The impact of different antibiotic injection regimens on patients with severe infections: A meta-analysis.

Severe infection is a critical health threat to humans, and antibiotic treatment is one of the main therapeutic approaches. Nevertheless, the efficacy of various antibiotic injection regimens in severe infection patients remains uncertain. This study aimed to comprehensively evaluate the impact of various antibiotic injection strategies on patients with severe infection through a meta-analysis.

Novel Sigma-2 receptor ligand A011 overcomes MDR in adriamycin-resistant human breast cancer cells by modulating ABCB1 and ABCG2 transporter function.

Multidrug resistance (MDR) is thought to be one of the main reasons for the failure of chemotherapy in cancers. ATP-binding cassette subfamily B member 1 (ABCB1) or P-glycoprotein (P-gp) and ATP-binding cassette subfamily G member 2 (ABCG2) play indispensable roles in cancer cell MDR. Sigma-2 (σ) receptor is considered to be a cancer biomarker and a potential therapeutic target due to its high expression in various proliferative tumors.

Research on the function of the Cend1 regulatory mechanism on p75NTR signaling in spinal cord injury.

How to use NSC repair mechanisms, minimize the loss of neurons, and recover the damaged spinal cord functions are hotspots and difficulties in spinal cord injury research. Studies have shown that Cend1 signaling is involved in regulating the NSC differentiation, that p75NTR signaling is involved in the regulation of mature neuronal apoptosis and that NSC differentiation decreases mature neuron apoptosis. Our research group found an interaction between Cend1 and p75NTR, and there was a correlation with spinal cord injury.

A011, a novel small-molecule ligand of σ receptor, potently suppresses breast cancer progression via endoplasmic reticulum stress and autophagy.

Breast cancer has surpassed lung cancer to become the most commonly diagnosed cancer in women worldwide. Sigma-2 (σ) receptor is considered to be a potential therapeutic target for breast cancer because of its high expression in breast cancer cells and low expression in normal breast cells. Many σ ligands have been reported to have excellent anticancer activity, but their mechanism of action has not been fully elucidated.

Subacute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.

As a novel heat shock protein 90 inhibitor, AT-533 exhibits various biological activities , including anti-viral, anti-tumor and anti-inflammatory activities. Moreover, AT-533 gel, a gel dosage form of AT-533, has been suggested to have anti-keratitis and herpes simplex virus type-1 infection-induced effects on the skin lesions of animals. However, the safety evaluation of AT-533 and AT-533 gel has, to the best of our knowledge, not been examined in toxicological tests.

[Mn(PaPy2Q)(NO)]ClO, a Near-Infrared Light activated release of Nitric Oxide drug as a nitric oxide donor for therapy of human prostate cancer cells in vitro and in vivo.

This study was the first to investigate the synthesis of near-infrared light-sensitive NO prodrug [Mn(PaPy2Q)(NO)]ClO, and detection the amount of NO released by the drug in different time and near infrared light (10 mW, 20 mW). It showed that with the increase of light power, the time required for the drug to release NO was shortened, and we selected 20 mW, 10 min as a follow-up study of light power and irradiation time while ensuring the near-infrared light did not affect tumor cells. The cells were irradiated with 20 mW of near-infrared light for 10 min at 6 h after treatment with the drug on PC-3, LNCaP and 22RV1 cells, and NO concentration and cell survival rate were tested at 12 h, 24 h and 48 h.

Synthesis, binding, and functional properties of tetrahydroisoquinolino-2-alkyl phenones as selective σR/TMEM97 ligands.

Sigma-2 receptor (σR/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σR/TMEM97.

Sigma ligands as potent inhibitors of Aβ and AβOs in neurons and promising therapeutic agents of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease and characterized by dementia, memory decline, loss of learning and cognitive disorder. The main pathological features of AD are the deposition of amyloid plaques and the formation of neurofibrillary tangles (NFTs) in the brain. The current anti-AD drugs have shown unsatisfactory therapeutic results.

Sigma-2 Receptor as a Potential Drug Target.

Sigma-2 receptor plays key roles in promoting tumor cell apoptosis, enhancing efficacy of anti-tumor drugs, blocking signal transduction controlled by Aβ oligomers, regulating Ca homeostasis and protecting nerve cells. Studies indicated that sigma-2 receptor may be closely coupled with ROS, LDL, mTOR, RAS, PLC/PKC, lysosomal autophagy and mitochondrial super oxidative stress. In addition, the high expression of this receptor in proliferating cells and nerve cells indicates that sigma-2 receptor is an ideal molecular target for imaging and therapeutic development for cancer, Alzheimer's disease, schizophrenia and traumatic brain injury.

A novel quinolinylmethyl substituted ethylenediamine compound exerts anti-cancer effects via stimulating the accumulation of reactive oxygen species and NO in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Owing to the limitations in the current therapeutic strategies for treating HCC, development of novel chemotherapeutic drugs is urgently needed. In the present study, we found that QQM, a newly-synthesized quinolinylmethyl substituted ethylenediamine compound, exhibited anti-HCC effects both in vitro and in vivo.

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion.

The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients.

Isolation, synthesis, and cytotoxicity evaluation of two impurities in nomegestrol acetate.

Nomegestrol acetate (NOMAc) is a synthetic progesterone analog and classified as a fourth-generation progestin. It has been approved in many countries for oral contraception, hormonal replacement therapy (HRT), and treatment of various gynecological disorders. There are several synthetic routes reported for the synthesis of NOMAc and they all share the very similar last three to five steps toward the conversion of 6-methylene to 6-methyl-6,7-unsaturated structure.

Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands.

Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy.

Synthesis and evaluation of tetrahydroindazole derivatives as sigma-2 receptor ligands.

A series of tetrahydroindazole derivatives were synthesized and evaluated for their affinities for both sigma-1 and sigma-2 receptors. These compounds are hybrid structures of a tetrahydroindazole substituted benzamide and a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety or a 9-azabicyclo[3.3.

Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis.

We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein.

Sigma-2 receptor ligands and their perspectives in cancer diagnosis and therapy.

The sigma-2 receptor is highly expressed in various rapidly proliferating cancer cells and regarded as a cancer cell biomarker. Selective sigma-2 ligands have been shown to specifically label the tumor sites, induce cancer cells to undergo apoptosis, and inhibit tumor growth. Sigma-2 ligands are potentially useful as cancer diagnostics, anticancer therapeutics, or adjuvant anticancer treatment agents.

catena-Poly[[[aqua-(1,10-phenanthro-line)manganese(II)]-μ-adamantane-1,3-dicarboxyl-ato] monohydrate].

In the title coordination polymer, {[Mn(C(12)H(14)O(4))(C(12)H(8)N(2))(H(2)O)]·H(2)O}(n), the Mn(II) atom has a highly distorted cis-MnN(2)O(4) octa-hedral geometry arising from its coordination by a bidentate phenanthroline ligand, a water mol-ecule and monodentate and bidentate adamantane-1,3-dicarboxyl-ate dianions. The bridging dianion leads to [001] chains in the crystal. The chains are linked by O-H⋯O hydrogen bonds, involving both the coordinated and uncoordinated water mol-ecules, thereby forming a two-dimensional network.

[Observation on therapeutic effect of electroacupuncture for treatment of sudden hearing loss].

Objective: To observe the therapeutic effect of electroacupuncture for treatment of sudden hearing loss and to compare with western medicine therapy.

Methods: Sixty cases were randomly divided into an electroacupuncture group and a medication group, 30 cases in each group. The electroacupuncture group was treated with electroacupuncture at Tinghui (GB 2), Yifeng (TE 17), Hegu (LI 4), Xiaxi (GB 43), Zhongzhu (TE 3), etc.

[Effects of Feiji Formula on lung cancer metastasis in mice].

Objective: To observe the effects of Feiji Formula, a compound traditional Chinese herbal medicine, on lung cancer metastasis in mice.

Methods: The lung cancer metastasis model of mice was established in this experiment study. Twenty-four mice were randomly divided into three groups: untreated group, cisplatin group and Feiji Formula group.

[Intervention effect of Feiji Recipe on immune escape of lung cancer].

Objective: To evaluate the intervention effect of Feiji Recipe (FJR) on tumor immune escape.

Methods: In the prospective randomized control study, 60 cases of middle stage and advanced non-small cell lung cancer (NSCLC) with qi-yin deficiency syndrome were randomly assigned to the treatment group and the control group, 30 in each group. The levels of CD+ CD25+ Tr, interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), sCD44v6 and transforming growth factor-beta1 (TGF-beta1) of peripheral blood were observed before and after treatment, and the clinical efficacy of FJR was evaluated depending upon the changes in tumor size, Karnofsky Performance scoring (KPS) and TCM syndrome.

[Changes of trace elements in regional lymph nodes of gastric carcinoma].

Objective: To explore the relationship between the changes of trace elements and lymphatic metastasis in gastric carcinoma.

Methods: Trace elements including Fe, Mg, Mn, Ca, Cu, Zn, Se were measured in primary gastric carcinoma and regional lymph nodes from 40 patients with gastric carcinoma, and compared among the primary tumor, metastatic, and non-metastatic nodes.

Results: There were no significant differences in the contents of Fe, Mg, Mn and Ca among primary gastric tumors, regional lymph nodes with or without metastasis (P=0.

N-[18F]4'-fluorobenzylpiperidin-4yl-(2-fluorophenyl) acetamide ([18F]FBFPA): a potential fluorine-18 labeled PET radiotracer for imaging sigma-1 receptors in the CNS.

A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selective imaging agent, [(18)F]FBFPA. The results of the study indicate that this radiotracer readily crosses the blood-brain barrier and labels sigma(1) receptors in vivo. In vivo blocking studies with a sigma(1) selective ligand and a nonselective sigma(1)/sigma(2) receptor ligand indicates that [(18)F]FBFPA labels sigma(1) and not sigma(2) receptors in rodent brain.

[Effect of saikosaponins on epileptic rat electroenciphalogram].

Objective: To study the effect of saikosaponins on the electroencephalogram (EEG) of epileptic rats to evaluate its therapeutic effect against epilepsies.

Methods: Sixty 8-week-old healthy SD rats were randomized into normal control group (A), epileptic model group (B), lamotrigine group (C), and 3 saikosaponin groups of small, moderate and high doses (D, E, and F groups, respectively), with 10 rats in each group. Penicillin was used to induce epilepsy in the latter 5 groups, and the EEG and onset of epileptic seizures were observed in each group.

Conformationally-flexible benzamide analogues as dopamine D3 and sigma 2 receptor ligands.

A series of conformationally-flexible analogues was prepared and their affinities for D2-like dopamine (D2, D3 and D4) were determined using in vitro radioligand binding assays. The results of this structure-activity relationship study identified one compound, 15, that bound with high affinity (K(i) value=2nM) and moderate selectivity (30-fold) for D3 compared to D2 receptors. In addition, this series of compounds were also tested for affinity at sigma1 and sigma2 receptors.

Synthesis of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors.

A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D(2), D(3), and D(4) receptors was measured using in vitro binding assays. The results of receptor binding studies indicated that the incorporation of a pyrrole moiety between the phenyl ring and the basic nitrogen resulted in a significant increase in the selectivity for dopamine D(3) receptors. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-5-(2-(3-pyridal)piperidinyl)methyl-1H-pyrrole (6p), which has a D(3) receptor affinity of 4.