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1.
iScience ; 27(7): 110279, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39045104

RESUMO

Breast cancer is the second leading cause of carcinoma-linked death in women. We developed a multi-modal deep-learning model (BreNet) to differentiate breast cancer from benign lesions. BreNet was constructed and trained on 10,108 images from one center and tested on 3,762 images from two centers in three steps. The diagnostic ability of BreNet was first compared with that of six radiologists; a BreNet-aided scheme was constructed to improve the diagnostic ability of the radiologists; and the diagnosis of real-world radiologists' scheme was then compared with the BreNet-aided scheme. The diagnostic performance of BreNet was superior to that of the radiologists (area under the curve [AUC]: 0.996 vs. 0.841). BreNet-aided scheme increased the pooled AUC of the radiologists from 0.841 to 0.934 for reviewing images, and from 0.892 to 0.934 in the real-world test. The use of BreNet significantly enhances the diagnostic ability of radiologists in the detection of breast cancer.

3.
Breast Cancer Res ; 26(1): 94, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844963

RESUMO

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.


Assuntos
Neoplasias da Mama , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Metiltransferases , Estabilidade de RNA , Proteína 1 de Ligação a Y-Box , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Metilação , Metiltransferases/metabolismo , Metiltransferases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Proteína 1 de Ligação a Y-Box/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
4.
Eur J Case Rep Intern Med ; 11(6): 004491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846664

RESUMO

Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of metastatic disease. Sebaceous carcinoma is an uncommon malignant tumour that typically originates in the skin of the eyelid. In this case report, we present a unique case involving a metastatic sebaceous carcinoma that was not initially detected by a PET/CT scan in an 88-year-old female. Therefore, clinicians must maintain a heightened awareness of sebaceous carcinoma and exercise caution when making decisions solely based on PET scan results. It is crucial to recognise this potential limitation of PET scans in sebaceous carcinoma and consider further diagnostic approaches to ensure timely and accurate detection of sebaceous carcinoma. LEARNING POINTS: PET scans may miss slow-growing tumours such as sebaceous carcinoma.A high index of suspicion for sebaceous carcinoma is crucial, even with negative PET scans. Additional diagnostic approaches might be necessary for accurate detection.Sebaceous carcinoma is a rare but aggressive cancer. Diagnosis can be challenging due to its varied presentations.

5.
Orphanet J Rare Dis ; 19(1): 214, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778412

RESUMO

BACKGROUNDS: Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. RESULTS: Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of "fear and worry about choriocarcinoma recurrence". We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. CONCLUSIONS: IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. CLINICAL TRIAL REGISTRATION: N/A.


Assuntos
Coriocarcinoma , Humanos , Feminino , Estudos Retrospectivos , Adulto , Coriocarcinoma/patologia , Coriocarcinoma/tratamento farmacológico , Gravidez , Fertilidade , Adulto Jovem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/tratamento farmacológico
8.
Reprod Biomed Online ; 48(2): 103584, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38061975

RESUMO

RESEARCH QUESTION: Are the observed associations between female reproductive factors and sex hormones with the risk of uterine leiomyoma truly causal associations? DESIGN: The putative causal relationships between female reproductive factors and sex hormones with uterine leiomyoma were investigated using two-sample Mendelian randomization. Statistics on exposure-associated genetic variants were obtained from genome-wide association studies (GWAS). The uterine leiomyoma GWAS from the FinnGen and FibroGENE consortia were used as outcome data for discovery and replication analyses, respectively. Results were pooled by meta-analysis. Sensitivity analyses ensured robustness of the Mendelian randomization analysis. RESULTS: When FinnGen GWAS were used as outcome data, a causal relationship was found between age at menarche (OR 0.84, P < 0.0001), age at menopause (OR 1.08, P < 0.0001), number of live births (OR 0.25, P < 0.001) and total testosterone levels (OR 0.90, P < 0.001) with the risk of uterine leiomyoma. When FibroGENE GWAS were used as outcome data, Mendelian randomization results for age at menopause, the number of live births and total testosterone levels were replicated. In the meta-analysis, a later age at menopause (OR 1.08, P < 0.0001) was associated with an increased risk of uterine leiomyoma. A higher number of live births (OR 0.25, P < 0.0001) and higher total testosterone levels (OR 0.90, P < 0.0001) were associated with a decreased risk of uterine leiomyoma. CONCLUSIONS: A causal relationship between later age at menopause, lower number of live births and lower total testosterone levels with increased risk of uterine leiomyoma was found.


Assuntos
Estudo de Associação Genômica Ampla , Leiomioma , Humanos , Feminino , Análise da Randomização Mendeliana , Fatores Sexuais , Hormônios Esteroides Gonadais , Leiomioma/genética , Testosterona
9.
Sci Rep ; 13(1): 20858, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012281

RESUMO

In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Lapatinib/farmacologia , Quinazolinas/farmacologia , Receptor ErbB-2/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1 , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
11.
Sci Total Environ ; 904: 166596, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37640079

RESUMO

The use of catalyst materials to mediate the enhancement of microbial degradation in wastewater is a new economic and energy saving breakthrough in water treatment technology. In this study, γ-Al2O3, which is commonly used as catalyst/carrier, is used as biological filler to treat kitchen-oil wastewater with low biodegradability, and the COD removal rate is about 50 %. It is found that the complexation of cationic vacancies on Al2O3 surface with extracellular polymeric substance (EPS) secreted by microorganisms in wastewater lead to the polarization of electron distribution on biofilm. The efficient degrading bacteria are enriched on reaction interface and obtain electrons to maintain electron dynamic balance by enhancing the transmembrane metabolism of pollutants. The aluminum vacancies on Al2O3 surface accelerate the microbial degradation of pollutants. The cationic vacancies in the structure of catalyst accelerate the acquisition of exogenous electrons by microorganisms without the addition of external energy, which provides a new idea for catalytic fillers to enhance wastewater degradation.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Matriz Extracelular de Substâncias Poliméricas/química , Óxido de Alumínio/química , Catálise , Poluentes Químicos da Água/análise
12.
Medicine (Baltimore) ; 102(31): e34517, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37543799

RESUMO

BACKGROUND: The transversus abdominis plane (TAP) block is commonly used in surgical practice for postoperative analgesia in abdominal surgery. However, numerous studies have demonstrated that TAP block is also suitable for intraoperative anesthesia of peritoneal dialysis catheter (PDC) insertion, although its efficacy and safety are still controversial. Local anesthetic infiltration (LAI) is currently the most general anesthesia strategy for PDC insertion. Consequently, we conducted this systematic review and meta-analysis to identify which anesthesia strategy is better between TAP block and LAI. METHODS: A systematic and comprehensive search was conducted on 5 databases, retrieving published and registered randomized controlled trials as of March 10, 2022, comparing the anesthesia effects of TAP block and LAI. The primary outcomes are the visual analogue scale (VAS) pain score of patients at various time points in the surgery. The secondary outcomes are the VAS pain score at rest at 2 and 24 hours postoperatively, intraoperative rescue anesthesia, general anesthesia switching rate, and PD-related complications. RESULTS: There were 9 trials with 432 patients identified. TAP block was more effective than LAI at reducing intraoperative and postoperative VAS pain scores in patients. Compared to LAI, TAP block significantly reduces the dosage of anesthetics used to rescue anesthesia during surgery, the general anesthesia switching rate, and the incidence of postoperative PD-related complications in patients. CONCLUSIONS: Our systematic review and meta-analysis proved that TAP block could be used as the primary anesthetic technique for PDC insertion, with superior anesthetic effects to LAI.


Assuntos
Bloqueio Nervoso , Diálise Peritoneal , Humanos , Anestésicos Locais , Músculos Abdominais , Bloqueio Nervoso/métodos , Diálise Peritoneal/efeitos adversos , Catéteres/efeitos adversos , Dor/complicações , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides
13.
BMC Cancer ; 23(1): 784, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612621

RESUMO

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).


Assuntos
Doença Trofoblástica Gestacional , Metotrexato , Humanos , Gravidez , Feminino , Dactinomicina/efeitos adversos , Metotrexato/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Doença Trofoblástica Gestacional/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
14.
Int J Gynecol Cancer ; 33(9): 1376-1382, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37524495

RESUMO

OBJECTIVE: To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS: A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS: Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION: After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood ß human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/cirurgia , Doença Trofoblástica Gestacional/patologia , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico
15.
Inorg Chem ; 62(28): 11121-11133, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37390479

RESUMO

The complexes [FeIII(HMC)(C2DMA)2]CF3SO3 ([2]OTf) and [FeIII(HMTI)(C2Y)2]CF3SO3 ([3a-c]OTf) have been prepared and thoroughly characterized (HMC = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; HMTI = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene; Y = Fc (ferrocenyl, [3a]OTf), 4-(N,N-dimethyl)anilino (DMA, [3b]OTf), or 4-(N,N-bis(4-methoxyphenyl)anilino (TPA, [3c]OTf); OTf- = CF3SO3-)). Vibrational and electronic absorption spectroelectrochemical analyses following one-electron oxidation of the ethynyl substituent Y revealed evidence of strong coupling in the resultant mixed valent species for all HMTI-based complexes. However, the analogous mixed valent ion based on [2]OTf appeared to be more localized. Thus, the tetra-imino macrocycle HMTI has enabled significant valence delocalization along the -C2-FeIII-C2- bridge. Electron paramagnetic resonance and Mössbauer spectroscopic studies of [3b]OTf reveal that the π-acidity of HMTI lowers the energy of the FeIII dπ orbitals compared to the purely σ-donating HMC. This observation provides a basis for the interpretation of the macrocycle-dependent valence (de)localization.

16.
Int J Gynecol Cancer ; 33(8): 1222-1226, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37290904

RESUMO

OBJECTIVE: This study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy. METHODS: This study recruited premenopausal women aged 15 to 45 with a newly diagnosed low-risk gestational trophoblastic neoplasia needing actinomycin D. AMH was measured at baseline, during chemotherapy, and 1, 3, and 6 months after the last chemotherapy. The reproductive outcomes were also documented. RESULTS: Of the 42 women recruited, we analyzed 37 (median: 29 years; range 19-45) with a complete dataset. The follow-up was 36 months (range 34-39). Actinomycin D significantly decreased AMH concentrations during treatment, from 2.38±0.92 ng/mL to 1.02±0.96 ng/mL (p<0.05). Partial recovery was seen at 1 month and 3 months after treatment. Full recovery was reached 6 months after treatment among patients younger than 35 years. The only factor correlated with the extent of AMH reduction at 3 months was age (r=0.447, p<0.05). Notably, the number of courses of actinomycin D was not associated with the extent of AMH reduction. A total of 18 (90%) of 20 patients who had a desire to conceive had live births with no adverse pregnancy outcomes. CONCLUSION: Actinomycin D has a transient and minor effect on ovarian function. Age is the only factor that impacts the patient's rate of recovery. Patients will achieve favorable reproductive outcomes after actinomycin D treatment.


Assuntos
Doença Trofoblástica Gestacional , Reserva Ovariana , Gravidez , Humanos , Feminino , Dactinomicina/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Resultado da Gravidez , Hormônio Antimülleriano
17.
EClinicalMedicine ; 59: 101974, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37152364

RESUMO

Background: Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. Methods: This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings: This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p < 0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P = 0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p = 0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p < 0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p = 0.729). Interpretation: Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy. Funding: The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084).

18.
Artif Cells Nanomed Biotechnol ; 51(1): 276-285, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37218975

RESUMO

As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.


Assuntos
Aterosclerose , Humanos , Aterosclerose/genética , Apoptose , Biologia Computacional , Bases de Dados Factuais , Macrófagos , Perfilação da Expressão Gênica
19.
Environ Int ; 174: 107878, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963154

RESUMO

The stable structure and toxic effect of refractory organic pollutants in wastewater lead to the problem of high energy consumption in water treatment technology. Herein, we propose a synergistic purification of refractory wastewater driven by microorganisms and surface microelectric fields (SMEF) over a dual-reaction-center (DRC) catalyst HCLL-S8-M prepared by an in situ growth method of carbon nitride on the Cu-Al2O3 surface. Characterization techniques demonstrate the successful construction of SMEF with strong electrostatic force over HCLL-S8-M based on cation-π interactions between metal copper ions and carbon nitride rings. With the catalyst as the core filler, an innovative fixed bed bioreactor is constructed to purify the actual kitchen-oil wastewater. The removal efficiency of the wastewater even with a very low biodegradability (BOD5/COD = 0.33) can reach 60% after passing through this bioreactor. An innovative reaction mechanism is revealed for the first time that under the condition of a small amount of biodegradable organic matter, the SMEF induces the enrichment of electric active microorganisms (Desulfobulbus and Geobacter) in the wastewater, accelerates the interspecies electron transfer of intertrophic metabolism with the biodegradable bacteria through the extracellular electron transfer mechanism such as cytochrome C and self-secreted electron shuttle. The electrons of the refractory organic pollutants adsorbed on the surface of the catalyst are delocalized by the SMEF, which can be directly utilized by microorganisms through EPS conduction. The SMEF generated by electron polarization can maximize the utilization of pollutants and microorganisms in wastewater and further enhance degradation without adding any external energy, which is of great significance to the development of water self-purification technology.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Nitrilas , Cobre/química , Purificação da Água/métodos , Poluentes Químicos da Água/análise
20.
Gynecol Oncol ; 171: 1-8, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804610

RESUMO

OBJECTIVE: To analyze the methods, feasibility, efficiency, and fertility outcomes of fertility-sparing treatment for patients with placental site trophoblastic tumor (PSTT). METHODS: Clinical data of patients diagnosed with PSTT between April 1998 and April 2020 from Peking Union Medical College Hospital (PUMCH) were retrospectively collected. The clinical features, treatment, and outcomes of patients received fertility-sparing treatment were analyzed and compared with patients suffered hysterectomy. RESULTS: In total, 126 patients were included in the study and 29 of them received fertility-sparing treatment. Besides significantly younger age and lower proportion of antecedent term delivery were seen in fertility-sparing group than hysterectomy group, no significant differences were observed in stage, serum ß-hCG level, or interval from antecedent pregnancy between the two groups. Conservative surgery was selected individualized and none of them suffered salvage hysterectomy. Patients with clinical or pathological high-risk factors received adjuvant chemotherapy, yet the fertility-sparing treatment did not significantly lengthen chemotherapy duration. All patients in fertility-sparing group achieved complete remission without relapse after 36 to 176 months of follow-up and had sixteen healthy term delivery more than one year after the treatment. CONCLUSIONS: Fertility-sparing treatment for PSTT can be considered for young patients with localized uterine lesions who strongly desire to preserve their fertility potential. With individualized conservative surgery and selected adjuvant chemotherapy, fertility-sparing treatment will not influence the risk of relapse or overall survival and patients will achieve favorable pregnancy and live birth outcomes.


Assuntos
Tumor Trofoblástico de Localização Placentária , Neoplasias Uterinas , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgia , Tumor Trofoblástico de Localização Placentária/cirurgia , Recidiva Local de Neoplasia , Placenta/patologia
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