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.

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.

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*

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 investigate independent risk factors for lower extremity amputation (LEA) in hospitalized patients with diabetic foot ulcers ( DFUs) . Methods: A multicenter retrospective analysis was conducted on the clinical data of 329 DFUs hospitalized patients with diabetic foot ulcers from four general hospitals across the na⁃tion. A multivariate Logistic regression model was constructed , and prediction analysis was performed using R 4. 2. 1 . The discriminative ability of the model was assessed using receiver operating characteristic curves , while calibration accuracy and clinical applicability were evaluated via calibration curves and decision curve analysis. Results : The study revealed that patients with higher education backgrounds showed lower disease severity (Wagnergrade) (Z = - 4. 331 , P < 0. 05) . A history of amputation , pre⁃existing lower extremity vascular disease , abnormal dorsalis pedis artery pulsation , and a history of coronary heart disease were significantly associated with the severity of DFUs , resulting in higher Wagner scores (P < 0. 05) . In the amputation prognosis analysis , prolonged duration of diabetes and elevated white blood cell count were positively correlated with amputation risk ( both P < 0. 01) .Multivariable regression identified non⁃higher education , low hemoglobin levels , decreased total cholesterol , and abnormally elevated platelet counts as independent risk factors for high Wagner grades ( ≥ grade 3 ) ( all P <0. 05) . The integrated predictive model incorporating these factors demonstrated strong discriminative performance ,with an area under curve of 0. 880 (95% CI: 0. 801 - 0. 960) . The calibration curve slope approached the ideal value , and decision curve analysis confirmed the model ′s clinical net benefit within a threshold probability range of 10% - 65% . Conclusion Lower education level , poor baseline nutritional status , infection , hypercoagulability ,and underlying vascular diseases collectively constitute key factors contributing to elevated amputation risk in DFUs patients. The developed predictive model exhibits high accuracy and may assist clinicians in formulating individual⁃ized intervention strategies.

In the differentiation and treatment of recurrent urinary tract infection （rUTI） from the perspective of the seminal orifice， it is proposed that the urinary tract belongs to the category of "seminal orifice"， and the physiological process of urination is closely related to the function of the seminal orifice. From the three dimensions of orifice body， orifice pivot and orifice spirit， the physiological relationship between seminal orifice and the function of five zang-organs （脏） is constructed， that is， lung heat， yin damage and pathogen counter-restriction lead to malnutrition of orifice body； burning heart fire and spirit disorder lead to unfavorable orifice spirit， and kidney deficiency， liver constraint and spleen stagnation lead to unfavorable orifice pivot. In the early stage of rUTI， there is usually unfavo-rable orifice pivot， for which the treatment principle should be treating the root and the branch simultaneously， consi-dering both deficiency and excess， and paying attention to the management of accompanied symptoms. Zishui Qinggan Beverage （滋水清肝饮） and Modified Shenzhuo Decoction （肾着汤加减） are often selected based on syndrome differentiation. In the middle stage， lack of nourishment of the orifice body and unfavorable orifice spirit and pivot coexist， and the treatment should be draining the orifice and unblocking strangury， commonly withmodified Qingxin Lianzi Beverage （清心莲子饮）. In the late stage， loss of nourishment of the orifice body is the main pathogenesis， and it is necessary to further nourish the orifice body to prevent recurrence， and modifed Wuzi Yanzong Pills and Erxian Decoction （五子衍宗丸合二仙汤） is often used. Furthermore， the specific medicinals should be selected targeting at the orifice body， orifice pivot， and orifice spirit， so as to nourish orifice body by dispelling external pathogens and rectify healthy qi， to drain orifice pivot by freeing emotions and minds and unblocking qi movement， and to calm orifice spirit by unblocking heart and kidney and nourishing heart spirit.

OBJECTIVE To study the pharmacological substance basis of Shaoyao gancao decoction for relieving acute and chronic pain. METHODS The antispasmodic effect of Shaoyao gancao decoction， ethyl acetate extract of Shaoyao gancao decoction and its effluent part of macroporous resin and 90% ethanol elution part of macroporous resin （the concentration of 4 drugs was 13.44 g/mL according to crude drug） was observed by in vitro small intestine tension test in rats. The acetic acid writhing test was conducted in mice to evaluate the analgesic effects of macroporous resin efflux site and macroporous resin 90% ethanol elution site （the dosage of 2.4 g/kg according to crude drug）. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL- 1β）， prostaglandin E2 （PGE2） and cyclooxygenase-2 （COX-2） in serum of mice were detected. The serum prototype and metabolites of mice after intragastric administration of macroporous resin 90% ethanol elution site were identified by high performance liquid chromatogre-time-of-flight mass spectrometry. RESULTS In vitro experiment showed that 90% ethanol eluting part of macroporous resin represented the best antispasmodic effect， and the inhibitory rate of small intestine tension was significantly higher than macroporous resin efflux site of Shaoyao gancao decoction （P＜0.05） without statistical significance， compared with Shaoyao gancao decoction （P＞0.05）. In the acetic acid writhing experiment， compared with model group， the writhing times of mice in the macroporous resin 90% ethanol elution part group were reduced significantly （P＜0.05）， the writhing latency was prolonged significantly （P＜0.05）， and the levels of COX-2， IL-1β， PGE2 and TNF-α in serum were decreased significantly （P＜0.05）. Ten kinds of protoproducts including paeoniflorin and glycyrrhizic acid were identified from serum of mice， and twenty-two kinds of metabolites including hydroxylated glycyrrhizin and glucosylated liquiritin were identified. CONCLUSIONS The effective part of Shaoyao gancao decoction for relieving acute and chronic pain is 90% ethanol elution part prepared by macroporous resin from the ethyl acetate extract. Ten components， including glycyrrhetinic acid and paeoniflorin， may be the basis of its pharmacological substances.