ObjectiveTo observe the effect of modified Shenling Baizhu Powder （参苓白术散， SBP） on peripheral blood counts and immune function in breast cancer patients with chemotherapy-induced myelosuppression and spleen-kidney insufficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 102 breast cancer patients with chemotherapy-induced myelosuppression and spleen-kidney insufficiency syndrome were randomly divided into a treatment group and a control group， with 51 cases in each group. Both groups received granulocyte colony-stimulating factor （G-CSF） support therapy and blood component transfusion therapy after chemotherapy. The treatment group additionally took modified SBP orally at one dose per day， while the control group was administered with placebo orally at the same dosage. Each chemotherapy cycle lasted 21 days and was defined as one treatment course. A total of four treatment courses were administered， with either herbal medicine or placebo taken orally for three weeks during each course. The primary outcome measures were peripheral blood para-meters including white blood cell count （WBC）， red blood cell count （RBC）， platelet count （PLT）， and hemoglobin （Hb） levels； secondary outcome measures were comprised of immune function parameters including CD3⁺ lymphocyte percentage， CD4⁺ lymphocyte percentage， CD8⁺ lymphocyte percentage， immunoglobulin A （IgA）， immunoglobulin G （IgG）， and immunoglobulin M （IgM）， traditional Chinese medicine （TCM） syndrome scores， chemotherapy completion rate， and incidence of adverse reactions. ResultsDuring the study， 2 cases in the treatment group and 3 cases in the control group were lost， resulting in a final analysis of 49 cases in the treatment group and 48 cases in the control group. Compared with baseline values， WBC， RBC， PLT， Hb， CD3⁺， CD4⁺， CD4⁺/CD8⁺ ratio， IgA， IgG and IgM levels increased in both groups， while CD8⁺ lymphocyte percentage and TCM syndrome scores decreased （P＜0.05）. Compared to the control group after treatment， the treatment group had higher levels of WBC， PLT， Hb， CD3⁺， CD4⁺， IgA， IgG and IgM， and lower levels of CD8⁺ lymphocyte percentage and TCM syndrome scores （P＜0.05）. The chemotherapy completion rate in the treatment group was 91.84% （45/49）， which was higher than 77.08% （37/48） in the control group （P＜0.05）. The overall incidence of adverse reactions in the treatment group was 30.61% （15/49）， significantly lower than 56.25% （26/48） in the control group （P＜0.05）. ConclusionModified SBP as an adjuvant therapy can effectively improve the peripheral blood counts， enhance the body's immune function， and demonstrate favorable safety in breast cancer patients with myelosuppression and spleen-kidney insufficiency syndrome during chemotherapy.

ObjectiveTo observe the effect of modified Shenling Baizhu Powder （参苓白术散， SBP） on peripheral blood counts and immune function in breast cancer patients with chemotherapy-induced myelosuppression and spleen-kidney insufficiency syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 102 breast cancer patients with chemotherapy-induced myelosuppression and spleen-kidney insufficiency syndrome were randomly divided into a treatment group and a control group， with 51 cases in each group. Both groups received granulocyte colony-stimulating factor （G-CSF） support therapy and blood component transfusion therapy after chemotherapy. The treatment group additionally took modified SBP orally at one dose per day， while the control group was administered with placebo orally at the same dosage. Each chemotherapy cycle lasted 21 days and was defined as one treatment course. A total of four treatment courses were administered， with either herbal medicine or placebo taken orally for three weeks during each course. The primary outcome measures were peripheral blood para-meters including white blood cell count （WBC）， red blood cell count （RBC）， platelet count （PLT）， and hemoglobin （Hb） levels； secondary outcome measures were comprised of immune function parameters including CD3⁺ lymphocyte percentage， CD4⁺ lymphocyte percentage， CD8⁺ lymphocyte percentage， immunoglobulin A （IgA）， immunoglobulin G （IgG）， and immunoglobulin M （IgM）， traditional Chinese medicine （TCM） syndrome scores， chemotherapy completion rate， and incidence of adverse reactions. ResultsDuring the study， 2 cases in the treatment group and 3 cases in the control group were lost， resulting in a final analysis of 49 cases in the treatment group and 48 cases in the control group. Compared with baseline values， WBC， RBC， PLT， Hb， CD3⁺， CD4⁺， CD4⁺/CD8⁺ ratio， IgA， IgG and IgM levels increased in both groups， while CD8⁺ lymphocyte percentage and TCM syndrome scores decreased （P＜0.05）. Compared to the control group after treatment， the treatment group had higher levels of WBC， PLT， Hb， CD3⁺， CD4⁺， IgA， IgG and IgM， and lower levels of CD8⁺ lymphocyte percentage and TCM syndrome scores （P＜0.05）. The chemotherapy completion rate in the treatment group was 91.84% （45/49）， which was higher than 77.08% （37/48） in the control group （P＜0.05）. The overall incidence of adverse reactions in the treatment group was 30.61% （15/49）， significantly lower than 56.25% （26/48） in the control group （P＜0.05）. ConclusionModified SBP as an adjuvant therapy can effectively improve the peripheral blood counts， enhance the body's immune function， and demonstrate favorable safety in breast cancer patients with myelosuppression and spleen-kidney insufficiency syndrome during chemotherapy.

Objective To investigate the protective effect of Indigo Naturalis on cerebral ischemia-reperfusion injury in mice. Methods The mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established using the filament ligation method. Mice were randomly divided into five groups: sham surgery, model, positive drug control, low-dose Indigo Naturalis, and high-dose Indigo Naturalis. After 7 d of drug administration, the relevant experiments were performed. Neurological function was assessed via behavioral scoring, balance beam test, forelimb grip strength, and tail lift test. Brain infarct volume was quantified using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Histopathological changes and neuronal apoptosis were systematically analyzed through hematoxylin-eosin (HE) staining, Nissl staining, and TUNEL staining. Finally, polymerase chain reaction (PCR) was employed to detect mRNA expression levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and microglial polarization markers (CD32, CD206) in the mouse cerebral cortex. Results Compared with the model group, the neurological function scores of mice in the high-dose Indigo Naturalis group showed significant improvement, and the motor ability recovery in each drug-administration group was remarkable (P<0.05, P<0.01). The cerebral infarct volume in the high-dose Indigo Naturalis group was significantly reduced (P<0.05). Histological results revealed that Indigo Naturalis could alleviate pathological damage in brain tissue and reduce neuronal apoptosis (P<0.01). PCR results demonstrated that after treatment with Indigo Naturalis, the expression of inflammatory factors and CD32 was significantly downregulated (P<0.05, P<0.01), while the expression of CD206 was significantly upregulated (P<0.05). Conclusion Indigo Naturalis could improve motor function in mice with cerebral ischemia-reperfusion injury, and its effects might be related to regulating inflammatory responses and reducing neuronal damage.

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of post-stroke cognitive impairment(PSCI)by using network pharmacology methods and clinical trial validation.Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024.The patients were randomly divided into the control group and the trial group by random number table method,with 45 cases in each group.The control group was treated with conventional treatment for PSCI,and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group.The treatment course for the two groups covered 28 days.The changes of Mini-Mental State Examination(MMSE)score,Montreal Cognitive Assessment(MoCA)score,and the serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the patients of the two groups were observed before and after treatment.Moreover,the incidences of adverse events in the two groups were recorded,thus to evaluate the safety of the treatment regimens in the two groups.And then the network pharmacological research was performed.TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule,GeneCards and other databases were used to obtain the PSCI disease targets,and the common targets were inputted into the STRING database to construct the PPI network.Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets,DAVID was used to perform GO and KEGG pathway enrichment analysis,and then molecular docking was used to verify the binding activity.Results(1)The results of clinical trial showed that after 28 days of treatment,the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment(P<0.05),and the increase of the scores in the trial group was significantly superior to that in the control group(P<0.05).The serum levels of TNF-α and IL-6 were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).During the trial,both groups of patients did not show obvious adverse reactions,with high safety.(2)The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients,803 targets,5 209 disease targets and 556 intersection targets.The core targets were AKT1,TNF,IL-6,TP53 and IL-1B,and the key compounds were deoxyharringtonine,senkyunone and genkwanin.The GO enrichment analysis obtained 1 812 GO entries,of which 154 entries were related with cellular component(CC),1 332 entries were related with biological process(BP),and 326 entries were related with molecular function(MF).The KEGG pathway enrichment analysis yielded 195 signaling pathways.The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets.Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable,and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1,TNF,and IL-6.The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.

Objective To investigate the effects of dienogest on pain relief and inflammation in endometriosis(EMs),as well as its impact on the brain-derived neurotrophic factor(BDNF)/tropo-myosin receptor kinase B(TrkB)and nuclear factor kappa-B(NF-κB)/NOD-like receptor protein 3(NLRP3)inflammatory pathways.Methods An allograft method was used to establish an EMs rat model.The rats were randomly divided into sham-operated group(n=16),model group(n=16),low-dose dienogest group(n=16),medium-dose dienogest group(n=16)and high-dose dienogest group(n=16).After 7 days of treatment,the implantation volume and writhing response frequency were recorded.Enzyme-linked immunosorbent assay(ELISA),reverse transcription-polymerase chain reaction and Western blotting were employed to measure the expression levels of vascular endothelial growth factor(VEGF),inducible nitric oxide synthase(iNOS),interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α in the EMs rat models.Serum levels of BDNF,TrkB,NF-κB and NLRP3 were detected.Results Compared with model group,dinorgestrel significantly reduced ectopic endo-metrial volume and torsion response of EMs(P＜0.05).Compared with model group,dinorgestrel significantly decreased the expression of VEGF,iNOS,IL6,IL-1 β and TNF-α in EMs model(P＜0.05).In addition,compared with model group,dienogest significantly decreased the expressions of BDNF,TrkB,NF-κB and NLRP3 in ectopic endometrium(P＜0.05).Conclusion Dinorgestrel can relieve EMS-related dysmenorrhea and inflammation,and its mechanism of action may be partly mediated by BDNF/TrkB pathway and NF-κB/NLRP3 pathway.

Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.

OBJECTIVE To investigate the incidence of hospital-associated infections among the neurosurgery de-partment patients undergoing brain tumor resection and analyze the economic cost so as to provide scientific bases for formulating prevention strategies.METHODS Totally 1027 patients who underwent brain tumor resection in neurosurgery department of the First Affiliated Hospital of Shandong First Medical University from Jan.1,2020 to Dec.31,2024 were recruited as the research subjects.The 36 patients who had postoperative hos-pital-associated infections were assigned as the infection group,and 991 patients who did not have hospital-associ-ated infection were assigned as the no infection group.The patients of the infection group and the non-infection group were matched in a 1∶1 ratio by using propensity score matching method(caliper value 0.005).The length of hospital stay and costs of medical items were compared between the infection group and the non-infection group,and the economic burden due to the hospital-associated infections was estimated.RESULTS The incidence of hospital-associated infections was 3.51％among the patients undergoing brain tumor resection,and totally 36 pairs were matched successfully with the propensity score.The hospitalization cost of the infection group was 109,103.81(73,370.21,163,628.37)yuan after the matching,which was increased by 50,087.69 yuan as com-pared with the non-infection group(Z=-5.237,P＜0.001);the length of hospital stay was 23.00(17.25,36.00)days,which was prolonged by 8.50 days(Z=-3.764,P＜0.001).Among the costs of medical items,the medial costs of western medicine,treatment materials and clinical laboratory tests increased most.CONCLUSIONS The control of the costs of western medicine,treatment materials and clinical laboratory tests is the key to reduce the costs of brain tumor resection patients with hospital-associated infections.It is necessary to carry out the real-time monitoring of the hospital-associated infections and early warning of suspected cases and reduce the incidence of hospital-associated infections so as to reduce the economic costs.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides