Sepsis is a complex syndrome caused by multiple pathogens and involves multiple organ failure, particularly spleen dysfunction. In 2017, the worldwide incidence was 48.9 million sepsis cases and 11 million sepsis-related deaths were reported (Rudd et al., 2020). Inflammation, oxidative stress, and apoptosis are the most common pathologies seen in sepsis. Liensinine (LIE) is a bisbenzylisoquinoline-type alkaloid extracted from the seed embryo of Nelumbo nucifera. Lotus seed hearts have high content of LIE which mainly has antihypertensive and antiarrhythmic pharmacological effects. It can exert anti-carcinogenic activity by regulating cell, inflammation, and apoptosis signaling pathways (Manogaran et al., 2019). However, its protective effect from sepsis-induced spleen damage is unknown. In this research, we established a mouse sepsis model induced by lipopolysaccharide (LPS) and investigated the protective effects of LIE on sepsis spleen injury in terms of inflammatory response, oxidative stress, and apoptosis.
Mice ; Animals ; Lipopolysaccharides/pharmacology* ; Spleen ; Inflammation ; Apoptosis ; Sepsis ; Oxidative Stress

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objective:To examine the effects of heart rate control during hospitalization on short-term prognosis of heart failure in elderly patients.Methods:As a prospective study, 150 elderly patients with heart failure were selected from the Department of Geriatrics, Qilu Hospital of Shandong University.The subjects were divided into an experimental group and a control group by digitally generated random numbers, with 75 individuals in each group.Both groups received conventional anti-heart failure therapy during hospitalization, but patients from the control group had doses of heart rate control drugs adjusted every 2-4 weeks, with no special requirement for the heart rate before hospital discharge.In contrast, patients from the experimental group were given heart rate control drugs with timely dose adjustment to achieve more proactive heart rate control, aiming for a rate <70 beat/min, as long as heart failure symptom improvement and good volume management could be maintained.Values of cardiac function indexes were compared between the two groups at discharge and 6 months after discharge.Heart failure readmission rates within 6 months, cardiovascular disease mortality rates and the incidences of composite endpoint events after readmission due to heart failure aggravation were compared between the two groups.Treatment safety was also evaluated.Results:There was no statistical difference in blood pressure, heart rate, N-terminal pro-B-type natriuretic peptide(NT-pro-BNP), left ventricular ejection fraction(LVEF), left ventricular end systolic diameter(LVESD), or left ventricular end diastolic diameter(LVEDD)between the two groups at admission( P>0.05), and there was no statistical difference in the average length of hospitalization between the two groups( P>0.05). The experimental group had a lower average heart rate and diastolic pressure than the control group at discharge and 6 months latter[at discharge: (61.6±4.2)beat/min(1 mmHg=0.133 kPa) vs.(78.0±7.1)beat/min, (62.1±10.4)mmHg vs.(66.1±10.2)mmHg; at 6 months: (64.7±12.1)beat/min vs.(71.8±11.2)beat/min, (62.8±11.2)mmHg vs.(68.6±10.2)mmHg; P<0.05 or P<0.01]. NT-pro-BNP in the experimental group was significantly lower than that in the control group at discharge[(1 706±1 408)ng/L vs.(2 806±3 812)ng/L, P<0.05]. The absolute values of changes in LVEF(ΔLVEF), LVESD(ΔLVESD)and LVEDD(ΔLVEDD)after 6 months in the experimental group were significantly higher than those in the control group[ΔLVEF: (0.08±0.09) vs.(0.02±0.09), P<0.05; ΔLVESD: (-5.82±7.44)mm vs.(-1.63±6.07)mm, P<0.01; ΔLVEDD: (-2.76±5.52)mm vs.(-0.86±4.44)mm, P<0.05]. The rate of readmission and the incidence of composite endpoint events within 6 months in the experimental group were significantly lower than those in the control group[21.3%(16 cases) vs.36.0%(27 cases), P<0.05]; 25.3%(19 cases) vs.44.0%(33 cases), P<0.05.There was no significant difference in all-cause mortality between the two groups( P>0.05). Conclusions:For elderly patients with heart failure, proactive active heart rate control during hospitalization and a rate <70 beat/min before discharge will improve cardiac function indexes and lower the rate of readmission with exacerbation of heart failure, cardiovascular disease mortality and the incidence of composite end-point events after readmission.This strategy has good safety and is beneficial for short-term prognosis.

Objective:To explore the short-term outcomes of dual kidney transplantation and summarize its safety and feasibility.Methods:From September 2018 to September 2019, a total of 7 dual kidney transplantations were performed. And retrospective analysis was performed for baseline profiles, clinical data and postoperative complications.Results:The mean age was (62.7±8.5) years for donors and (43.9±9.3) years for recipients. The Remuzzi score of 6 paired kidneys ranged from 4 to 6 points. During follow-ups, the survival rate of 7 dual kidney transplantation grafts and recipients was 100%. The median follow-up period was 16 months. Renal function of 6 recipients normalized within 1 week and delayed graft function (DGF) occurred in one case. All of them underwent unilateral kidney transplantation with an average operative duration of (5.6±1.4) hours. There was no onset of operative complications. One case of rejection was not confirmed by biopsy. Among three patients of lung infections, there was one case of severe pneumonia. In 3 cases, lateral plasma flow of transplanted kidney exceeded that of medial plasma flow.Conclusions:Dual kidney transplantation in adults is both safe and feasible so as to expand the availability of donated kidney.

Objective:To summarize the clinical experiences of pediatric en-bloc kidney transplantation (EBKT) at a single center and explore the measures of improving its efficacy.Methods:Clinical data and outcomes retrospectively analyzed for 38 EBKT children between September 2014 and November 2019 from Department of Urology Affiliated Union Hospital Tongji Medical College Huazhong University of Science & Technology. The pediatric donors were aged (63.6±5.7) days with a weight of (4.1±0.2) kg. And the transplant recipients were aged (28.1±1.4) years with a weight of (48.7±4.9) kg. Serum levels of creatinine and basic profiles of both donors and recipients were recorded at Day 0/7/30/90/80/360 post-EBKT. The postoperative occurrences of such complications such as thrombosis, urine leakage, delayed graft function (DGF), proteinuria and hematoma were measured.Results:The one-year graft survival rate was 76.3%(29/38) and the recipient survival rate 100.0%(38/38). Among 29 recipients with long-term graft survival, no dialysis was required at Week 2 post-EBKT and the serum level of creatinine dropped to normal at Year 1. Thrombosis was a major post-EBKT complication with an incidence of 18.4%(7/38). The other complications included urine leakage (20.7%, 6/29), hematoma (6.9%, 2/29) and primary non-functioning kidney (2.6%, 1/38).Conclusions:As an effective way of expanding the pool of donors, pediatric EBKT is clinically feasible.

Organ transplantation is the most effective method to treat end-stage organ failure. As the increase of transmission risk of donor-derived diseases, the quality, safety and selection criteria of transplanted organs become more and more important. Chapter 7 of the European Union's Guide to the Quality and Safety of Organs for Transplantation (6th Edition) proposed basic requirements in terms of donor and organ quality assessment, selection criteria and procedures, which were worthy of study and practice in clinical practice.

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.

Objective: To understand characteristics of vaginal cervical microbiota in high-risk HPV (hrHPV) infected women and to uncover the relationship between hrHPV infection and vaginal cervical microbiota. Methods: All participants were randomly selected from Peking University First Hospital from September to October of 2017, including 5 subjects of control group, 5 cases of HPV16/18 group, 5 cases of other hrHPV infected group and 3 cases of cervical squamous carcinoma group. All subjects were required to fill in a questionnaire, and cervical and vaginal discharges were separately collected for microscopic examination and new generation sequencing targeting the variable region (V3-V4) of bacterial 16S rRNA gene. Results: Vaginal microbiota analysis: (1) 6 major phylum were found in vaginal microbiota:Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria, Tenericutes and Proteobacteria. Firmicutes contributed to the majority of normal vaginal flora, Bacteroidetes and Fusobacteria increased in hrHPV infected ones, while Fusobacteria showed significant difference in cervical carcinoma group. (2) Lactobacillus occupied most of normal vaginal flora while genus like Gardnella, Prevotella, Atopobium, Megasphaera and Sneathia increased in hrHPV infected subjects, Sneathia showed significant difference in cervical carcinoma group. (3) No significant difference had been calculated in Alpha diversity of four groups (P=0.073) . Cervical microbiota analysis: (1) Microbial diversity of cervical microbiota was higher than that of vaginal microbiota. (2) Significant difference had been found in Alpha diversity of four groups (P=0.046) . (3) Proteobacteria in normal cervical flora was much more than that in vagina, and Proteobacteria increased significantly in hrHPV infected cervical discharge. (3) Chlamydia increased significantly in cervical carcinoma group. Conclusions The diversity of cervical microbiota is higher than that of vaginal microbiota. Change in cervical microbiota is more obvious than that of vagina in hrHPV infected subjects. Fusobacteria-Sneathia and Chlamydia significantly increase in cervical carcinoma group. Proteobacteria might relate to hrHPV infection.

Background: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment out?comes. We conducted a phase II randomized controlled trial to evaluate the efcacy of intensity?modulated radio?therapy with concomitant weekly cisplatin on locally recurrent NPC. Methods: Between April 2002 and January 2008, 69 patients diagnosed with non?metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group(n= 35). All patients received intensity?modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. Results: The median follow?up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3?year and 5?year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showedthat concomitant chemoradiotherapy significantly improved the 5?year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%,P= 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Conclusion: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.

BACKGROUNDSeveral previous studies have shown that diffusion-weighted imaging (DWI) can provide additional information for focal pancreatic lesions by demonstrating more restricted diffusion in solid malignant tumors than in chronic pancreatitis, which can be indicated by a decreased apparent diffusion coefficient (ADC). However, these studies have a modest sample size and convey inconclusive results. The aim of this study was to determine, in a meta-analysis, the diagnostic performance of quantitative diffusion-weighted magnetic resonance imaging in distinguishing pancreatic carcinoma from mass-forming chronic pancreatitis.

METHODSWe determined the sensitivities and specificities across studies. A summary receiver operator characteristic (sROC) curve was constructed to calculate the area under the curve (AUC).

RESULTSThe pooled sensitivity of DWI was 0.86 (95% CI: 0.80-0.91) and the pooled specificity was 0.82 (95% CI: 0.72-0.89). The AUC of the sROC was 0.91 (95% CI: 0.88-0.93).

CONCLUSIONSDWI may be a potentially technically feasible tool for differentiating pancreatic carcinoma from mass-forming chronic pancreatitis. However, large-scale randomized control trials are necessary to assess its clinical value.