Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

Dynamic characteristics of net anthropogenic phosphorus input to the upper Yangtze River Basin from 1989 to 2019: Focus on the phosphate ore rich area in China.

Phosphorus (P), a non-renewable essential resource, faces heavy exploitation and contributes to eutrophication in aquatic environments. Assessing P input is vital for a healthier P cycle in the Upper Yangtze River (UYR), a phosphate ore rich basin, where P mining and P chemical enterprises have prominent pollution problems. This study modified the net anthropogenic phosphorus input (NAPI) model to include ore mining P input (Pore). We analyzed the evolutionary characteristics of P input in five sub-basins of UYR from 1989 to 2019 using prefecture-level data, and assessed the uncertainty of the data. NAPI in all sub-basins exhibited an upward and then downward trend during 1989-2019, with the inflection point occurring in 2015 or 2016, showing a net increase of about 1.1 times (568-1162 kg P km-2 yr-1) in the whole UYR basin. Among the components of NAPI, P fertilizer inputs (Pfer) and food/non-food and feed P inputs (Pf/nf&feed) contributed comparably, though the growth rate of Pfer was most notable basin-wide. Pore proportion increased significantly (about 3-fold), with a peak of 20%, especially in Wujiang sub-basin. The multi-year (1989-2019) average NAPI in UYR rose sequentially from west to east, with hotspot areas mainly concentrated in the Sichuan-Chongqing urban agglomeration and cities of Hubei province. The regional P input closely related to the population density and the level of agricultural development, certainly the phosphate mining was also unignorable. This study emphasizes that based on current status of NAPI development in UYR, targeted management for different regions should focus on improving agricultural P use efficiency and rational exploitation of P mineral resources.

Macrophages release IL11-containing filopodial tip vesicles and contribute to renal interstitial inflammation.

Macrophage filopodia, which are dynamic nanotube-like protrusions, have mainly been studied in the context of pathogen clearance. The mechanisms by which they facilitate intercellular communication and mediate tissue inflammation remain poorly understood. Here, we show that macrophage filopodia produce a unique membrane structure called "filopodial tip vesicle" (FTV) that originate from the tip of macrophages filopodia. Filopodia tip-derived particles contain numerous internal-vesicles and function as cargo storage depots via nanotubular transport. Functional studies indicate that the shedding of FTV from filopodia tip allows the delivery of many molecular signalling molecules to fibroblasts. We observed that FTV derived from M1 macrophages and high glucose (HG)-stimulated macrophages (HG/M1-ftv) exhibit an enrichment of the chemokine IL11, which is critical for fibroblast transdifferentiation. HG/M1-ftv induce renal interstitial fibrosis in diabetic mice, while FTV inhibition or targeting FTV IL11- alleviates renal interstitial fibrosis, suggesting that the HG/M1-ftvIL11 pathway may be a novel mechanism underlying renal fibrosis in diabetic nephropathy. Collectively, FTV release could represent a novel function by which filopodia contribute to cell biological processes, and FTV is potentially associated with macrophage filopodia-related fibrotic diseases. Video Abstract.

Organising pneumonia caused by hormone (tamoxifen) therapy after radiotherapy for breast cancer: a case report and review of the literature.

Background: Five-year treatment with tamoxifen (TAM) has been the traditional standard of care for breast cancer. Organising pneumonia (OP) is a rare but significant complication of radiation therapy for breast cancer. The effect of TAM leading to OP has not yet been clearly documented. Case Description: This report describes the case of a 38-year-old female who developed progressive aggravation of round-like patchy bilateral pulmonary infiltrated with a reverse halo sign but without any clinical symptoms 5 months after TAM therapy, following breast-conserving surgery and radiotherapy (RT) for breast carcinoma. A lung biopsy was performed and revealed a histological pattern of OP. TAM therapy was discontinued, and subsequent gradual radiological improvement was observed. As there was no proof for TAM had caused the incident, TAM was re-administrated. Eight months after reinstitution of TAM, the same patchy migratory bilateral pulmonary infiltrated with reverse halo sign was found on chest CT with the patient claiming no discomforts nor any clinical symptoms. The diagnosis of TAM-related OP was made based on the exclusion of other causes and recurrence with the re-administration of TAM. The multidisciplinary team (MDT) concluded that TAM should be withdrawn and a "wait-and-see" approach was taken after a comprehensive assessment, instead of altering the medication or performing prophylactic mastectomy. Conclusions: The withdrawal and rechallenge of TAM strongly suggest that it may play a role as a cofactor in the occurrence of OP after RT for breast cancer, and RT may also be a cofactor in the occurrence of OP. It is extremely important to be alerted to the possibility of OP after concurrent or sequential hormonal therapy and RT.

Facile one-precursor and one-pot synthesis of Girard's reagent T-based carbon dots for bacteria-resistant and anti-biofilm applications.

Based on the promising development of carbon dots in antibacterial applications, Girard's reagent T-based carbon dots (GRT-CDs) with a mean size of 2.41 nm and excellent antibacterial performance were synthesized through a one-step method. The minimum inhibitory concentration ofGRT-CDswas 200 µg ml-1for bothEscherichia coli (E. coli)andStaphylococcus aureus (S. aureus). The bacterial growth curves showed that the inhibitory effect ofGRT-CDson bacterial multiplication was strongly concentration-dependent. The bactericidal effect ofGRT-CDswas further demonstrated by the large differences in bacterial fluorescence staining plots. Zeta potential measurements and scanning electron microscope images indicated thatGRT-CDsformed complexes with bacteria, which affected the normal physiological activities of bacteria, causing their rupture and death. In addition,GRT-CDsefficiently inhibited biofilm formation and removed mature biofilms. Furthermore,GRT-CDsalso exhibited a remarkable inhibitory activity on MRSA. Cytotoxicity experiments showed thatGRT-CDshad good cytocompatibility and even promoted cell proliferation at low concentrations. Therefore, theGRT-CDsobtained from a one-precursor and one-pot synthesis show good prospects for antibacterial applications.

Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors vs. erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis.

Objective: To compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Method: Five electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method. Results: Of 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level-raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = -49.09, 95% CI: -98.13 to -0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%). Conclusion: For NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.

A prospective, open-label, multicenter phase IV clinical trial on the safety and efficacy of lobaplatin-based chemotherapy in advanced breast cancer.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2-5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

The effects of cognitive behavioral therapy in women with polycystic ovary syndrome: A meta-analysis.

Background: Cognitive behavioral therapy (CBT) has well-characterized benefits in alleviating diseases associated with depression, anxiety, and obesity, resulting in a marked improvement in the patient's quality of life. There are some studies regarding the effects of CBT on patients with polycystic ovary syndrome (PCOS). However, there is still no report of a meta-analysis for systematic assessment. Objectives: This study aimed to evaluate the effectiveness of CBT in improving weight loss, anxiety, depression, life quality, compliance, and pregnancy outcomes in patients with PCOS. Methods: Studies regarding CBT related to PCOS in PubMed, Cochrane library, Embase, ClinicalTrials.gov, CNKI, and WANFANG DATA were searched for up to 19 November 2020. A random-effects model was used to perform a meta-analysis. Results: Eight trials regarding CBT compared with lifestyle modification and routine treatments were included. No differences in depression (SMD -1.11; 95% CI -2.28, 0.07; P > 0.05), body mass index (BMI) (SMD 0.88; 95% CI -0.94, 2.71; P > 0.05), or overall life quality (SMD 1.24; 95% CI -0.44, 2.92; P > 0.05) were evident between CBT and control groups; however, anxiety (SMD -1.12; 95% CI -2.1, -0.13; P < 0.05) and quality of life in hirsutism (SMD 0.92; 95% CI 0.48, 1.35; P < 0.05) were significantly improved. For secondary outcomes, both patient compliance and pregnancy rate were improved, but no significant change in pregnancy loss rate was identified. Conclusion: CBT exhibited obvious advantages in the alleviation of anxiety, improvement of quality of life in hirsutism, and increase of compliance and pregnancy rate in patients with PCOS. Larger and higher-quality randomized controlled trials are needed to clarify the role of CBT in PCOS. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021225856].

Effectiveness of a community-based peer support service among persons suffering severe mental illness in China.

Background: Community-based peer support service is widely and effectively deployed for persons suffering severe mental illness (SMI) in countries with well-developed outpatient mental health systems. The objective of this study is to evaluate the effectiveness of a 1-year peer service project among persons with SMI implemented in China. Methods: A total of 101 consumers (service recipients) and 66 family caregivers were recruited at baseline from communities located in Beijing and Chengdu. Severity of psychiatric symptoms, personal and social functioning, self-esteem, life satisfaction, and medication adherence were evaluated among consumers. Self-esteem, life satisfaction, anxiety, and depressive symptoms were assessed among family caregivers. Participants were reevaluated at 1 year with the same measures. Changes in outcomes from baseline to 1-year follow-up were examined using paired sample t tests or Stuart-Maxwell tests. Results: Consumers' psychiatric symptoms were decreased at 1 year (p < 0.001). Their personal and social functioning (p = 0.003) and life satisfaction (p < 0.001) were increased. There were no improvements in self-esteem (p = 0.108) and medication adherence (ps ≥ 0.827) among consumers. For caregivers, no increases were presented in outcomes at the 1-year assessment (ps ≥ 0.164). Conclusions: The findings suggest that peer support services could be sustainably implemented across China, with positive impacts on the psychiatric symptoms, social functioning, and life satisfaction of participants suffering SMI.

[Evaluation and Source Analysis of Heavy Metal Pollution in Sediments of the Yellow River Basin Based on Monte Carlo Simulation and PMF Model].

As sediment is an essential component of rivers, the enrichment of heavy metals in sediment presents a serious threat to the aquatic environment. Many industrial cities are located along the Yellow River, and heavy metal pollution is a prominent problem in these areas. Thus, the study of heavy metal pollution in sediments of the Yellow River basin is of vital significance to the safety of the Yellow River basin ecosystem. In this study, we collected data on the concentrations of heavy metals (Pb, Cd, Cr, As, Zn, Cu, Ni, and Hg) in the sediments of the Yellow River basin from 2000 to 2020. We first analyzed the spatial distribution characteristics of heavy metals based on descriptive statistics and geostatistics and then used the Monte Carlo method to evaluate the probability of the ground accumulation index(Igeo), potential ecological risk, and toxicity units. Finally, the number of pollution sources and their contribution rates were determined by combining the positive definite matrix factor (PMF) decomposition model and Pearson correlation analysis. It was found that the mean values of ω(Pb), ω(As), ω(Zn), ω(Ni), ω(Cu), ω(Hg), ω(Cr), and ω(Cd) in the Yellow River basin sediments were 26.92, 11.78, 87.17, 31.13, 24.96, 0.07, 73.36, and 0.58 mg·kg-1, which exceeded the mean soil background values in the Yellow River basin provinces by 1.27, 1.08, 1.26, 1.05, 1.09, 2.32, 1.14, and 5.95 times, respectively, among which Cd exceeded the standard by the largest factor and should be taken seriously. The Igeo was ranked as Cd>Hg>Cr>Cu>Pb>Zn>As>Ni, and Cd and Hg showed medium-severe pollution. The proportions of heavy ecological risk in sediments in the upper, middle, and lower reaches of the Yellow River basin were 18.6%, 15.7%, and 7.1%, respectively, with a decreasing trend. Heavy metals in the sediments of the Yellow River basin were in a low-toxicity state. The PMF-Pearson correlation analysis showed that the four sources of heavy metals in the Yellow River basin sediments were mining sources (42.2%), natural activities (38.3%), agricultural activities (11.6%), and electroplating wastewater (7.9%). The results of this study can provide a basis for developing relevant pollution prevention and control measures in the Yellow River basin.

Birthweight After Frozen Embryos Formed on the Fifth Day Versus the Sixth Day: A Retrospective Analysis Including 17,127 Singleton Newborns.

Background: Transferring blastocysts frozen on day 6 (D6) may adversely affect the pregnancy rate compared with day 5 (D5). Moreover, it remains unclear whether delayed embryo transfer affects neonatal birth weight. Methods: A retrospective cohort study consisting of 17,127 singleton births from single frozen embryo transfer (FET) cycles, between January 2011 and January 2020, was performed including 14,166 blastocysts frozen on D5 and 2,961 on D6. The primary outcomes of this study were neonatal birth weight and incidence of small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), and macrosomia. Results: The mean neonatal birth weight in the D5 group (3.47 ± 0.49 kg) was significantly higher compared with the D6 group (3.45 ± 0.50 kg), although the discrepancy was only 0.02 kg. Multiple linear regression analysis for birth weight between the two groups showed no statistically significant difference (ß= -0.01 t= -1.218; P>0.05). Logistic regression analysis revealed that the risks of SGA (OR 1.166; 95%CI, 0.911-1.491; P>0.05), LGA (OR 0.917; 95%CI, 0.831-1.012; P>0.05), LBW (OR 1.192; 95%CI, 0.926-1.533; P>0.05), and macrosomia (OR 0.975; 95%CI, 0.864-1.100; P>0.05) were similar in the two groups after adjusting for confounders. Conclusions: In the FET cycle, the neonatal birth weight and incidence of LGA, SGA, LBW, or macrosomia were similar between the D5 and D6 groups, suggesting that delayed blastocyst transfer would not affect the neonatal birth weight.

A luminescent Eu3+-functionalized MOF for sensitive and rapid detection of tetracycline antibiotics in swine wastewater and pig kidney.

Tetracyclines (TCs), a type of antibiotics, are widely used in human therapy and animal husbandry. Public concerns about tetracyclines residues have been raised due to their negative impact on the environment and food, causing bacterias drug resistance and human health concerns. In this work, a luminescent europium MOF (EuUCBA) is constructed via post-synthetic attachment of Eu3+ into a UiO-66 type MOF. The luminescent of EuUCBA exhibits high stability in aqueous media in the pH range of 4-11. Among 36 common veterinary drugs, the synthesized probe is highly selective and sensitive to six tetracyclines with low detection limits of 0.118 µM, 0.228 µM, 0.102 µM, 0.138 µM, 0.206 µM, and 0.078 µM for oxytetracycline (OTC), chlortetracycline (CTC), methylenetetracycline (MTC), minocycline (MOC), tetracycline (TC), and doxycycline (DOXY), respectively. Furthermore, the probe shows good anti-interference ability and fast response. Finally, EuUCBA was successfully to detect DOXY in swine wastewater and pig kidney with good recoveries. This work provides an excellent fluorescent sensor for highly selective and rapid detection of TCs residues in wastewater and complex biological samples.

Combined effects of levetiracetam and sodium valproate on paediatric patients with epilepsy: a systematic review and meta-analysis.

OBJECTIVE: To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs). METHODS: The Cochrane Library, PubMed, Web of Science, Chinese Journal Full-Text Database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and May 2021. The included literature was randomized controlled clinical trials focusing on sodium valproate combined with levetiracetam in paediatric patients with epilepsy. Two evaluators separately collected the data based on the retrieval strategy, filtered the literature in accordance with the inclusion and exclusion criteria, and summarized the literature that satisfied the criteria. The statistical programme used for the meta-analysis was Stata V14.0. RESULTS: Of 577 original titles screened, data were extracted from 7 studies (617 participants). Compared with sodium valproate alone or sodium valproate combined with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy significantly improved the overall therapeutic effect (RR=1.24, 95% CI: 1.16 to 1.33, p=0.927). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) (RR=0.54, 95% CI: 0.37 to 0.79, p=0.602). Egger's regression test of the overall therapeutic effect showed no potential publication bias (p=0.122). CONCLUSION: Based on this meta-analysis, compared with sodium valproate alone or sodium valproate with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy can significantly improve the overall therapeutic effect and simultaneously reduce the occurrence of ADR. Therefore, we recommend sodium valproate combined with levetiracetam for the therapy of paediatric patients with epilepsy.

Effects of lanthanum carbonate and calcium carbonate on cardiovascular calcification in hemodialysis patients: A systematic review and meta-analysis.

OBJECTIVE: This paper was written to systematically review and meta-analyze the evidence on the efficacy of lanthanum carbonate (LC) and calcium carbonate (CC) and the risk of cardiovascular calcification on hemodialysis (HD) patients. MATERIALS AND METHODS: The Cochrane library, PubMed, Web of Science, Chinese journal full-text database (CNKI), WANGFANG DATA, and Sino Med were searched between January 1946 and December 2020. The literature with respect to the randomized controlled clinical trial comparing LC and CC in HD patients was selected. The main outcomes include coronary artery calcification score (CACS), cardiovascular events, and serum phosphorus (mmol/L). The statistical program used for meta-analysis was Stata V14.0. RESULTS: Of 388 original titles screened, data was extracted from 9 studies (625 participants). LC can significantly reduce the progression of coronary artery calcification compared to CC (standardized mean deviation (SMD) = -0.59, 95% CI: -0.94 to -0.25, p < 0.01). The LC group had lower serum phosphorus levels (SMD = -1.35, 95% CI: -2.33 to -0.36, p < 0.01), lower serum calcium levels (SMD = -1.03, 95% CI: -1.83 to -0.23, p = 0.012), and lower fibroblast growth factor 23 (FGF-23) level (SMD = -4.80, 95% CI: -7.96 to -1.64, p = 0.003) than the CC group. The Egger regression test of CACS showed no potential publication bias (p = 0.72). CONCLUSION: Compared with CC, LC can significantly delay the process of coronary artery calcification, and at the same time reduce patients' serum phosphate, serum calcium, and FGF-23. Therefore, we recommend LC as a phosphorus-lowering drug for HD patients.

Efficacy and safety of inetetamab in combination with chemotherapy as first-line treatment of HER2-positive metastatic breast cancer: a subgroup analysis in the HOPES study.

Background: Our aim was to evaluate the efficacy and safety of inetetamab plus chemotherapy in the first-line treatment of HER2-positive metastatic breast cancer. Methods: A HOPES study was conducted on patients with HER2-positive metastatic breast cancer. Eligible patients were randomly divided into test group and control group at a 2:1 ratio. Among them, patients in test group received inetetamab plus vinorelbine. Concurrently, patients in the control group received vinorelbine. During the trial, safety evaluation was conducted every 4 weeks and efficacy evaluation was conducted every 8 weeks. As assessed by the Response Criteria Evaluation in Solid Tumors (RECIST) 1.0 criteria, the primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Safety was estimated according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. Efficacy and safety of the postoperative recurrent-metastases first-line subgroup in the HOPES registry study of inetetamab was analyzed and compared with previous clinical studies of trastuzumab in the first-line treatment of HER2-positive metastatic breast cancer. Results: In total, we included 315 patients. Among them, 114 patients in the postoperative recurrent-metastases first-line subgroup were assigned to the full analysis set (FAS) (test group, 72; and control group, 42). The test group significantly prolonged median PFS (mPFS) (11.1 vs. 3.3 months of the control group; P<0.0001). ORR and DCR were remarkably higher than the control group (ORR, 61.5% vs. 29.7% with an increase of 31.8%, P=0.0224; DCR, 93.8% vs. 59.4% with an increase of 34.4%, P=0.0003). Efficacy and safety of postoperative recurrent-metastases first-line subgroup in the HOPES study was comparable to previous clinical studies of trastuzumab as first-line treatment of HER2-positive metastatic breast cancer. Conclusions: Inetetamab has shown efficacy and safety equivalent to trastuzumab for patients in the first-line treatment of postoperative recurrence-metastases HER2-positive breast cancer, which confirms its important status and potential as first-line treatment. Inetetamab provides more first-line targeted therapy options for patients with HER2-positive metastatic breast cancer.

Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis.

OBJECTIVE: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM. METHODS: This trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint. RESULTS: We evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0-28.5; 95% confidence interval (95% CI): 2.1-8.3] months and 18 (range: 3-55; 95% CI: 12.9-23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2-11.8) monthsvs. 2.3 (95% CI: 1.2-3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6-19.5) monthsvs. 3.0 (95% CI: 1.3-4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014). CONCLUSIONS: Apatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.

Chinese expert consensus on the clinical diagnosis and treatment of advanced breast cancer (2018).

Breast cancer is the most common malignant tumor among women in the world. In 2005, there were approximately 272,000 new cases diagnosed and more than 70,000 deaths from breast cancer in China. Of the patients who are newly diagnosed with breast cancer each year, approximately 3% to 10% have distant metastases at the time of diagnosis. Of those who have early stage disease at diagnosis, from 30% to 40% will develop advanced breast cancer. The 5-year survival rate for patients with advanced breast cancer is only 20%, and the median overall survival (OS) is 2 to 3 years. Although advanced breast cancer is still difficult to cure, physicians can relieve clinical symptoms, improve quality of life, and further prolong survival through the development of new drugs and the optimization model of treatment. Patients with advanced breast cancer have their own preferences in the choice of treatment options. Moreover, there is no standard recommendation for the treatment of refractory breast cancer after multiline therapy. To offer a reference for clinicians, a Chinese expert group has analyzed, summarized, and discussed related research data on the diagnosis, treatment, and prognosis of inoperable, locally advanced breast cancer and recurrent or metastatic breast cancer and has developed the Chinese expert consensus on the clinical diagnosis and treatment of advanced breast carcinoma (2018).

Efficacy, safety and proper dose analysis of PEGylated granulocyte colony-stimulating factor as support for dose-dense adjuvant chemotherapy in node positive Chinese breast cancer patients.

For high-risk breast cancer patients with positive axillary lymph nodes, dose-dense every-two-week epirubicin/cyclophosphamide-paclitaxel (ddEC-P) regimen is the optimal postoperative adjuvant therapy. However, this regimen is limited by the grade 3/4 neutropenia and febrile neutropenia (FN). There is an urgent need to explore the efficacy, safety and proper dosage of PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) as support for ddEC-P in Chinese breast cancer patients with positive axillary lymph nodes. Prospectively, 40 women with stage IIIA to IIIC breast cancer received ddEC-P ± trastuzumab as adjuvant treatment. PEG-G-CSF was injected subcutaneously in a dose of 6 mg or 3 mg on the 2th day of each treatment cycle. With administration of PEG-G-CSF, all of the 40 patients completed 8 cycles of ddEC-P ± trastuzumab regimen without dose reductions or treatment delays. Moreover, no FN cases were observed. Further analysis showed that the proper dosage of PEG-G-CSF was 6 mg for ddEC treatment, and 3 mg for ddP treatment. PEG-G-CSF exhibits advantages compared with G-CSF in convenient of administration and tolerance for high risk Chinese breast cancer patients. More importantly, the proper dose of PEG-G-CSF for high risk Chinese breast cancer patients during ddEC-P chemotherapy may be 6 mg for ddEC treatment and 3 mg for ddP treatment.

Inhibition of glutathione metabolism attenuates esophageal cancer progression.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model. In addition, treatment with L-buthionine-sulfoximine (BSO) to deplete glutathione decreased the ESCC tumor burden in mice, thus demonstrating the critical role of glutathione metabolism in ESCC progression. BSO treatment also led to decreased cell proliferation and activation of cell apoptosis in ESCC. Finally, BSO treatment blocked NF-kB pathway activation in ESCC. Our study reveals a new pathway that regulates ESCC progression and suggests that inhibition of glutathione metabolism may be a potential strategy for ESCC treatment.