Id1 expression in CD4 T cells promotes differentiation and function of follicular helper T cells and upregulation of related functional molecules.

Although the roles of E proteins and inhibitors of DNA-binding (Id) in T follicular helper (TFH) and T follicular regulatory (TFR) cells have been previously reported, direct models demonstrating the impact of multiple E protein members have been lacking. To suppress all E proteins including E2A, HEB and E2-2, we overexpressed Id1 in CD4 cells using a CD4-Id1 mouse model, to observe any changes in TFH and TFR cell differentiation. Our objective was to gain better understanding of the roles that E proteins and Id molecules play in the differentiation of TFH and TFR cells. The CD4-Id1 transgenic (TG) mice that we constructed overexpressed Id1 in CD4 cells, inhibiting E protein function. Our results showed an increase in the proportion and absolute numbers of Treg, TFH and TFR cells in the spleen of TG mice. Additionally, the expression of surface characterisation molecules PD-1 and ICOS was significantly upregulated in TFH and TFR cells. The study also revealed a downregulation of the marginal zone B cell precursor and an increase in the activation and secretion of IgG1 in spleen B cells. Furthermore, the peripheral TFH cells of TG mice enhanced the function of assisting B cells. RNA sequencing results indicated that a variety of TFH-related functional molecules were upregulated in TFH cells of Id1 TG mice. In conclusion, E proteins play a crucial role in regulating TFH/TFR cell differentiation and function and suppressing E protein activity promotes germinal centre humoral immunity, which has important implications for immune regulation and treating related diseases.

Vacuolar H+-ATPase in Diabetes, Hypertension, and Atherosclerosis.

Vacuolar H+-ATPase (V-ATPase) is a multisubunit protein complex which, along with its accessory proteins, resides in almost every eukaryotic cell. It acts as a proton pump and as such is responsible for regulating pH in lysosomes, endosomes, and the extracellular space. Moreover, V-ATPase has been implicated in receptor-mediated signaling. Although numerous studies have explored the role of V-ATPase in cancer, osteoporosis, and neurodegenerative diseases, research on its involvement in vascular disease remains limited. Vascular diseases pose significant challenges to human health. This review aimed to shed light on the role of V-ATPase in hypertension and atherosclerosis. Furthermore, given that vascular complications are major complications of diabetes, this review also discusses the pathways through which V-ATPase may contribute to such complications. Beginning with an overview of the structure and function of V-ATPase in hypertension, atherosclerosis, and diabetes, this review ends by exploring the pharmacological potential of targeting V-ATPase.

Prostaglandin E2-Induced AKT Activation Regulates the Life Span of Short-Lived Plasma Cells by Attenuating IRE1α Hyperactivation.

The mechanism regulating the life span of short-lived plasma cells (SLPCs) remains poorly understood. Here we demonstrated that the EP4-mediated activation of AKT by PGE2 was required for the proper control of inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) hyperactivation and hence the endoplasmic reticulum (ER) homeostasis in IgM-producing SLPCs. Disruption of the PGE2-EP4-AKT signaling pathway resulted in IRE1α-induced activation of JNK, leading to accelerated death of SLPCs. Consequently, Ptger4-deficient mice (C57BL/6) exhibited a markedly impaired IgM response to T-independent Ags and increased susceptibility to Streptococcus pneumoniae infection. This study reveals a highly selective impact of the PGE2-EP4 signal on the humoral immunity and provides a link between ER stress response and the life span of SLPCs.

Comparison of anaesthesia strategies on postoperative nausea and vomiting in laparoscopic sleeve gastrectomy: a randomised controlled trial.

BACKGROUND: Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy. METHODS: A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h. RESULTS: Postoperative nausea and vomiting assessment at 0-3 h post-surgery revealed no significant differences between groups. However, at 3-24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group. CONCLUSIONS: The incidence and severity of postoperative nausea and vomiting 3-24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).

A Comparative Study of Nanobio Interaction of Zn-Doped CdTe Quantum Dots with Lactoferrin Using Different Spectroscopic Methods.

In this paper, glutathione (GSH)-coated Zn-doped CdTe quantum dots (QDs) with different particle sizes were synthesized using the "reflow method", and the interaction mechanism between the two QDs and lactoferrin (LF) was investigated systemically with different spectroscopic methods. The steady-state fluorescence spectra showed that the LF formed a tight complex with the two QDs through static bursting and that the electrostatic force was the main driving force between the two LF-QDs systems. The complex generation process was found to be spontaneous (ΔG < 0) and accompanied by exothermic and increasing degrees of freedom (ΔH < 0, ΔS > 0) by using the temperature-dependent fluorescence spectroscopy. The critical transfer distance (R0) and donor-acceptor distance (r) of the two LF-QDs systems were obtained based on the fluorescence resonance energy transfer theory. In addition, it was observed that the QDs changed the secondary and tertiary structures of LF, leading to an increase in the hydrophobicity of LF. Further, the nano-effect of orange QDs on LF is much larger than that of green QDs. The above results provide a basis for metal-doped QDs with LF in safe nano-bio applications.

No evidence for brain renin-angiotensin system activation during DOCA-salt hypertension.

Brain renin-angiotensin system (RAS) activation is thought to mediate deoxycorticosterone acetate (DOCA)-salt hypertension, an animal model for human primary hyperaldosteronism. Here, we determined whether brainstem angiotensin II is generated from locally synthesized angiotensinogen and mediates DOCA-salt hypertension. To this end, chronic DOCA-salt-hypertensive rats were treated with liver-directed siRNA targeted to angiotensinogen, the angiotensin II type 1 receptor antagonist valsartan, or the mineralocorticoid receptor antagonist spironolactone (n = 6-8/group). We quantified circulating angiotensinogen and renin by enzyme-kinetic assay, tissue angiotensinogen by Western blotting, and angiotensin metabolites by LC-MS/MS. In rats without DOCA-salt, circulating angiotensin II was detected in all rats, whereas brainstem angiotensin II was detected in 5 out of 7 rats. DOCA-salt increased mean arterial pressure by 19 ± 1 mmHg and suppressed circulating renin and angiotensin II by >90%, while brainstem angiotensin II became undetectable in 5 out of 7 rats (<6 fmol/g). Gene silencing of liver angiotensinogen using siRNA lowered circulating angiotensinogen by 97 ± 0.3%, and made brainstem angiotensin II undetectable in all rats (P<0.05 vs. non-DOCA-salt), although brainstem angiotensinogen remained intact. As expected for this model, neither siRNA nor valsartan attenuated the hypertensive response to DOCA-salt, whereas spironolactone normalized blood pressure and restored brain angiotensin II together with circulating renin and angiotensin II. In conclusion, despite local synthesis of angiotensinogen in the brain, brain angiotensin II depended on circulating angiotensinogen. That DOCA-salt suppressed circulating and brain angiotensin II in parallel, while spironolactone simultaneously increased brain angiotensin II and lowered blood pressure, indicates that DOCA-salt hypertension is not mediated by brain RAS activation.

Targeting angiotensinogen with RNA-based therapeutics.

PURPOSE OF REVIEW: To summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases. RECENT FINDINGS: Liver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease. SUMMARY: Targeting angiotensinogen with RNA-based therapeutics is a promising new tool to treat hypertension and diseases beyond. Their long-lasting effects are particularly exciting, and if translated to a clinical application of at most a few administrations per year, may help to eliminate nonadherence.

(Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis.

RATIONALE: An elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin-angiotensin system. OBJECTIVES: To investigate the physiological role of (P)RR in lipid metabolism in vivo. METHODS AND RESULTS: We used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis. CONCLUSIONS: Collectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism.

GABAergic regulation of pancreatic islet cells: Physiology and antidiabetic effects.

Diabetes occurs when pancreatic ß-cell death exceeds ß-cell growth, which leads to loss of ß-cell mass. An effective therapy must have two actions: promotion of ß-cell replication and suppression of ß-cell death. Previous studies have established an important role for γ-aminobutyric acid (GABA) in islet-cell hormone homeostasis, as well as the maintenance of the ß-cell mass. GABA exerts paracrine actions on α cells in suppressing glucagon secretion, and it has autocrine actions on ß cells that increase insulin secretion. Multiple studies have shown that GABA increases the mitotic rate of ß cells. In mice, following ß-cell depletion with streptozotocin, GABA therapy can restore the ß-cell mass. Enhanced ß-cell replication appears to depend on growth and survival pathways involving Akt activation. Some studies have also suggested that it induces transdifferentiation of α cells into ß cells, but this has been disputed and requires further investigation. In addition to proliferative effects, GABA protects ß cells against injury and markedly reduces their apoptosis under a variety of conditions. The antiapoptotic effects depend at least in part on the enhancement of sirtuin-1 and Klotho activity, which both inhibit activation of the NF-κB inflammatory pathway. Importantly, in xenotransplanted human islets, GABA therapy stimulates ß-cell replication and insulin secretion. Thus, the intraislet GABAergic system is a target for the amelioration of diabetes therapy, including ß-cell survival and regeneration. GABA (or GABAergic drugs) can be combined with other antidiabetic drugs for greater effect.

Curcumin upregulates the Nrf2 system by repressing inflammatory signaling-mediated Keap1 expression in insulin-resistant conditions.

Both oxidative stress and inflammation contribute to the development of insulin resistance (IR). Curcumin (Cur) not only has an anti-inflammatory effect but also has an antioxidative stress effect via the activation of NF-E2-related factor 2 (Nrf2). Since there is close cross-communication between inflammation and oxidative stress, we examined whether Cur could modulate Nrf2 function via its anti-inflammatory ability and investigated its underlying mechanism. In this study, we show that Cur inhibits inflammatory signaling and Kelch-like ECH-associated protein 1 (Keap1) expression, which is accompanied by the activation of the Nrf2 system. We further identified that the proinflammatory cytokine tumor necrosis factor alpha (TNFα) could stimulate Keap1 synthesis and increase Nrf2 polyubiquitination, but these effects could be significantly inhibited by Cur treatment. This study demonstrates that Cur-induced Nrf2 activation occurs through the inhibition of inflammatory signaling-mediated upregulation of Keap1, contributing to its beneficial effects on redox homeostasis and insulin sensitivity.

Revisiting the Brain Renin-Angiotensin System-Focus on Novel Therapies.

PURPOSE OF REVIEW: Although an independent brain renin-angiotensin system is often assumed to exist, evidence for this concept is weak. Most importantly, renin is lacking in the brain, and both brain angiotensinogen and angiotensin (Ang) II levels are exceptionally low. In fact, brain Ang II levels may well represent uptake of circulating Ang II via Ang II type 1 (AT1) receptors. RECENT FINDINGS: Nevertheless, novel drugs are now aimed at the brain RAS, i.e., aminopeptidase A inhibitors should block Ang III formation from Ang II, and hence diminish AT1 receptor stimulation by Ang III, while AT2 and Mas receptor agonists are reported to induce neuroprotection after stroke. The endogenous agonists of these receptors and their origin remain unknown. This review addresses the questions whether independent angiotensin generation truly occurs in the brain, what its relationship with the kidney is, and how centrally acting RAS blockers/agonists might work.

In Situ Oxidation of Cu2O Crystal for Electrochemical Detection of Glucose.

The development of a sensitive, quick-responding, and robust glucose sensor is consistently pursued for use in numerous applications. Here, we propose a new method for preparing a Cu2O electrode for the electrochemical detection of glucose concentration. The Cu2O glucose electrode was prepared by in situ electrical oxidation in an alkaline solution, in which Cu2O nanoparticles were deposited on the electrode surface to form a thin film, followed by the growth of Cu(OH)2 nanorods or nanotubes. The morphology and electrocatalytic activity of a Cu2O glucose electrode can be tuned by the current density, reaction time, and NaOH concentration. The results from XRD, SEM, and a Raman spectrum show that the electrode surface was coated with cubic Cu2O nanoparticles with diameters ranging from 50 to 150 nm. The electrode exhibited a detection limit of 0.0275 mM, a peak sensitivity of 2524.9 µA·cm-2·mM-1, and a linear response range from 0.1 to 1 mM. The presence of high concentrations of ascorbic acid, uric acid, dopamine and lactose appeared to have no effects on the detection of glucose, indicating a high specificity and robustness of this electrode.

Angiotensin generation in the brain: a re-evaluation.

The existence of a so-called brain renin-angiotensin system (RAS) is controversial. Given the presence of the blood-brain barrier, angiotensin generation in the brain, if occurring, should depend on local synthesis of renin and angiotensinogen. Yet, although initially brain-selective expression of intracellular renin was reported, data in intracellular renin knockout animals argue against a role for this renin in angiotensin generation. Moreover, renin levels in brain tissue at most represented renin in trapped blood. Additionally, in neurogenic hypertension brain prorenin up-regulation has been claimed, which would generate angiotensin following its binding to the (pro)renin receptor. However, recent studies reported no evidence for prorenin expression in the brain, nor for its selective up-regulation in neurogenic hypertension, and the (pro)renin receptor rather displays RAS-unrelated functions. Finally, although angiotensinogen mRNA is detectable in the brain, brain angiotensinogen protein levels are low, and even these low levels might be an overestimation due to assay artefacts. Taken together, independent angiotensin generation in the brain is unlikely. Indeed, brain angiotensin levels are extremely low, with angiotensin (Ang) I levels corresponding to the small amounts of Ang I in trapped blood plasma, and Ang II levels at most representing Ang II bound to (vascular) brain Ang II type 1 receptors. This review concludes with a unifying concept proposing the blood origin of angiotensin in the brain, possibly resulting in increased levels following blood-brain barrier disruption (e.g. due to hypertension), and suggesting that interfering with either intracellular renin or the (pro)renin receptor has consequences in an RAS-independent manner.

Antagonistic interaction between Nodal and insulin modulates pancreatic ß-cell proliferation and survival.

BACKGROUND: Insulin signaling pathway in ß-cell is essential to promote ß-cells proliferation and survival, while Nodal-ALK7-Smad3 signaling involves ß-cells apoptosis. We attempted to address inter-relationship between Nodal and insulin in modulating ß-cell proliferation and apoptosis. METHODS: Using INS-1 ß-cells and isolated rat islets, we examined the effects of Nodal, insulin, or the two combined on ß-cell proliferation and/or apoptosis. RESULTS: The ß-cells under high-glucose or palmitate conditions showed significant up-regulation of Nodal expression and activation of its downstream signaling pathway resulted in increased cleaved caspase-3. Insulin treatment led to significantly attenuated Nodal-induced cell apoptotic pathway. Similar results were found in directly Nodal-treated ß-cell that insulin could partially block Nodal-induced up-regulation of ALK7-Smad3-caspase-3 signaling pathways with significantly attenuated ß-cell apoptosis. Interestingly, we found that insulin-induced Akt activation and downstream molecules including GSK-3ß, ß-catenin and ERK1/2 was significantly attenuated by the co-treatment with Nodal, resulted in decreased cell proliferation. Furthermore, Nodal decreased glucose-evoked calcium influx and played a negative role during glucose-stimulated insulin secretion in the ß-cells. Immunocytochemistry studies showed that Nodal treatment translocated Smad3 from cytosol mostly to the nucleus; however, co-treatment with insulin significantly decreased Smad3 nuclear localization. Co-immunoprecipitation experiments showed a directly interaction between Smad3 and Akt, and this interaction was enhanced by co-treatment with insulin. CONCLUSIONS: Our data suggest that the antagonistic interaction between Nodal and insulin has a role in the regulation of ß-cell mass and secretion.

In vivo direct reprogramming of liver cells to insulin producing cells by virus-free overexpression of defined factors.

Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet ß cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice. We found that hepatocytes could be directly reprogrammed into insulin-producing cells after PNM gene transfection by non-viral hydrodynamics injection, and fasting blood glucose was reduced to normal, and lasted until 100 days after transfection. Intraperitoneal glucose tolerance test (IPGTT) showed that glucose regulation ability was improved gradually and the serum insulin level approached to the level of normal mice with time. Insulin-positive cells were found in the liver tissue, and the expression of various islet ß-cell-specific genes were detected at the mRNA level, including islet mature marker gene Ucn3. In conclusion, we provide a new approach for the treatment of diabetes by in vivo direct reprogramming of liver cells to insulin producing cells through non-viral methods.

Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling.

AIM: Accumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice. METHODS: Mice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg(-1)·d(-1)) for 4 weeks. Another group was treated with LPS (50 µg·kg(-1)·d(-1), sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured. RESULTS: In high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin. CONCLUSION: Metformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects.

Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells.

Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells.

Controlled synthesis and tunable upconversion luminescence of NaYW2O8:Yb3+/Ho3+ nanocrystals.

Tetragonal phase NaYW2O8:Yb3+/Ho3+ nanocrystals were successfully synthesized using a hydrothermal method with a subsequent calcination treatment. Under 980 nm excitation, the 5S2/5F4 --> 5I8 and 5F5 --> 5I8 emissions were observed. The relative intensity of the 5F5 --> 5I8 to the 5S2/5F4 -->5I8 in the samples increased with increasing the pH values of the resultant solutions. The CIE coordinates of the upconversion luminescence were (0.43, 0.54), (0.41, 0.55), (0.40, 0.56), (0.39, 0.54), (0.37, 0.49), (0.35, 0.44), and (0.33, 0.37) for the samples prepared at pH = 7, 8, 9, 10, 11, 13, and 14, respectively. In addition, the upconversion mechanism was also investigated.

Relationship between iNOS expression and apoptosis in cerebral tissue, and the effect of sini injection in endotoxin shock rats.

OBJECTIVE: To investigate the dynamic changes and relationship of inducible nitric oxide synthase (iNOS) and apoptosis in endotoxin shock rats, as well as the effects of Sini injection. METHODS: In total, 102 Sprague-Dawley (SD) rats were randomly divided into a normal group (n = 6, NG), sham operation group (n = 24, OG), model group (n = 24, MG), dexamethasone group (n = 24, DG), and Sini group (n = 24, SG). The endotoxin shock model was induced by an intravenous injection of lipopolysaccharide (LPS) (8 mg/kg). Rats in the OG, MG, DG, and SG groups were further divided into 4 groups: 1, 2, 3 and 6 h after shock groups (n = 6 per group). iNOS expression was detected by immunohistochemistry. Terminal Deoxynucleotidyl Transferase Mediated Deoxyuridine Triphosphate-biotin Nick End Labeling was employed to measure apoptosis. RESULTS: No iNOS expression was found in the OG group. Compared with the OG group, iNOS expression in the MG group was markedly elevated, reached a peak at 1 h (P < 0.01), decreased at 2 and 3 h, and rebounded at 6 h. Compared with the MG group, iNOS expression decreased significantly in both the DG (P < 0.05) and SG (P < 0.01) groups at 6 h. The number of apoptotic cells in the MG group was markedly increased than that in the NG and OG (P < 0.01) groups, and reached a peak at 6 h. The number of apoptotic cells in the DG group at 1 and 2 h (P < 0.01) and SG group at 2, 3 and 6 h (P < 0.01) decreased when compared with the MG group. CONCLUSION: Sini injection can significantly inhibit NO generation, which decreases apoptosis and subsequently protects the brain from endotoxic shock.

Diffuse large B­cell lymphoma and monoclonal gammopathy secondary to immune thrombocytopenic purpura: A case report.

The present study reports the case of a patient with diffuse large B-cell lymphoma (DLBCL) and monoclonal gammopathy (MG) secondary to immune thrombocytopenia purpura (ITP). The clinical diagnoses and investigations of this case are reported. To the best of our knowledge, this is the first study to report DLBCL and MG secondary to ITP. The patient presented with a rare constellation of diseases, which made the diagnosis and treatment difficult for the physicians. The patient was followed up for 10 years using the morphological examination of bone marrow cells after chemotherapy, and currently continues with follow-up examinations. Treatments and prognoses for ITP, DLBCL and MG are common. However, treatments and prognoses are unclear for patients with all three conditions. The different clinical manifestations and disease processes of DLBCL and MG secondary to ITP cause difficulties for physicians in terms of treatment and prognosis. The present case report describes the comprehensive evaluation, diagnosis and treatment of a patient with DLBCL and MG secondary to, and concurrent with, ITP.