Association of caesarean scar defect with risk of abnormal uterine bleeding: results from meta-analysis.

OBJECTIVE: To investigate the association between caesarean scar defects and abnormal uterine bleeding through systematic literature review. METHODS: PubMed, Web of Science, Cochrane Library and Embase databases were searched based on PRISMA 2020 to include studies exploring abnormal uterine bleeding in women with caesarean scar defects. The combined relative risk (RR) of uterine bleeding, combined prevalence of abnormal uterine bleeding and combined RR of intermenstrual uterine bleeding were calculated using a fixed- or random-effects model. RESULTS: Ten studies involving 1,183 women with caesarean scar defects met the inclusion criteria for this study. Compared with women without caesarean scar defects, those with caesarean scar defects had a higher risk of abnormal uterine bleeding (RR: 3.22, 95% CI: 1.83-5.66) and intermenstrual bleeding (RR: 2.93, 95% CI: 1.91-4.50). The prevalence of abnormal uterine bleeding was approximately 0.46 (95% CI: 0.27-0.64), and across populations, women with a previous caesarean section who had undergone imaging specifically for gynaecological disease had a significantly higher prevalence of abnormal uterine bleeding (0.77, 95% CI: 0.65-0.89) than those with at least one caesarean Sect. (0.25, 95% CI: 0.10-0.39). CONCLUSION: A significant association was observed between caesarean scar defects and abnormal uterine bleeding, with the former being a risk factor for the latter. However, previous studies have differed in the definition of caesarean scar defects and abnormal uterine bleeding, and more high-quality studies are needed to further investigate the relevant definitions and study results in the future.

RETINAL VASCULAR OCCLUSION AND COVID-19 DIAGNOSIS: A Multicenter Population-Based Study.

BACKGROUND: Several ocular diseases have been reported in patients with coronavirus disease 2019 (COVID-19), especially retinal vascular occlusion. This study aimed to examine the risk of retinal vascular occlusion after COVID-19 diagnosis. METHODS: This retrospective cohort study was based on 46 health care organizations in the United States using the TriNetX network. Individuals who had laboratory confirmation of COVID-19 from January 1, 2020, to December 31, 2021, were included. Multivariate analysis was adjusted on age, sex, race, and comorbidities, and hazard ratio was calculated using the Cox proportional hazard regression model. RESULTS: A total of 1,460,634 paired individuals were enrolled for analysis. Patients with COVID-19 had a significantly higher risk of branch retinal vein occlusion (hazard ratio 1.27, 95% confidence interval [CI] 1.04-1.52) than those without COVID-19. The cumulative incidence rate of branch retinal vein occlusion was also significantly higher in patients with COVID-19 compared with those without COVID-19 (log-rank P = 0.014). Within 12 weeks after COVID-19 diagnosis, the transient effect of central retinal vein occlusion (hazard ratio 1.59, 95% confidence interval 1.15-2.17) and branch retinal vein occlusion (hazard ratio 2.11, 95% confidence interval 1.51-2.95) were observed. CONCLUSION: This large-scale multicenter study demonstrated that retinal vein occlusion may be associated with COVID-19.

The risk assessment of uveitis after COVID-19 diagnosis: A multicenter population-based study.

Reports on uveitis after COVID-19 have been limited. Our objective was to examine the risk of uveitis among COVID-19 patients. This was a retrospective cohort study based on the TriNetX platform. The exposure group was patients with positive laboratory test result for SARS-CoV-2 and the comparison group was those tested negative for COVID-19 throughout the study period. The endpoint is the new diagnoses of uveitis. This study composed of 2 105 424 patients diagnosed with COVID-19 (55.4% female; 62.5% white; mean age at index 40.7 years) and 2 105 424 patients (55.4% female; 62.4% white; mean age at index 40.7 years) who never had COVID-19. There was significantly increased risk of new diagnosis of uveitis since the first month after diagnosis of COVID-19 compared with matched controls (HR: 1.18, 95% CI: 1.03-1.34) up to 24 months (HR: 1.16, 95% CI: 1.09-1.22). Our findings strengthen those previously raised by case series with a larger and multicenter study. We found that uveitis was significantly associated with COVID-19 infection. Our findings reiterate the need for careful investigation as well as increased awareness from ophthalmologists in considering the possibility of COVID-19 in vulnerable patients with new presentation of uveitis.

Clinical Pharmacology of RNA Interference-Based Therapeutics: A Summary Based on Food and Drug Administration-Approved Small Interfering RNAs.

RNA-based oligonucleotide therapeutics are revolutionizing drug development for disease treatment. This class of therapeutics differs from small molecules and protein therapeutics in various ways, including both its mechanism of action and clinical pharmacology characteristics. These unique characteristics, along with evolving oligonucleotide-associated conjugates allowing specific tissue targeting, have fueled interest in the evaluation of RNA-based oligonucleotide therapeutics in a rapidly increasing number of therapeutic areas. With these unique attributes as well as growing therapeutic potential, oligonucleotide therapeutics have generated significant interest from a clinical pharmacology perspective. The Food and Drug Administration (FDA) previously published results of a survey that summarized clinical pharmacology studies supporting oligonucleotide therapies approved and in development between 2012 and 2018. Since the first approval of a small interfering RNA (siRNA) therapeutic in 2018, this class of modalities has gained momentum in various therapeutic areas. Hence, a comprehensive examination of the clinical pharmacology of FDA-approved siRNA therapeutics would benefit the path forward for many stakeholders. Thus, in this current review, we thoroughly examine and summarize clinical pharmacology data of the FDA-approved siRNA therapeutics approved from 2018 (year of first approval) to 2022, aimed at facilitating future drug development and regulatory decision making. SIGNIFICANCE STATEMENT: This review systematically summarizes the clinical pharmacology information of Food and Drug Administration (FDA)-approved small interfering RNAs (siRNA) therapeutics. SiRNAs are revolutionizing the drug development field. Unique clinical pharmacology characteristics represent a differentiating factor for this class of therapeutics. The FDArecently published a draft guidance for clinical pharmacology considerations for developing oligonucleotide therapeutics. As clinical development of this class of therapeutics is fast growing, this review will inform discovery and clinical-stage evaluation of upcoming siRNA-associated drug candidates.

Role of L-Arginine on the Expression of Coagulation Factor VIII Gene.

Objective: To explore the key sites in which L-arginine affects the expression of human coagulation factor VIII gene, and to create new drug targets for the treatment of hemophilia. Methods: A total of 5 human FVIII genes (A1, A2, A3, C1 and C2) with B domain deletion were transfected into human umbilical vein endothelial cells (HUVECs) as promoters. Run-on assay and ELISA analysis were performed to observe the driving effect of each domain gene on chloramphenicol acetyl transferase (CAT) gene transcription and expression, and the effect of L-arginine on each promoter. Results: In co-culture with L-arginine, transcriptional expression of the CAT gene was not detected in the PCAT3-Basic group (negative control without promoters), PA3-CAT3-Enhancer group or PC1-CAT3-Enhancer group. The transcriptional expression of CAT gene in the PCAT3-Control group (positive control with promoters) and PA1-CAT3-Enhancer group was unchanged compared with the non-L-arginine intervention, while the transcriptional expression of CAT gene in the PA2-CAT3-Enhancer group was significantly enhanced. Conclusions: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.

Sharpening up tumor microenvironment to enhance the efficacy of immune checkpoint blockade on head and neck cancer using a CpG-oligodeoxynucleotide.

Head and neck cancers are a type of life-threatening cancers characterized by an immunosuppressive tumor microenvironment. Only less than 20% of the patients respond to immune checkpoint blockade therapy, indicating the need for a strategy to increase the efficacy of immunotherapy for this type of cancers. Previously, we identified a type B CpG-oligodeoxynucleotide (CpG-ODN) called CpG-2722, which has the universal activity of eliciting an immune response in grouper, mouse, and human cells. In this study, we further characterized and compared its cytokine-inducing profiles with different types of CpG-ODNs. The antitumor effect of CpG-2722 was further investigated alone and in combination with an immune checkpoint inhibitor in a newly developed syngeneic orthotopic head and neck cancer animal model. Along with other inflammatory cytokines, CpG-2722 induces the gene expressions of interleukin-12 and different types of interferons, which are critical for the antitumor response. Both CpG-2722 and anti-programmed death (PD)-1 alone suppressed tumor growth. Their tumor suppression efficacies were further enhanced when CpG-2722 and anti-PD-1 were used in combination. Mechanistically, CpG-2722 shaped a tumor microenvironment that is favorable for the action of anti-PD-1, which included promoting the expression of different cytokines such as IL-12, IFN-ß, and IFN-γ, and increasing the presence of plasmacytoid dendritic cells, M1 macrophages, and CD8 positive T cells. Overall, CpG-2722 provided a priming effect for CD8 positive T cells by sharpening the tumor microenvironment, whereas anti-PD-1 released the brake for their tumor-killing effect, resulting in an enhanced efficacy of the combined CpG-2722 and anti-PD-1.

Investigation on abnormal gene loci of a Chinese pedigree with hereditary combined deficiency of blood coagulation factor XI, XII, and protein S.

OBJECTIVE: In order to clarify the interaction mechanism, the phenotype and abnormal gene loci of FXI, FXII, and PS were investigated in this study. METHODS: Chinese pedigree with hereditary combined deficiency of coagulation factor (F) XI, FXII, and PS was enrolled in our study. Activated partial thromboplastin time (APTT), partial thromboplastin time (PT), FXI:C, FXII:C, and protein S (PS):C were determined using the one-stage coagulation method. FXI:antigen (Ag), FXII:Ag, and PS:Ag were detected using enzyme-linked immunosorbent assay (ELISA). Exons and introns of the FXI, FXII, and PS genes were amplified by polymerase chain reaction (PCR), and gene sequencing results were analyzed using Chromas software. RESULTS: A deletion of two bases located in introns A-149 and-150 within the FXI gene of the proband, his father, wife, and both sons. A missense variant in exon 14 (GGT â†’ AGT, Gly542Ser) within FXII of the proband, his parents, and both sons. Four variants in exon 4 within the PS gene of all members of the pedigree: GTT â†’ GTG (Val46Val), CGC â†’ CTC (Arg49Leu), CGT â†’ CAT (Arg60His), and CAG â†’ TAG (Gln61stop). CONCLUSIONS: None of the pedigree members showed a tendency for bleeding or thrombosis. Therefore, we speculated that the lack of coagulation factors counteracted the lack of PS, restoring the balance between the coagulation and anticoagulation systems. Another possible explanation is that these defects individually have only partial penetrance.

Association between Mean Corpuscular Hemoglobin and Platelet Distribution Width Ratio and Knee Osteoarthritis Severity.

BACKGROUND: The goal was to simply and efficiently predict the indicators of disease severity in knee osteoarthritis (KOA) patients. METHODS: One hundred eighty-four patients with KOA and 126 healthy subjects were included. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was used as a reference index for disease severity in KOA patients, in which WOMAC < 80 was classified as mild and WOMAC ≥ 80 as moderate and severe. Blood routine parameters of the KOA and the healthy groups were analyzed by the Mann Whitney U test. Receiver operating characteristic curves were used to analyze the sensitivity and specificity of mean corpuscular hemoglobin and platelet distribution width ratio (MPR) and monocyte and hemoglobin ratio (MHR) indicators. The correlation between MPR and MHR and disease severity of KOA was determined by bivariate regression analysis. Independent predictors of disease severity in patients with KOA were assessed by multivariate regression analysis. RESULTS: MPR, MHR, and WOMAC were significantly higher in the KOA group. The ROC curve indicated that the cutoff values of MPR and MHR were 2.09 and 0.0030, respectively, with sensitivity of 86.4% and 68.5% and specificity of 99.2% and 79.4%. Bivariate regression analysis found that MPR was better correlated with disease severity than MHR. The results of multivariate regression analysis demonstrated that the MPR values of moderate and severe patients were more than 19 times that of mild patients, and the OR values were 21.695 and 19.558, respectively. CONCLUSIONS: MPR and MHR demonstrated a good correlation with disease severity in patients with KOA. MPR is a potential independent predictor of disease severity in patients with KOA.

Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway.

Fasudil is reported to be effective at protecting against ischaemic diseases, and at augmenting axon growth. In this study, we aim to evaluate its efficacy in promoting flap survival and reinnervation. Ninety-two Institute of Cancer Research (ICR) mice were used and divided into the control, Fasudil, LY294002, Fasudil+LY294002 groups, receiving a daily intraperitoneal injection of normal saline, Fasudil (10 mg/kg), LY294002 (5 mg/kg), and Fasudil (10 mg/kg) + LY294002 (5 mg/kg), respectively. On days 0 and 5, the blood perfusion and diameter of the iliolumbar artery in the pedicle of the flaps in the four groups were evaluated using laser speckling contrast imaging (LSCI). On day 5, the flaps were photographed and the necrosis rate of the flaps was calculated using Photoshop CS6. In addition, tissues were harvested from the flaps and divided into two parts. One part underwent routine cryosection and immunofluorescent staining using the antibody against CD31 for evaluation of the microvascular density in the four groups. In the other part, the expression of RhoA, ROCK1+2, p-CPI-17, p-MYPT, p-PTEN, p-PI3K, p-Akt, and vascular endothelial growth factor (VEGF) within the flaps were determined using western blotting. Moreover, at days 0, 7, 15, and 30 after flap surgery, the axons within the flaps were evaluated using immunofluorescent staining with the antibody against Neurofilament-200. It turned out that the necrosis rate was (24.4 ± 7.7)%, (5.2 ± 1.6)%, (29.8 ± 4.2)%, and (30.9 ± 7.1)%, respectively, in the control, Fasudil, LY294002, LY294002+Fasudil groups. There was a significant reduction in the necrosis rate of the flaps in the Fasudil group (P < .001). The LSCI and immunofluorescent staining demonstrated that Fasudil could significantly expand the diameter of the iliolumbar artery in the pedicle, boost the overall blood perfusion, and increase the microvascular density of the flaps in the Fasudil group (P < .05), which could all be abolished by PI3K inhibitor LY294002. On day 5, the expression of p-CPI-17, p-MYPT, and p-PTEN were downregulated, whereas pPI3K, p-Akt, and VEGF were upregulated in the Fasudil group (P < .001). As for reinnervation, Neurofilament-200 fluorescent staining revealed that at days 15 and 30 after flap harvest, only in the Fasudil group could new axons be observed. It can be concluded that Fasudil could simultaneously improve the survival and axon growth after flap harvest, a dual efficacy achieved by inhibition of the RhoA/ROCK pathway, which in turn activates /PI3K/AKT pathway.

[Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics].

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Genetic Variations of Ionotropic Glutamate Receptor Pathways on Interferon-α-induced Depression in Patients with Hepatitis C Viral Infection.

IMPORTANCE: The most supportive evidence of the inflammation theory of depression is that up to one-third of patients with Hepatitis C virus infection (HCV) develop clinical depressive episodes during interferon-α (IFN-α) therapy. As glutamate-mediated excitotoxicity has been found to be a consequence of excessive inflammation and a pathogenic mechanism of depression, it is plausible to investigate genes on ionotropic glutamate receptor pathways. OBJECTIVE: To identify the at-risk genetic variations on ionotropic glutamate receptor pathways for interferon-α-induced depression. METHOD: We assessed 291 patients with chronic HCV undergoing IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes related to ionotropic glutamate receptors in this prospective case-control study. Patients who developed IFN-α-induced depression anytime during the treatment were defined as the case group, while those who did not were defined as the control group. Genomic DNA was extracted from peripheral blood and analyzed by Affymetrix TWB array. Allelic and haplotype association tests were conducted using χ2 tests to assess the difference in allele and haplotype frequencies between cases and controls. Additionally, we performed 5000 permutations to control gene-wide family-wise error rates and create empirical p-values. Stratified analyses were then done to control for confounders and adjust odds ratios for our significant SNPs. We also did an additional stratified analysis to re-assess genes with near-significant SNPs (empirical p-value=0.05-0.10), employing Bonferroni correction with the effective number of independent tests to control gene-wide family-wise error rates. RESULTS: The minor and major allele frequencies of rs7542 (empirical p-value=0.0310) in MAPK3, rs3026685 (empirical p-value=0.0378) in PICK1, rs56005409 (empirical p-value=0.0332) in PRKCA, rs12914792 (empirical p-value=0.0096), rs17245773 (empirical p-value=0.0340) in RASGRF1, and rs78387863 (empirical p-value=0.0086), rs74365480 (empirical p-value=0.0200) in RASGRF2 were found significantly different between cases and controls. Haplotype association tests also revealed one significant haplotype in PRKCA (empirical p-value=0.0200) and one in RASGRF1 (empirical p-value=0.0048). Stratified analyses showed no signs of confounders for most of our significant SNPs, except for rs78387863 in RASGRF2. After a re-assessment of our near-significant genes by stratified analyses, two SNPs in GRIN2B turned significant. CONCLUSIONS: This study provided supportive evidence of the involvement of the RAS/RAF/mitogen-activated protein kinase (MAPK) signaling pathway and glutamate ionotropic receptor AMPA type subunit 2(GluR2) transportation in the pathogenesis of IFN-α-induced depression.

A rare case of multiple primary extragastrointestinal stromal tumors in the abdominopelvic cavity detected by 18F-FDG PET/CT.

An extragastrointestinal stromal tumor (EGIST) refers to the gastrointestinal stromal tumor in any location outside the gastrointestinal tract originates from mesenchymal tumors. The majority of the EGIST appeared as isolated mass, and multiple primary EGIST is quite rare. Here, we report a 36-year-old man of multiple EGIST in the abdominopelvic cavity, which was misdiagnosed as lymphoma on fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging. The patient received adjuvant drug treatment (imatinib, 400mg/day) for three months, and then further resection of all lesions was performed. No recurrence was found in CT follow-up one year after the operation.

Key Physicochemical Characteristics Influencing ADME Properties of Therapeutic Proteins.

Therapeutic proteins are a rapidly growing class of drugs in clinical settings. The pharmacokinetics (PK) of therapeutic proteins relies on their absorption, distribution, metabolism, and excretion (ADME) properties. Moreover, the ADME properties of therapeutic proteins are impacted by their physicochemical characteristics. Comprehensive evaluation of these characteristics and their impact on ADME properties are critical to successful drug development. This chapter summarizes all relevant physicochemical characteristics and their effect on ADME properties of therapeutic proteins.

Optimization of nano-honeycomb structures for flexible w-LEDs.

This study presents the low cost fabrication of flexible white-light-emitting diodes (w-LEDs) with nano-honeycomb-structured phosphor films. Extending the dimensions of the nano-honeycomb structures improved the color uniformity of the flexible samples, and the 950-nm pattern sample demonstrated optimal color uniformity because this nano-pattern exhibited an excellent diffusion ability owing to its pitch size. In addition to color uniformity, the use of this nano-pattern improved the luminous efficiency. The 750-nm pattern exhibited the highest luminous efficiency (235.8 lm/W), which was approximately 7% higher than that exhibited by a non-patterned phosphor film sample. Thus, flexible w-LEDs with nano-honeycomb structure optimization have great potential to be used as next-generation lighting sources.

Iron-, Cobalt-, and Nickel-Catalyzed Asymmetric Transfer Hydrogenation and Asymmetric Hydrogenation of Ketones.

Chiral alcohols are important building blocks in the pharmaceutical and fine chemical industries. The enantioselective reduction of prochiral ketones catalyzed by transition metal complexes, especially asymmetric transfer hydrogenation (ATH) and asymmetric hydrogenation (AH), is one of the most efficient and practical methods for producing chiral alcohols. In both academic laboratories and industrial operations, catalysts based on noble metals such as ruthenium, rhodium, and iridium dominated the asymmetric reduction of ketones. However, the limited availability, high price, and toxicity of these critical metals demand their replacement with abundant, nonprecious, and biocommon metals. In this respect, the reactions catalyzed by first-row transition metals, which are more abundant and benign, have attracted more and more attention. As one of the most abundant metals on earth, iron is inexpensive, environmentally benign, and of low toxicity, and as such it is a fascinating alternative to the precious metals for catalysis and sustainable chemical manufacturing. However, iron catalysts have been undeveloped compared to other transition metals. Compared with the examples of iron-catalyzed asymmetric reduction, cobalt- and nickel-catalyzed ATH and AH of ketones are even seldom reported. In early 2004, we reported the first ATH of ketones with catalysts generated in situ from iron cluster complex and chiral PNNP ligand. Since then, we have devoted ourselves to the development of ATH and AH of ketones with iron, cobalt, and nickel catalysts containing novel chiral aminophosphine ligands. In our study, the iron catalyst containing chiral aminophosphine ligands, which are expected to control the stereochemistry at the metal atom, restrict the number of possible diastereoisomers, and effectively transfer chiral information, are successful catalysts for enantioselective reduction of ketones. Among these novel chiral aminophosphine ligands, 22-membered macrocycle P2N4 exhibited extraordinary enantioselectivities when combined with iron(0) cluster Fe3(CO)12. A broad scope of ketones including aromatic, heteroaromatic, and ß-ketoesters can be reduced smoothly with excellent enantioselectivities (up to 99% ee) approaching or exceeding those achievable with the noble metal catalysts. Notably, the chiral iron-based catalyst proved to be highly efficient for both ATH as well as AH of various ketones. Until now, such "universal" catalyst is very rare. Preliminary studies suggest that the AH reaction most likely involved iron particles as the active catalytic species. These research results point to a new direction in developing viable effective nonprecious metal catalysts for asymmetric reduction and probably for other asymmetric catalytic reactions as well.

Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury.

Classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) macrophages populate the local microenvironment after spinal cord injury (SCI). The former type is neurotoxic while the latter has positive effects on neuroregeneration and is less toxic. In addition, while the M1 macrophage response is rapidly induced and sustained, M2 induction is transient. A promising strategy for the repair of SCI is to increase the fraction of M2 cells and prolong their residence time. This study investigated the effect of M2 macrophages induced from bone marrow-derived macrophages on the local microenvironment and their possible role in neuroprotection after SCI. M2 macrophages produced anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor ß and infiltrated into the injured spinal cord, stimulated M2 and helper T (Th)2 cells, and produced high levels of IL-10 and -13 at the site of injury. M2 cell transfer decreased spinal cord lesion volume and resulted in increased myelination of axons and preservation of neurons. This was accompanied by significant locomotor improvement as revealed by Basso, Beattie and Bresnahan locomotor rating scale, grid walk and footprint analyses. These results indicate that M2 adoptive transfer has beneficial effects for the injured spinal cord, in which the increased number of M2 macrophages causes a shift in the immunological response from Th1- to Th2-dominated through the production of anti-inflammatory cytokines, which in turn induces the polarization of local microglia and/or macrophages to the M2 subtype, and creates a local microenvironment that is conducive to the rescue of residual myelin and neurons and preservation of neuronal function.

Blood safety and availability: continuing challenges in China's blood banking system.

Social and economic development, along with increased health care coverage, has caused a sharp increase in the clinical demand for blood in China. Whole blood collection has increased rapidly in the past decade but has failed to keep pace with the ever-increasing demand. Overall, the country's blood safety has been improved with 99% of whole blood donations collected from voluntary unpaid donors. However, the unmet clinical demand for blood and the increasing incidence of human immunodeficiency virus and syphilis in the general population pose new challenges to China's blood banking system. To ensure a safe and adequate blood supply, continued efforts are required to recruit and retain a sufficient number of low-risk voluntary blood donors, improve donor prescreening and blood testing process, ease donor restrictions, and strengthen patient blood management.