored.Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues.HE staining was performed to observe the pathological changes in major organs(heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured to evaluate the safety of the recombinant oncolytic virus.Results The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells.At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0(P＜0.01).The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time(P＜0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells(HPDE6-C7).In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment(P＜0.01),and enhanced the infiltration of T cells in the tumor tissues.No obvious pathological changes were observed in the above-mentioned major organs.Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.Conclusion RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host's anti-tumor immune response.

Objective To explore the change trend and related mechanism of resting metabolic rate induced by corticosterone in mice,and observe the intervention effects of Zhibai Dihuang Pill and Jinkui Shenqi pill.Methods Sixty-four mice were randomly divided into short-term and long-term groups,and each group was randomly divided into four groups.Mice in CORT group,ZBDH group and JKSQ group were given sterile drinking water containing corticosterone,and mice in Ctrl group were given sterile drinking water containing 1%anhydrous ethanol.Mice in ZBDH group and JKSQ group were given Chinese medicine by gavage.RMR of mice in each group was dynamically monitored during modeling and Chinese medicine intervention.The morphology of mitochondria in liver and muscle were observed by transmission electron microscope.The TR expression level in liver and muscle tissues of each group was observed by immunofluorescence,and MDA and ATP levels were detected in liver and muscle tissues of each group.levels of ACTH,TSH,INS,T3,T4,FT3,FT4,8-OHdG,FGF-21,GDF-15,L-lactic acid and pyruvic acid in serum were also detected.Results Compared with Ctrl group,the mitochondrial morphology of liver and muscle tissues in CORT group was damaged,and the expression of TR was decreased.In short-term(Day 8),RMR,ATP in liver,serum T4,ACTH and INS levels were significantly increased in the CORT group,while serum FGF-21,TSH levels and MDA in liver were significantly decreased.In long term(Day 56),RMR,serum 8-OhdG,INS,and ATP in liver and muscle were significantly decreased in the CORT group,serum FGF-21,GDF-15,T3,T4,FT3,FT4,MDA in liver and muscle were significantly increased.Compared with CORT group,in short term,RMR,serum L(+)-lactate in ZBDH group were significantly decreased,while serum 8-OHdG and the expression of TRα in muscle were significantly increased.In JKSQ group,the mitochondrial morphology of muscle tissue was improved,the expression of TRα and serum FGF-21 were significantly increased,while serum L(+)-lactic acid,FT4 and ATP in liver were significantly decreased.In long term,serum FGF-21 was significantly lower in ZBDH group,and in JKSQ group,RMR,ATP in liver tissue and TRα expression in muscle were significantly increased,while the levels of FGF-21,GDF-15,T3,FT4 in serum and MDA in muscle tissue were significantly decreased.Conclusion CORT induced RMR to increase first and then decrease with the intervention time.In the short term,Zhibai Dihuang Pill significantly decreased RMR in mice,while in the long term,Jinkui Shenqi Pill significantly increased RMR.The mechanism may be related to mitochondrial injury,thyroxine secretion and thyroxine receptor expression.

The aim of this study is to explore the mechanism of apigenin against transmissible gas-troenteritis virus(TGEV)infection based on network pharmacology and molecular docking.The potential targets of apigenin were obtained from Pharmmapper,Pubchem and other databases.The PubMed database was searched to obtain the relevant targets of TGEV infection.The intersection targets of apigenin and TGEV infection were identified by Draw Venn Diagram online program.A"drug-disease-target"network was constructed using STRING database and Cytoscape 3.8.2 soft-ware.Protein-protein interaction relationships were obtained from the STRING database,and core targets were analyzed.The intersection targets were subjected to GO function and KEGG pathway enrichment analysis using the DAVID database.Finally,the analysis results were validated through molecular docking and in vitro cell experiments.The study identified 431 targets for apigenin,1 177 targets for TGEV infection,and 50 intersection targets for apigenin and TGEV infection.GO enrichment analysis indicated that apigenin was mainly involved in regulating cell differentiation,cell membrane raft formation,apoptosis,and inflammatory responses.The top 15 statistically sig-nificant KEGG enrichment results mainly involve the PI3K-Akt signaling pathway and TNF signa-ling pathway.Docking analysis showed that apigenin had the strongest interaction with matrix metalloproteinase 3(MMP3)with an affinity of-9.5 kJ/mol and the binding activity of MMP3 was the best.The results of in vitro experiments demonstrated that treatment of different concen-trations of apigenin significantly reduced virus titers,virus genome copies,and the expression lev-els of MMP3 and its upstream and downstream proteins compared to the virus-infected group.Api-genin may exert its anti-TGEV effects through multiple targets and pathways,possibly by regula-ting the NF-κB-MMP3-IL-1β signaling pathway.