Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer.

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) is a promising therapy. However, the relationship between individual TME components, particularly cancer-associated fibroblasts (CAFs), and tumor recurrence is unclear. Here, TME heterogeneity in primary and recurrent BC is investigated using single-cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified in recurrent BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with BC recurrence is also identified. iCAFs are found to secrete FGF2, which acts on the CD44 receptor of rCSC-M, thereby maintaining tumor stemness and epithelial-mesenchymal transition. Additionally, THBS1+ monocytes, a group of myeloid-derived suppressor cells (MDSCs), are enriched in recurrent BC and interacted with CAFs. ICAM1+ iCAFs are found to secrete CCL2, which binds to CCR2 in MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, and CTGF levels in iCAFs reshape the TME in recurrent tumors. CCL2 inhibition in an in situ BC mouse model suppressed tumor growth, decreased MDSCs and Tregs, and fostered tumor immune suppression. The study results highlight the role of iCAFs in TME cell-cell crosstalk during recurrent BC. The identification of pivotal signaling factors driving BC relapse is promising for the development of novel therapies.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

Automatic depression diagnosis through hybrid EEG and near-infrared spectroscopy features using support vector machine.

Depression is a common mental disorder that seriously affects patients' social function and daily life. Its accurate diagnosis remains a big challenge in depression treatment. In this study, we used electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) and measured the whole brain EEG signals and forehead hemodynamic signals from 25 depression patients and 30 healthy subjects during the resting state. On one hand, we explored the EEG brain functional network properties, and found that the clustering coefficient and local efficiency of the delta and theta bands in patients were significantly higher than those in normal subjects. On the other hand, we extracted brain network properties, asymmetry, and brain oxygen entropy as alternative features, used a data-driven automated method to select features, and established a support vector machine model for automatic depression classification. The results showed the classification accuracy was 81.8% when using EEG features alone and increased to 92.7% when using hybrid EEG and fNIRS features. The brain network local efficiency in the delta band, hemispheric asymmetry in the theta band and brain oxygen sample entropy features differed significantly between the two groups (p < 0.05) and showed high depression distinguishing ability indicating that they may be effective biological markers for identifying depression. EEG, fNIRS and machine learning constitute an effective method for classifying depression at the individual level.

Radio- and Photosensitizing Os(II)-Based Nanocage for Combined Radio-/Chemo-/X-ray-Induced Photodynamic Therapies, NIR Imaging, and Drug Delivery.

Integration of clinical imaging and collaborative multimodal therapies into a single nanomaterial for multipurpose diagnosis and treatment is of great interest to theranostic nanomedicine. Here, we report a rational design of a discrete Os-based metal-organic nanocage Pd6(OsL3)828+ (MOC-43) as a versatile theranostic nanoplatform to meet the following demands simultaneously: (1) synergistic treatments of radio-, chemo-, and X-ray-induced photodynamic therapies (X-PDT) for breast cancer, (2) NIR imaging for cancer cell tracking and tumor-targeting, and (3) anticancer drug transport through a host-guest strategy. The nanoscale MOC-43 incorporates high-Z Os-element to interact with X-ray irradiation for dual radiosensitization and photosensitization, showing efficient energy transfer to endogenous oxygen in cancer cells to enhance X-PDT efficacy. It also features intrinsic NIR emission originating from metal-to-ligand charge transfer (MLCT) as an excellent imaging probe. Meanwhile, its 12 pockets can capture and concentrate low-water-soluble molecules for anticancer drug delivery. These multifunctions are implemented and demonstrated by micellization of coumarin-loaded cages with DSPE-PEG2000 into coumarin ⊂ MOC-43 nanoparticles (CMNPs) for efficient subcellular endocytosis and uptake. The cancer treatments in vitro/in vivo show promising antitumor performance, providing a conceptual protocol to combine cage-cargo drug transport with diagnosis and treatment for collaborative cancer theranostics by virtue of multifunction synergism on a single-nanomaterial platform.

Comparison of National Early Warning Score with shock index in patients with necrotizing fasciitis.

Shock index (SI) and national early warning score (NEWS) are more frequently used as assessment tools in acute illnesses, patient disposition and early identification of critical condition. Both they are consisted of common vital signs and parameters including heart rate, systolic blood pressure, respiratory rate, oxygen saturation and level of conscious, which made it easy to evaluate in medical facilities. Its ability to predict mortality in patients with necrotizing fasciitis (NF) in the emergency department remains unclear. This study was conducted to compare the predictive capability of the risk scores among NF patients. A retrospective cohort study of hospitalized patients with NF was conducted in 2 tertiary teaching hospitals in Taiwan between January 2013 and March 2015. We investigated the association of NEWS and SI with mortality in NF patients. Of the 395 NF patients, 32 (8.1%) died in the hospital. For mortality, the area under the receiver curve value of NEWS (0.81, 95% confidence interval 0.76-0.86) was significantly higher than SI (0.76, 95% confidence interval 0.73-0.79, P = .016). The sensitivities of NEWS of 3, 4, and 5 for mortality were 98.1%, 95.6%, and 92.3%. On the contrast, the sensitivities of SI of 0.5, 0.6, and 0.7 for mortality were 87.8%, 84.7%, and 81.5%. NEWS had advantage in better discriminative performance of mortality in NF patients. The NEWS may be used to identify relative low risk patients among NF patients.

Evaluation of teaching method for fluid mechanics course in engineering education.

The professional technology training of student is the important objective of engineering education, which could present the specialized ability in the future. This task is conducted to evaluation of teaching methods for fluid mechanics course in the mechanical engineering. With the teaching practice, the advantage of teaching method is found, and the teaching quality can be revealed by the scores of integrated test. The improvement of teaching quality is contribute the development of social. According to the self-assessment, the effects of teaching method on the professional course is revealed.•The diversified teaching method is advantage to the understanding of theory and knowledge of application.•The practical training is suitable to develop the inner potential and innovation of different students.•The method allows the investigation of teaching method evaluation for the other courses with practicality.

Artificial intelligence techniques for ground fault line selection in power systems: State-of-the-art and research challenges.

In modern power systems, efficient ground fault line selection is crucial for maintaining stability and reliability within distribution networks, especially given the increasing demand for energy and integration of renewable energy sources. This systematic review aims to examine various artificial intelligence (AI) techniques employed in ground fault line selection, encompassing artificial neural networks, support vector machines, decision trees, fuzzy logic, genetic algorithms, and other emerging methods. This review separately discusses the application, strengths, limitations, and successful case studies of each technique, providing valuable insights for researchers and professionals in the field. Furthermore, this review investigates challenges faced by current AI approaches, such as data collection, algorithm performance, and real-time requirements. Lastly, the review highlights future trends and potential avenues for further research in the field, focusing on the promising potential of deep learning, big data analytics, and edge computing to further improve ground fault line selection in distribution networks, ultimately enhancing their overall efficiency, resilience, and adaptability to evolving demands.

Value-added conversion of ethanol on morphologically controlled and defect-engineered titanium dioxide nanorods.

Developing an environmentally benign and highly effective strategy for the value-added conversion of biomass platform molecules such as ethanol has emerged as a significant challenge and opportunity. This challenge stems from the need to harness renewable solar energy and conduct thermodynamically unfavorable reactions at room temperature. To tackle this challenge, one-dimensional titanium dioxide photocatalysts gave been designed and fabricated to achieve a remarkable photocatalytic selectivity of almost 100% for transforming ethanol into value-added 1,1-diethoxyethane, contrasting the primary production of acetaldehyde in titanium dioxide nanoparticles. By incorporating a Pt co-catalyst and infusing oxygen vacancies into the one-dimensional catalyst, the ethanol transformation rate has doubled to be 128.78 mmol/g/h with respect to that of its unmodified counterpart, about 66.66 mmol/g/h. The underlying mechanism for this increased conversion and selectivity resides in the narrowed bandgap of the catalyst and the prolonged lifetime of the photo-generated carriers. This research offers a promising strategy that intertwines morphological control and defect engineering, offering a promising way for the photocatalytic transformation of essential biomass platform molecules.

Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS.

Steroid cell tumors, not otherwise specified (SCT-NOS) are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.

Evaluation of whole-brain oxygen metabolism in Alzheimer's disease using QSM and quantitative BOLD.

OBJECTIVE: The objective of this study was to evaluate the whole-brain pattern of oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) perturbation in Alzheimer's disease (AD) and investigate the relationship between regional cerebral oxygen metabolism and global cognition. METHODS: Twenty-six AD patients and 25 age-matched healthy controls (HC) were prospectively recruited in this study. Mini-Mental State Examination (MMSE) was used to evaluate cognitive status. We applied QQ-CCTV algorithm which combines quantitative susceptibility mapping and quantitative blood oxygen level-dependent models (QQ) for OEF calculation. CBF map was computed from arterial spin labeling and CMRO2 was generated based on Fick's principle. Whole-brain and regional OEF, CBF, and CMRO2 analyses were performed. The associations between these measures in substructures of deep brain gray matter and MMSE scores were assessed. RESULTS: Whole brain voxel-wise analysis showed that CBF and CMRO2 values significantly decreased in AD predominantly in the bilateral angular gyrus, precuneus gyrus and parieto-temporal regions. Regional analysis showed that CBF value decreased in the bilateral caudal hippocampus and left rostral hippocampus and CMRO2 value decreased in left caudal and rostral hippocampus in AD patients. The mean CBF and CMRO2 values in the bilateral hippocampus positively correlated with the MMSE score over the AD and HC groups combined. CONCLUSION: CMRO2 mapping with the QQ-CCTV method - which is readily available in MR systems for clinical practice - can be a potential biomarker for AD. In addition, CMRO2 in the hippocampus may be a useful tool for monitoring cognitive impairment.

Giant Magnetoresistance Based Biosensors for Cancer Screening and Detection.

Early-stage screening of cancer is critical in preventing its development and therefore can improve the prognosis of the disease. One accurate and effective method of cancer screening is using high sensitivity biosensors to detect optically, chemically, or magnetically labeled cancer biomarkers. Among a wide range of biosensors, giant magnetoresistance (GMR) based devices offer high sensitivity, low background noise, robustness, and low cost. With state-of-the-art micro- and nanofabrication techniques, tens to hundreds of independently working GMR biosensors can be integrated into fingernail-sized chips for the simultaneous detection of multiple cancer biomarkers (i.e., multiplexed assay). Meanwhile, the miniaturization of GMR chips makes them able to be integrated into point-of-care (POC) devices. In this review, we first introduce three types of GMR biosensors in terms of their structures and physics, followed by a discussion on fabrication techniques for those sensors. In order to achieve target cancer biomarker detection, the GMR biosensor surface needs to be subjected to biological decoration. Thus, commonly used methods for surface functionalization are also reviewed. The robustness of GMR-based biosensors in cancer detection has been demonstrated by multiple research groups worldwide and we review some representative examples. At the end of this review, the challenges and future development prospects of GMR biosensor platforms are commented on. With all their benefits and opportunities, it can be foreseen that GMR biosensor platforms will transition from a promising candidate to a robust product for cancer screening in the near future.

Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2.

With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).

Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway.

Background: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. Methods: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. Results: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. Conclusions: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

Treponema pallidum promoted microglia apoptosis and prevented itself from clearing by human microglia via blocking autophagic flux.

Treponema pallidum (Tp) has a well-known ability to evade the immune system and can cause neurosyphilis by invading the central nervous system (CNS). Microglia are resident macrophages of the CNS that are essential for host defense against pathogens, this study aims to investigate the interaction between Tp and microglia and the potential mechanism. Here, we found that Tp can exert significant toxic effects on microglia in vivo in Tg (mpeg1: EGFP) transgenic zebrafish embryos. Single-cell RNA sequencing results showed that Tp downregulated autophagy-related genes in human HMC3 microglial cells, which is negatively associated with apoptotic gene expression. Biochemical and cell biology assays further established that Tp inhibits microglial autophagy by interfering with the autophagosome-lysosome fusion process. Transcription factor EB (TFEB) is a master regulator of lysosome biogenesis, Tp activates the mechanistic target of rapamycin complex 1 (mTORC1) signaling to inhibit the nuclear translocation of TFEB, leading to decreased lysosomal biogenesis and accumulated autophagosome. Importantly, the inhibition of autophagosome formation reversed Tp-induced apoptosis and promoted microglial clearance of Tp. Taken together, these findings show that Tp blocks autophagic flux by inhibiting TFEB-mediated lysosomal biosynthesis in human microglia. Autophagosome accumulation was demonstrated to be a key mechanism underlying the effects of Tp in promoting apoptosis and preventing itself from clearing by human microglia. This study offers novel perspectives on the potential mechanism of immune evasion employed by Tp within CNS. The results not only establish the pivotal role of autophagy dysregulation in the detrimental effects of Tp on microglial cells but also bear considerable implications for the development of therapeutic strategies against Tp, specifically involving mTORC1 inhibitors and autophagosome formation inhibitors, in the context of neurosyphilis patients.

CD4+ T cells help myeloid-mediated killing of immune-evasive tumors.

In a recent study published in Nature, Kruse et al. demonstrated an indirect tumor-killing mechanism orchestrated by a small number of CD4+ effector T cells. These CD4+ T cells can reprogram myeloid cells not just into IFNγ-induced antigen-presenting cells but also into iNOS-expressing tumoricidal effectors that can eradicate immune-evasive tumors.

In-modified Sn-MOFs with high catalytic performance in formate electrosynthesis from aqueous carbon dioxide.

Electrochemical reduction of carbon dioxide (CO2ER) has become an effective solution to relieve the energy crisis and tackle climate change. In this study, a series of tin-based organic frameworks modified by In (Sn-MOF/Inx) were successfully synthesized via a simple hydrothermal method and explored for high formate-selective CO2ER. The pure Sn-MOF exhibits maximum formate selectivity with a faradaic efficiency (FEformate) of approximately 85.0% and a current density of 15 mA cm-2 at -1.16 VRHE, while the In (6%)-modified Sn-MOF (Sn-MOF/In6) delivers a much higher maximum FEformate (around 97.5%) and a current density of 16 mA cm-2 at -0.96 VRHE. Remarkably, the Sn-MOF/In6 exhibits a significantly larger specific surface area (183.3 m2 g-1) compared to the Sn-MOF (65.2 m2 g-1). These findings indicate that introducing In, an alien element with a slightly different outer orbital electron number from that of Sn, can significantly boost the selectivity and activity for CO2ER to formate. This study presents an efficient way to modify MOF catalysts through a well-designed introducing process.

The unique gut microbiome of giant pandas involved in protein metabolism contributes to the host's dietary adaption to bamboo.

BACKGROUND: The gut microbiota of the giant panda (Ailuropoda melanoleuca), a global symbol of conservation, are believed to be involved in the host's dietary switch to a fibrous bamboo diet. However, their exact roles are still largely unknown. RESULTS: In this study, we first comprehensively analyzed a large number of gut metagenomes giant pandas (n = 322), including 98 pandas sequenced in this study with deep sequencing (Illumina) and third-generation sequencing (nanopore). We reconstructed 408 metagenome-assembled genomes (MAGs), and 148 of which (36.27%) were near complete. The most abundant MAG was classified as Streptococcus alactolyticus. A pairwise comparison of the metagenomes and meta-transcriptomes in 14 feces revealed genes involved in carbohydrate metabolism were lower, but those involved in protein metabolism were greater in abundance and expression in giant pandas compared to those in herbivores and omnivores. Of note, S. alactolyticus was positively correlated to the KEGG modules of essential amino-acid biosynthesis. After being isolated from pandas and gavaged to mice, S. alactolyticus significantly increased the relative abundance of essential amino acids in mice jejunum. CONCLUSIONS: The study highlights the unique protein metabolic profiles in the giant panda's gut microbiome. The findings suggest that S. alactolyticus is an important player in the gut microbiota that contributes to the giant panda's dietary adaptation by more involvement in protein rather than carbohydrate metabolism. Video Abstract.

GPCR activation and GRK2 assembly by a biased intracellular agonist.

Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands1-6. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gαq and the arrestin-biased ligand SBI-5537. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gαq protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.