Based on WANG Xugao's"thirty liver-regulating methods,"this paper summarized the clinical thinking of treating diabetic kidney disease from the liver.The liver is closely associated with the pathogenesis of diabetic kidney disease,including internal heat,essence depletion,latent wind,and the accumulation and dissipation of a conglomeration of kidney collateral zhengjia.WANG Xugao's"thirty liver-regulating methods"comprehensively reveals the physiological and pathological changes of the liver,as well as clinical approaches for liver treatment.Liver qi stagnation can lead to the generation of internal heat,liver stagnation and deficiency can cause essence depletion and collateral obstruction,and disharmony of the liver wood can cause internal wind disturbance,which all contribute to the progression of diabetic kidney disease at different stages.Treatment generally follows the essence of"thirty liver-regulating methods."In the early stage,treatment should focus on treating liver heat by soothing the liver qi,clearing the liver fire,and removing damp-heat to resolve stagnation and heat.In the middle stage,treatment should focus on treating liver deficiency by nourishing the liver yin to clear heat,replenishing the essence and blood to tonify deficiency,and promoting blood circulation to remove stasis,thereby strengthening the foundation and nurturing the primal essence.In the later stage,treatment should focus on treating liver wind to prevent complications and improve the patient's quality of life.Throughout the entire process,liver collaterals are treated using pungent herbs to invigorate qi and open the liver channels,relieving blood stasis and promoting circulation.In conjunction with the above methods,flexible selection of effective formulas and drug pairs should be used,each addressing specific treatment goals.

Diabetic kidney disease(DKD),a prevalent complication of diabetes mellitus,remains a leading cause of end-stage renal disease.Recent research has identified lipophagy,a novel mechanism in DKD pathogenesis,drawing increasing attention in the field.This paper explores the biological connotation of the"internal heat leading to Zheng"pathogenesis based on lipophagy.The study proposes that lipophagy represents the microscopic biological correlation of liver-spleen coordination in regulating spleen transport and the ascending-descending dynamics of the middle jiao.Under persistent hyperglycemia,the suppression of lipophagic activity mirrors the traditional Chinese medicine(TCM)pathophysiological process described as"excessive fire consuming healthy qi,"whereas aberrant lipid accumulation in the kidney corresponds to the dynamic aggregation and dispersion of micro-zhengjia.Lipotoxicity,a key driver of DKD progression,is interpreted as the biological manifestation of accumulated turbidity transforming into toxicity,resulting in progressive impairment of renal essence and function.The dynamic process of lipophagy dysfunction under hyperglycemia,marked by renal microangiopathy,glomerular and tubular dysfunction,and renal fibrosis,closely mirrors the pathological evolution of"micro-zhengjia"and"internal heat leading to Zheng."Consequently,TCM strategies for DKD prevention and treatment should emphasize heat regulation,stage-specific interventions,liver-spleen harmonization,metabolic modulation,early collateral protection,and blood-activating approaches.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective:To investigate the risk factors for patients with hypertriglyceridemia-related acute pancreatitis (HTG-AP) developing into severe acute pancreatitis or experiencing organ failure.Methods:This retrospective cohort study collected clinical data from 2 429 patients diagnosed with acute pancreatitis from five hospitals in China between January 2019 and December 2023 using a pre-designed data collection form. The cohort included 1 516 males and 913 females,with an age of (50.2±16.5)years(range: 11 to 99 years). Among them,353 patients (16.1%) had HTG-AP,while 1 846 (83.9%) had non-HTG-AP. HTG-AP was defined as serum triglyceride levels>500 mg/dl with other etiologies excluded. Intergroup comparisons were performed using t-tests,Mann-Whitney U test or χ2 tests,respectively. Univariate and multivariate logistic regression analyses were conducted to assess risk factors for severe acute pancreatitis after adjusting for potential confounders,and a predictive model was developed and validated. Results:Compared with other etiologies,HTG-AP patients had a higher risk of progressing to SAP ( OR=1.415,95% CI: 0.866 to 2.312, P=0.017) and organ failure ( OR=1.256,95% CI: 1.015 to 1.554, P=0.036). Among HTG-AP patients,risk factors for SAP included body mass index ( OR=1.856,95% CI: 1.742 to 1.987, P=0.033),fasting blood glucose ( OR=1.128,95% CI: 1.036 to 1.229, P=0.006),white blood cell count( OR=1.162,95% CI: 1.055 to 1.281, P=0.002),and the presence of pleural effusion ( OR=13.151,95% CI: 4.330 to 19.946, P<0.01). A nomogram prediction model for SAP in HTG-AP was constructed based on these risk factors,demonstrating good discriminative ability with area under the curve values of 0.877 in the training set and 0.894 in the validation set,along with satisfactory calibration. Conclusions:HTG-AP patients are at higher risk of developing SAP and organ failure. The risk prediction model incorporating body mass index,fasting blood glucose,white blood cell count,and pleural effusion shows good predictive value for SAP.

Based on WANG Xugao's"thirty liver-regulating methods,"this paper summarized the clinical thinking of treating diabetic kidney disease from the liver.The liver is closely associated with the pathogenesis of diabetic kidney disease,including internal heat,essence depletion,latent wind,and the accumulation and dissipation of a conglomeration of kidney collateral zhengjia.WANG Xugao's"thirty liver-regulating methods"comprehensively reveals the physiological and pathological changes of the liver,as well as clinical approaches for liver treatment.Liver qi stagnation can lead to the generation of internal heat,liver stagnation and deficiency can cause essence depletion and collateral obstruction,and disharmony of the liver wood can cause internal wind disturbance,which all contribute to the progression of diabetic kidney disease at different stages.Treatment generally follows the essence of"thirty liver-regulating methods."In the early stage,treatment should focus on treating liver heat by soothing the liver qi,clearing the liver fire,and removing damp-heat to resolve stagnation and heat.In the middle stage,treatment should focus on treating liver deficiency by nourishing the liver yin to clear heat,replenishing the essence and blood to tonify deficiency,and promoting blood circulation to remove stasis,thereby strengthening the foundation and nurturing the primal essence.In the later stage,treatment should focus on treating liver wind to prevent complications and improve the patient's quality of life.Throughout the entire process,liver collaterals are treated using pungent herbs to invigorate qi and open the liver channels,relieving blood stasis and promoting circulation.In conjunction with the above methods,flexible selection of effective formulas and drug pairs should be used,each addressing specific treatment goals.

Diabetic kidney disease(DKD),a prevalent complication of diabetes mellitus,remains a leading cause of end-stage renal disease.Recent research has identified lipophagy,a novel mechanism in DKD pathogenesis,drawing increasing attention in the field.This paper explores the biological connotation of the"internal heat leading to Zheng"pathogenesis based on lipophagy.The study proposes that lipophagy represents the microscopic biological correlation of liver-spleen coordination in regulating spleen transport and the ascending-descending dynamics of the middle jiao.Under persistent hyperglycemia,the suppression of lipophagic activity mirrors the traditional Chinese medicine(TCM)pathophysiological process described as"excessive fire consuming healthy qi,"whereas aberrant lipid accumulation in the kidney corresponds to the dynamic aggregation and dispersion of micro-zhengjia.Lipotoxicity,a key driver of DKD progression,is interpreted as the biological manifestation of accumulated turbidity transforming into toxicity,resulting in progressive impairment of renal essence and function.The dynamic process of lipophagy dysfunction under hyperglycemia,marked by renal microangiopathy,glomerular and tubular dysfunction,and renal fibrosis,closely mirrors the pathological evolution of"micro-zhengjia"and"internal heat leading to Zheng."Consequently,TCM strategies for DKD prevention and treatment should emphasize heat regulation,stage-specific interventions,liver-spleen harmonization,metabolic modulation,early collateral protection,and blood-activating approaches.

Objective:To investigate the risk factors for patients with hypertriglyceridemia-related acute pancreatitis (HTG-AP) developing into severe acute pancreatitis or experiencing organ failure.Methods:This retrospective cohort study collected clinical data from 2 429 patients diagnosed with acute pancreatitis from five hospitals in China between January 2019 and December 2023 using a pre-designed data collection form. The cohort included 1 516 males and 913 females,with an age of (50.2±16.5)years(range: 11 to 99 years). Among them,353 patients (16.1%) had HTG-AP,while 1 846 (83.9%) had non-HTG-AP. HTG-AP was defined as serum triglyceride levels>500 mg/dl with other etiologies excluded. Intergroup comparisons were performed using t-tests,Mann-Whitney U test or χ2 tests,respectively. Univariate and multivariate logistic regression analyses were conducted to assess risk factors for severe acute pancreatitis after adjusting for potential confounders,and a predictive model was developed and validated. Results:Compared with other etiologies,HTG-AP patients had a higher risk of progressing to SAP ( OR=1.415,95% CI: 0.866 to 2.312, P=0.017) and organ failure ( OR=1.256,95% CI: 1.015 to 1.554, P=0.036). Among HTG-AP patients,risk factors for SAP included body mass index ( OR=1.856,95% CI: 1.742 to 1.987, P=0.033),fasting blood glucose ( OR=1.128,95% CI: 1.036 to 1.229, P=0.006),white blood cell count( OR=1.162,95% CI: 1.055 to 1.281, P=0.002),and the presence of pleural effusion ( OR=13.151,95% CI: 4.330 to 19.946, P<0.01). A nomogram prediction model for SAP in HTG-AP was constructed based on these risk factors,demonstrating good discriminative ability with area under the curve values of 0.877 in the training set and 0.894 in the validation set,along with satisfactory calibration. Conclusions:HTG-AP patients are at higher risk of developing SAP and organ failure. The risk prediction model incorporating body mass index,fasting blood glucose,white blood cell count,and pleural effusion shows good predictive value for SAP.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.