[The Preventive Effect of Levofloxacin Combined with G-CSF or Only G-CSF Supportive Therapy on Infection in Autologous Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46，P =0.50; χ2=0.03，P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04，P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00，P =0.09; t =0.94，P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53，P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice.

BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

Effect of Dexmedetomidine on Postoperative Renal Function in Patients Undergoing Cardiac Valve Surgery Under Cardiopulmonary Bypass: A Randomized Clinical Trial.

OBJECTIVE: The effect of dexmedetomidine on postoperative renal function was investigated in patients undergoing cardiac valve surgery under cardiopulmonary bypass (CPB). DESIGN: A randomized controlled trial. SETTING: University teaching, grade A tertiary hospital. PARTICIPANTS: A total of 70 patients scheduled to undergo cardiac valve replacement or valvuloplasty under CPB were eligible and randomly divided into groups D (n = 35) and C (n = 35) between January 2020 and March 2021. INTERVENTIONS: Patients in group D were administered 0.6 µg/kg/h of dexmedetomidine intravenously from 10 minutes before anesthesia induction to 6 hours after surgery; normal saline was used instead of dexmedetomidine in group C. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of acute kidney injury (AKI). Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes (2012). It was 22.86% and 48.57% in groups D and C, respectively (p = 0.025). The secondary outcomes were intraoperative hemodynamics and various indices in serum. Ten minutes before CPB (T1), 10 minutes after CPB (T2), and 30 minutes after CPB (T3), mean arterial pressure in group D was lower than that in group C, with statistical significance (74.94 ± 8.52 v 81.89 ± 13.66 mmHg, p=0.013; 62.83 ± 11.27 v 71.86 ± 7.89 mmHg, p < 0.001; 72.26 ± 8.75 v 78.57 ± 8.83 mmHg, p = 0.004). At T1, the heart rate in group D was significantly lower than in group C (80.89 ± 14.04 v 95.54 ± 12.53 bpm, p=0.022). The tumor necrosis factor α, interleukin-6, C-reactive protein, and cystatin C levels in group D were lower than those in group C after the surgery (T4) and 24 hours after surgery (T5), with statistical significance. The duration of mechanical ventilation, intensive-care-unit stay time, and hospital stay time in group D were significantly shorter than in group C. The incidences of tachycardia, hypertension, nausea, and vomiting in group D were similar to those in group C. CONCLUSIONS: Dexmedetomidine may be considered as a way to reduce the incidence and severity of postoperative AKI in patients undergoing cardiac valve surgery under cardiopulmonary bypass.

[Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 µmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION: Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Dysregulated miR-222-3p in plasma exosomes of preeclampsia patients and its In vitro effect on HTR8/SVneo extravillous trophoblast cells by targeting STMN1.

OBJECTIVE: To investigate the diagnostic efficiency of miR-222-3p in plasma exosomes (Exos) and plasma for preeclampsia (PE) and the effect of miR-222-3p targeting STMN1 in PE. METHODS: MiR-222-3p levels in total plasma and plasma Exos were detected in PE patients and healthy controls. A bioinformatics database and dual-luciferase reporter assay were employed to verify the targeting relationship between miR-222-3p and STMN1. Trophoblast HTR-8/Svneo cells were transfected with miR-222-3p inhibitors with/without STMN1 shRNA, followed by MTT, wound healing and Transwell invasion assays. The mRNA and protein expressions were measured by qRT‒PCR and Western blotting, respectively. RESULTS: MiR-222-3p levels in total plasma and plasma Exos were higher in PE patients than in healthy controls, particularly in severe PE patients. In addition, miR-222-3p levels in total plasma and plasma Exos from PE patients were positively correlated with diastolic and systolic blood pressure. The area under the curve (AUC) of miR-222-3p in total plasma for PE diagnostic efficiency was 0.798, with a sensitivity of 76.67% and specificity of 71.93%, while the AUC of miR-222-3p in plasma Exos was 0.708 (sensitivity: 61.67%; specificity: 78.95%). In vitro, miR-222-3p targeted STMN1 in HTR-8/Svneo cells. Low miR-222-3p expression reversed the inhibitory effect of STMN1 shRNA on the proliferation, invasion and migration of HTR/SVneo cells. CONCLUSION: PE patients had increased miR-222-3p expression in total plasma and plasma Exos, which both have high diagnostic efficiency for PE. MiR-222-3p can target STMN1 to promote the proliferation, invasion and migration of HTR-8/Svneo cells and is a potential therapeutic target of PE.

[Effect of ethanol extract of Gastrodiae Rhizoma on mitochondrial dysfunction in cerebral ischemia-reperfusion injury].

This study observed the effects of ethanol extract of Gastrodiae Rhizoma(GE) on multiple aspects of mitochondrial dysfunction by investigating the mitochondria isolated from rat brains subjected to focal middle cerebral artery occlusion/reperfusion(MCAO/R). SD rats were randomly divided into a sham operation group(Sham), a model group(MCAO/R), low-and high-dose ethanol extract of GE groups(262.3 and 524.6 mg·kg~(-1)), and a nimodipine group(Nim, 15 mg·kg~(-1)). After continuous intragastric administration for 7 days, the MCAO/R model was induced in rats by the suture method. The neurological function and percentage of cerebral infarction volume were measured 24 h after reperfusion, and mitochondrial ultrastructure was observed under an electron microscope. Mitochondria were separated by gradient centrifugation and detected for reactive oxygen species(ROS), malondialdehyde(MDA), respiratory chain enzyme complex Ⅰ-Ⅳ activity, mitochondrial permeability transition pore(mPTP), mitochondrial membrane potential(MMP), and mitochondrial adenosine triphosphate(ATP) content. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression of cytochrome C(Cyt C) in different sites. TUNEL staining was used to observe the apoptosis of brain tissues in each group, and Western blot was used to detect the expression of B-cell lymphoma 2(Bcl-2) and Bcl-2-associated X protein(Bax) in brain tissues. The experimental results revealed that compared with the Sham group, the MCAO/R group showed evident neurological dysfunction and cerebral infarction(P<0.01) accompanied by mitochondrial swelling and crest disappearance, increased ROS level and MDA content, inhibited activity of respiratory chain enzyme complex Ⅰ-Ⅳ, abnormal opening of mPTP, and reduced MMP and mitochondrial ATP(P<0.01). Besides, many Cyt C was released from mitochondria into the cytoplasm to induce apoptosis(P<0.01). The ethanol extract of GE positively affected the behavior deficit and mitochondrial health of MCAO/R rats, with the manifestations of decreased production of ROS and MDA(P<0.01), potentiated activity of mitochondrial respiratory chain enzyme complex Ⅰ-Ⅳ, and restored the level of mPTP(P<0.05). In addition, the ethanol extract of GE reduced the loss of MMP and the escape of Cyt C to the cytoplasm(P<0.05), reduced the number of TUNEL positive cells(P<0.01) accompanied by the decrease in Bax and the up-regulation of Bcl-2(P<0.01), and increased the level of ATP(P<0.01). In conclusion, GE ethanol extract has a protective effect against MCAO/R-induced mitochondrial dysfunction, and the mechanism may be related to the regulation of oxidative stress, maintenance of functional morphology of mitochondria, and inhibition of endogenous apoptosis.

New bio-based polyester with excellent spinning performance: poly(tetrahydrofuran dimethanol-co-ethylene terephthalate).

With the excessive consumption of fossil energy, technologies that transform bio-based resources into materials have received more and more attention from researchers in recent decades. In this paper, a series of poly(ethylene 2,5-tetrahydrofuran dimethyl terephthalate; PEFTs) with different components were synthesized from 2,5-tetrahydrofuran dimethanol (THFDM), terephthalic acid (TPA), and ethylene glycol (EG). Their chemical structures and compositions were determined by FTIR, 1H NMR, and 13C NMR. With the increase in THFDM content, the crystallization, T m, and tensile strength of PEFTs gradually decrease because the introduced THFDM breaks the order of molecular chains, while the thermal stability and T g remain stable. PEFTs seem to present a significant shear thinning phenomenon, which was indicated by the rheological test. Electrospinning technology was used to explore the spinnability of PEFT; it was found that PEFTs have better spinning performance than PET. In addition, due to the good hydrophobicity and porosity of PEFT nanofiber films, they have potential application value in the manufacture of hydrophobic nanofiber and filter films.

Treatment outcome and efficacy of therapeutic plasma exchange for transplant-associated thrombotic microangiopathy in a large real-world cohort study.

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.

[Effect of Desmodium renifolium on ovariectomized rat model of osteoporosis via BMP-2/Smads signaling pathway].

This study aimed to investigate the effect of Desmodium renifolium(Linn.) Schindl on ovariectomized rat model of osteoporosis and explore the underlying mechanism. Rats were randomized into a sham group, a model group, a Xianlin Gubao group, and low-, medium-, and high-dose D. renifolium groups. Bilateral oophorectomy was performed in other groups except sham group(removal of bilateral peri-ovarian adipose tissue). The sham group and model group were administrated with equal volume of 0.5% CMC-Na, Xianlin Gubao group with Xianlin Gubao, and D. renifolium groups with different concentrations of alcoholic extract of D. renifolium once a day for 14 weeks. The body weight of rats were recorded during the experiment. The levels of estradiol(E_2), 1,25-dihydroxyvitamin D_3 [1,25(OH)_2D_3], calcium(Ca), and phosphorus(P) in serum were determined after the administration. The femur microstructure was analyzed via micro-CT. RT-PCR and Western blot were employed to respectively determine the mRNA and protein levels of bone morphogenetic protein 2(BMP-2), Runt-related transcription factor 2(Runx2), and osterix(OSX) in the tibia of rats. The results indicated that D. renifolium significantly inhibited the weight growth, improved the uterus appearance, elevated the levels of E_2, Ca, P, and 1,25(OH)_2D_3 in serum, increased the number and reduced the fracture of bone trabeculae, ameliorated the bone microstructure parameters, and up-regulated the mRNA and protein levels of BMP-2, Runx2, and OSX. All the results demonstrated that D. renifolium had significant protective effect on the ovariectomized rat model of osteoporosis by regulating the BMP-2/Smads signaling pathway.

[Review of Research Progress in Biliary Substitutes].

Research and development of artificial biliary substitutes is an indispensable part of modern biliary surgery, bearing great clinical significance on the recovery of the normal functions of the biliary system. The implantation of artificial biliary substitutes may cause the blockage or stenosis of the biliary duct at the transplantation site, which is the most urgent problem in the research of artificial biliary substitutes. The fundamental cause of the problem is tissue hyperplasia caused by chronic inflammatory stimulation of artificial biliary substitutes. The regeneration of new bile duct tissue at the transplantation site can provide a solution to this problem. By looking at the literature from China and abroad, this paper reviewed the research and development of non-degradable artificial bile duct, degradable artificial bile duct and tissue-engineered artificial bile duct in order to provide reference for the further development of biliary replacements. Future studies should focus on the rapid formation of biliary epithelial layer on the tissue-engineered artificial biliary wall, the promotion of new biliary tissue formation, and the regulation of the degradation performance and mechanical properties of artificial biliary duct in order to fundamentally solve the problems encountered in the research of artificial biliary substitutes and accelerate the development of artificial biliary duct.

Intervention for reducing anxiety during screening mammography: A protocol for systematic review and meta-analysis.

BACKGROUND: Mammography is considered a fundamental part of diagnosis in modern health care services. It provides low dose images of normal structures and pathological soft tissues in the breast. Many reports suggested that intervention is playing a positive role in anxiety related to mammography, but there is no high-quality evidence to prove its effects. This paper reports the protocol of a systematic review (SR) and meta-analysis (MA) to clarify effectiveness of intervention during screening mammography. METHODS: A systematic literature search will be performed in the Cochrane Library, PubMed, Embase and Web of Science from inception to July 2020. Randomized controlled trials (RCTs) will be included to evaluate any interventions in the treatment of anxiety related to mammography screening. The main outcome measure is the impact on patient anxiety, and the impact on patient breast cancer worry, the impact on patient satisfaction are the additional outcome measure. Risk of bias assessment of the included RCTs will be carried out using Cochrane Collaboration's tool for RCTs. The Review Manager 5.4 for Windows will be used to perform the MA and generate the result figures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to evaluate the quality of evidence. Subgroup analysis and sensitivity analysis will be conducted to assess the robustness of the results. RESULTS: A total of 782 English studies of anxiety related to mammography screening were obtained through search. After preliminary screening, 773 non-conforming studies were excluded. Finally, nine English studies of anxiety related to mammography screening will be included for full-text assessment. We will submit the results of this SR and MA to a peer-reviewed journal for publication. CONCLUSIONS: This study will provide reliable evidence for intervention for reducing anxiety in women receiving screening mammography. INPLASY REGISTRATION NUMBER: INPLASY202070131.

Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology.

BACKGROUND: Ginseng, a traditional Chinese medicine, was used to prevent and treat many diseases such as diabetes, inflammation, and cancer. In recent years, there are some reports about the treatment of lung adenocarcinoma with ginseng monomer compounds, but there is no systematic study on the related core targets and mechanism of ginseng in the treatment of lung adenocarcinoma up to now. Therefore, this study systematically and comprehensively studied the molecular mechanism of ginseng in the treatment of lung adenocarcinoma based on network pharmacology and further proved the potential targets by A549 cell experiments for the first time. METHODS: The targets of disease and drug were obtained from Gene database. Subsequently, the compound-target network was constructed, and the core potential targets were screened out by plug-in into Cytoscape. Furthermore, the core targets and mechanism of ginseng in the treatment of lung adenocarcinoma were verified by MTT test, cell scratch test, immunohistochemistry, and qRT-PCR. RESULTS: 1791 disease targets and 144 drug targets were obtained by searching the Gene database. Meanwhile, 15 core targets were screened out: JUN, MAPK8, PTGS2, CASP3, VEGFA, MMP9, AKT1, TNF, FN1, FOS, MMP782, IL-1ß, IL-2, ICAM1, and HMOX1. The results of cell experiments indicate that ginseng could treat lung adenocarcinoma by cell proliferation, migration, and apoptosis. In addition, according to the results of the 15 core targets by qRT-PCR, JUN, IL-1ß, IL-2, ICAM1, HMOX1, MMP9, and MMP2 are upregulated core targets, while PTGS2 and TNF are downregulated core targets. CONCLUSION: This study systematically and comprehensively studied 15 core targets by network pharmacology for the first time. Subsequently, it is verified that 9 core targets for ginseng treatment of lung adenocarcinoma, namely, JUN, IL-1ß, IL-2, ICAM1, HMOX1, MMP9, MMP2, PTGS2, and TNF, are closely related to the proliferation, migration, and apoptosis of lung adenocarcinoma cells. This study has reference value for the clinical application of ginseng in the treatment of lung adenocarcinoma.

Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications.

Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.

SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.

This study aimed to compare the sirtuin 2 (SIRT2) expression between tumor tissue and adjacent tissue, and to investigate the association of tumor SIRT2 expression with clinical characteristics and survival profiles in cervical cancer patients.One hundred ninety-one cervical cancer patients were reviewed in this retrospective study. All patients underwent surgical resection and had well-preserved tumor tissue and adjacent tissue, which were obtained for SIRT2 expression detection by immunohistochemistry (IHC). Clinical parameters were obtained. Disease free survival (DFS) and overall survival (OS) were calculated.Both SIRT2 expression by IHC score (P < .001) and the percentage of SIRT2 high expression (defined as IHC score >3) (P < .001) were declined in tumor tissue compared with paired adjacent tissue. In addition, SIRT2 expression in tumor tissue was negatively correlated with tumor size (P = .047), lymph node metastasis (P = .009) and FIGO stage (P = .001). And the DFS (P = .007) as well as OS (P = .008) were better in patients with SIRT2 high expression compared with patents with SIRT2 low expression. Univariate Cox's proportional hazards regression model analyses revealed that high SIRT2 expression in tumor tissue was a predictive factor for more prolonged DFS (P = .009) and OS (P = .011), while multivariate Cox's proportional hazards regression model analysis disclosed that it lacks independent predictive value for DFS (P = .084) or OS (P = .132).SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.

Shengxuening versus Oral Iron Supplementation for the Treatment of Renal Anemia: A Systematic Review.

Shengxuening (SXN), as an effective supplement to heme-like iron, has been widely used in China to treat renal anemia. However, proof of its use for improving inflammation is scarce in the past decades. This work aimed to evaluate the effectiveness of SXN with inflammatory factors as primary endpoints. By searching PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP Information/ China Science and Technology Journal Database, and WANFANG Database, we identified previous studies that met the inclusion criteria and included them in the systematic review. Analyses were performed using STATA. Nine randomized controlled trials were included in this systematic review. The results revealed that, when compared with oral iron supplementation, SXN can reduce the level of inflammatory factors, including hs-CRP (WMD -1.93 mg/L; 95% CI -2.14 to -1.72), IL-6 (P< 0.05), and TNF-α (P< 0.05), and significantly enhance the level of Hb (WMD 13.40 g/L; 95% CI 12.95 to 13.84), TSAT (WMD 6.88%; 95% CI 6.50 to 7.26), and SF (WMD 38.46 µg/L; 95% CI 23.26 to 53.67). Moreover, SXN exhibits a superior security than oral iron supplementation with less gastrointestinal adverse reactions (RR 0.14; 95% CI 0.06 to 0.32). In patients with renal anemia, SXN is more efective and safer than oral iron supplementation, especially in reducing the level of inflammation.

Treatment with Stem Cells from Human Exfoliated Deciduous Teeth and Their Derived Conditioned Medium Improves Retinal Visual Function and Delays the Degeneration of Photoreceptors.

Retinitis pigmentosa (RP) is a hereditary disease characterized by degeneration and the loss of photoreceptors. Stem cell-based therapy has emerged as a promising strategy for treating RP. Stem cells from exfoliated deciduous teeth (SHEDs), a type of mesenchymal stem cell from human exfoliated deciduous teeth, have the potential to differentiate into photoreceptor-like cells under specific induction in vitro. It has been confirmed that through paracrine secreta, SHEDs exert neurotrophic, angiogenic, immunoregulatory, and antiapoptotic functions in injured tissues. This study was designed to determine whether retinal-differentiated SHEDs and the conditioned medium derived from SHEDs (SHEDs-CM) have therapeutic effects in a mouse model of RP. The results showed that both SHEDs and SHEDs-CM improved electroretinogram responses, ameliorated photoreceptor degeneration, and maintained the structure of the outer segments of photoreceptors. The therapeutic effects were related to antiapoptotic activity of SHEDs and SHEDs-CM. Thus, SHEDs may be a promising stem cell source for treating retinal degeneration.

[Electroacupuncture Relieves Pain by Down-regulating Expression of Hippocampal High Mobility Group Protein 1 and Contents of TNF-α and IL-1 ß in Rats with Chronic Neuropathic Pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of high mobility group protein 1 (HMGB 1) and related downstream effectors of proinflammatory cytokines in the hippocampus in chronic neuropathic pain rats, so as to investigate its mechanism underlying neuropathic pain relief. METHODS: Male SD rats were randomized into sham, model, and EA groups, with 12 rats in each group. The neuropathic pain model was established by ligature of the left sciatic nerve to induce chronic constriction injury (CCI). EA was applied to bilateral "Zusanli"(ST 36) and "Yanglingquan"(GB 34) for 30 min, once daily for 7 days. The mechanical withdrawal threshold (WMT) was detected using an electronic von Frey anesthesiometer. The expression level of HMGB 1 in the hippocampus was determined using quantitative RT-PCR and Western blot, separately, and the contents of hippocampal TNF-α and IL-1 ß were detected by ELISA. RESULTS: Compared with the sham group, the MWT values were markedly decreased on day 7, 10 and 14 after modeling in the model group (P<0.001). On day 10 and 14 after modeling, the MWT values were significantly up-regulated in the EA group relevant to those of the model group (P<0.05, P<0.01). The expression levels of HMGB1 mRNA and protein, and the contents of hippocampal TNF-α and IL-1 ß were markedly increased in the model group relevant to the sham group (P<0.001), and significantly down-regulated in the EA group relevant to the model group (P<0.001, P<0.01, P<0.05). CONCLUSION: EA stimulation of ST 36-GB 34 can relieve pain in chronic neuropathic pain rats, which may be related to its actions in down-regulating the levels of HMGB 1 and its downstream proinflammatory cytokines TNF-α and IL-1 ß in the hippocampus.

Cancer survival in patients from a hospital-based cancer registry, China.

Purpose: There are few reports on survival rate analysis from hospital-based cancer registries (HBCR) in China, although the National Center of Cancer Registry of China has launched such an effort with the mission to expand the scope of registration and follow-up. Our study aimed to evaluate survival and outcomes of cancer patients from a HBCR in eastern China. Methods: Active and passive follow-up methods were used to obtain information on survival status for all patients from Qidong City and Haimen City in the databases of our hospital-based registrations from 2002 to 2014. Censor time for survival was 31st March, 2016. Survival probability was estimated using the life-table method with SPSS Statistics software, and comparison of significant differences in survival rates was tested by Wilcoxon (Gehan) statistic. Results: The outcomes of 5010 patients were identified in the follow-up for 5244 cases from Qidong and Haimen, with a follow-up rate of 95.65%, and a rate of lost to follow-up of 4.35%. The 1-, 3-, 5-, and 10-year observed survival (OS) rate in all-combined cancer sites were 59.80%, 37.70%, 30.82%, and 22.60%, respectively. The top 10 cancer sites in rank were cancers of lung, esophagus, liver, cervix, stomach, breast, colon-rectum, non-Hodgkin's lymphoma, nasopharynx, and ovary, with 5-year OS rates of 12.63%, 19.62%, 11.69%, 66.61%, 21.35%, 59.43%, 36.36%, 37.03%, 48.95% and 36.17%, respectively. Females experienced better survival than males for lung, esophageal, liver, nasopharyngeal and pancreatic cancers (P<0.05), but not for other sites (P>0.05). A significant difference was also found between males and females when all-sites were combined (P<0.01). There are significant differences (P<0.05) between the 2015 patients (from Qidong) and the 3001 patients (from Haimen) with 5-year OS rates of 32.72% vs 29.57%; no significant differences were found for 5-year OS rates for individual cancer sites (P>0.05) except for liver (P=0.0005) and ovary (P=0.0460) between the two cities. Younger patients had better prognosis, but significance was only seen in cervical (P=0.0102) and nasopharyngeal (P=0.0305) cancers. Conclusion: The survival rates of each site or of all sites-combined in this setting are consistent with those elsewhere in China and abroad. Discrepancies in overall survival could be affected by the proportion of sites with or without better prognosis. Hospital-based cancer survival is a better index to evaluate outcomes that reflect the levels of comprehensive treatment and improvement of medical and health services.

Astragalus Saponins and Liposome Constitute an Efficacious Adjuvant Formulation for Cancer Vaccines.

Cancer vaccines mostly aim to induce cytotoxic T lymphocytes (CTLs) against tumors. An appropriate adjuvant is of fundamental importance for inducing cellular immune response. Since the antigen in particulate form is substantially more immunogenic than soluble form antigen, it is beneficial to interact with antigen-presenting cells membrane to induce robust CD8+ T cell activation following vaccination. Based on previous research, we designed an adjuvant formulation by combining Astragalus saponins, cholesterol, and liposome to incorporate antigen into a particulate delivery system, so as to enhance cellular immune response. Meanwhile, angiogenesis contributes to tumor growth and metastasis, and basic fibroblast growth factor (bFGF) is involved in tumor angiogenesis. Therefore, using lipo-saponins adjuvant formulation and a human recombinant bFGF antigen protein, we tried to induce bFGF-specific CTL response to inhibit tumor angiogenesis to achieve antitumor activity. After five immunizations, the lipo-saponins/bFGF complex elicited robust antibody response and markedly higher amount of interferon-γ in BALB/c mice, resulting in superior antitumor activities. Decreased microvessel density in CD31 immunohistochemistry and the lysis of vascular endothelial cells by the T lymphocytes from the immunized mice indicated that the immunity inhibited the angiogenesis of tumors and further led to the inhibition of tumors. Our data suggest that the approach to construct adjuvant formulation between liposome and Astragalus saponins appeared highly desirable, and that Astragalus saponins may be utilized as a valuable additive for enhancing the effectiveness of vaccines and stimulating an appropriate immune response that can benefit tumor therapy.

A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.

Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response.