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1.
Article in Chinese | WPRIM | ID: wpr-1013360

ABSTRACT

Osteoporosis (OP) is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA (miRNA) plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation, forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases, including inflammatory diseases, metabolic diseases, and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP, mainly regulating the balance among bone construction, bone resorption, and osteoblast differentiation. Therefore, miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation, differentiation, survival, and apoptosis, reviewed and classified their mechanisms of action and targets, and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.

2.
Article in Chinese | WPRIM | ID: wpr-1019185

ABSTRACT

Neuropathic pain(NP)is caused by leision or disease of the somatic sensory nervous system,and its pathological mechanism is complex,mainly related to abnormal neural structure and function.It is hard for existing treatment methods to obtain satisfactory results.With the deepening of the study of peroxisome proliferate activation receptor-γ(PPAR-γ),its role in neuroinflammation,oxidative stress,ion channels,mitochondrial function,neuroprotection and other aspects have been discovered succes-sively,PPAR-γ may be one new target for pain prevention and treatment.This paper reviews the role of PPAR-γ in NP and related mechanisms,in order to provide new thinking for the clinical treatment of NP.

3.
Article in Chinese | WPRIM | ID: wpr-1021939

ABSTRACT

BACKGROUND:Osteoarthritis is a common chronic inflammation of joints caused by degenerative changes of articular cartilage.More and more studies have shown that mechanical stress is closely related to the development of osteoarthritis.The Hippo pathway is not only involved in the development of tissue cells,but also an effecting factor of mechanical stress,which is involved in the regulation of bone metabolism and cartilage metabolism. OBJECTIVE:Regulation of the Hippo pathway may become one of the new targets for intervention in osteoarthritis.Therefore,this paper reviewed the research on the effect of mechanical stress regulation of the Hippo pathway on osteoarthritis to provide ideas for the pathogenesis of osteoarthritis and provide a new theoretical basis for the treatment of osteoarthritis. METHODS:PubMed,Web of Science,Embase,CNKI,VIP,and WanFang databases were used for a literature search for articles published from inception to 2023 concerning the influence of mechanical stress on osteoarthritis and mechanical stress,Hippo pathway,and osteoarthritis.A total of 75 articles were finally reviewed. RESULTS AND CONCLUSION:(1)Different mechanical stresses may play different roles in cell proliferation,apoptosis and differentiation,osteoarthritis inflammation,and vascular homeostasis in osteoarthritis.(2)Hard extracellular matrix,low cell density,medium shear force,medium tensile force,and compression force can achieve cell proliferation,osteogenic differentiation,and vascular homeostasis,and inhibit inflammatory response by activating YAP/TAZ.(3)Soft extracellular matrix,high cell density,excessive shear force,excessive tensile force,and compressive force inhibit cell proliferation,enhance cartilage differentiation,disrupt vascular homeostasis,and promote inflammation through inactivation of YAP/TAZ,thus promoting the process of osteoarthritis.

4.
Article in Chinese | WPRIM | ID: wpr-1024234

ABSTRACT

Objective:To evaluate the clinical efficacy of individualized thrombolysis-assisted comprehensive intervention for deep vein thrombosis (DVT) in the lower limbs.Methods:This study included 32 patients with acute lower limb DVT diagnosed by angiography who received treatment at the Jianhu Clinical Medical College of Yangzhou University from March 2012 to November 2021. These patients first received implantation of an inferior vena cava filter. Then they were divided into a control group and an observation group based on treatment methods. The control group received thrombolytic catheterization and a routine infusion of urokinase. In the observation group, balloon dilation was performed first, and a large lumen catheter was used to draw blood clots. Subsequently, urokinase at a dose based on fibrinogen measurement was injected through a thrombolytic catheter. Swelling reduction, venous patency, and complications of the affected limbs were monitored.Results:In the control group, the difference in thigh circumference before treatment was (4.65 ± 1.06) cm, and after treatment, it was (2.76 ± 1.25) cm. In the observation group, the difference in thigh circumference before treatment was (4.73 ± 1.03) cm, and it was (1.40 ± 0.83) cm after treatment. In the control group, the difference in calf circumference before treatment was (2.24 ± 0.90) cm, and it was (1.56 ± 0.86) cm after treatment. In the observation group, the difference in calf circumference before treatment was (2.40 ± 0.83) cm, and it was (0.80 ± 0.73) cm after treatment. After treatment, the differences in thigh circumference and calf circumference between the healthy and affected sides were statistically significant ( t = 3.58, 2.67, both P < 0.05). After treatment, there was a significant difference in venous patency between the control and observation groups (34.02% [33/97] vs. 68.18% [60/88], t = 3.44, P < 0.05). After 12 months of follow-up, the Villalta scale score, which was used to evaluate post-thrombotic syndrome, was (9.23 ± 4.07) points in the control group, which was significantly different from (5.73 ± 3.39) points in the observation group ( t = 2.62, P < 0.05). Conclusion:Individualized thrombolysis-assisted comprehensive intervention is highly effective in the treatment of DVT in the lower limbs and results in few complications.

5.
Frontiers of Medicine ; (4): 119-131, 2023.
Article in English | WPRIM | ID: wpr-971625

ABSTRACT

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.


Subject(s)
Humans , Esophageal Squamous Cell Carcinoma/drug therapy , Cisplatin/metabolism , Esophageal Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Carcinoma, Squamous Cell/genetics , Growth Differentiation Factor 15/therapeutic use , Receptor, Transforming Growth Factor-beta Type II/therapeutic use , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic
6.
China Tropical Medicine ; (12): 473-2023.
Article in Chinese | WPRIM | ID: wpr-979737

ABSTRACT

@#Abstract: Objective To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

7.
Zhonghua zhong liu za zhi ; (12): 88-94, 2023.
Article in Chinese | WPRIM | ID: wpr-969810

ABSTRACT

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.


Subject(s)
Humans , Female , Breast Neoplasms/chemically induced , Paclitaxel/adverse effects , Liposomes/therapeutic use , Retrospective Studies , Treatment Outcome , Trastuzumab/therapeutic use , Capecitabine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
8.
China Medical Equipment ; (12): 166-169, 2023.
Article in Chinese | WPRIM | ID: wpr-1026424

ABSTRACT

Objective:To build a systematic,uninterrupted and all-round continuous collaborative protection strategy for network security control of gene sequencing equipment.Methods:The network transmission,electronic interface,data system and other parts were incorporated into the comprehensive consideration of network security control of gene sequencing equipment.Based on the"overall network security",the risk points that manufacturers of genetic sequencing equipment and institutions using the testing need to pay attention to and control at this stage were proposed from seven aspects including product data architecture,security capability system construction,residual risk maintenance plan,malicious attack defense,vulnerability assessment,cyber security of off-the-shelf software,and remote operation and maintenance support,and further expanded to the whole lifecycle network security control of gene sequencing equipment.Results:By sorting out the risk points of gene sequencing,a systematic,uninterrupted and all-round continuous collaborative protection strategy of network security control of gene sequencing equipment was constructed.Conclusion:Network security supervision of gene sequencing equipment is an important tool to ensure product quality.It is necessary to pay attention to comprehensive risk points in product development,production and maintenance,and network security control should be implemented throughout the whole life cycle of gene sequencing equipment.

9.
Zhonghua zhong liu za zhi ; (12): 709-716, 2023.
Article in Chinese | WPRIM | ID: wpr-1045811

ABSTRACT

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.


Subject(s)
Female , Humans , Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Chemotherapy, Adjuvant , Hormones/therapeutic use , Neoadjuvant Therapy , Paclitaxel/therapeutic use , Prospective Studies , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use , Triple Negative Breast Neoplasms/drug therapy
10.
Zhonghua zhong liu za zhi ; (12): 787-795, 2023.
Article in Chinese | WPRIM | ID: wpr-1045814

ABSTRACT

Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.


Subject(s)
Humans , Triple Negative Breast Neoplasms/pathology , DNA Repair , Mutation , Combined Modality Therapy , DNA Damage
11.
Zhonghua zhong liu za zhi ; (12): 948-954, 2023.
Article in Chinese | WPRIM | ID: wpr-1045826

ABSTRACT

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.


Subject(s)
Humans , Female , Lymphatic Metastasis , B7-H1 Antigen/metabolism , Triple Negative Breast Neoplasms/pathology , Breast Neoplasms , Osteonectin/therapeutic use , Prognosis
12.
Zhonghua zhong liu za zhi ; (12): 709-716, 2023.
Article in Chinese | WPRIM | ID: wpr-1046134

ABSTRACT

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.


Subject(s)
Female , Humans , Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Chemotherapy, Adjuvant , Hormones/therapeutic use , Neoadjuvant Therapy , Paclitaxel/therapeutic use , Prospective Studies , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use , Triple Negative Breast Neoplasms/drug therapy
13.
Zhonghua zhong liu za zhi ; (12): 787-795, 2023.
Article in Chinese | WPRIM | ID: wpr-1046137

ABSTRACT

Objective: To investigate the correlation between adjuvant chemotherapy with platinum-containing regimens and DNA damage repair (DDR) defects in early-stage triple negative breast cancer (TNBC), and to provide a basis for precise treatment of TNBC. Methods: Next-generation sequencing (NGS) testing was performed on postoperative breast cancer specimens selected from the Cancer Hospital of Chinese Academy of Medical Sciences from June 2009 to October 2015 to analyze the correlation between DDR gene variants and the efficacy of adjuvant chemotherapy with TNBC platinum-containing regimens, and thus to screen the superior population for adjuvant chemotherapy with TNBC platinum-containing regimens. The study used t-test, χ(2) test, Fisher's exact test, rank sum test and multifactorial logistic analysis to assess the associations between mutated genes and clinicopathological characteristics and prognosis, and Log-rank test and Cox proportional risk model were used for survival and correlation analysis. Results: NGS results were successfully obtained in 149 patients (74 in the platinum-containing group and 75 in the platinum-free group), with a 97.3% (145/149) DDR gene mutation rate and a median number of 4 mutations in all patients. 5-year disease-free survival (DFS) was 85.4% and 75.0% for patients with DDR gene mutations and DDR gene wild-type, respectively, without statistical difference (P=0.825). The 5-year DFS rates of patients with homologous recombination repair (HRR) pathway mutation were 84.6% in platinum-containing (TCb) group and 84.9% in platinum-free (EC-T) group (P=0.554), respectively. The 5-year DFS rates of patients with and without mutations in the platinite-containing HRR pathway were 84.9% and 85.0%, respectively (P=0.751). The number of DDR pathways with mutations and the number of DDR gene mutations were not associated with prognosis (both P>0.05). PIK3CA mutation patients in TCb group had a worse prognosis than wild-type patients (5-year DFS were 71.4% and 88.1%, P=0.037), and KMT2D mutation patients in EC-T group had a worse prognosis than wild-type patients (5-year DFS were 76.9% and 86.8%, P=0.039). Conclusions: DDR gene variation is common in TNBC, more clinical studies are needed to prove whether DDR variation can serve as effective biomarkers for treatment with platinum.


Subject(s)
Humans , Triple Negative Breast Neoplasms/pathology , DNA Repair , Mutation , Combined Modality Therapy , DNA Damage
14.
Zhonghua zhong liu za zhi ; (12): 948-954, 2023.
Article in Chinese | WPRIM | ID: wpr-1046149

ABSTRACT

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.


Subject(s)
Humans , Female , Lymphatic Metastasis , B7-H1 Antigen/metabolism , Triple Negative Breast Neoplasms/pathology , Breast Neoplasms , Osteonectin/therapeutic use , Prognosis
15.
Article in Chinese | WPRIM | ID: wpr-1009467

ABSTRACT

Bone homeostasis is based on the dynamic balance of bone formation and bone resorption. An imbalance in bone homeostasis is a major contributor to many skeletal diseases, including osteoporosis. Changes in the composition and diversity of the gut microbiota (GM) are supposed to have a significant impact on bone homeostasis and are closely correlated with changes in bone mass and bone microarchitecture. The "gut-immune" axis, which is formed by the interaction between the host intestinal immune system and GM, is essential for maintaining bone homeostasis, as well as regulating the body's immunological response and maintaining immune homeostasis throughout the intestine and body. The article reviews recent advances in the study of GM, the immune system, and their synergistic impact on bone homeostasis.


Subject(s)
Gastrointestinal Tract , Gastrointestinal Microbiome , Immune System , Bone Density , Homeostasis
16.
Zhongguo Yi Liao Qi Xie Za Zhi ; (6): 428-432, 2022.
Article in Chinese | WPRIM | ID: wpr-939761

ABSTRACT

The evolution throughout the whole supervision history of Class II/III safety and effectiveness related NMPA submission dossier requirements was studied in this study, meanwhile elaborating the revolution progress of clinical evaluation domestically. The relationship between submission dossier requirements and Essential Principles of Safety and Performance of Medical Devices as well as IMDRF relevant documents was deeply analyzed and illustrated, in order to comprehensively understanding the background and future reform direction of NMPA submission dossier requirements under the background of the government's deepening reform of medical device evaluation and approval system strategy.


Subject(s)
Humans , China , Device Approval
17.
Zhonghua zhong liu za zhi ; (12): 68-72, 2022.
Article in Chinese | WPRIM | ID: wpr-935183

ABSTRACT

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , DNA Damage , DNA Repair , Pharmaceutical Preparations , Platinum/therapeutic use , Platinum Compounds/therapeutic use , Triple Negative Breast Neoplasms/genetics
18.
Zhonghua zhong liu za zhi ; (12): 364-369, 2022.
Article in Chinese | WPRIM | ID: wpr-935222

ABSTRACT

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.


Subject(s)
Female , Humans , Breast Neoplasms/pathology , Furans/adverse effects , Ketones/adverse effects , Paclitaxel/adverse effects , Treatment Outcome , Triple Negative Breast Neoplasms/drug therapy
19.
Article in Chinese | WPRIM | ID: wpr-986571

ABSTRACT

As the first cyclin-dependent kinases 4 and 6 inhibitors, palbociclib significantly improved the survival of the patients with the hormone receptor-positive and human epidermal growth factor receptor-2 negative breast cancer. Palbociclib is a crucial landmark in the development history of antineoplastic drugs. This article reviews the mechanism of palbociclib, and summarizes the clinical trials, side effects, and the application of palbociclib.

20.
Article in Chinese | WPRIM | ID: wpr-986589

ABSTRACT

TNBC is a special type of breast cancer with strong aggressiveness and poor prognosis. Chemotherapy is still the main treatment for TNBC, due to poor efficacy of endocrine therapy and targeted therapy. However, TNBC is a kind of heterogeneous disease, so it is urgent to study the precise molecular types and explore new precision treatment. This paper will summarize the results of clinical trials and analyze treatment strategies for TNBC, including surgical treatment, radiotherapy, chemotherapy, targeted therapy and immunotherapy, in order to provide evidence for clinical management.

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