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1.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 812-817, 2023.
Article in Chinese | WPRIM | ID: wpr-996622

ABSTRACT

@#Objective    To analyze the research hotspots and progress of surgical treatment of myasthenia gravis. Methods    The top 100 most cited articles on surgical treatment of myasthenia gravis were identified by searching the Web of Science database, and a bibliometric analysis was conducted. Results    The publication year of the top 100 most cited articles ranged from 1939 to 2021, and the number of citations ranged from 55 to 850 per article. Most of the included articles were original research articles (75/100), which were mainly retrospective studies (64/75). The United States was the country with the most published articles and most citations, and Annals of Thoracic Surgery was the most sourced journal (n=20). Through VOSviewer analysis, high-density keywords were thymectomy, maximal thymectomy, extended thymectomy, transcervical thymectomy, thymoma, and autoantibodies. Conclusion    The scope of surgical resection, surgical approach and pathogenesis are the current hotspots in the field of surgical treatment of myasthenia gravis. It is hoped that this paper can provide references for future researches in this field.

2.
Chinese Journal of Radiation Oncology ; (6): 313-318, 2023.
Article in Chinese | WPRIM | ID: wpr-993193

ABSTRACT

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

3.
Chinese Journal of Behavioral Medicine and Brain Science ; (12): 564-569, 2023.
Article in Chinese | WPRIM | ID: wpr-992134

ABSTRACT

Motoric cognitive risk syndrome (MCR), as a new type of "pre-dementia" , is a sensitive prediction indicators of falls.There may be multiple attribution pathways between MCR and falls, which provides a new health management strategy in the fall prevention for community-dwelling elderly.The paper reviews the current status of MCR-related falling, attribution characteristics, the methods of risk assessment and health management strategies for older adults with MCR, with the aim of providing a reference for promoting systematic research on falls among senior citizens with MCR and the practice of falls prevention in the community.

4.
Chinese Journal of Applied Clinical Pediatrics ; (24): 331-338, 2023.
Article in Chinese | WPRIM | ID: wpr-990037

ABSTRACT

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

5.
Chinese Pharmacological Bulletin ; (12): 5-8, 2023.
Article in Chinese | WPRIM | ID: wpr-1013870

ABSTRACT

IFIT1 is a highly inducible member of the interferon stimulating gene family (ISGs) with tetrapeptide repeats. It mainly exists in the cytoplasm and is regulated by interferon, a variety of antiviral role through a variety of mechanisms and pathways, and many viruses have evolved unique mechanisms to evade the limiting effects of IFIT1 and thus counter the body' s antiviral immunity, the unique anti-inflammatory effect of IFIT1 has been extensively studied in inflammatory diseases, Therefore, we mainly review the anti-inflammatory and antiviral effects of IFIT1 and the related mechanisms, so as to provide new therapeutic targets and ideas for the treatment of related diseases.

6.
Chinese Journal of Surgery ; (12): 681-687, 2023.
Article in Chinese | WPRIM | ID: wpr-985798

ABSTRACT

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

7.
Neuroscience Bulletin ; (6): 273-291, 2023.
Article in English | WPRIM | ID: wpr-971555

ABSTRACT

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.


Subject(s)
Humans , Tumor Necrosis Factor-alpha , DNA-Binding Proteins/metabolism , Ubiquitin-Specific Peptidase 7 , Cisplatin , Temozolomide , Transcription Factors , Glioma , Cell Proliferation , Melanoma , Cell Line, Tumor , Apoptosis , Nuclear Proteins/genetics
8.
China Journal of Orthopaedics and Traumatology ; (12): 873-879, 2023.
Article in Chinese | WPRIM | ID: wpr-1009152

ABSTRACT

OBJECTIVE@#To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI).@*METHODS@#Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function.@*RESULTS@#Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05).@*CONCLUSION@#cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.


Subject(s)
Female , Animals , Rats , Rats, Sprague-Dawley , Neuroprotective Agents/pharmacology , Spinal Cord Injuries/drug therapy , Spinal Cord Compression
9.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 488-498, 2022.
Article in Chinese | WPRIM | ID: wpr-923445

ABSTRACT

@#Thymic neuroendocrine tumors (TNETs) are a series of rare diseases with aggressive biology and poor prognosis. Clinical manifestations of TNETs are atypical, and ectopic secretion of adrenocorticotropic hormone can be found in some cases, resulting in associated endocrine symptoms. Due to the low morbidity and strong heterogeneity, it’s difficult to diagnose, treat and obtain new treatment regimen. Early complete surgical resection is an effective treatment. For advanced cancer, clinical trials of new drugs are expected to improve the survival of patients.

10.
Chinese Journal of Hepatobiliary Surgery ; (12): 21-27, 2022.
Article in Chinese | WPRIM | ID: wpr-932728

ABSTRACT

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.

11.
Chinese Journal of Lung Cancer ; (12): 118-123, 2022.
Article in Chinese | WPRIM | ID: wpr-928788

ABSTRACT

Lung cancer ranks the first cancer-related morbidity and mortality in China. With the development and penetration of imaging technology, increasing small pulmonary peripheral Nodules (SPPNs) have been detected. However, precise location and diagnosis of SPPNs is still a tough problem for clinical diagnosis and treatment in department of thoracic surgery. With the development of electromagnetic navigation bronchoscopy (ENB), it provides a novel minimally invasive method for the diagnosis and treatment of SPPNs. In this review, we summarized the application and progress of ENB in preoperative positioning, diagnosis, and local treatment, then, discussed the clinical application of ENB in the hybrid operating room.
.


Subject(s)
Humans , Bronchoscopy/methods , Electromagnetic Phenomena , Lung Neoplasms/surgery , Multiple Pulmonary Nodules/diagnosis , Thoracic Surgery
12.
Chinese Journal of Hepatobiliary Surgery ; (12): 486-490, 2022.
Article in Chinese | WPRIM | ID: wpr-956989

ABSTRACT

Objective:To study the risk factors of very early recurrence (VER, within 3 months) after R 0 resection of hepatocellular carcinoma (HCC), and to establish a predictive model. Methods:Of 427 HCC patients [with 368 males, 59 females, aged (52.7±12.1) years] who developed early recurrence (within 2 years) after R 0 resection from January to December 2008 at Zhongshan Hospital, Fudan University were enrolled in the test cohort. Another 590 patients [with 525 males, 65 females, aged (54.7±11.0) years] who underwent R 0 resection from January to June 2009 were enrolled in the validation cohort. Risk factors were investigated and a predictive model was established. Results:In the test cohort, 126 patients (29.5%) developed VER and their survival outcomes were extremely poor. Serum α-fetoprotein (AFP) level >827 μg/L, multiple tumors, microvascular invasion (MVI) and tumor number were independent risk factors for VER. A new predictive model (0.809·AFP+ 1.262·tumor number+ 0.983·MVI) was established by logistic regression in predicting VER after surgery. The receiver operating characteristic curve showed that the area under the curve (AUC) in predicting VER was 0.722 (95% CI: 0.669-0.774, P<0.001). In the validation cohort, the AUC of this model was 0.785 (95% CI: 0.715-0.855, P<0.001). Conclusions:A high AFP level, multiple tumors, and MVI were independent risk factors for VER of HCC after R 0 resection. The prediction model consisting of these three factors demonstrated robustness and it has the potential in clinical application.

13.
Chinese Pharmacological Bulletin ; (12): 450-454, 2021.
Article in Chinese | WPRIM | ID: wpr-1014380

ABSTRACT

Aging is one of the most important risk factors for human diseases such as cancer, cardiovascular diseases, diabetes and neurodegenerative diseases, and many aging diseases are related to cellular aging. Cells show profound phenotypic changes during aging, which are driven by changes in metabolism, chromatin organizationand transcriptional activity. A significant feature of aging is the secretion of inflammatory mediators, including various cytokines, chemokines, extracellular matrix proteins and growth factors, collectively known as the aging-related secreted phenotype (SASP). By secreting SASP, senescent cells have important effects on many biological processes, such as wound healing, tissue repair, tumor formation, or in vivo reorganization. In addition, the inflammatory response associated with SASP is considered to be the basis of aging-related diseases, and the discovery of new targets to control the response of aging effects is crucial. Recent scientific advances have shown that innate immune responses, particularly those involving the cGAS-STING pathway, trigger SASP. In this article, we review the biological function and regulatory mechanism of SASP through the cGAS-STING signaling pathway in aging diseases.

14.
Chinese Pharmacological Bulletin ; (12): 171-175, 2021.
Article in Chinese | WPRIM | ID: wpr-1014311

ABSTRACT

Liver fibrosis is one of the main diseases with high morbidity and mortality worldwide. It is the common pathological results of several chronic irritant disease such as viral hepatitis ,alcohol abuse, autoimmune diseases, metabolic diseases and cholestatic liver diseases and will further develop into cirrhosis ,liver failure, portal hypertension and even death. The excessive accumulation of extracellular matrix (ECM) that leads to disorder of liver structure is the main factor in the development of liver fibrosis. MicroRNAs are a class of 2225 nt endogenous noncoding small RNAs. Sufficient studies have shown that the abnormal expression of microRNAs is closely related to the progression of liver fibrosis. In this review, we summarize the regulatory effects of microRNAs discovered in recent years on the activation ,proliferation apoptosis and senescence of HSCs in liver fibrosisand the underlying mechanisms, putting forward the prospect.

15.
Chinese Journal of Thoracic and Cardiovascular Surgery ; (12): 635-640, 2021.
Article in Chinese | WPRIM | ID: wpr-912338

ABSTRACT

Small cell lung cancer carries the worst prognosis among lung cancer. The current guidelines only recommend surgical treatment for patients in the Ⅰ-ⅡA stage, but surgical treatment is often in a neglected position in clinical practice. More and more recent studies have focused on this aspect. This article reviews the recent research literatures and reviews the progress of surgery in the multidisciplinary treatment of small cell lung cancer.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 28-34, 2021.
Article in Chinese | WPRIM | ID: wpr-906296

ABSTRACT

Objective:To investigate the possible mechanism of Wenjing Tongluo decoction (WTD) in alleviating articular cartilage defect in knee osteoarthritis (KOA) and delaying joint degeneration. Method:The KOA model was established by anterior cruciate ligament transection (ACLT). Mice were classified into sham-operated group, model group, WTD high-dose and low-dose groups, and positive control group. Four weeks after modeling, WTD groups and the positive control group were given WTD (80, 20 g·kg<sup>-1</sup>) and glucosamine sulfate capsules (0.29 g·kg<sup>-1</sup>), respectively, and the sham-operated group and model group received normal saline of the equivalent volume. After continuous intervention for 4 weeks, hemoxylin-eosin (HE) staining was used to observe the morphological changes of cartilage and Mankin scoring system was employed to score the knee cartilage. Western blot was combined with Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) to detect the protein and mRNA levels of vascular endothelial growth factor <italic>α</italic> (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-related kinase 1/2 (ERK1/2) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4). Result:The Mankin score in the model group increased as compared with that in the sham-operated group (<italic>P</italic><0.01). Compared with the model group, administration groups demonstrated alleviated articular cartilage defect and low Mankin score (<italic>P</italic><0.01), but there was no statistical significance in Mankin score between the WTD groups and positive control group. The protein and mRNA levels of VEGFA, VEGFR2, ERK1/2, and ADAMTS4 in the model group were significantly higher than those in the sham-operated group (<italic>P</italic><0.01). The protein expression of VEGFA and ERK1/2 was inhibited in each administration group as compared with that in the model group (<italic>P</italic><0.01), and the inhibition in the positive control group was stronger than that in the WTD low-dose group (<italic>P</italic><0.05) but weaker than that in the WTD high-dose group (<italic>P</italic><0.01). Glucosamine Sulfate capsules suppressed the expression of VEGFR2 and ADAMTS4 to the extent the same with low-dose WTD but weaker than the high-dose WTD (<italic>P</italic><0.05). Conclusion:WTD can relieve the articular cartilage injury in KOA mice, and the mechanism may be related to VEGF/VEGFR2/ERK1/2 signaling pathway.

17.
Gut and Liver ; : 500-516, 2021.
Article in English | WPRIM | ID: wpr-898444

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it has diverse etiologies with multiple mechanisms. The diagnosis of HCC typically occurs at advanced stages when there are limited therapeutic options. Hepatocarcinogenesis is considered a multistep process, and hepatic macrophages play a critical role in the inflammatory process leading to HCC. Emerging evidence has shown that tumor-associated macrophages (TAMs) are crucial components defining the HCC immune microenvironment and represent an appealing option for disrupting the formation and development of HCC. In this review, we summarize the current knowledge of the polarization and function of TAMs in the pathogenesis of HCC, as well as the mechanisms underlying TAM-related anti-HCC therapies. Eventually, novel insights into these important aspects of TAMs and their roles in the HCC microenvironment might lead to promising TAM-focused therapeutic strategies for HCC.

18.
Chinese Journal of Digestive Surgery ; (12): 197-204, 2021.
Article in Chinese | WPRIM | ID: wpr-883228

ABSTRACT

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

19.
Chinese Journal of Applied Clinical Pediatrics ; (24): 1138-1142, 2021.
Article in Chinese | WPRIM | ID: wpr-907918

ABSTRACT

Objective:To summarize the causes of death and severe complication in the early diagnosis of children with neuroblastoma (NB), and to analyze the relative factors of early death of children with NB, so as to raise awareness and reduce early mortality by early detection and early intervention.Methods:Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively, and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients, immediate causes of death, complications, time elapsed between death and diagnosis, whether to receive chemotherapy and other information were collected.Results:A total of 654 cases were included for diagnosis, treatment and follow-up, 31 cases of which died in early stage, accounting for 4.7% of the total.The major complication were pulmonary infection in 18 cases (58.1%) and bone marrow suppression after chemotherapy in 17 cases (54.8%), tumor rupture hemorrhage in 16 cases (51.6%), multiple organ failure in 8 cases (25.8%). Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis: there were statistical differences between early death group and non-early death group in risk grouping ( P=0.006 6), bone marrow invasion ( P=0.020 7), site of primary tumor ( P=0.016 7), age ( P=0.003 3), lactate dehydrogenase (LDH) level ( P<0.000 1), neuron-specific enolase (NSE) level ( P<0.000 1), serum ferritin level ( P=0.016 0), D dimer level ( P<0.000 1), fibrinogen level ( P=0.002 7), diameter of tumor ( P<0.000 1), hemoglobin ( P<0.000 1), platelet level ( P<0.000 1), serum albumin level ( P<0.000 1). Multiple-factor analysis: age younger than 30 months, OR=2.824 (95% CI: 1.084-7.359), LDH level greater than 1 004 IU/L, OR=6.991 (95% CI: 2.135-22.887), albumin level less than 36 g/L, OR= 65.237 (95% CI: 2.024-13.545), hemoglobin level less than 92 g/L, OR=5.358 (95% CI: 2.024-13.545), platelet level less than 192×10 9/L, OR=3.554 (95% CI: 1.267-9.965). Conclusions:Strengthening vital signs detection after admission, identifying severe life-threatening complications such as rupture of tumors as early as possible, implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation, and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.

20.
Gut and Liver ; : 500-516, 2021.
Article in English | WPRIM | ID: wpr-890740

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it has diverse etiologies with multiple mechanisms. The diagnosis of HCC typically occurs at advanced stages when there are limited therapeutic options. Hepatocarcinogenesis is considered a multistep process, and hepatic macrophages play a critical role in the inflammatory process leading to HCC. Emerging evidence has shown that tumor-associated macrophages (TAMs) are crucial components defining the HCC immune microenvironment and represent an appealing option for disrupting the formation and development of HCC. In this review, we summarize the current knowledge of the polarization and function of TAMs in the pathogenesis of HCC, as well as the mechanisms underlying TAM-related anti-HCC therapies. Eventually, novel insights into these important aspects of TAMs and their roles in the HCC microenvironment might lead to promising TAM-focused therapeutic strategies for HCC.

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