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Objective: Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro. This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) recurrent or metastatic breast cancer. Methods: Patients were intramuscularly administered fulvestrant 500 mg (day 1 per cycle for 28 days) and oral vinorelbine (60 mg/m2 on days 1, 8, and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, objective response rate, disease control rate, duration of response, and safety. Results: A total of 38 patients with HR+/HER2− advanced breast cancer included in the study were followed up for a median time of 25.1 months. The overall median PFS was 9.86 months [95% confidence interval (CI) 7.2–23.13], and the median PFS of the first-line and the second-line treatment population was 20.73 months (95% CI 9.82 to NR) and 4.27 months (95% CI 3.68 to NR), respectively. Most adverse events reported were of grade 1/2, and none were of grade 4/5. Conclusions: This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2− recurrent and metastatic breast cancer. The combination chemo-endocrine therapy was efficacious, safe, and promising for patients with HR+/HER2− advanced breast cancer.

OBJECTIVE The correlation between the spinopelvic type and morphological characteristics of lumbar facet joints in patients with degenerative lumbar spondylolisthesis (DLS) was investigated. METHODS One hundred forty-two patients with L4 DLS were enrolled (DLS group), and 100 patients with lumbar disc herniation without DLS were selected as the control group (i.e., non–lumbar spondylolisthesis [NL] group). Morphological parameters of L4–5 facet joints and L4–5 disc height and angle were measured on 3D reconstructed CT images; namely, the facet joint angle (FJA), pedicle–facet joint angle (PFA), facet joint tropism, and facet joint osteoarthritis (OA). The L4 slip percentage, sacral slope, and lumbar lordosis were measured on radiographs. Patients in the DLS and NL groups were divided into 4 subgroups according to Roussouly classification (types I, II, III, and IV). RESULTS In the DLS and NL groups, as the spinopelvic type changed from type II to type IV, the facet joint morphology showed a gradual sagittal orientation in the FJA, a gradual horizontal orientation in the PFA, a gradual severity in OA, and a gradual increase in the slip percentage, but changes were completely opposite from type I to type II. Additionally, compared with the NL group, the facet joint morphology in the DLS group had more horizontal orientation in PFA, more sagittal orientation in the FJA, and the facet joint tropism and OA were more severe. CONCLUSIONS Facet joint morphology was correlated with spinopelvic type in the slip segment of DLS. Facet joint morphology was part of the joint configuration in different spinopelvic types, not just the result of joint remodeling after DLS. Moreover, morphological changes of the facet joints and DLS interacted with each other. Additionally, morphological remodeling of the facet joints in DLS played an important role in spinal balance and should be taken into consideration when designing a surgical approach.

Fargesia, the largest genus within the temperate bamboo tribe Arundinarieae, has more than 90 species mainly distributed in the mountains of Southwest China. The Fargesia bamboos are important components of the subalpine forest ecosystems that provide food and habitat for many endangered animals, including the giant panda. However, species-level identification of Fargesia is difficult. Moreover, the rapid radiation and slow molecular evolutionary rate of Fargesia pose a significant challenge to using DNA barcoding with standard plant barcodes (rbcL, matK, and ITS) in bamboos. With progress in the sequencing technologies, complete plastid genomes (plastomes) and nuclear ribosomal DNA (nrDNA) sequences have been proposed as organelle barcodes for species identification; however, these have not been tested in bamboos. We collected 196 individuals representing 62 species of Fargesia to comprehensively evaluate the discriminatory power of plastomes and nrDNA sequences compared to standard barcodes. Our analysis indicates that complete plastomes have substantially higher discriminatory power (28.6%) than standard barcodes (5.7%), whereas nrDNA sequences show a moderate improvement (65.4%) compared to ITS (47.2%). We also found that nuclear markers performed better than plastid markers, and ITS alone had higher discriminatory power than complete plastomes. The study also demonstrated that plastomes and nrDNA sequences can contribute to intrageneric phylogenetic resolution in Fargesia. However, neither of these sequences were able to discriminate all the sampled species, and therefore, more nuclear markers need to be identified.

Patients with higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) unfit for hematopoietic stem cell transplantation have poor outcomes. Novel therapies that provide durable benefit with favorable tolerability and clinically meaningful improvement in survival are needed. T-cell immunoglobulin domain and mucin domain-3 (TIM-3) is an immuno-myeloid regulator expressed on immune and leukemic stem cells in myeloid malignancies. Sabatolimab is a novel immunotherapy targeting TIM-3 with a potential dual mechanism of reactivating the immune system and directly targeting TIM-3+ leukemic blasts suppressing the growth of cancer cells. Here, we describe the aims and design of the phase III STIMULUS-MDS2 trial, which aims to demonstrate the potential for sabatolimab plus azacitidine to improve survival for patients with higher-risk MDS and CMML-2 (NCT04266301). Clinical Trial Registration: NCT04266301 ( ClinicalTrials.gov )

The reservoir is an important component of hydraulic projects for supplying water to the city. For guaranteeing reservoir safe operation, stepped spillways are often used to discharge the flood from the reservoir. But under large unit discharges, cavitation erosion and low energy dissipation may occur on stepped spillways, which possibly leads to the hydraulic structures being instable and the reservoir outwork for water supply. Herein, an orifice plate is introduced as a pre-aeration device for the stepped spillways to avoid cavitation damage. To detail the effect of orifice plate on the flow over the stepped spillways, experiments were conducted. The results demonstrate that the orifice plate contracted the flow into a jet. Large amounts of air were entrained, and cavitation damage could be avoided according to the air concentration distributions along the stepped spillways. The orifice plate also significantly increased the energy dissipation of stepped spillways. Further, flow depth before the orifice plate increased because of flow block, and was emphatically discussed for providing a calculation formula to estimate the jet trajectory.

Advanced safe battery storage systems with health prognostic performance are vital for electric vehicles. Various faults of lithium-ion batteries are usually undetectable in their early stage due to their concealment and graduality. This paper presents a real-time fault diagnosis and isolation scheme for real-scenario batteries using the normalized discrete wavelet decomposition. The early frequency-domain features of the fault signals are extracted utilizing the high-frequency detail wavelet components, and a multi-level fault prognosis strategy is developed considering complex charging/driving characteristics under real-vehicle operating conditions. The verification results, implemented on loose wire connection batteries and real-scenario thermal runaway batteries, demonstrate that the proposed method can accurately extract and locate the hidden fault signals even under small magnitudes, as well as effectively detecting and isolating battery faults before thermal runaway. Furthermore, significant reliability and stability of the proposed method are verified on more real-vehicle operation data, enabling online monitorable and traceable of battery faults before triggering thermal runaway, safeguarding drivers and passengers in real-world vehicular operation.

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse event of anticancer drugs. In recent years, the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents. Due to the diverse clinical manifestations and the lack of specific diagnostic criteria, DILD is difficult to diagnose and may even become fatal if not treated properly. Herein, a multidisciplinary group of experts from oncology, respiratory, imaging, pharmacology, pathology, and radiology departments in China has reached the “expert consensus on the diagnosis and treatment of anticancer DILD” after several rounds of a comprehensive investigation. This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening, diagnosis, and treatment of anticancer DILD. This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Refractory or relapsing metastatic triple-negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate, targeting human trophoblast cell-surface antigen 2 (Trop-2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. 80 female Chinese patients (median age 47.6 years; range 24-69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0-8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06-50.30) and 43.8% (95% CI: 32.68- 55.30) of patients, respectively. The median PFS was 5.55 months (95% CI: 4.14-N/A). SG-related Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%), and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pre-treated Chinese patients with mTNBC. The observed safety profile was generally manageable.

Plant cells contain only small amounts of mitochondrial DNA, with the genomic information shared among multiple mitochondria. The biological relevance and molecular mechanism underlying this hallmark of plant cells has been unclear. Here, we report that Arabidopsis thaliana plants exhibited significantly reduced growth and mitochondrial dysfunction when the mitochondrial DNA copy number was increased to the degree that each mitochondrion possessed DNA. The amounts of mitochondrion-encoded transcripts increased several fold in the presence of elevated mitochondrial DNA levels. However, the efficiency of RNA editing decreased with this excess of mitochondrion-encoded transcripts, resulting in impaired assembly of mitochondrial complexes containing mitochondrial DNA-encoded subunits, such as respiratory complexes I and IV. These observations indicate the occurrence of nuclear-mitochondrial incompatibility in the cells with increased amounts of mitochondrial DNA and provide an initial answer to the fundamental question of why plant cells have much lower mitochondrial DNA levels than animal cells. We propose that keeping mitochondrial DNA levels low moderates nuclear-mitochondrial incompatibility and that this may be a crucial factor driving plant cells to restrict the copy numbers of mitochondrial DNA. This article is protected by copyright. All rights reserved.

Controllable liquid transport through the deformation of shape memory microcolumns in an open-channel microfluidic chip.

TM SAs-optimized CNNS have been synthesized for the neutral electrosynthesis of H2O2. Compared with CNNS, the selectivity of Ni0.10 SA/CNNS for H2O2 increased from 61% to 98%. The H2O2 production rate of Ni0.10 SA/CNNS is 503 mmol gcat−1 h−1.

The hydrogen spillover strategy was demonstrated to enhance the HER activity of Ru in alkaline electrolytes through Co doping into NiSe. 1.5 wt% Ru–Ni0.85Co0.15Se/NF with a smaller |ΔΦ| value showed a superior HER performance and stability.

The association between betaine and hypertension risk remains uncertain. Few prospective studies were originally designed to investigate this association.

We develop a new fluorescent biosensor for flap endonuclease 1 assay based on CRISPR/Cas12-enhanced single-molecule counting.

Polygonum viviparum L. (PV) is a widely used resource plant with high medicinal, feeding and ecological values.

To build and validate a multi-parametric MRI (mpMRI)-based radiomics nomogram for early prediction of treatment response to neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer.Baseline MRI were retrospectively enrolled from 141 patients with gastric adenocarcinoma who received NAC followed by radical gastrectomy. According to pathologic response of tumor regression grading (TRG), patients were labeled as responders (TRG = 0 + 1) and non-responders (TRG = 2 + 3) and further divided into a training (n = 85) and validation dataset (n = 56). Radiomics score (Radscore) were built from T2WI, ADC, and venous phase of dynamic-contrasted-enhanced MR imaging. Clinical information, laboratory indicators, MRI parameters, and follow-up data were also recorded. According to multivariable regression analysis, an mpMRI radiomics nomogram was built and its predictive ability was evaluated by ROC analysis. Decision curve analysis was applied to evaluate the clinical usefulness. Kaplan-Meier survival curves based on the nomogram were used to estimate the progression-free survival (PFS) and overall survival (OS) in the validation dataset.Both single sequence-based Radscores and mpMRI radiomics nomogram were associated with pathologic response (p0.001). The nomogram achieved the highest diagnostic ability with area under ROC curve of 0.844 (95% CI, 0.749-0.914) and 0.820 (95% CI, 0.695-0.910) in the training and validation datasets. The hazard ratio of the nomogram for PFS and OS prediction was 2.597 (95% CI: 1.046-6.451, log-rank p = 0.023) and 2.570 (95% CI: 1.166-5.666, log-rank p = 0.011).The mpMRI-based radiomics nomogram showed preferable performance in predicting pathologic response to NAC in LAGC.• This study investigated the value of multi-parametric MRI-based radiomics in predicting pathologic response to neoadjuvant chemotherapy in locally advanced gastric cancer. • The nomogram incorporating T2WI Radscore, ADC Radscore, and DCE Radscore as well as Borrmann classification outperformed the single sequence-based Radscore. • The nomogram also exhibited a promising prognostic ability for patient survival and enriched radiomics studies in gastric cancer.

Background: The high cost, limited availability, and perceived invasiveness of amyloid PET and cerebrospinal fluid biomarkers limit their use for the diagnosis of Alzheimer’s disease. Objective: The present study aimed to assess the associations of mild cognitive impairment (MCI) with circulating amyloid-β (Aβ), methionine circulating metabolites (MCMs), and their downstream products, and to develop a nomogram based on these easily accessible blood indexes for the individualized prediction of MCI risk in older adults. Methods: In this nested case-control study, we recruited 74 MCI patients and, for each, 3 matched controls (n = 222) within the context of the Tianjin Elderly Nutrition and Cognition (TENC) cohort, a population-based prospective study in China. Concentrations of Aβ, MCMs, and their circulating downstream factors (i.e., leukocyte telomere length and inflammatory cytokines) were evaluated in fasting blood sample using standard procedures. We constructed a nomogram for MCI harnessed multivariable logistic models incorporating variables selected in the Lasso regression. Results: Among the many biomarkers examined, the final prediction nomogram retained only 3 factors: Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio. The model achieved favorable discrimination, with a C-statistic of 0.75 (95% confidence interval 0.69–0.81) in internal validation after adjustment of optimism. The calibration accuracy was satisfactory; the Brier score of the model was 0.161 in internal validation after adjustment of optimism. Conclusion: his study presents an individualized prediction nomogram incorporating only three blood biomarkers (i.e., Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio), which can be conveniently utilized to facilitate early identification and the development of high-risk prevention strategies for MCI in older adults.

Double tract reconstruction (DTR) is the main digestive tract reconstruction method after proximal gastrectomy (PG). Single tract jejunal interposition (STJI) derived from the double tract reconstruction is also increasingly used in clinical practice. However, there is still a great controversy as to which of the two reconstruction methods can achieve better results. In this study, we systematically reviewed studies on DTR and STJI after PG and performed a meta-analysis. We searched PubMed, Embase, and Cochrane Library databases for clinical studies comparing DTR and STJI after PG to December 2021 without language restriction. Review Manager (version5.4) software was used to perform meta-analysis on operative outcomes, postoperative complications and nutritional outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42022301455). Five randomized controlled trials involving 453 patients were included in the meta-analysis. There were no significant differences between DTR and STJI in terms of intraoperative blood loss, postoperative hospital stay, incidence of reflux esophagitis, anastomotic complications and total complications. The operation time of STJI group was longer than that of DTR group [WMD - 0.79; 95% CI (- 1.55, - 0.03)] [heterogeneity: χ

Background. Irritable bowel syndrome (IBS) is a clinical disease mainly characterized as a syndrome of abdominal pain and discomfort, which frequently occurs in humans aged 20–50. Abdomen massage is of great medical significance for the health of the human body, including promoting intestinal peristalsis, relieving constipation, and facilitating weight loss. However, its potential benefits in alleviating IBS and the underlying mechanisms remain elusive. Methods. In this study, we established an IBS model in rats to evaluate the effects of abdomen massage. Forty male Sprague Dawley (SD) rats were randomly assigned into 4 groups: the normal (control) group, IBS group, abdominal massage group, and abdominal massage + ketotifen treatment group (n = 10 rats in each group). Abdominal massage was performed once a day for 5 minutes for 14 days. On day 14, the rats were euthanized and the tissues were analyzed by transmission electron microscopy (TEM), immunohistochemistry or immunofluorescence staining, and laser confocal focus to visualize the micromorphology of the intestinal mucosa. The expression of TRPV1 and the release of trypase were determined by RT-qPCR and western blot. Results. We found that compared with the control group, the mast cells in the IBS group were significantly increased and the increased MC was partially decreased by an abdominal massage with or without ketotifen treatment. We also found that TRPV1 was upregulated in the IBS group. Abdominal massage with or without ketotifen treatment could attenuate the upregulation of TRPV1 in IBS. Mechanically, results of IHC and western Blot suggested that abdominal massage reduces the sensitivity of IBS by regulating the trypase-PAR2-PKCε pathway. Conclusion. Overall, our results suggested that abdominal massage produces a beneficial effect in improving the symptoms of IBS through reducing mast cell recruitment and attenuating the trypase-PAR2-PKCε pathway. Ketotifen could promote the effect of abdominal massage on IBS treatment, which can serve as a potential therapeutic strategy for IBS.

Transthyretin cardiac amyloidosis (ATTR-CA) has been realized as an important cause of heart failure with preserved ejection fraction (HFpEF). We aim to provide insights into its prevalence in Chinese HFpEF patients, which is not known to date, using increased wall thickness (IWT) score by echocardiography.Consecutive patients with HFpEF (EF ≥ 40%) and IWT (≥12 mm) were prospectively screened. Echocardiography was performed, and the IWT score incorporated relative wall thickness, E/e' ratio, longitudinal strains, and tricuspid annular plane systolic excursion, and septal apical-to-base ratio was calculated. ATTR-CA was defined as score ≥8 in the absence of serum and urine free light chain.Six hundred twenty-four HFpEF patients from January 2019 to December 2021 were enrolled, of which 65.2% were males and the median (interquartile range [IQR]) age was 66 (IQR 57, 73) years. Thirty-three patients (5.3%, 95% CI 3.5-7.0%) were with score ≥8, and 33.3% were females. They were younger (58 vs. 69 years, P 0.001), had higher NT-proBNP (6525.0 vs. 1741.5 pg/mL, P 0.001) and troponin I (105.2 vs. 27.7 pg/mL, P = 0.001) level, and lower LVEF (47% vs. 57%, P 0.001) compared with the patients with score5. In the internal cohort (82 patients) who had undergone scintigraphy, the IWT score ≥8 was shown to have a sensitivity of 85.7% (95% CI 56.2-97.5%) and a specificity of 92.6% (95% CI 83.0-97.3%) for diagnosing CA, and the IWT score5 had great accuracy in excluding CA with the negative predictive value of 100%, supporting the clinical usefulness of the IWT score to guide further dedicated testing for ATTR-CA.The IWT score by echocardiography was an excellent tool for screening ATTR-CA in HFpEF. In Chinese HFpEF patients associated with a hypertrophic phenotype, the proportion of highly suspected ATTR-CA as detected by IWT score ≥8 was 5.3%, lower than the reported prevalence of ATTR-CA in non-Asian patients with the disease.