The value of the malignant subregion-based texture analysis in predicting the Ki-67 status in breast cancer.

Objective: To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer. Materials and methods: The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation. Results: Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68-0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14. Conclusion: The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

A newly evolved rice-specific gene JAUP1 regulates jasmonate biosynthesis and signalling to promote root development and multi-stress tolerance.

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Characteristics of the chloroplast genome of Camellia insularis / 生物工程学报

In this study, the chloroplast genome of Camellia insularis Orel & Curry was sequenced using high-throughput sequencing technology. The results showed that the chloroplast genome of C. insularis was 156 882 bp in length with a typical tetrad structure, encoding 132 genes, including 88 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Codon preference analysis revealed that the highest number of codons coded for leucine, with a high A/U preference in the third codon position. Additionally, 67 simple sequence repeats (SSR) loci were identified, with a preference for A and T bases. The inverted repeat (IR) boundary regions of the chloroplast genome of C. insularis were relatively conserved, except for a few variable regions. Phylogenetic analysis indicated that C. insularis was most closely related to C. fascicularis. Yellow camellia is a valuable material for genetic engineering breeding. This study provides fundamental genetic information on chloroplast engineering and offers valuable resources for conducting in-depth research on the evolution, species identification, and genomic breeding of yellow Camellia.

Identification of (E)-1-((1H-indol-3-yl)methylene)-4-substitute-thiosemicarbazones as potential anti-hepatic fibrosis agents.

Liver fibrosis remains a global health challenge due to its rapidly rising prevalence and limited treatment options. The orphan nuclear receptor Nur77 has been implicated in regulation of autophagy and liver fibrosis. Targeting Nur77-mediated autophagic flux may thus be a new promising strategy against hepatic fibrosis. In this study, we synthesized four types of Nur77-based thiourea derivatives to determine their anti-hepatic fibrosis activity. Among the synthesized thiourea derivatives, 9e was the most potent inhibitor of hepatic stellate cells (HSCs) proliferation and activation. This compound could directly bind to Nur77 and inhibit TGF-ß1-induced α-SMA and COLA1 expression in a Nur77-dependent manner. In vivo, 9e significantly reduced CCl4-mediated hepatic inflammation response and extracellular matrix (ECM) production, revealing that 9e is capable of blocking the progression of hepatic fibrosis. Mechanistically, 9e induced Nur77 expression and enhanced autophagic flux by inhibiting the mTORC1 signaling pathway in vitro and in vivo. Thus, the Nur77-targeted lead 9e may serve as a promising candidate for treatment of chronic liver fibrosis.

A prediction model for osteonecrosis of femoral head after internal fixation with multiple cannulated compression screws for adult femoral neck fractures.

OBJECTIVES: This study aims to investigate the high-risk factors for osteonecrosis of the femoral head (ONFH) after internal fixation with multiple cannulated compression screws for adult femoral neck fractures and to construct a prediction model. PATIENTS AND METHODS: Between from January 2012 and December 2020, a total of 268 patients (138 males, 130 females; mean age: 53±10 years; range, 23 to 70 years) with ONFH who had complete follow-up data were included. Closed reduction in combination with open reduction were performed. All patients received internal fixation with multiple cannulated compression screws and were assigned to ONFH and non-ONFH groups. Logistic regression model was utilized to identify independent risk factors for postoperative ONFH, followed by constructing a nomogram prediction model. The predictive ability of the model was evaluated by receiver operating characteristic curve, Hosmer-Lemeshow test, and calibration curve. RESULTS: Multivariate analysis revealed that older age (odds ratio [OR]: 2.307, 95% confidence interval [CI]: 1.295-4.108], Charlson Comorbidity Index (CCI) ≥2 (OR: 2.214, 95% CI: 1.035-4.739), fracture displacement (OR: 2.426, 95% CI: 1.122-5.247), unsatisfactory reduction (OR: 2.629, 95% CI: 1.275-5.423), postoperative removal of internal fixation implant (OR: 2.200, 95% CI: 1.051-4.604) were independent risk factors for postoperative ONFH (p<0.05). The nomogram prediction model constructed based on these clinical characteristics showed high predictive value (AUC=0.807) and consistency (p>0.05). CONCLUSION: Age, comorbidity index, fracture type, reduction quality and postoperative removal of internal fixation implant are of utmost importance for postoperative ONFH in patients with femoral neck fractures. The established nomogram prediction model can accurately predict the occurrence of postoperative ONFH.

Spinosin inhibits activated hepatic stellate cell to attenuate liver fibrosis by targeting Nur77/ASK1/p38 MAPK signaling pathway.

AIM: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action. METHODS: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl4-induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration. RESULTS: SPI can strongly suppress TGF-ß1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-ß1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1ß), which is followed by improved liver function in the CCl4-induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 µM. CONCLUSION: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway.

A case report of dermatomyositis mimicking myasthenia gravis.

RATIONALE: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease. PATIENT CONCERNS: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis. DIAGNOSES: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma. INTERVENTIONS: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma. OUTCOMES: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared. CONCLUSION: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies.

High precision measurements of lithium isotopic composition at sub-nanogram by MC-ICP-MS with membrane desolvation.

The geochemistry of Li and Li isotopes is a promising tracer of chemical weathering processes for both modern and ancient times. Therefore, accurate and precise determination of the isotopic composition of Li is required for a large variety of complex geological samples with different Li concentrations and matrix/Li ratios. Especially, geochemical studies of precious geological samples with ultra-low lithium content and high matrix. In this study, the accuracy and the precision corresponding to Li isotopic measurements of low-level samples using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) with membrane desolvation introduction system was evaluated. The method of MC-ICP-MS with membrane desolvation and a high-sensitivity X-skimmer cone, together with a simple one-step column separation enabled the high-precision isotopic analysis of Li quantities as small as 2 ng. The long-term instrumental external reproducibility of δ7Li values for the L-SVEC and SPEX-Li were 0.0 ± 0.1‰ (n = 20) and 12.1 ± 0.4‰ (n = 20), respectively. Based on the measurements on a series of international reference materials over the last two years. The measured δ7Li values for the standards with a variety of matrices, including BHVO-2, AGV-2 and seawater (NASS-6). The δ7Li values of BHVO-2 (4.58 ± 0.35‰), AGV-2 (6.85 ± 0.40‰) and NASS-6 (30.88 ± 0.20‰) are in agreement with the published data within the uncertainty. We also present analytical results for South China Sea surface seawater water, meteorite, limestones and rain water. These results demonstrate the validity of the method for obtaining highly precise and accurate outcomes.

Design, synthesis, and biological evaluation of carbonyl-hydrazine-1-carboxamide derivatives as anti-hepatic fibrosis agents targeting Nur77.

Hepatic fibrosis remains a great challenge clinically. The orphan nuclear receptor Nur77 is recently suggested as the critical regulator of transforming growth factor-ß (TGF-ß) signaling, which plays a central role in multi-organic fibrosis. Herein, we optimized our previously reported Nur77-targeted compound 9 h for attempting to develop effective and safe anti-hepatic fibrosis agents. The critical pharmacophore scaffold of pyridine-carbonyl-hydrazine-1-carboxamide was retained, while the naphthalene ring was replaced with an aromatic ring containing pyridyl or indole groups. Four series of derivatives were thus generated, among which the compound 16f had excellent binding activity toward Nur77-LBD (KD = 470 nM) with the best inhibitory activity against the TGF- ß 1 activation of hepatic stellate cells (HSCs) and low cytotoxicity to normal mice liver AML-12 cells (IC50 > 80 µM). In mice, 16f displayed potent activity against CCl4-induced liver fibrosis with improved liver function. Mechanistically, 16f-mediated inactivation of HSC and suppression of liver fibrosis were associated with its enhancement of autophagic flux in a Nur77-dependent manner. Together, 16f was identified as a potential anti-liver fibrosis agent. Our study suggests that Nur77 may serve as a critical anti-hepatic fibrosis target.

Cultural differences in intertemporal decision making: A comparison between Chile and China.

A cross-cultural comparison is made of delay discounting in samples of participants from Chile and China. Comparisons are made based on previous literature that suggests that individuals from an Asian culture should be willing to postpone delayed rewards more than are individuals from a Latin American culture. To test the cross-cultural validity of a hyperbolic discounting model, the model was fitted to both data sets. Additionally, a self-enhancement measure was evaluated as a potential mediator between culture of origin and delay discounting. Seventy-eight college students from China and 120 college students from Chile, with similar demographic backgrounds, discounted hypothetical monetary outcomes using an adjusting-amount titration procedure. Additionally, participants completed a self-enhancement measure. Age, academic major, gender, and grade point average were controlled. Chilean participants discounted much more steeply than Chinese nationals did. No support was obtained for the mediation of self-enhancement between culture of origin and degree of delay discounting. In both samples, delay discounting was better described by a hyperboloid than an exponential function, the only exception being the $10,000 condition in which the medians for Chilean participants' present subjective value were equally well explained by a hyperboloid and an exponential function.

Synergistic effect of porous carbon shell confinement and catalytic conversion of nickel nanoparticle cores for improved lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) are some of the most promising energy storage systems to break the ceiling of Li-ion batteries. However, the notorious shuttle effect and slow redox kinetics give rise to low sulfur utilization and discharge capacity, poor rate performance, and fast capacity decay. It is proved that the reasonable design of the electrocatalyst is one of the important ways to improve the electrochemical performance of LSBs. Here, a core-shell structure with gradient adsorption capacity for reactants and sulfur products was designed. The Ni nanoparticles core coated with graphite carbon shell was prepared by one-step pyrolysis of Ni-MOF precursors. The design takes advantage of the principle that the adsorption capacity decreases from the core to the shell, and the Ni core with strong adsorption capacity is easy to attract and capture soluble lithium polysulfide (LiPS) during the discharge/charging process. This trapping mechanism prevents the diffusion of LiPSs to the outer shell and effectively inhibits the shuttle effect. In addition, the Ni nanoparticles within the porous carbon, as the active center, expose most of the inherent active sites to the surface area, thus achieving a rapid transformation of LiPSs, significantly reducing the reaction polarization, and improving the cyclic stability and reaction kinetics of LSB. Therefore, the S/Ni@PC composites exhibited excellent cycle stability (a capacity of 417.4 mA h g-1 for 500 cycles at 1C with a fading rate of 0.11%) and outstanding rate performance (1014.6 mA h g-1 at 2C). This study provides a promising design solution of Ni nanoparticles embedded in porous carbon for high-performance, safe and reliable LSB.

Remote Sensing Image Characteristics and Typical Area Analysis of Taiyuan Xishan Ecological Restoration Area.

The Taiyuan Xishan Ecological Restoration Zone is located in the west of Taiyuan City and belongs to the Xishan Coalfield. Due to the resource development activity of coal mining, which is caused by coal gangue accumulation, surface vegetation degradation, bare surfaces, and other phenomena, it is most common in this area. These have an impact on the surface ecology; however, after ecological restoration, the surface ecology has been greatly improved. There are many extraction models of vegetation coverage based on pixel dichotomology combined with multispectral vegetation index, but we believe that the combination of visible light vegetation index to construct models is relatively unexplored. The main problem of how to use the RGB image data in order to quickly and accurately extract vegetation coverage information is still under investigation and needs researchers' attention. In this paper, through selecting the vegetation coverage as the evaluation index of ecological restoration effect, a new RGB vegetation coverage CIVE calculation model is innovatively proposed to solve the above problem, and on the basis of this model, the vegetation cover change analysis is carried out in the Xishan ecological restoration area of Taiyuan. According to the analysis of vegetation coverage change, relevant paper data, and the characteristics of multiple historical remote sensing images, the ecological restoration area of Taiyuan Xishan is divided into six typical areas. Through empirical evaluation, we summarize and analyze these six typical areas, which can provide typical demonstration roles for other ecological restoration areas. Our findings suggest that the proposed CIVE model realizes the extraction of vegetation cover information and long-term series dynamic monitoring of vegetation coverage.

Study on quality standard for Miao medicine Clinopodium gracile / 中国药房

OBJECTIVE To establish the quality standard of Clinopodium gracile. METHODS Ten batches of C. gracile were collected to perform appearance and property identification， microscopic identification and thin layer chromatography （TLC） identification. Moisture， total ash， acid-insoluble ash and dilute ethanol extract were detected， and the content of rosmarinic acid was determined by HPLC. RESULTS The stem of C. gracile was slender， square columnar， covered by white fluff， the surface was grayish green or greenish brown； epidermal cells， non-glandular hairs， cortical cells and so on were seen in the cross section of the stem. Non-glandular hairs， ducts， wood fibers， mesophyll cells and so on could be seen in the powder. Results of TLC identification showed that there were spots of the same color in the chromatographic position corresponding to the chromatographic position of buddlejasaponin Ⅳb control. The contents of water， total ash， acid-insoluble ash， dilute ethanol extract and rosmarinic acid in 10 batches of samples were 8.69%-12.33%， 5.96%-13.33%， 0.14%-3.29%， 18.57%-32.61%， 0.35%-0.82%， respectively. The average values were 10.10%， 9.73%， 1.06%， 23.54% and 0.56%， respectively. CONCLUSIONS The established method can be used for quality control of C. gracile. It is preliminarily proposed that the ash content in the herb should not exceed 12.0%， the total ash content should not exceed 12.0%， the acid-insoluble ash content should not exceed 1.5%， the dilute ethanol extract should not be less than 18.0%， and the rosmarinic acid content should not be less than 0.45%.

Maternal liver damage induced by cadmium exposure in pregnant mice through hypoxia inducible factor-1α-mediated upregulation in DRP1 / 环境与职业医学

Background Mitochondrial dynamin-related protein 1 (DRP1) regulates mitochondrial division and plays an important role in maintaining hepatocyte function. However, the role of DRP1 in cadmium exposure-induced maternal liver damage in pregnant mice remains unclear. Objective To investigate the role and mechanism of DRP1 in maternal liver damage induced by cadmium exposure during pregnancy. Methods This study consisted of animal experiments and cell experiments. (1) Animal experiments. Mice at 14 days of gestation were randomly divided into three groups: a control group, a low-dose cadmium group (LCd group: 2.5 mg·kg−1), and a high-dose cadmium group (HCd group: 5 mg·kg−1). The pregnant mice were intraperitoneally injected with cadmium chloride (CdCl2) for 6 and 24 h in the next morning. The weights of pregnant mice, uterus, maternal liver, and fetal mice were recorded after sacrifice. Serum and liver of pregnant mice were collected, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver tissues were stained with HE to observe changes in liver function and liver tissue structure. The expressions of oxidative phosphorylation-related proteins, hypoxia inducible factor-1α (HIF-1α) and DRP1 proteins in liver of pregnant mice were detected by Western blotting. (2) Cell experiments. AML12 cells were treated with CdCl2 (10 μmol·L−1) for 0, 2, 6, 12, and 24 h. The expressions of oxidative phosphorylation-related proteins, DRP1, and hypoxia inducible factor-1α (HIF-1α) proteins were detected. AML12 cells were pretreated with DRP1 inhibitor Mdivi-1 for 1 h and then CdCl2 (10 μmol·L−1) for 12 h to detect the expression of oxidative phosphorylation-related proteins and DRP1 protein. AML12 cells were treated with Hif-1α siRNA for 48 h and CdCl2 (10 μmol·L−1) for 6 h to detect the expression of HIF-1α and DRP1 proteins. Results The results of animal experiments showed that cadmium exposure in pregnant mice had no effects on maternal liver weight and liver coefficient. However, the histomorphological changes and necrosis in hepatocytes were observed. Compared with the control group, the serum ALT and AST levels of pregnant mice in the LCd group were significantly increased after 6 h (P＜0.05), and the levels in the HCd group were significantly increased after 6 and 24 h (P＜0.05). Cadmium exposure during pregnancy significantly up-regulated HIF-1α and DRP1 expressions and down-regulated the expressions of oxidative phosphorylation-related proteins in maternal livers. In vitro cell experiments showed that the expressions of oxidative phosphorylation-related proteins was significantly decreased and HIF-1α and DRP1 protein expressions were significantly increased in the AML12 cells treated with CdCl2 for 6 h. Mdivi-1 pretreatment significantly antagonized the inhibitory effect of cadmium on the expressions of oxidative phosphorylation-related proteins in AML12 cells, while Hif-1α siRNA pretreatment significantly antagonized the up-regulative effect of cadmium on DRP1 expression in AML12 cells. Conclusion Cadmium exposure in pregnant mice may up-regulate DRP1 expression by activating HIF-1α signaling, then inhibit oxidative phosphorylation level of hepatic cells, and ultimately lead to maternal liver damage.

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Dental erosion caused by glucocorticoid therapy in a patient with optic neuritis: a case report / 华西口腔医学杂志

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.

Current status and prospect of composite nano-phototherapy agents in the phototherapy for breast cancer treatment / 中国药房

As an adjuvant alternative therapy， phototherapy is widely used for early diagnosis and late treatment of breast cancer due to its non-invasive treatment characteristics. But the application of phototherapeutic agents has been limited in the clinic due to poor hydrophobicity and tissue targeting， low photostability， and obvious toxic side effects in vivo. With the development of nanotechnology， new composite nano-phototherapy agents have emerged. This paper summarizes the latest developments and findings of new composite nano-phototherapy agents for phototherapy in the field of breast cancer treatment in the past 5 years. With the development of multifunctional nanomaterials in the field of breast cancer imaging diagnosis and treatment， the modified phototherapy agent achieved further development respectively from improving light response to improve the light thermal conversion or increasing the generation of reactive oxygen species， targeting tumor microenvironment， immune cells and cancer cell surface receptors to achieve drug controllable response release， using biomimetic materials and endogenous substances to improve biocompatibility. Although phototherapeutic agents exhibit high cell-killing rates in the treatment of metastatic breast cancer models and effectively inhibit their recurrence and metastasis， problems remain regarding the safety and compatibility of synergistic therapy. Future studies can not only improve the existing effects of phototherapeutic agents， but also develop oral drugs with more convenient routes based on immunotherapy to amplify the immune response and resist breast cancer through multiple routes.

Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.