The pathogenesis of painful diabetic peripheral neuropathy(PDPN)is very complicated and tricky treat,which seriously affects the physical and mental health of patients.TCM has certain advantages in treating PDPN,but lacks theoretical guidance centered on pathogenesis.The dynamic evolution of the pathogenesis of PDPN fits the theory of"deficient-qi induced stagnation".PDPN is mainly characterized by pain,with prolonged pain entering the collaterals.This article discussed the pathogenesis of PDPN from the theory of"deficient-qi induced stagnation"based on collateral disease.Among them,the"deficient qi"is mainly responsible for the deficiency of qi,blood,yin and yang,and the collaterals are not be nourished;"stagnation"includes the pathological state of qi stagnation,phlegm and stasis caused by the abnormal movement of qi,blood and body fluid,and the obstruction of collaterals."Deficient qi"and"stagnation"interact with each other to promote the progress of PDPN.The article concluded that the key point of treatment is to regulate the deficiency qi(tonify deficiency)and remove stagnation and clear collaterals(smooth the stagnation),which could provide a new diagnosis and treatment idea and theoretical basis for the clinical differentiation and treatment of PDPN.

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.

Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

The pathogenesis of painful diabetic peripheral neuropathy(PDPN)is very complicated and tricky treat,which seriously affects the physical and mental health of patients.TCM has certain advantages in treating PDPN,but lacks theoretical guidance centered on pathogenesis.The dynamic evolution of the pathogenesis of PDPN fits the theory of"deficient-qi induced stagnation".PDPN is mainly characterized by pain,with prolonged pain entering the collaterals.This article discussed the pathogenesis of PDPN from the theory of"deficient-qi induced stagnation"based on collateral disease.Among them,the"deficient qi"is mainly responsible for the deficiency of qi,blood,yin and yang,and the collaterals are not be nourished;"stagnation"includes the pathological state of qi stagnation,phlegm and stasis caused by the abnormal movement of qi,blood and body fluid,and the obstruction of collaterals."Deficient qi"and"stagnation"interact with each other to promote the progress of PDPN.The article concluded that the key point of treatment is to regulate the deficiency qi(tonify deficiency)and remove stagnation and clear collaterals(smooth the stagnation),which could provide a new diagnosis and treatment idea and theoretical basis for the clinical differentiation and treatment of PDPN.

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To investigate the distribution of the traditional Chinese medicine(TCM)constitution types in the patients with nonspecific low back pain(NLBP)and to explore the correlation of the thickness of ligamentum flavum with the age,body mass index(BMI),gender,the presence of diabetes mellitus,and the grading of hypertension.Methods Sixty patients with NLBP admitted to Guangdong Second Traditional Chinese Medicine Hospital from January 2023 to June 2023 were selected as the study subjects.The TCM constitution types of the patients were identified,the thickness of the ligamentum flavum at lumbar vertebrae 4/5 segment(L4/5)disc level was measured by computerized tomography(CT)scanning,and the patients'age,genders,TCM constitution types,BMI,the presence or absence of diabetes mellitus,and hypertension grading were recorded.Correlation analysis and linear regression analysis were used for the exploration of the relevant influencing factors for the thickness of the ligamentum flavum of patients with NLBP.Results(1)The average thickness of ligamentum flavum in the 60 patients with NLBP was(2.60±0.72)mm.(2)The TCM constitutions of NLBP patients were classified into four types,of which blood stasis constitution was the most common,accounting for 21 cases(35.0%),followed by 19 cases(31.7%)of damp-heat constitution,12 cases(20.0%)of phlegm-damp constitution,and 8 cases(13.3%)of qi deficiency constitution.(3)The results of correlation analysis showed that BMI,gender,TCM constitution type and the presence or absence of diabetes mellitus had no influence on the thickness of ligamentum flavum in NLBP patients(P＞0.05),while the age and hypertension grading had an influence on the thickness of ligamentum flavum(P＜0.01).(4)The results of linear regression analysis showed that the age had an influence on the thickness of the ligamentum flavum(b = 0.034,t = 6.282,P＜0.01),while the influence of the hypertension grading had no influence on the thickness of the ligamentum flavum(P＞0.05).Conclusion The TCM constitution type of NLBP patients is predominated by blood stasis constitution,the thickness of ligamentum flavum is significantly affected by the age,and hypertension may be a potential factor affecting the thickness of ligamentum flavum.

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

This article introduced the basic theory of non-parametric regression and its application in medical and public health research for methodological reference.We conducted Cox proportional hazard models with restricted cubic splines using chronic disease management data from a Center for Disease Control and Prevention.We aimed to explore the separate and combined effects of mean fasting blood glucose level and glucose variability on all-cause mortality among individuals with type 2 diabetes.A non-linear association was observed between glucose variability and the risk of all-cause mortality.The association between glucose variability and all-cause mortality was stronger at higher mean fasting blood glucose levels compared to lower levels.The non-parametric regression methods comprehensively explored dose-response relationships between continuous exposure and outcome,revealing the combined effects of continuous exposures,which provided recommendations for targeted interventions.The method showed promising application value in medical and public health research.