Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Breast cancer is a highly heterogeneous malignancy,including a variety of different subtypes,which differ in genetics,pathology,clinical treatment and prognosis.The traditional research model of breast cancer cell lines cannot fully conform to the actual pathological process of clinical tumor pathogenesis and the characteristics of tumor heterogeneity.Breast cancer organoid is a model based on 3D cell culture system,which can reproduce the heterogeneity of the primary tumor while retaining the molecular phenotype and genotype changes of the patient's tumor.Therefore,it has been applied in the study of tumor pathogenesis and anti-tumor drug screening.At present,the traditional Chinese medicine research on breast cancer is mainly focused on cell lines and patient-derived tumor xenografts,while the related research on organoids is relatively lacking.This review briefly introduces the development of breast cancer organoid culture system and its application in life science research,in order to provide ideas for breast cancer related research with traditional Chinese medicine.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Circadian rhythm is an internal regulatory mechanism formed in organisms in response to the circadian periodicity in the environment, which modulates the pathophysiological events, occurrence and development of diseases, and the response to treatment in mammals. It significantly influences the susceptibility, injury, and recovery of ischemic stroke, and the response to therapy. Accumulating evidence indicates that circadian rhythms not only regulate the important physiological factors of ischemic stroke events, such as blood pressure and coagulation-fibrinolysis system, but also participate in the immuno-inflammatory reaction mediated by glial cells and peripheral immune cells after ischemic injury and the regulation of neurovascular unit(NVU). This article aims to link molecular, cellular, and physiological pathways in circadian biology to the clinical consequences of ischemic stroke and to illustrate the impact of circadian rhythms on ischemic stroke pathogenesis, the regulation of NVU, and the immuno-inflammatory responses. The regulation of circadian rhythm by traditional Chinese medicine is reviewed, and the research progress of traditional Chinese medicine intervention in circadian rhythm is summarized to provide a reasonable and valuable reference for the follow-up traditional Chinese medicine research and molecular mechanism research of circadian rhythm.
Animals ; Ischemic Stroke ; Medicine, Chinese Traditional ; Circadian Rhythm ; Blood Coagulation ; Blood Pressure ; Mammals

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Humans ; Gemcitabine ; Neoplasms

Objective To design a modularization-based ultrasound biomicroscopy to solve the problems of the existing ultra-sound biomicroscopy in large size,display terminal and scanning probe manipulation inflexibility.Methods The modulariza-tion-based ultrasound biomicroscopy was composed of an acquisition module and an upper computer module.The acquisition module was made up of a scanning probe module,a host module and a power adapter module,in which the scan-ning probe module adopted a small-angle sector scanning scheme and consisted of an ultrasonic transducer,a preamplification circuit and a motor drive device,the host module included a field programmable gate array(FPGA)control unit,an ultrasonic emission circuit,a motor drive circuit,a gain adjustment circuit,a postamplification circuit and a USB communication interface.The upper computer module was compatible with Android and Windows platforms,which had the program developed with Java language and Eclipse(V4.5)platform for Android platform and Microsoft Visual Studio 2015 and MFC platform for Windows platform.Results The ultrasound biomicroscopy developed had the lateral and axial resolutions reaching 50 μm and could display skin and eye images clearly.Conclusion The ultrasound biomicroscopy developed behaves well in performance,portability and manipulation inflexibility,and thus can be used for clinical high-definition image acquisition.[Chinese Medical Equipment Journal,2023,44(9):19-23]

Pseudostellaria heterophylla in large-scale cultivation needs to apply pesticides to control diseases, and non-standard use of pesticide may cause excessive pesticide residues in medicinal materials, increasing the risk of clinical medication. To accurately monitor the residual pesticides, this paper investigated the drug use during the process of P. heterophylla disease prevention in 25 P. he-terophylla planting enterprises or individual households in Guizhou province. It was found that there were 8 common diseases in P. he-terophylla planting, including leaf spot, downy mildew, virus disease, root rot, dropping disease, purple feather disease, white silk disease, and damping-off disease. Twenty-three kinds of pesticides were used in disease control, mainly chemical synthetic pesticides, accounting for 78.3%, followed by biological pesticides and mineral pesticides, accounting for 13.0% and 8.7%, respectively. The disease prevention and control drugs were all low-toxic pesticides, and there were no varieties banned in the Chinese Pharmacopoeia(2020 edition). However, the pesticides used have not been registered on P. heterophylla, and the excessive use of drugs was serious. The present monitoring of pesticide residues in P. heterophylla is mainly based on traditional pesticides such as organochlorine, organophosphorus, and carbamate, which does not effectively cover the production of drugs and had certain safety risks. It is suggested to speed up the research and registration of drug use in the production of P. heterophylla, increase the use of biological pesticides, and further improve the monitoring indicators of pesticide residues in combination with the actual production of drugs, so as to promote the high-quality development of P. heterophylla industry.
Biological Control Agents ; Caryophyllaceae ; Pesticide Residues ; Pesticides ; Plants, Medicinal

Objective: To compare the clinical performance of posterior single implant-supported monolithic zirconia crowns fabricated by full digital workflow and that of those fabricated by conventional workflow. Methods: This is prospective clinical research. Thirty-five patients who participated in a previous study during August 2017 to October 2018 at Department of Prosthodontics, Peking University School and Hospital of Stomatology were included in this 3-year follow-up study. The 35 patients, 17 females and 18 males, aged (49.0±15.4) years (24-86 years old), was allocated into two groups. In the full digital workflow group, intraoral scanning was taken immediately after implant placement, and a full zirconia implant crown was fabricated using model-free computer aided design/computer aided manufacturing (CAD/CAM) procedure (n=14). In the conventional group, a conventional impression was taken 3 months after implant placement and the stone model was produced. A full zirconia implant crown was fabricated using conventional model-based procedure (n=21). Three years following crown delivery, all the prostheses were evaluated in the aspect of color, surface roughness, contour and marginal integrity using modified US Public Health Service criteria (MUSPHS criteria). The soft and hard tissue around implant was evaluated using modified plaque index, probing depth (PD), number of implants with bleeding on probing, marginal bone loss (MBL). The biological and mechanical complication were also recorded. Statistical analysis was performed using independent samples t test, Mann-Whitney U test and Fisher's exact test. Results: The total survival rate of prosthesis and implant was 100% (35/35). No significant difference in MUSPHS criteria ratings on color, surface roughness, contour and marginal integrity of these crowns were found between the full digital workflow group and the conventional group (P>0.05). Sixteen out of the 35 crowns had a contour score of B due to loss of interproximal contact. Ten out of the 35 crowns had the screw hole sealing resin sinking or falling off, four in the full digital workflow group and six in the conventional group. There was no significant difference in the rate of prostheses mechanical complications between the two groups (P=1.000). For all the implants, there was no significant difference in MBL, PD, the modified plaque index, and number of implants with bleeding on probing between the two groups (U=119.50,133.00,142.50, t=-0.53, P>0.05). Conclusions: The clinical performance of implant-supported posterior single monolithic zirconia crowns fabricated by full digital workflow was stable. There was no significant difference in the clinical performance of the single implant crowns between the full digital workflow group and the conventional group.
Adult ; Aged ; Aged, 80 and over ; Crowns ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; United States ; Workflow ; Young Adult ; Zirconium

With the aging of population and the development of social economy, the incidence of chronic wounds is increasing day by day, while the incidence of burns and trauma remains at a high level, making wound repair an increasingly concerned area in clinical practice. Thymosin β4 is a naturally occurring small molecule protein in vivo, which is widely distributed in a variety of body fluids and cells, especially in platelets. Thymosin β4 has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. Thymosin β4 has been observed to promote the healing of various wounds, such as burns, diabetic ulcers, pressure ulcers. This paper will review the molecular structure, mechanism of wound healing promotion, pharmacokinetics, and clinical application of thymosin β4, aiming to introduce its potential in wound treatment and the shortcomings of current researches.
Burns/drug therapy* ; Humans ; Pressure Ulcer ; Thymosin/therapeutic use* ; Wound Healing/physiology*