Corrigendum: High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia.

[This corrects the article DOI: 10.3389/fonc.2022.1068094.].

Consensus on clinical diagnosis and medical treatment of HER2-low breast cancer (2022 edition).

Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry [IHC] 1+, or IHC2+/in situ hybridization [ISH]-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia.

Acute myelogenous leukemia (AML) is a disease that severely affects the physical health of children. Thus, we aimed to identify biomarkers associated with AML prognosis in children. Using transcriptomics on an mRNA dataset from 27 children with non-M3 AML, we selected genes from among those with the top 5000 median absolute deviation (MAD) values for subsequent analysis which showed that two modules were associated with AML risk groups. Thus, enrichment analysis was performed using genes from these modules. A one-way Cox analysis was performed on a dataset of 149 non-M3 AML patients downloaded from the TCGA. This identified four genes as significant: FTH1, RCC2, ABHD17B, and IRAK1. Through survival analysis, FTH1 was identified as a key gene associated with AML prognosis. We verified the proliferative and regulatory effects of ferroptosis on MOLM-13 and THP-1 cells using Liproxstatin-1 and Erastin respectively by CCK-8 and flow cytometry assays. Furthermore, we assayed expression levels of FTH1 in MOLM-13 and THP-1 cells after induction and inhibition of ferroptosis by real-time quantitative PCR, which showed that upregulated FTH1 expression promoted proliferation and inhibited apoptosis in leukemia cells. In conclusion, high expression of FTH1 promoted proliferation and inhibited apoptosis of leukemic cells through the ferroptosis pathway and is thus a potential risk factor that affects the prognosis of non-M3 AML in children.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Full Reference Quality Assessment for Image Retargeting Based on Natural Scene Statistics Modeling and Bi-Directional Saliency Similarity.

Image retargeting technology has been widely studied to adapt images for the devices with heterogeneous screen resolutions. Meanwhile effective objective retargeting quality assessment algorithms are also very important for optimizing and selecting favorable retargeting methods. Unlike previous assessment algorithms which rely on image local structure features and unidirectional prediction of information loss, we propose a bi-directional natural salient scene distortion model (BNSSD) including image natural scene statistics (NSS) measurement, salient global structure distortion measurement, and bi-directional salient information loss measurement. First, we propose a new NSS model in log-Gabor domain and verify its effectiveness in reflecting nature scene statistical distortions introduced during the retargeting process. Second, the concept of salient global structure distortion is proposed to measure the global structure uniformity in the corresponding salient regions between original and retargeted images. Finally, we propose a bidirectional salient information loss metric to measure the information loss between salient areas in original image and retargeted image. The effectiveness of the BNSSD model is verified on two widely recognized public databases, and the experimental results show that our method outperforms the state-of-the-art algorithms under different statistical assessment criteria.

Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy.

This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.

Treatment of Graves Hyperthyroidism by Jiakangling Capsule Combined with Reduction of 131I: an Efficacy Observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Jiakangling Capsule (JC) combined with reduction of 1311 in treatment of Graves hyperthyroidism.</p><p><b>METHODS</b>Totally 387 Graves hyperthyroidism patients were randomly assigned to the treatment group (200 cases) and the control group (187 cases). Patients in the treatment group took JC combined with reduction of 131I. The 131I dosage per gram of thyroid tissue was 50-80 microCi. They additionally took JC one week after taking 1311 for one consecutive month. Patients in the control group took 131 routinely as one disposable treatment. The 131I dosage per gram of thyroid tissue was 70-120 microCi, without using JC or other anti-thyroid drugs. All patients were reexamined after 24-month treatment. Whether hyperthyroidism was cured, incurred, or permanent was observed. Efficacies of thyroglobulin antibody (TGAb) and thyroid microsome antibody (TMAb) were compared between the two groups.</p><p><b>RESULTS</b>Compared with the control group, the incurred ratio increased in the treatment group [3.2% (6/187) vs. 16.0% (32/200), P < 0.01], the incurred ratio of strong positive TGAb and TMAb patients increased [3.5% (2/57) vs. 27.1% (16/59), P < 0.01], the permanent hypothyroidism ratio decreased [21.1% (12/57) vs. 3.4% (2/59), P < 0.05 ].</p><p><b>CONCLUSION</b>JC combined with reduction of 1311 was superior in treating Graves hyperthyroidism induced permanent hypothyroidism than routine 1311 treatment, especially for strong positive TGAb and TMAb patients.</p>

Relationship between genotypes and clinical phenotypes in patients from 7 hemophilia A families / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the mutation types of factor VIII (FVIII) gene in patients from 7 hemophilia A (HA) families and the relationship between FVIII gene mutations and clinical phenotypes.</p><p><b>METHODS</b>A total of 8 patients from 7 HA families were recruited. The activated partial thromboplastin time (APTT) and factor VIII coagulant activity (VIII:C) in these patients were measured. Polymerase chain reaction (PCR) was performed to analyze FVIII gene intron 1 and 22 inversions. For patients without the FVIII intron inversions, direct sequencing was performed to determine their mutation types and other related members of their families were also tested by PCR and sequencing to analyze the corresponding mutation sites.</p><p><b>RESULTS</b>The ranges of APTT and VIII:C of the 8 patients were 91.6-131 seconds and 0.8%-2%, respectively. FVIII gene intron 22 inversion was not detected, while intron 1 inversion was detected in one patient. There were 5 types of mutations in FVIII gene detected in the remaining 7 patients, including 6 patients with mutations in exon 14 and 1 patient with mutation in exon 23; all of the 5 types of mutations were single nucleotide mutations. Among the detected mutations in FVIII gene, p.His1202LeufsX16 (c.3666delA) detected in one patient was found to be a previously unreported mutation in FVIII gene.</p><p><b>CONCLUSIONS</b>FVIII gene exon 14 is a hot-spot mutation region and p.His1202LeufsX16 is found to be a novel mutation in FVIII gene.</p>

Implantation metastasis of breast cancer in vacuum-assisted breast biopsy needle tract and the impact of neoadjuvant chemotherapy / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the incidence of implantation metastasis of breast cancer in vacuum-assisted breast biopsy (VABB) needle tract in Chinese patients and evaluate the effect of neoadjuvant chemotherapy on needle tract metastasis following VABB.</p><p><b>METHODS</b>The breast cancer patients with established diagnosis by VABB were divided into two groups to receive open surgery or neoadjuvant chemotherapy prior to open surgery. The incidence of needle tract metastasis, disease-free survival (DFS) and overall survival (OS) were compared between the two groups.</p><p><b>RESULTS</b>A total of 214 patients were enrolled, among whom 94 directly underwent surgeries and 120 had neoadjuvant chemotherapy before surgery. The two groups showed no significant differences in the incidence of needle tract metastasis (3.2% vs 0.8%, P=0.206), DFS (P=0.221), or OS (P=0.531).</p><p><b>CONCLUSION</b>The incidence of needle tract metastasis is low after VABB, and neoadjuvant chemotherapy does not increase this risk.</p>

Analysis of 5-year-follow-up of pediatric blood oncology patients with intrathecal injection of methotrexate mixed microcontent vincristine / 中华实用儿科临床杂志

Objective To analyze the clinical manifestation,auxiliary examination,treatment,prognosis of 16 cases who experienced inadvertent injection of intrathecal microcontent vincristine,and and they were followed up for 5 years.Methods To collect detailed medical record material for 5 years of 16 pediatric blood oncology patients who appeared with nervous system damage symptoms caused by inadvertent administration of microcontent vincristine intrathecally,combined with subsequent visits at the clinic,or through telephone and letters followed-up.Results Clinical manifestations of lumbosacral radicular dysfunction were found in all 16 cases,among them 2 cases also had cervicothoracic radicular damage symptoms.The first sign was weakness in lower limbs,subsequently,walking difficulty.Cerebrospinal fluid protein was higher than normal in 3 cases.Magnetic resonance imagine of the brain and spinal cord revealed demyelination in the white matter of 2 cases.Electromyographic revealed neurogenic damage and showed complete or partial denervation changes in 11 cases that received this examination.After the treatment consisted of medication use to improve nerve nutrition metabolism and promote nervous function recovery,combined with positive rehabilitation therapy,13 cases had improvement from level Ⅰ to Ⅲ in myodynamia.Of 9 cases with neurogenic bladder,4 cases were back to normal,3 cases were improved to different extent.Till Oct.2012,6 cases lived in remission,9 cases including 6 cases of recurrence died of the primary disease or complication in the treatment process,and 1 case died of penicillin anaphylactic shock almost 1 year after chemotherapy.Conclusions Inadvertent intrathecal injection of microcontent vincristine can cause lumbosacral radicular dysfunction.Trace amounts of vincristine intrathecally cumulative can also cause serious damage to the nervous system.The early application of horrmone and nerve nutrition drugs combined with positive rehabilitation therapy have surely curative effect to alleviate the neuropathy for inadvertent administration of microcontent vincristine intrathecally.

Efficacy and safety assessment of neoadjuvant paclitaxel and trastuzumab in Chinese women with Her-2 positive operable breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab (TH) in Chinese women with Her-2 overexpressing operable breast cancer.</p><p><b>METHODS</b>This is a single center open-label phase II clinical trial. The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery. The primary endpoint was pathologic complete response rate (pCR rate) and the secondary endpoint was overall response rate (OR rate). Patients were also stratified according to hormone receptor status, and pCR rate and OR rate were compared between subgroups. Adverse events were graded according to CTCAE v3.0.</p><p><b>RESULTS</b>There were 40 eligible patients entering this study with median age of 49 years. All patients completed 4 cycles of neoadjuvant treatment. pCR rate was 52.5% and OR rate was 87.5%. The differences of pCR and OR rates between subgroups were of no statistical significance. No cardiac toxicity event severer than grade 2 was recorded.</p><p><b>CONCLUSION</b>3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety.</p>

A meta-analysis of neoadjuvant chemotherapy combined with trastuzumab for HER2-positive breast cancers / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with trastuzumab for HER2 positive breast cancers.</p><p><b>METHODS</b>PubMed online database, ASCO abstract database, SABCS abstract database, ESMO abstract database and CBMdisc database were searched for literatures related to trastuzumab in neoadjuvant chemotherapy for breast cancers. A meta-analysis was performed for retrieved literatures meeting the inclusion criteria.</p><p><b>RESULTS</b>Three clinical trials were included. Meta-analysis showed that compared to chemotherapy only, regimens combined with trastuzumab could significantly improved the pCR rate of HER2-positive breast cancers (RR=1.65, 95% CI 1.28-2.13, P<0.0001) without increasing the frequencies of cardiac toxicity (RR=1.16, 95% CI 0.82-1.64, P=0.41).</p><p><b>CONCLUSION</b>In neoadjuvant chemotherapy for HER2-positive breast cancers, chemotherapy combined with trastuzumab is superior to exclusive chemotherapy.</p>

Progress in the research on 21-gene Oncotype Dx in breast cancer prognosis / 中国癌症杂志

Currently the most effective treatment strategy for breast cancer is standardized multi-discipline comprehensive treatment. However, there are no effective models that can accurately predict prognosis, so that no guidance of individualized treatment has yet been set up, resulting in a proportion of patients with low risk who received chemotherapy with little benefit. With the development of genomics, several gene sets have been demonstrated to be helpful in predicting of breast cancer prognosis and grading the patients' benefit from chemotherapy, thus avoid overtreatment. 21-gene Oncotype Dx was reported as one of them and has been demonstrated to be effective and accurate in various clinical studies. This paper summarizes researches on 21-gene Oncotype Dx in breast cancer.

Efficacy and prognosis analysis in 188 children with acute lymphoblastic leukemia of China / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the therapeutic effect and the influencing factors of event-free survival (EFS) of childhood acute lymphoblastic leukemia (ALL) in Xiangya Hospital of Central South University and the First Affiliated Hospital of Guangxi Medical University.</p><p><b>METHODS</b>All the patients adopted chemotherapy according to therapeutic guideline revised by the Subspecialty Group of Hematology, The Society of Pediatrics, Chinese Medical Association for the second-time in 1998 (the Rongcheng ALL-98 Protocol). Kaplan-Meier method was used to estimate the survival rates of 188 patients who received therapy with good compliance. The differences of EFS between groups were assessed by Log-rank test. The independent influencing factors on EFS were analyzed by the Cox proportional hazards regression model.</p><p><b>RESULTS</b>After receiving inductive treatment, 354 of 374 (93.6%) patients demonstrated a complete remission; 188 patients who received complete courses of treatment with good compliance showed (68.1 +/- 5.6)% five-year EFS. Meanwhile, the five-year EFS in standard-risk (SR) group and high-risk (HR) group were (75.2 +/- 6.0)% and (47.6 +/- 11.6)%, respectively. The total relapse rate was 10.6% and the median time to relapse was 13 months. Twenty-nine of 188 patients (15.4%) were dead, and 13 patients (7.0%) died from treatment-related complications. Independent adverse prognostic factors included risk grouping, t (9; 22)/bcr-abl gene and leukocyte count.</p><p><b>CONCLUSIONS</b>The total EFS of childhood ALL patients treated with Rongcheng ALL-98 Protocol in two hospitals was close to 70%. Therefore, it is necessary to evaluate risk factors and consider the grouping in more detail to reduce the treatment-related mortality and to increase the compliance of treatment which can ultimately improve the EFS.</p>

Correlation of expression of RhoA (RhoC and their effector ROCK-1 with malignant phenotype of ovarian cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of RhoA, RhoC and their effector ROCK-1 in four ovarian cancer cell lines in vitro and their correlation with invasiveness.</p><p><b>METHODS</b>Expression of RhoA, RhoC and ROCK-1 mRNA and protein in four ovarian cancer cell lines SW626, Skov-3, A2780 and Caov-3 was detected by RT-PCR and Western blot assay. Invasion assay was done in Boyden chamber.</p><p><b>RESULTS</b>The expression levels of RhoA, RhoC and ROCK-1 mRNA and protein varied in the four different cell lines examined. The expression level of RhoC, but not RhoA and ROCK-1, was significantly correlated with the invasive capability of these cells in vitro (r = 0.95, P < 0.01). Expression of RhoA at the level of transcription was not correlated with that at the translation level. The expression of RhoA and RhoC did not correlate with that of ROCK-1.</p><p><b>CONCLUSION</b>Expression level of RhoC may serve as an independent parameter in evaluating metastasis and become a new target in inhibiting ovarian cancer metastasis.</p>

The mechanism of topotecan resistance in ovarian cancer cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the mechanism of topotecan (TPT) resistance in ovarian cancer cell line.</p><p><b>METHODS</b>A TPT-resistant ovarian cancer cell line A2780/TPT established in this laboratory was used in this study. Intracellular rhodamine fluorescence intensity of the TPT-resistant cells and parental cells were measured by flow cytometry. The gene expression of membrane protein transporter such as transporter P-glycoprotein (P-gp), multidrug resistance associated protein (MRP), breast cancer resistance protein (BCRP) was evaluated by RT-PCR. The antisense-phosphorothioate oligonucleotide (ASODN) including a translation initiation site of BCRP mRNA was transferred into resistant cells by liposome.</p><p><b>RESULTS</b>Intracellular rhodamine fluorescence intensity of the resistant cells was 31.19% of that in the parental cells (P < 0.01). No expression of P-gp was demonstrated, and that of MRP was very weak in the TPT-resistant cells (relative expression value = 0.057). BCRP was overexpressed in the TPT-resistant cells (relative expression = 0.66), but not in the parental cells. Transfer of ASODN into resistant cells resulted in a 59.42% reduction of BCRP gene expression (P < 0.05) and an obviously increased intracellular rhodamine fluorescence intensity from 5.42 to 16.63 (P < 0.05).</p><p><b>CONCLUSION</b>The overexpression of BCRP which mediated drug efflux may play an important role in the induction of TPT-resistance in ovarian cancer.</p>

Significance of expression of T lymphoma invasion/metastasis gene in ovarian cancer cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the role of T lymphoma invasion/metastasis gene 1 (Tiam1) and protein in ovarian tumor cells.</p><p><b>METHODS</b>Expressions of Tiam1 mRNA, Rac1 mRNA, and Tiam1 protein in four ovarian tumor cells A2780, Caov3, Skov3, and SW626 were studied by using RT-PCR and Western blot, respectively. The cell migration ability was analyzed by in vitro invasion assay.</p><p><b>RESULTS</b>Expressions of Tiam1 mRNA and protein, as well as Rac1 mRNA were detected in all four ovarian tumor cells. There was a strong direct correlation between the levels of Tiam1 and Rac1 mRNA expression and migration potentials of all four ovarian cancer cells in vitro experiments. The increased expressions of Tiam1 mRNA were coincident with those of Rac1 mRNA, with a parallel relationship (P = 0.003, r = 0.874). Levels of Rac1 mRNA expression were significantly correlated with the potentials of tumor cell migration (P = 0.042, r = 0.814).</p><p><b>CONCLUSION</b>Tiam1-Rac1 signaling pathway plays a positive role in assessing tumor cell invasion and metastasis and provides a new target for gene therapy of ovarian cancer.</p>

Beta-blockers in the treatment of heart failure / 第二军医大学学报

It is now clear that continued stimulation o f the neurohormonal system in heart failure (HF) has serious deleterious effects on the heart. The increase of circulating catecholamines exerts direct toxic ef fect on cardiac myocytes, increases membrane permeability and myocardial fibrosi s; lead to aggravation of HF. β-blockers are commonly used in the treatment of HF including propranolol, metoprolol, bisoprolol, bucindolol and carvedilol. These drugs are used in combination with ACEIs, digitalis and diuretics. Genera lly, the benefits of β-blockade therapy in HF include improving symptoms, decr easing morbidity, mortality, elevating need for hospitalization and quality of l ife. β- blockade therapy arrests and reverts LV remodeling and improves the ri sk of life threatening arrhythmias and sudden cardiac death. A few serious adver se effects include hypotension, heart blocks, bradycardia and fluid retention.

Influence of sotalol on the QT dispersion in patients with radiofrequency cathet er ablation / 第二军医大学学报

Objective: To observe the influence of sot alol on the QT dispersion in patients with atrioventricular accessory pathways u nderwent radiofrequency catheter ablation (RFCA). Methods: Thirt y-six patients were divided into 2 groups by random. One was the drug group(18 cases) treated by RFCA， and sotalol 160 mg was orally administered and intracar diac electrophysiological study was performed every 30 min for 5 times. Th e other group(control group, 18 cases) only treated by RFCA.QTd,QTcd and QTLcd w ere measured before and after RFCA. Results: There was no signif icant difference with QT dispersion before and after RFCA in control group. When compared with before RFCA, QTd in patients administered sotalol was (30.9 ±14.3) ms vs (24.7±9.6) ms; QTcd(33.7±17.1) ms vs (25.2±10.1) ms; QT Lcd(30.8±14.1)ms vs (25.6±19.4) ms (P<0.05). Conclusion: Sotalol can slightly lower QT dispersion, which is beneficial for preventing malignant ventricular arrthythmia. It is safe in RFCA in pateints with accessory pathway.

Beta-blockers in the treatment of heart failure / 第二军医大学学报

It is now clear that continued stimulation o f the neurohormonal system in heart failure (HF) has serious deleterious effects on the heart. The increase of circulating catecholamines exerts direct toxic ef fect on cardiac myocytes, increases membrane permeability and myocardial fibrosi s; lead to aggravation of HF. β-blockers are commonly used in the treatment of HF including propranolol, metoprolol, bisoprolol, bucindolol and carvedilol. These drugs are used in combination with ACEIs, digitalis and diuretics. Genera lly, the benefits of β-blockade therapy in HF include improving symptoms, decr easing morbidity, mortality, elevating need for hospitalization and quality of l ife. β- blockade therapy arrests and reverts LV remodeling and improves the ri sk of life threatening arrhythmias and sudden cardiac death. A few serious adver se effects include hypotension, heart blocks, bradycardia and fluid retention.