Objective:To investigate the expression of indoleamine 2,3-dioxygenase 1(IDO1)in different types of breast cancer tissues and its relationship with patient prognosis and immune cell infiltration.Methods:RNA sequencing data of breast cancer and corresponding clinical information from the TCGA database were collected.The differential expression of IDO1 mRNA in various breast cancer tissues(different subtypes,stages,menopause statuses,and age groups)and adjacent normal tissues were analyzed.Breast cancer patients with significant differences in IDO1 mRNA expression were divided into high and low expression groups,and their disease-specific survival(DSS)was compared between the two groups.The relationship between IDO1 mRNA expression and immune cell infiltration in cancer tissues with significant DSS differences was analyzed.Immunohistochemistry was used to detect IDO1 protein expression in ER-negative,PR-negative,HER2-positive,and stage Ⅱ breast cancer tissues,to verify the data from the database.Results:IDO1 mRNA was highly expressed in breast cancer tissues but varied across different breast cancer types.IDO1 mRNA was highly expressed in breast cancer tissues of patients with ER-negative,PR-negative,HER2-positive,HER2-negative subtypes,stage Ⅱ,T2 stage,N0 stage,M0 stage,premenopausal,postmenopausal,and age≤60 years(P<0.05 or P<0.01,or P<0.001).In the ER-negative,PR-negative,HER2-positive,and stage Ⅱ subgroups,breast cancer tissues patients with high IDO1 mRNA expression had significantly higher DSS than those with low expression(P<0.05 or P<0.01).In ER-negative,PR-negative,HER2-positive,and stageⅡ breast cancer tissues,IDO1 mRNA expression was associated with immune cell infiltration,including activated dendritic cells(aDCs),Th1 cells,T cells,CD56dim NK cells,CTLs,and Treg cells(all P<0.001).IDO1 protein was highly expressed in ER-negative,PR-negative,HER2-positive,and stage Ⅱ breast cancer tissues(all P<0.001),consistent with the data from the database.Conclusion:IDO1 expression varies across different types of breast cancer tissues.The expression of IDO1 is associated with the prognosis and immune cell infiltration in ER-negative,PR-negative,HER2-positive,and at stage Ⅱ breast cancer patients.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

OBJECTIVE: To explore the differences in clinical efficacy between enhanced workflows and express workflows in robotic-assisted total hip arthroplasty(THA). METHODS: A retrospective analysis was conducted on 46 patients who underwent robotic-assisted THA between November 2020 and May 2021. They were divided into the enhanced workflows group and the express workflows group based on the surgical methods. There were 20 patients in the enhanced workflows group, including 11 males and 9 females;aged from 51 to 78 years old with an average of (67.30±7.52) years old. The BMI ranged from 18.24 to 24.03 kg·m^-2 with an average of(23.80±3.01) kg·m^-2. There were 26 patients in the express workflows group, including 12 males and 14 females;aged from 57 to 84 years old with a mean age of (67.58±7.29) years old, and their BMI ranged from 19.72 to 30.08 kg·m^-2 with an average of (24.41 ±2.92) kg·m^-2. The operation time, hospital stay, and perioperative complications of the patients were recorded. The postoperative acetabular prosthesis anteversion angle, abduction angle, limb length, and offset distance data were measured. The Harris hip score at the latest follow-up was recorded. RESULTS: All patients completed the surgery as planned and were followed up, with the follow-up period ranging from 47 to 54 months with a mean of (49.78±1.85) months and the length of hospital stay ranging from 2 to 11 days with an average of (6.57±1.82 ) days. The operation time of enhanced workflows group was (93.41±16.41) minutes, which was longer than that of the express workflow groups (75.19±18.36) minutes, and the difference was statistically significant (P<0.05). In enhanced workflows group, the postoperative acetabular anteversion angle was (19.20±4.46)°, the limb length discrepancy was (-1.55±9.13) mm, and changes of the offset was (-5.15±6.77) mm. The corresponding values in express workflows group were (20.46±3.29)°, (2.19±4.39) mm, and (-2.39±4.34) mm, respectively. There was no statistically significant difference in these indicators between the two groups(P>0.05). One patient in the enhanced workflows group developed deep venous thrombosis after surgery. No cases of dislocation or periprosthetic infection. At the latest follow-up, all patients had well-positioned prostheses without loosening. Harris hip score was (90.50±1.67) points in enhanced workflows group and (90.73±2.36) points in the express workflows group, with no statistically significant difference between the two groups (P>0.05). CONCLUSION The clinical efficacy of robot assisted total hip arthroplasty technology is satisfactory. The enhanced workflows will increase the surgical time. For patients with normal anatomical hip joint disease, this study did not find significant advantages in joint stability and functional scoring for the enhanced workflows.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Male ; Female ; Aged ; Middle Aged ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Aged, 80 and over ; Workflow ; Treatment Outcome

OBJECTIVE: Investigation on the clinical application of HURWA robot and Smith & Nephew Cori robot in total knee arthroplasty(TKA). METHODS: A retrospective analysis was performed on 84 patients with knee osteoarthritis who underwent robotic-assisted TKA (RATKA) between June 2023 and March 2025. According to the different robotic systems used, the patients were divided into the domestic HUARUN robotic-assisted total knee arthroplasty group (HRATKA group) and the Smith & Nephew Cori robotic-assisted total knee arthroplasty group (CRATKA group). There were 42 patients in the HRATKA group, including 16 males and 26 females; the age ranged from 56 to 73 years old, with an average of (64.70±8.30) years old;the body mass index (BMI) was (25.10±2.30) kg·m^-2;21 cases were on the right side and 21 cases on the left side;in terms of Kellgren-Lawrence(K-L) classification, there were 15 cases of Grade Ⅲ and 27 cases of Grade Ⅳ;the disease duration ranged from 3 to 25 years, with an average of (15.5±7.5) years. The CRATKA group also included 42 patients, with 14 males and 28 females;the age ranged from 58 to 74 years old, with an average of (65.60±7.50) years old;the BMI was (24.50±2.70) kg·m^-2; 20 cases were on the right side and 22 cases on the left side;regarding K-L classification, there were 11 cases of Grade Ⅲ and 31 cases of Grade Ⅳ;the disease duration ranged from 2 to 26 years, with an average of (16.5±8.8) years. Collect general data of all patients, including age, gender, height, weight, surgical site, K-L classification, incision length, and operation time. To evaluate prosthesis position, compare the frontal tibia component (FTC) angle, lateral femoral component (LFC) angle, lateral tibia component (LTC) angle, and frontal femoral component angle between the two groups of patients after surgery. Measure the deviation of the hip-knee-ankle (HKA) angle to assess lower limb alignment. Additionally, compare the following indicators between the two groups:Knee Society Score (KSS), Visual Analogue Scale (VAS) for pain, knee range of motion (ROM), hemoglobin (HB) level, hematocrit (HCT) level, complication rate, and in-hospital satisfaction. RESULTS: All patients successfully completed the surgery as scheduled, and all were followed up after the operation. The follow-up period ranged from 5 to 17 months with an average of (11.2±6.1) months. There were 4 cases of venous thrombosis in the HRATKA group and 3 cases in the CRATKA group;each group had 2 cases of wound exudation. No mechanical-related complications, pulmonary embolism, or other severe complications occurred. Comparison of the incision length and hospital stay between the HRATKA group and the CRATKA group showed no statistically significant difference (P>0.05). The operation time in the HRATKA group was (96.80±7.10) minutes, which was longer than that in the CRATKA group (90.10±8.80) minutes, and the difference was statistically significant (P<0.05). In the HRATKA group, the HKA angle was (178.93±1.11) degree, the FFC angle was (89.00±0.91)°, and the LFC angle was (7.31±2.17) degree;the corresponding values in the CRATKA group were (178.05±1.34)°, (87.88±1.74)°, and (10.60±2.84) degree respectively. The differences in these three indicators between the two groups were all statistically significant (P<0.05). However, there were no statistically significant differences in the FTC angle or LTC angle between the two groups (P>0.05). There was also no statistically significant difference in the total perioperative blood loss between the two groups (P>0.05). At 3 days after surgery, the VAS score for movement in the HRATKA group (5.95±1.45) points was higher than that in the CRATKA group (4.50±0.97) points, with a statistically significant difference (P<0.05);at 90 days after surgery, there was no statistically significant difference in the movement VAS score between the two groups (P>0.05). Additionally, no statistically significant differences were observed between the two groups in the KSS, ROM at 3 and 90 days after surgery, or satisfaction degree during hospitalization (all P>0.05). CONCLUSION The domestic HURWA robot demonstrates excellent performance in osteotomy efficiency and lower limb alignment recovery. The Smith & Nephew Cori robot has a significant advantage in soft tissue assessment and joint stability optimization. Both robotic systems offer high-quality surgical treatments that significantly improve short-term knee function.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/instrumentation* ; Aged ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Osteoarthritis, Knee/surgery*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To investigate the effects of Wnt5a on the vasculogenic mimicry(VM)and cancer stem cell(CSC)properties of prostate cancer(PCa)cells by upregulating the expression of miR-141-3p.Methods:Human prostate epithelial cell line RWPE-1 and PCa cell lines PC-3,LNCaP,and DU145 were cultured.qPCR was employed to detect miR-141-3p expression,and Western blotting(WB)was used to measure Wnt5a protein levels.Stable Wnt5a-knockdown or miR-141-3p-knockdown LNCaP and DU145 cell lines were established respectively via plasmid transfection.VM formation ability was assessed by three-dimensional culture assay.Cell proliferation ability and drug sensitivity were measured by CCK-8 assay.Cell migration and invasion abilities were detected using wound healing and Transwell assays,respectively.The expressions of VM-related molecules and CSC markers were detected by qPCR and WB.Colony formation ability was determined by clonogenic assay.The proportion of CD133+cells was sorted and calculated by flow cytometry.The expressions of miR-141-3p and Wnt5a in CD133+and CD133-cells were detected by qPCR and WB.Stable Wnt5a-overexpressing PCa cell lines were constructed via plasmid transfection.The effects of Wnt5a and different Wnt pathway downstream inhibitors on miR-141-3p expression and promoter activity were detected by qPCR and dual-luciferase reporter assays.Expression of c-Jun was knocked down in Wnt5a-overexpressing cells using si-c-Jun transfection.The target binding relationship between c-Jun and the miR-141-3p promoter was verified by qPCR,dual-luciferase reporter assay,and chromatin immunoprecipitation assay.Results:The expressions of miR-141-3p and Wnt5a were significantly higher in PCa cells compared with those in RWPE-1 cells,with the highest relative expression in DU145 cells and the lowest in LNCaP cells(P<0.001).Downregulation of Wnt5a or miR-141-3p significantly inhibited VM formation ability and stemness of PCa cells,and significantly suppressed the proliferation,migration,invasion abilities,and enhanced the sensitivity to bicalutamide of PCa cells(P<0.05 or P<0.01 or P<0.001).Downregulation of Wnt5a significantly inhibited miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.05),whereas upregulation of Wnt5a significantly promoted miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.001).The promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity could be inhibited by a JNK/c-Jun pathway inhibitor(P>0.05).Downregulation of c-Jun significantly inhibited the promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity(P>0.05).c-Jun could bind to the-348 to-295 sequence of the miR-141-3p promoter.In absence of this fragment Wnt5a wouldn't promote miR-141-3p expression(P>0.05).Conclusion:The Wnt5a/JNK/c-Jun signaling pathway can upregulate miR-141-3p expression,and thereby promote VM formation in PCa cells,possibly by activating CSC properties.

Working memory is a core component of human cognitive functions, responsible for the temporary storage and manipulation of information, and plays a vital role in the execution of daily tasks. Working memory includes information encoding, maintenance, manipulation, and retrieval, with the underlying mechanisms corresponding to neural oscillations. The frequency bands most related to each step of working memory are θ (4-8 Hz), α (8-13 Hz), and γ (>30 Hz) waves. θ waves mainly correspond to the temporal organization of memory items; γ waves are related to information maintenance; α waves indicate inhibition of irrelevant information. These neural oscillations can be regulated by external rhythmic stimulation, gradually synchronizing to the rhythm and phase of external stimulation. This phenomenon is called neural entrainment. Non-invasive brain stimulation (NIBS) can regulate working memory related neural oscillations through entrainment, and has the potential to become a method to enhance working memory performance. Another possible intervention approach to improve working memory is to enhance the excitability of key brain regions involved in working memory through NIBS. In this review, we reviewed more than 50 studies applying NIBS for working memory in healthy adults, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and other NIBS techniques. In terms of research paradigm, working memory NIBS studies with healthy adults usually adopt classic working memory behavioral paradigms, e.g., n-back tasks with numbers or space positions, Sternberg tasks, relatively few stimulating sessions, mainly focus on the simultaneous or short-term effects on behavioral performance. For stimulation sites, the prefrontal cortex (especially dorsolateral prefrontal cortex (DLPFC) is the most commonly choice for it’s a vital role in functions such as information maintenance and cognitive resource allocation. The parietal lobe (especially the intraparietal sulcus (IPS) also plays an important role in information maintenance and manipulation, and is the second common stimulation site after DLPFC. Studies targeting the temporal lobe, occipital lobe, and motor cortex are relatively limited. For stimulation methods, TMS studies mainly use repetitive TMS (rTMS) and θ burst stimulation (TBS) with stimulating frequency in θ or γ band, one-sided or bilateral prefrontal cortex as the stimulation site. The specific intervention effects may also depend on the phase of the neural oscillation that TMS targets. For tDCS studies, anodal stimulation of DLPFC or parietal lobe is widely utilized. The heterogeneous intervention effects such as relatively weak enhancement or impairment of working memory performance after intervention, may result from varied stimulation protocol or participants’ factors (e.g., small sample size, inconsistent baseline levels). For tACS studies, the most widely used stimulation frequencies are θ and γ bands, usually with in-phase manner, fixed or individualized frequencies. Enhancement of working memory performance has been reported for both settings, and the effects are also affected by stimulation parameters, task difficulty and baseline levels of participants. Transcranial random noise stimulation (tRNS), temporal interference stimulation (TIS), transcranial ultrasound stimulation (TUS) are emerging NIBS techniques, of which TIS and TUS can stimulate deep brain regions. Current studies modulating working memory based on these cutting-edge techniques are limited, but they have potential in mechanism exploration and clinical applications in working memory research.

The coronary artery disease is a frequent severe disease of cardiovascular system in recent years. Meanwhile, lung cancer, with its high morbidity and mortality, is the most frequent malignant tumor of respiratory system in the world. Clinical studies have shown that the incidence of coronary artery disease and lung cancer is high throughout the year, and comorbidities are becoming more common, especially in elderly patients. The incidence of lung cancer and coronary heart disease may be related. This article summarizes the common risk factors (smoking and environmental pollution, fibrinogen, estrogen, and age), and treatment (surgical treatment, neoadjuvant therapy, and targeted therapy) progress of the two diseases, providing a theoretical basis for clinical prevention and treatment.