ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

Given the limitations of traditional scientific research methods in revealing the complex and dynamic evolution of disease pathomechanisms， this paper analyzes the current state and challenges of the traditional Chinese medicine （TCM） pathomechanism syndrome differentiation system within the framework of systems thinking. The challenges include insufficient experimental models， low data standardization， complex nonlinear characteristics， and difficulties in integrating expert experience. By leveraging qualitative-quantitative comprehensive integration methods， this paper proposes specific research strategies， including constructing qualitative models of pathomechanism evolution， employing mathematical models for validation and quantitative analysis to reveal pathomechanism patterns， and incorporating a "human-centered" approach to achieve human-machine collaboration. These strategies aim to provide insights for the modernization and development of a new TCM pathomechanism syndrome differentiation system.

OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Toxic Chinese materia medica has been highly valued by its specialized and effective effects， but its safe application has become an urgent clinical problem to be solved. Compatibility for toxic attenuation is an important method for the rational clinical application of toxic Chinese materia medica as well as the promotion of its therapeutic advantages. The theory of “heterogeneous medicinals mutual restriction” elaborated in this article has been formed through long-term clinical practice and cognition， and refinement of clinical experience， which means that the nature partiality of toxic Chinese materia medica can be adjusted， and the toxicity can be suppressed through reasonable combination with herbal medicinalsof different properties， flavors， and effects. This theory covers the modes of compatibility for toxicity attenuation and the interaction relationships， like the restriction of medicinals with different properties and flavors， restriction of medicinals with different effects， and inhibiting toxins by reinforcing healthy qi. The opposite and complementary effects of various medicinals combinations are an extension of the connotations of this theory， and the principles can be explained from material basis and mechanism of action. Under the guidance of this theory， it is possible to optimize the compound prescription strategies of toxic Chinese materia medica， and provide new strategies for the clinical combinations of toxic Chinese materia medica， thereby achieving the reduction of toxicity and enhancement of effectiveness of the compound formulas.

Objective To construct a predictive model for the risk of non-suicidal self-injury(NSSI)in young and middle-aged patients with major depressive disorder based on the decision tree algorithm.Methods Young and middle-aged patients with major depressive disorder admitted to the Chongqing Mental Health Center from January 2021 to June 2023 were selected as the research subjects and their clinical data were collected.According to whether NSSI occurred or not,the patients were divided into the NSSI group(n=72)and the non-NSSI group(n=82).Univariate and multivariate logistic regression analyses were used to analyze the risk factors of NSSI in young and middle-aged patients with major depressive disorder.A deci-sion tree predictive model was established based on the results of logistic regression analysis and the Chi-square Automatic Interaction Detection(CHAID)algorithm.The predictive value of the model was evaluated using Receiver Operating Characteristic(ROC)curve.Results The incidence of NSSI in 154 young and mid-dle-aged patients with major depressive disorder was 46.8％.The results of single-factor analysis showed that there were no statistically significant differences(P＞0.05)in gender,age,education level,occupation,family composition,only child status,relationship status,fertility status,main place of residence,family economic source,and housing conditions between the two groups.Statistically significant differences(P＜0.05)were observed in living conditions,family economic status,duration of depression,SSRS score,PSS-Fa score,and DS score between the two groups.Multi-factor logistic regression analysis showed that lower family economic lev-el,longer duration of depression,SSRS score＜20 points,PSS-Fa score＜6 points,and DS score ≥47.2 points were independent risk factors for NSSI in young and middle-aged patients with major depressive disorder(P＜0.05).The constructed decision tree model had five layers and ten nodes,with family economic situation,duration of depression,SSRS score,and PSS-Fa score selected as the nodes of the model,among which the PSS-Fa score was the most important predictive factor.ROC curve analysis showed that the AUC of the model was 0.881(95％CI:0.844-0.918).Conclusion There are many influencing factors for the occurrence of NSSI in young and middle-aged patients with major depressive disorder.The decision tree model constructed based on these factors has a high predictive value for the risk of NSSI in young and middle-aged patients with major depressive disorder.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Objective:To fabricate the composite scaffolds for bone regeneration with silk fibroin (SF), bacterial cellulose nanofibers (BCNR) and hydroxyapatite (HAp) and evaluate their osteogenic activity.Methods:HAp particles, BCNR and bone morphogenetic protein-2 (BMP2) were added into SF aqueous solution in turn, poured into molds of different sizes after being mixed evenly and processed at -25 ℃ for 24 hours to obtain frozen molds, and the composite scaffolds were frozen-dried by freezing-drying machine. The composite scaffolds with different mass ratios of SF and BCNR were divided into groups A (2∶1), B (4∶1) and C (6∶1), and the inactive composite scaffolds without BMP2 fell into group D. The surface morphology and pore structure of the scaffolds were detected by scanning electron microscopy. The porosity of the scaffolds was measured by mercury intrusion porosimeter. The stress-strain curve was obtained by using the universal material testing machine to compress the scaffolds, with which their compressive strength and Young′s modulus were analyzed. Immortalized mouse embryonic fibroblasts (iMEF) were inoculated on the composite scaffolds of group A, B, C and D. At 4 and 8 days after cell inoculation, the proportion of alive and dead cells in each group was detected by cell survival/death staining; the cell counting kit-8 (CCK-8) was used to detect cell proliferation activity in each group; the positive staining cells were detected in each group by alkaline phosphatase (ALP) staining; the ALP activity was observed in each group with ALP activity detection. A total of 15 female SD rats were selected to establish osteogenesis models with ectopic muscle bag. The composite scaffolds implanted with different SF/BCNR mass ratios and the inactive composite scaffolds without BMP2 fell into group A′ (2∶1), B′ (4∶1), C′ (6∶1) and D′ respectively, and a sham operation group was set at the same time, with 3 rats in each groups. In the sham operation group, the muscle bag and skin were sutured without scaffold implantation after the incision of skin, the blunt separation of the quadriceps muscle, and the formation of muscle bag in the muscle. In the other four groups, the corresponding scaffolds were implanted in the muscle bag and the muscle bag and skin were sutured. X-ray examination was performed at 2 and 4 weeks after operation to observe the osteogenesis in each group. At 4 weeks after operation, the implanted scaffolds and tissue complexes were collected by pathological tissue sectioning, HE staining and Masson staining, and for observing the osteogenesis by in each group. Immunohistochemical staining was also performed on the tissue sections to observe the expression of osteogenic markers type I collagen (COL1) and osteopontin (OPN) in each group.Results:Scanning electron microscopy showed that the lamellar and micropore structures of group B were more regular and uniform than those of groups A and C. The porosity rate analysis showed that the porosity rates of groups B and C were (89.752±1.866)% and (84.257±1.013)% respectively, higher than that of group A [(81.171±1.268)%] ( P<0.05 or 0.01), with the porosity rate of group C lower than that of group B ( P<0.01). The mechanical property test showed that the compressive strengths of groups B and C were (0.373±0.009)MPa and (0.403±0.017)MPa respectively, higher than that of group A [(0.044±0.003)MPa] ( P<0.01), and the Young′s moduli of groups B and C were (7.413±0.094)MPa and (9.515±0.615)MPa respectively, higher than that of group A [(1.881±0.036)MPa] ( P<0.01), with the compressive strength and Young′s modulus of group C higher than those of group B ( P<0.05 or 0.01). The cell survival/death staining showed that the number of dead cells of group B was significantly smaller than that of groups A, C and D at 4 days after cell inoculation, and that group B had the most living cells and the fewest dead cells at 8 days after cell inoculation. The results of CCK-8 experiment showed that at 4 days after cell inoculation, the cell proliferation activity of groups A and B was 0.474±0.009 and 0.545±0.018 respectively, higher than 0.394±0.016 of group D ( P<0.01); the cell proliferation activity of group C was 0.419±0.005, with no significant difference from that of group D ( P>0.05), while the cell proliferation activity of groups A and C were both lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell proliferation activity of group B was 1.290±0.021, higher than 1.047±0.011 of group D ( P<0.01); the cell proliferation activity of group C was 0.794±0.032, lower than that of group D ( P<0.01); the cell proliferation activity of group A was 1.086±0.020, with no significant difference from that of group D ( P>0.05); the cell proliferation activity of groups A and C was lower than that of group B ( P<0.01). At 4 and 8 days after cell inoculation, ALP staining showed that more positive cells were found in groups A, B and C when compared with group D, and more positive cells were found in group B than in groups A and C. At 4 days after cell inoculation, the ALP activity detection showed that the ALP activity of groups A, B and C was 1.399±0.071, 1.934±0.011 and 1.565±0.034 respectively, higher than 0.082±0.003 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell activity of groups A, B and C was 2.602±0.055, 3.216±0.092 and 2.145±0.170 respectively, higher than 0.101±0.001 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). X-ray examination results showed that at 2 weeks after operation, no obvious osteogenesis was observed in the sham operation group, group D′, A′ and C′, while it was observed in group B′. At 4 weeks after operation, obvious osteogenesis was observed in group A′, B′ and C′, with significantly more osteogenesis in group B′ than in the other two groups, while there was no obvious osteogenesis in the sham operation group and group D′. At 4 weeks after operation, the HE staining and Masson staining showed that a large number of uniformly distributed new bone tissue was formed in group B′, while only a small amount of new bone tissue was found locally in groups A′ and C′, and only part of new tissue was found to grow in group D′ with no obvious new bone tissue observed. The maturity of new bone tissue formed in group B′ was higher than that in group A′ and C′. Immunohistochemical staining showed more COL1 and OPN positive staining in group B′ when compared with groups A′ and C′. The expression intensity analysis of COL1 and OPN showed that in groups A′, B′ and C′, the expression intensity of COL1 was 2.822±0.384, 22.810±2.435 and 12.480±0.912 respectively and the expression intensity of OPN was 1.545±0.081, 5.374±0.121 and 2.246±0.116 respectively, with higher expression intensity of COL1 and OPN in groups B′ and C′ than that in group A′ ( P<0.01) and lower expression intensity of COL1 and OPN in group C′ than that in B′ group ( P<0.01). Conclusions:The composite scaffold for bone regeneration is successfully fabricated with SF, BCNR and HAp. The composite scaffold with a mass ratio of SF to BCNR of 4∶1 has uniform pore structure, high porosity, good mechanical properties and biocompatibility, excellent pro-osteogenic properties in vitro, as well as excellent osteo-inductivity and osteo-conductivity.

Objective To explore the specific plasma exosomal protein expression in Coronary Heart Disease(CHD)with phlegm-turbidity syndrome(PTS),so as to provide biological reference for the diagnosis of CHD with PTS.Methods A total of 20 CHD patients with PTS and 20 healthy subjects at the same period were included.Plasma exosomes were extracted from all subjects using the qEV size exclusion method.First,10 CHD cases with PTS and 10 healthy subjects were randomly selected,and differentially expressed proteins between the two groups were screened using label free non-targeted protein quantification analysis.Then,MRM targeting protein labeling technique was applied to verify the differentially expressed proteins in the remaining subjects.Results Compared with healthy controls,214 differentially expressed plasma exosomal proteins(61 up-regulated and 153 down-regulated)were found in CHD patients with PTS,mainly related to cholesterol metabolism,complement and coagulation cascade,and immune effects.ANXA6,C4BPB,F8,CFB,APOE,C9,and CLU proteins were further validated by MRM targeting protein.Conclusion CHD patients with PTS had differences in plasma exosomal protein expression from healthy controls,and the differential proteins are mainly related to cholesterol metabolism,complement,and the coagulation cascade.

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing