The concept of "qi deficiency with stagnation" refers to a pathological state characterized by the depletion of primordial qi， impaired qi transformation， and the development of internal stagnation. Under the cyclic chemotherapy regimen in oncology， chemotherapy-induced myelosuppression follows a progressive pathological course from qi deficiency to increasing stagnation. This sequential evolution from mild to severe myelosuppression closely aligns with the dynamic syndrome differentiation and treatment framework of "qi deficiency with stagnation". "Qi deficiency" reflects the gradual depletion of qi， blood， and essence， while "stagnation" refers to the accumulation of phlegm， turbid dampness， and blood stasis. These two components interact reciprocally， forming a vicious cycle where deficiency leads to stagnation， and stagnation further damages the healthy qi. In the early stage of mild myelosuppression， chemotoxicity begins to accumulate in the bone marrow， leading to qi consumption， blood deficiency， yin injury， and the gradual formation of turbid phlegm and damp stagnation. In the advanced stage of severe myelosuppression， the accumulation of toxicity causes qi sinking， exhaustion of essence， and marrow depletion， along with blood stasis obstructing the collaterals. Treatment strategies should be based on syndrome differentiation， with an emphasis on assessing the severity of the condition， balancing deficiency and excess， and achieving both symptomatic relief and root cause resolution.

This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

ObjectiveTo observe the clinical efficacy of Shentong Zhuyutang combined with Dilongtang in the treatment of lumbar disc herniation （LDH） with Qi stagnation and blood stasis syndrome， and its effect on nucleus pulposus reabsorption and immune-inflammatory factors， exploring its therapeutic mechanism from the perspective of reabsorption. MethodsA total of 120 patients with LDH from the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine， treated between June 2020 and January 2023， were randomly divided into the control group （52 cases， with 8 dropouts） and the observation group （49 cases， with 11 dropouts） according to a random number table. The control group received routine treatment， while the observation group was treated with Shentong Zhuyutang combined with Dilongtang in addition to routine treatment. Visual Analogue Scale （VAS）， Oswestry Disability Index （ODI）， Japanese Orthopaedic Association （JOA） score， and traditional Chinese medicine （TCM） syndrome score were measured before treatment and after 3 courses of treatment. Venous blood samples were collected for the determination of serological indexes. MR examination was performed during the 6-month follow-up to calculate the absorption rate. ResultsAfter treatment， both groups showed significant reductions in VAS， ODI， TCM syndrome score， serum tumor necrosis factor （TNF）-α， matrix metalloproteinase （MMP）-9， and vascular endothelial growth factor （VEGF） levels， and a significant increase in JOA score compared with pre-treatment values （P<0.05）. Compared with the control group， the observation group showed significantly lower VAS， ODI， TCM syndrome score， serum TNF-α， MMP-9， and VEGF levels， and a significantly higher JOA score （P<0.05）. The proportion of nucleus pulposus reabsorption in the observation group was 57.14% （28/49）， significantly higher than 21.15% （11/52） in the control group （χ²=6.161， P<0.05）. ConclusionShentong Zhuyutang combined with Dilongtang can effectively relieve pain， improve lumbar function， and alleviate TCM clinical symptoms in LDH patients with Qi stagnation and blood stasis syndrome. Imaging findings suggest that the treatment promotes the reabsorption of nucleus pulposus protrusion， while laboratory testing shows reduced serum levels of TNF-α， MMP-9， and VEGF， which contribute to the rehabilitation of patients.

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OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Objective To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.Methods A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023.All of them underwent dual-energy CT examination.According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard(2020 Edition),they were divided into T2 group(n=43)and T3 group(n=48).Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis.The area under receiver operating characteristic curve(AUC)of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.Results Univariate analysis showed that carcinoembryonic antigen(CEA),N stage,tumor location,tumor longest diameter(LD),CT value of virtual noncontrast(CT-VNC),fat fraction,electron density(Rho)and dual energy index(DEI)were significantly different between the T2 and T3 groups(P＜0.05).Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3.The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671(95％CI:0.558～0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886(95％CI:0.815～0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model(P＜0.01).Conclusion The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

AIM To study the chemical constituents from the roots of Siraitia grosvenorii(Swingle)C.Jeffrey and their α-glucosidase inhibitory activities.METHODS The 95％ethanol extract was isolated and purified by silica gel,MCI,ODS and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were evaluated by PNPG method,after which molecular docking was performed.RESULTS Twenty-one compounds were isolated and identified as vanillin(1),siraitic acid B(2),cucurbitacin B(3),salicylic acid(4),ferulic acid(5),p-hydroxybenzaldehyde(6),(+)-lariciresinol(7),(+)-isolariciresinol(8),liballinol(9),3-(hydroxyacetyl)indole(10),2E-4-hydroxy-nonenoic acid(11),vomifolilol(12),vanillic acid(13),indole-3-carboxylic acid(14),ω-hydroxypropioguaiacone(15),p-hydroxybenzoic acid(16),p-coumaric acid(17),dehydrodipinocarpine(18),secoisolariciresinol(19),sesquimarocanol A(20),threo-guaiacylglycerol-β-O-4-lariciresinol ether(21).IC50 values of compounds 4,10,18 and 21 were(0.42±0.060)-(0.89±0.037)mg/mL.CONCLUSION Compounds 4,10-12,15,16,18,and 21 are isolated from the roots of this plant for the first time.Compounds 4,10,18,21 have α-glucosidase inhibitory activities,and 18 has the strongest activity.

This study aims to investigate the effects of Pulsatilla decoction(PD)on the 5-HT sig-naling system in the hippocampus of damp-heat diarrhoea(DHD)rats.Twenty-four male SD rats were randomly divided into four groups including the blank group,the model group,the PD group and the self-healing group.Except for the blank group,the rats in each group were induced by"high sugar and high fat,high temperature and high humidity,and E.coli poisoning"to establish a of rat model DHD,and were treated by gavage with PD.Changes in body weight,temperature,food intake and water intake,routine blood tests and histopathological changes in the colon were recor-ded to comprehensively determine the modelling condition of rats with DHD;histopathological changes in the hippocampus of rats were observed,and real-time fluorescence PCR was used to de-termine the expression of IL-1β3,IL-6,TNF-α,IFN-γ and TPH1 mRNA in the hippocampus;West-ern blot and immunohistochemistry were used to detect the protein expression of tryptophan hydroxylase 1(TPH1),receptors(5-HT3R,5-HT4R,5-HT7R)in 5-HT signaling pathway in the hippocampus.The results showed that:PD significantly regulated the abnormal changes of body weight,food and water intake and blood routine indexes in rats with DHD,and significantly im-proved the pathological damage of colonic tissues;PD significantly lowered the expression of in-flammatory cytokines IL-1β,IL-6,IFN-γ,and TNF-α in hippocampus of rats with DHD(P＜0.05),and significantly reduced the expression of TPH1 mRNA in hippocampus of rats with DHD(P＜0.05).PD could increased the expression of 5-HT4R and 5-HT7R in the hippocampus of rats with DHD;reduced the expression of 5-HT3R and TPH in the hippocampus,among which 5-HT3R expression was significantly reduced.This study suggests that PD can affect the function of hippocampus in rats with DHD by regulating the 5-HT signaling pathway.