[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Significance of Anthropogenic Factors to Freely Dissolved Polycyclic Aromatic Hydrocarbons in Freshwater of China.

Assessment of surface water pollution by organic pollutants is a top priority in many parts of the world, as it provides critical information for implementing effective measures to ensure drinking water safety. This is particularly important in China, where insufficient data of national scale have been acquired on the occurrence of any organic pollutants in the country's water bodies. To fill the knowledge gap, we employed passive samplers to survey polycyclic aromatic hydrocarbons (PAHs) in 42 freshwaters throughout the country. The dissolved Σ24PAH concentrations ranged from 0.28 to 538 ng L-1, with the highest and lowest values obtained in Southern Lake in Wuhan and in the Nam Co Lake in Tibet, respectively. Average Σ24PAH concentrations in West, Central, and East China correlated well with the population densities in these regions. The composition profiles of PAHs showed a mixed PAH source of coal combustion, fossil fuel combustion, and oil spills. In addition, all dissolved PAH concentrations were below the water guidelines developed by the U.S. Environmental Protection Agency, the European Union, and the Canadian government, except for anthracene in Southern Lake. Our results also demonstrated the feasibility of establishing a global network of monitoring organic pollutants in the aquatic environment with passive sampling techniques.

Correction: Aromatic amine electrochemical sensors based on a Co-MOF: a hydrogen bond-induced specific response.

Correction for 'Aromatic amine electrochemical sensors based on a Co-MOF: a hydrogen bond-induced specific response' by Xiao-qin Wu et al., Dalton Trans., 2022, 51, 16861-16869, https://doi.org/10.1039/d2dt02049a.

Aromatic amine electrochemical sensors based on a Co-MOF: a hydrogen bond-induced specific response.

A 2D Co-MOF, {[Co2(L2-)2(bipy)](DMA)·2H2O}n (Co-1, H2L = 2,5-thienedioic acid; bipy = 2,2'-bipyridine; DMA = N,N'-dimethyl acetamide), was synthesized by hydrothermal method. Co-1 has excellent air stability. When modifying the surface of a glassy carbon electrode (GCE) with Co-1, the obtained electrochemical senor Co-1/GCE shows excellent sensitivity towards 1,3-dinitrobenzene (m-DNB) and 2,4-dinitroaniline (2,4-DNA), although the electrochemical conductivity of Co-1 is not that good. The detection limits were as low as 0.0286 µM and 0.161 µM, respectively. DFT studies showed that the main interaction between Co-1 and the guest molecules is via hydrogen bonding, formed by the -NO2 group and the coordinated H2O molecule from the Co-1 skeleton. Furthermore, the characteristic signals of both m-DNB and 2,3-DNA can still be observed in a mimicked industrial waste-water system containing 17 kinds of organic interferents, indicating high selectivity of the Co-1/GCE sensor.

BAHD1 serves as a critical regulator of breast cancer cell proliferation and invasion.

Breast cancer patients with lymphatic metastasis suffer from poor prognoses. There is an urgent need for controlling lymph node metastasis, but it has proven challenging so far. Here, we implemented LASSO analysis of The Cancer Genome Atlas database to identify genes related to lymph node metastasis and prognosis, and 15 genes were selected. We constructed a functional protein association network and univariate Cox regression to identify significant genes. The results showed that BAHD1 could be predictive of lymph node metastasis as well as prognosis. In vitro studies demonstrated that BAHD1 exerted appreciable effects on the proliferation, migration, and invasion capacity of breast cancer cells. Furthermore, downregulation of BAHD1 induced cell cycle arrest in G1 phase. Additionally, the mRNA levels of CCND1, CDK1 and YWHAZ were decreased upon BAHD1 silencing. These findings indicate that the expression of BAHD1 is essential in the progression of breast cancer, which may provide novel therapeutic and diagnostic clues and insights into the prevention of lymph node metastasis in breast cancer.

Interaction of tetrahydrofuran and methyl tert-butyl ether in waste gas treatment by a biotrickling filter bioaugmented with Piscinibacter caeni MQ-18 and Pseudomonas oleovorans DT4.

Bioaugmented biotrickling filter (BTF) seeded with Piscinibacter caeni MQ-18, Pseudomonas oleovorans DT4, and activated sludge was established to investigate the treatment performance and biodegradation kinetics of the gaseous mixtures of tetrahydrofuran (THF) and methyl tert-butyl ether (MTBE). Experimental results showed an enhanced startup performance with a startup period of 9 d in bioaugmented BTF (25 d in control BTF seeded with activated sludge). The interaction parameter I2,1 of control (7.462) and bioaugmented BTF (3.267) obtained by the elimination capacity-sum kinetics with interaction parameter (EC-SKIP) model indicated that THF has a stronger inhibition of MTBE biodegradation in the control BTF than in the bioaugmented BTF. Similarly, the self-inhibition EC-SKIP model quantified the positive effects of MTBE on THF biodegradation, as well as the negative effects of THF on MTBE biodegradation and the self-inhibition of MTBE and THF. Metabolic intermediate analysis, real-time quantitative polymerase chain reaction, biofilm-biomass determination, and high-throughput sequencing revealed the possible mechanism of the enhanced treatment performance and biodegradation interactions of MTBE and THF.

TSH adenoma and syndrome of resistance to thyroid hormones-Two cases report of syndrome of inappropriate secretion of thyrotropin.

SITSH (syndrome of inappropriate secretion of thyrotropin) is a rare clinical state defined as uninhibited serum thyroid stimulating hormone in the presence of elevated thyroid hormone. This state is complicated and mainly caused by the abnormal feedback of hypothalamus-pituitary thyroid axis. The TSH adenoma (TSH-oma) and resistance to thyroid hormones (RTH) are the main etiologies of SITSH. As is well known that the treatment strategies of RTH and TSH-oma are apparently different, thus identifying the difference between RTH and TSH-oma is of great significance for the diagnosis and treatment of SITSH. CASE DESCRIPTION: A 62-year-old man with a state of elevated thyroid hormones and inappropriate elevated serum TSH level was hospitalized in 2016. Results of the pituitary enhanced magnetic resonance imaging and the somatostatin test respectively demonstrated a space-occupying lesion of pituitary and an elevated serum sex hormone binding globulin (SHBG) and inhibited TSH secretion, which indicated the occurrence of TSH-oma. In 2019, a 23-year-old girl with a state of elevated thyroid hormones and inappropriate normal serum TSH was hospitalized. Interestingly, whole exome sequencing detection suggested a pathogenic mutation in thyroid hormone receptor ß (THRB) gene, which has been shown to be associated with RTH. CONCLUSIONS: The difference between TSH-oma and RTH ought to be clarified for their accurate diagnose and treatment. The clinical experiences of the two cases reported here suggest that more detail information such as family medical history, serum SHBG level, and THRB gene test is helpful for the diagnose and treatment of TSH-oma and RTH. Additionally, we also summarized the identification points, diagnosis process, and treatment strategies for these two rare diseases.

Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer.

Given the heterogeneity of solid tumors, single-target CAR-T cell therapy often leads to recurrence, especially in ovarian cancer (OV). Here, we constructed a Tandem-CAR targeting two antigens with secretory activity (IL-12) to improve the effects of CAR-T cell therapy. Twenty coexpressed upregulated genes were identified from the GEO database, and we found FOLR1 (folate receptor 1) and MSLN (mesothelin) were specifically and highly expressed in cancer tissues and only 11.25% of samples were negative for both antigens. We observed an increased proliferation rate for these three CAR-T cells, and Tandem CAR-T cells could efficiently lyse antigen-positive OV cells in vitro and secrete higher levels of cytokines than single-target CAR-T cells. More importantly, in vivo experiments indicated that Tandem CAR-T cells markedly decreased tumor volume, exhibited enhanced antitumor activity, and prolonged mouse survival. Furthermore, the infiltration and persistence of T cells in the Tandem-CAR group were higher than those in the MSLN-CAR and Control-T groups but comparable to those in the FOLR1-CAR group. Collectively, this study demonstrated that Tandem CAR-T cells secreting IL-12 could enhance immunotherapeutic effects by reducing tumor antigen escape and increasing T cell functionality, which could be a promising therapeutic strategy for OV and other solid tumors.

[Treatment of floating knee injury in children with elastic intramedullary nail].

OBJECTIVE: To observe the clinical effect of elastic intramedullary nail in minimally invasive treatment of floating knee injury in children. METHODS: From January 2009 to September 2017, 11 children with floating knee injury were treated with one-off open reduction and elastic intramedullary nail or external fixator fixation, including 7 males and 4 females, aged 5.0 to 11.0 years, with an average age of 8.3 years. The treatment results were evaluated according to karlstrom's standard. RESULTS: Eleven patients were followed up for 8 to 48 months, with an average of 28 months. All the fractures healed at one time, and there were no complications such as nonunion, malunion and serious dysfunction of knee joint. The length of the affected limb in 2 cases was 1.2 to 1.5 cm longer than that in the opposite side without shortening. According to Karlstrom scoring standard, 8 cases were excellent, 1 case was good and 2 cases were middle. CONCLUSION: Elastic intramedullary nail minimally invasive treatment of floating knee injury in children is a safe and effective treatment, which can effectively reduce the fracture and promote bone healing, which is conducive to early functional recovery.

The role of WT1 in breast cancer: clinical implications, biological effects and molecular mechanism.

Although Wilms' tumor gene 1 (WT1) was first cloned and identified as a tumor suppressor gene in nephroblastoma, subsequent studies have demonstrated that it can also play an oncogenic role in leukemia and various solid tumors. WT1 exerts biological functions with high tissue- and cell-specificity. This article reviews the relationship between WT1 and breast cancer from two aspects: (1) clinical application of WT1, including the relationship between expression of WT1 and prognosis of breast cancer patients, and its effectiveness as a target for comprehensive therapy of breast cancer; (2) the biological effects and molecular mechanisms of WT1 in the development and progression of breast cancer, including proliferation, apoptosis, invasion, and metastasis of breast cancer cells.

The role of lysosomes in cancer development and progression.

Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.

Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) has a greater risk of recurrence and metastasis along with a worse prognosis compared with other subtypes of breast cancer. Studies have revealed that mitogenic estrogen signaling is involved in the malignant proliferation of TNBC cells through a novel variant of the estrogen receptor, estrogen receptor α-36 (ER-α36). The results of the present study demonstrated that knockdown of ER-α36 expression in TNBC cells using short hairpin RNA inhibited rapid estrogen signaling bypass activation of the PI3K/AKT signaling pathway. Moreover, the ER-α36 modulator icaritin inhibited the proliferation of TNBC cells both in vitro and in vivo. Here, it was revealed that the combination of icaritin and cetuximab, a therapeutic epidermal growth factor receptor (EGFR) neutralizing antibody, induced apoptosis and inhibited cell proliferation synergistically in TNBC cells. The results of the present study improved the understanding of the underlying mechanisms of TNBC progression and supported the therapeutic potential of combined treatment targeting the ER-α36 and EGFR.

Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN-amplified neuroblastoma growth.

MYCN-amplified neuroblastoma (NB) is characterized by poor prognosis, and directly targeting MYCN has proven challenging. Here, we showed that aldehyde dehydrogenase family 18 member A1 (ALDH18A1) exerts profound impacts on the proliferation, self-renewal, and tumorigenicity of NB cells and is a potential risk factor in patients with NB, especially those with MYCN amplification. Mechanistic studies revealed that ALDH18A1 could both transcriptionally and posttranscriptionally regulate MYCN expression, with MYCN reciprocally transactivating ALDH18A1 and thus forming a positive feedback loop. Using molecular docking and screening, we identified an ALDH18A1-specific inhibitor, YG1702, and demonstrated that pharmacological inhibition of ALDH18A1 was sufficient to induce a less proliferative phenotype and confer tumor regression and prolonged survival in NB xenograft models, providing therapeutic insights into the disruption of this reciprocal regulatory loop in MYCN-amplified NB.

TAZ and myostatin involved in muscle atrophy of congenital neurogenic clubfoot.

BACKGROUND: Muscular atrophy is the basic defect of neurogenic clubfoot. Muscle atrophy of clubfoot needs more scientific and reasonable imaging measurement parameters to evaluate. The Hippo pathway and myostatin pathway may be directly correlated in myogenesis. In this study, we will use congenital neurogenic clubfoot muscle atrophy model to verify in vivo. Further, the antagonistic mechanism of TAZ on myostatin was studied in the C2C12 cell differentiation model. AIM: To identify muscle atrophy in fetal neurogenic clubfoot by ultrasound imaging and detect the expression of TAZ and myostatin in gastrocnemius muscle. To elucidate the possible mechanisms by which TAZ antagonizes myostatin-induced atrophy in an in vitro cell model. METHODS: Muscle atrophy in eight cases of fetal unilateral clubfoot with nervous system abnormalities was identified by 2D and 3D ultrasound. Western blotting and immunostaining were performed to detect expression of myostatin and TAZ. TAZ overexpression in C2C12 myotubes and the expression of associated proteins were analyzed by western blotting. RESULTS: The maximum cross-sectional area of the fetal clubfoot on the varus side was reduced compared to the contralateral side. Myostatin was elevated in the atrophied gastrocnemius muscle, while TAZ expression was decreased. They were negatively correlated. TAZ overexpression reversed the diameter reduction of the myotube, downregulated phosphorylated Akt, and increased the expression of forkhead box O4 induced by myostatin. CONCLUSION: Ultrasound can detect muscle atrophy of fetal clubfoot. TAZ and myostatin are involved in the pathological process of neurogenic clubfoot muscle atrophy. TAZ antagonizes myostatin-induced myotube atrophy, potentially through regulation of the Akt/forkhead box O4 signaling pathway.

The successful treatment of systemic toxic induced paraquat poisoning by skin absorption: case reports and a literature review.

Paraquat (PQ) poisoning is life-threatening, can cause acute organ damage, and has a high mortality. However, cases of skin absorption induced by PQ poisoning are rare. This report describes a case where PQ was absorbed by the patient's skin, causing severe organ damage. Having accidentally touched PQ on his skin, the patient, whose skin festered, became damaged, red, and swollen, developed serious systemic toxic symptoms. The patient recovered after systemic treatment. Generally speaking, being poisoned by PQ through skin absorption is rare. By analyzing the reported PQ poisoning through skin absorption and by reviewing the relevant literature, this paper aims to explore successful treatments for PQ poisoning through skin absorption and to provide treatment guidance for physicians encountering such cases.

Targeting an Autocrine Regulatory Loop in Cancer Stem-like Cells Impairs the Progression and Chemotherapy Resistance of Bladder Cancer.

PURPOSE: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. EXPERIMENTAL DESIGN: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6+ and OV6- bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6+ CSCs in bladder cancer. RESULTS: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6- cells, OV6+ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6+ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6+ bladder cancer CSCs in an orthotopic bladder cancer model. CONCLUSIONS: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.

Author Correction: Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

The original and corrected figures are shown in the accompanying Author Correction.

Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133+Notch1+, whereas the nerve fibers express the Notch ligand Jagged1. The Notch-induced transcription factor Sox9 promotes the transcription of SOX2 and the methylation level of the NOTCH1 promoter is attenuated by the upregulation of SOX2 to reinforce NOTCH1 expression in GSCs. This positive-feedback loop in a cohort of glioma subjects is correlated with a poor prognosis. Inhibition of Notch signaling attenuates the white-matter-tract tropism of GSCs. These findings provide evidence indicating that the NOTCH1-SOX2 positive-feedback loop controls GSC invasion along white matter tracts.

Experimental verification of a model describing solid phase microextraction (SPME) of freely dissolved organic pollutants in sediment porewater.

To verify a theoretical mass balance and multiple compartment partitioning model developed to predict freely dissolved concentrations (FDCs) of hydrophobic organic chemicals (HOCs) using negligible depletion-solid phase microextraction (nd-SPME), a series of sediment slurry experiments were performed using disposable poly(dimethyl)siloxane (PDMS) coated-SPME fibers and (14)C-radiolabeled HOC analogs. First, pre-calibration of disposable PDMS coated fibers for four model compounds (phenanthrene, PCB 52, PCB 153 and p,p'-DDE) with good precision (PCB 52>PCB 153, and the measured and predicted C(pw) values were not substantially different from empirically determined values except for p,p'-DDE.