BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.

OBJECTIVE To investigate the effects of catalpol on H2O2-induced osteoblast injury and its mechanism. METHODS The osteoblasts MC3T3-E1 were separated into control group， model group， empty group （transfected with empty plasmid）， catalpol group （100 μmol/L）， catalpol+forkhead box O3 （FoxO3） overexpression group （100 μmol/L catalpol+ transfected with FoxO3 overexpression plasmid）. After catalpol treatment and transfection， except for control group， other groups were induced with H2O2 to establish osteoblast oxidative stress model. The cell viability， apoptotic rate， alkaline phosphatase （ALP） activity， optical density （OD） value of calcium nodule， mean fluorescence intensity （MFI） of reactive oxygen species （ROS）， antioxidant enzyme activity [superoxide dismutase （SOD）， catalase （CAT）]， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β]， and the expressions of FoxO3/Wnt/β-catenin signaling pathway-related proteins were detected in each group. RESULTS Compared with the control group， the cell viability， ALP activity， OD value of calcium nodule， activities of antioxidant enzyme， and the protein expressions of Wnt and β-catenin were decreased significantly in the model group， while apoptotic rate， MFI levels of ROS， inflammatory factor levels and the protein expression of FoxO3 were all increased significantly （P＜0.05）. Compared with the model group， above indicators of the empty group had no significant change （P＞0.05）， while those of catalpol group were reversed significantly （P＜0.05）. Compared with the catalpol group， the reversal effect of the changes in the above indicators was significantly weakened in the catalpol+FoxO3 overexpression group cells （P＜0.05）. CONCLUSIONS Catalpol can activate Wnt/β-catenin signaling pathway by down-regulating FoxO3， thereby inhibiting H2O2-induced MC3T3-E1 oxidative stress and inflammation reaction， enhancing cell viability and osteogenic differentiation activity， and alleviating apoptosis injury.

The pattern differentiation method is the most representative part of the inheritance of the experience of renowned practitioners of traditional Chinese medicine,reflecting their clinical thinking characteristics. Among them,Professor LYU Renhe proposed and developed the theory of abdominal masses in the long-term diagnosis and treatment of kidney diseases. Based on his clinical experience,he formed the method of differentiation of Shenluozhengjia (tangible or intangible abdominal masses of kidney collaterals). This differentiation method is characterized by its simple and easy clinical application. Tangible or intangible abdominal masses of kidney collaterals refer to chronic kidney disease,which is based on the basic cause of kidney deficiency. External or internal pathogenic factors cannot be eliminated,and prolonged illness invades the kidney collaterals,causing pathological products,such as qi stagnation,blood stasis,phlegm dampness,heat toxin,and turbid toxin to stagnate in the kidney collaterals,resulting in damage to the kidney body and loss of kidney function. The basic pathogenesis is a deficiency of kidney qi and the formation of tangible or intangible abdominal masses of the kidney collaterals. During pattern differentiation,the type is determined by the deficiency,which is fixed,and the pattern is determined by the excess,which is constantly changing with the condition and can be combined. Furthermore,he summarized the dietary principles as having more essence and less coarseness,more milk and less meat,a phased diet,and the selection of the symptomatic diet. To inherit and improve the theory and clinical practice of the pattern differentiation theory of tangible or intangible abdominal masses of kidney collaterals,this article reviews and summarizes the unique pattern differentiation method of the kidney collateral pattern from the aspects of definition,theoretical origin,etiology and pathogenesis,differentiation and treatment,and regulation,providing a basis for forming suitable diagnosis and treatment method for clinical promotion.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.

In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Objective:To investigate the efficacy and safety of Guihuang Formula(GHF)in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.Methods:This study included 120 cases of type Ⅲ prostatitis with damp-heat stasis syndrome in the essence chamber,which were randomly and equally divided into a GHF and a control group,the for-mer treated with GHF and the latter with Tamsulosin Hydrochloride Sustained-Release Capsules,both for 6 successive weeks.We fol-lowed up the patients for 4 weeks,recorded the NIH-CPSI,TCM symptom scores,and results of prostatic fluid routine,blood and u-rine routine,liver and kidney function and electrocardiogram examinations,and compared them between the two groups of patients be-fore and after treatment.Results:Compared with the baseline,the total NIH-CPSI scores were significantly decreased in both the GHF and control groups after 6 weeks of treatment,even more significantly in the former group(28.34±9.23 vs 6.78±3.53,P＜0.05)than in the latter(27.81±8.28 vs 14.48±4.27,P＜0.05),so were the scores on pain,voiding symptoms,quality of life(QOL)impact,TCM symptoms and WBC count(all P＜0.05),while the number of lecithin bodies remarkably increased(P＜0.05).There were statically significant differences in the above parameters at 4,6 and 10 weeks of medication(P＜0.05),but not at 2 weeks(P＞0.05).No obvious abnormalities or adverse reactions were observed in either of the two groups during the treatment.Conclusion:Guihuang Formula is safe and effective in the treatment of type Ⅲ prostatitis with the syndrome of damp-heat stasis in the essence chamber.