Objective: To identify the principal factors associated with the occurrence and development of medical device-related pressure injuries (MDRPI) in adults admitted to hospitals. MDRPI, a peculiar subtype of pressure in...Objective: To identify the principal factors associated with the occurrence and development of medical device-related pressure injuries (MDRPI) in adults admitted to hospitals. MDRPI, a peculiar subtype of pressure injuries (PI), result from the pression exerted by devices (or their fixation systems) applied for diagnostic and therapeutic purposes. MDRPI represent a serious problem for patients and healthcare systems. Understanding potential risk factors is an important step in implementing effective interventions. Methods: In this study, we will perform a systematic review;if possible, also a meta-analysis will be performed. The review will follow the preferred reporting items for systematic reviews and meta-analyses (PRISMA) reporting guidelines for systematic reviews. A rigorous literature search will be conducted both in electronic databases (Medline/PubMed, Embase, CINAHL, Web of Science, Scopus, Cochrane Library) to identify studies published since 2000 and in gray literature for unpublished studies. Pairs of researchers will identify relevant evidence, extract data, and assess risk of bias independently in each eligible study. Factors associated with the occurrence of MDRPI are considered the primary outcome. Secondary outcomes are prevalence and incidence of MDRPI, length of hospital stay, infections, and death. The evidence will be synthesized using the GRADE methodology. Results: Results are not currently available as this is a protocol for a systematic review. Conclusions: This systematic review will identify evidence on risk factors for developing MDRPI. We are confident that the results of this review will help to improve clinical practice and guide future research.展开更多
Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its his...Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain unexplored.In this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and osteoclastogenesis.Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks.Micro-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical properties.Enzyme-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)levels.Osteoclastogenesis-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB assay.Compared with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric parameters.Serum E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE group.CEE downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein expression.In bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast differentiation.Compared with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK),NF-kappa B-p65(p65)phosphorylation in osteoclasts.In conclusion,CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis,potentially through modulating the Estrogen Receptor(ER)/RANK/NFATc1 signaling pathway.展开更多
BACKGROUND Total mesorectal excision remains the gold standard for the management of rectal cancer however local excision of early rectal cancer is gaining popularity due to lower morbidity and higher acceptance by th...BACKGROUND Total mesorectal excision remains the gold standard for the management of rectal cancer however local excision of early rectal cancer is gaining popularity due to lower morbidity and higher acceptance by the elderly and frail patients.AIM To investigate the results of local excision of rectal cancer by transanal endoscopic microsurgery(TEMS)approach carried out at three large cancer centers in the United Kingdom.METHODS TEMS database was retrospectively reviewed to assess demographics,operative findings and post operative clinical and oncological outcomes.This is a retro-spective review of the prospective databases,which included all patients operated with TEMS approach,for early rectal cancer(Node-negative T1-T2),selected T3 in unfit/frail patients.RESULTS Two hundred and twenty-two patients underwent TEMS surgery.This included 144 males(64.9%)and 78 females(35.1%),Median age was 71 years.The median distance of the tumours from the anal verge 4.5 cm.Median tumour size was 2.6 cm.The most frequent operative position of the patient was lithotomy(32.3%),Full-thickness rectal wall excision was done in 204 patients.Median operating time was 90 minutes.Average blood loss was minimal.There were two 90-day mortalities.Complete excision of the tumour with free microscopic margins by>1mm were accomplished in 171 patients(76.7%).Salvage total mesorectal excision was performed in 42 patients(19.8%).Median disease-free survival was 65 months(range:3-146 months)(82.8%),and median overall survival was 59 months(0-146 months).CONCLUSION TEMS provides a promising option for early rectal cancers(Large adenomas-cT1/cT2N0),and selected therapy-responding cancers.Full-thickness complete excision of the tumour is mandatory to avoid jeopardising the oncological outcomes.展开更多
Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day live...Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day liver transplantation(LT)-free mortality in the cirrhotic Chinese population.We aimed to investigate the quantitative relationship between sCR on admission and 90-day mortality in hospitalized patients with cirrhosis in the Chinese population.Methods Data were prospectively collected from two multicenter cohorts,which enrolled hospitalized patients with chronic liver disease.After screening,2582 patients with cirrhosis from January 2015 to December 2016 and from July 2018 to January 2019 were included in the primary analysis.Creatinine values were collected on admission.Patients were regularly followed up at the end of 90 days.The univariate and multivariate Cox proportional hazard model was conducted to explore the relationship between sCR and 90-day LT-free mortality.A generalized additive model and second derivative(acceleration)were used to plot“creatinine-mortality correlation curves”,adjusting for potential confounders.Results Among 2582 hospitalized patients with cirrhosis,428(16.6%)experienced deaths at the end of 90 days.sCR levels on admission were significantly associated with 90-day LT-free mortality in both univariate and multivariate analyses(hazard ratio[HR],1.77,p<0.001;HR,1.22,p=0.003).sCR of 1.1 mg/dL was identified as the starting point(stage 1a)of disease deterioration of acute kidney injury(AKI)in hospitalized patients with cirrhosis.Patients with 1.1 mg/dL<sCR≤1.8 mg/dL had significantly higher 90-day mortality compared to those with sCR≤1.1 mg/dL(HR,1.90,p<0.001).The corresponding 28-day and 90-day LT-free mortality to sCR 1.1 mg/dL were 11%and 18%,respectively.Conclusions sCR was an independent risk factor for 90-day LT-free mortality in hospitalized cirrhotic patients.sCR of 1.1 mg/dL is the starting point of disease deterioration and serves as an important supplement for the diagnostic threshold of AKI stage 1a in the Chinese cirrhotic population without baseline sCR.展开更多
AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controll...AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P < 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P < 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P < 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P < 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P < 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.展开更多
AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was ind...AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histological and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema （E）, polymorphonuclear neutrophU （pIVlN） infiltration, cytoplasmic vacuolization （V）, zymogen granule depletion （ZD） and acinar disorganization （AD） were microscopically evaluated. Accumulation of pancreatitis- associated protein （PAP） and L13A mRNAs were quantified by real-time PCR. RESULTS： The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d. CONCLUSION： From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pan- creas occur and PAP expression is exclusively an acute response of pancreatitis.展开更多
Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.De...Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.Despite high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health Initiative.Subsequently,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes prolonged.Subsequent analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal women.Regarding cognitive function,the timing hypothesis is consistent with observations from basic and animal studies.There is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women.It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural tissues.In the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.展开更多
[Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of o...[Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of ovarian pathological morphological changes, apoptosis and expression of Wnt/β-β catenin signaling pathway protein. [Methods] Ten of 40 female SD rats were randomly selected as the normal group, and the other 30 rats were treated with letrozole combined with high-fat diet to establish the PCOS rat model. After successful modeling, the model group was randomly divided into Qigongwan group, positive Daying-35 (Ethinylestradiol and Cyproterone Acetate Tablets) group and model group, with 10 rats in each group. Qigongwan group was given 14.7 g/(kg·d) by gavage, Daying-35 group was given 0.21 mg/(kg·d) by oral gavage, and normal group and model group were given the same amount of distilled water, and the intervention lasted for 21 d. ELISA method was used to detect the levels of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E 2) and progesterone (P) in serum. HE staining was used to observe the pathological morphological changes of ovarian tissues;TUNEL staining was used to observe apoptosis of ovarian tissue granule cells;the expression of Wnt, β-catenin protein in rat ovarian tissue was detected by immunohistochemistry. [Results] (i) Compared with the model group, Qigongwan group and Daying-35 group could significantly increase serum E 2 and P levels, significantly reduce serum T levels ( P <0.01), significantly reduce serum LH levels and LH/FSH ratio ( P <0.01), and increase serum FSH levels ( P <0.05) in different degrees. (ii)The results of HE staining showed that compared with the model group, Qigongwan and Daying-35 groups could improve follicular development and reduce atretic follicles in different degrees. Compared with Daying-35 group, the number of GC layers in Qigongwan group was significantly increased. (iii) The results of TUNEL staining showed that compared with the model group, the rate of TUNEL-positive cells in the Qigongwan group and Daying-35 group decreased significantly ( P <0.01). (iv) The immunohistochemical results showed that compared with the model group, the expression levels of wnt and β-catenin in the Qigongwan group and the Daying-35 group increased in different degrees ( P <0.05), and the expression range increased. [Conclusions] Qigongwan can regulate the secretion level of sex hormones such as FSH and LH, improve the pathological damage of ovarian tissue, and inhibit apoptosis of ovarian granule cells, and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.展开更多
In recent decades,life expectancy has been increasing significantly.In this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiov...In recent decades,life expectancy has been increasing significantly.In this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease.However,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific re-commendations.This document aims to review prevention recommendations focused in patients≥75 years with high or very high cardiovascular risk,regarding objectives,medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs.Also,we will show why geriatric syndromes such as frailty,dependence,cognitive impair-ment,and nutritional status,as well as comorbidities,ought to be considered in this population regarding their important pro-gnostic impact.展开更多
Introduction: Human immunodeficiency virus infec- tion is associated with several different types of peripheral neuropathy: distal predominantly sensory axonal polyneuropathy, like Guillain Barre syndrome. Case presen...Introduction: Human immunodeficiency virus infec- tion is associated with several different types of peripheral neuropathy: distal predominantly sensory axonal polyneuropathy, like Guillain Barre syndrome. Case presentation: A 55-year-old Caucasian woman with Human immunodeficiency virus infection, diag- nosed with Guillain Barre syndrome was studied. Serum and CSF immunoglobulin G and Albumin levels were quantified by using an immunodiffusion technique. She had preceding viral symptoms. The clinical diagnosis of the illness in this patient was pa-resthesias or sensory loss, tendon reflexes. It was also observed cranial nerves abnormalities, acute mo- tor and sensory axonal neuropathy and ophthalmoplegia. The mean CD4 count was 367/mm3, CSF white blood cell 25 wbc/mm3. The serum sodium concentration was significantly low (133 mmol/L). She had a respiratory compromise as a result of their neuropa- thy and developed congestive heart failure and hy- potension and died of a cardiac arrest. The neuro-immunological response described by our patient was a blood/CSF barrier dysfunction without IgG intra-thecal synthesis. Conclusion: There is no doubt that this study is of great importance because will help clinicians increase their knowledge of the immune response in patients with this autoimmune disorder on the basis of this case report, in which, for first time, could be seen the neuroimmunological response through the reibergram in a patient with HIV- asso-ciated Guillain-Barre syndrome.展开更多
This study explored the antibiofilm efficacy of 3,3’-diindolylmethane(DIM)on Staphylococcus aureus and its disinfection on common food-contact surfaces.The minimum biofilm inhibitory concentration(MBIC)of DIM on S.au...This study explored the antibiofilm efficacy of 3,3’-diindolylmethane(DIM)on Staphylococcus aureus and its disinfection on common food-contact surfaces.The minimum biofilm inhibitory concentration(MBIC)of DIM on S.aureus was 62.5μmol/L,while it did not impede the bacterial growth evaluated by growth curve and XTT reduction assay.DIM in the concentration range of 31.2-62.5μmol/L demonstrated a dose-dependent antibiofilm activity to S.aureus,as confirmed by light microscopic(LM),confocal laser scanning microscopic(CLSM),and scanning electron microscopic(SEM)analyses.At DIM of62.5μmol/L,the biomass of S.aureus biofilm was significantly reduced by 97%and its average thickness by 58%(P<0.05).DIM of 62.5μmol/L inhibited the bacterial initial adhesion and proliferation,as well as cell motility;the release of extracellular DNA(eDNA)and extracellular polysaccharide(EPS)were reduced by 75%and 69%,respectively.DIM exhibited a strong inhibition to S.aureus biofilm formation on common food-contact surfaces,including 304 stainless steel,glass,and polyvinyl chloride(PVC)but not disperse the mature biofilm.Overall,our investigation identified DIM as a promising antibiofilm agent and its suitability to prevent the biofilm formation of S.aureus on common food-contact surfaces utilized during food processing.展开更多
Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated wit...Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated with AHF cases found in patients hospitalized in STP. Methods: Descriptive and quantitative analysis of AHF cases hospitalized in STP in the period December 2021 to May 19, 2022 through the variables: demographic data;clinical data;laboratory data and clinical outcome. Results: Analyzed 18 of 22 AHF cases, 50% of them male, mean age 33.7 years, 85.7% residing in the 2 largest districts of the country, 66.7% rural workers, administrative near maritime areas, sailors and domestics. 66.7% were healthy individuals. ≥50% had a fever, asthenia/weakness, myalgia, headache, lethargy, nausea, vomiting, and diarrhea. 22.2% to 33.3% had retro-orbital pain, abdominal pain, decreased consciousness, dyspnea/hypoxia, and cough. In a smaller register (5.6% - 11.1%), exanthema, convulsion, arthralgia, low back pain, chills, and chest pain. Bleeding from the digestive tract was found in 72.2%, followed by vaginal (33.3%), urethral (27.8%), nasal (22.2%), and oral (16.7%). 50% had laboratory confirmation for dengue, and another 50% with suspected clinical diagnosis without laboratory confirmation of the etiologic agent. Despite hemorrhage, 66.7% of confirmed cases were hemodynamically non-severe, and 88.9% of suspected cases were severe. Coinfection with malaria is evidenced in 11.1% of cases. 72.2% recovered and 27.8% died (deaths in 55.5% of suspected cases). Case deaths were male (100%), resident foreigners (40%), tool store employees, sailors and students, healthy (80%), and residing in the largest district in the country (60%). All deaths were hospitalized in serious condition, 80% were hospitalized for hemorrhage and shock, with bleeding arising between day 4 - 5 of illness in 60% and hospitalization on day 5 of illness. 60% died within ≤24 hours of hospitalization. 80% died from shock and multi-organ dysfunction and 20% from respiratory failure. Deaths had thrombocytopenia (100%), renal dysfunction (100%) and significantly increased transaminases (100%), anemia (75%) and leukocytosis (66.7%). 20% had a radiological change of pulmonary infiltrates. Conclusion: Our data reveal the complexity of the pathogens causing AHF and suggest the possible presence of other human pathogens usually unknown in the Santomean geographical territory.展开更多
Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety ...Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan potassium.Design,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical trial.Primary glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 mg.Main outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of treatment.Results:A total of 735 participants were enrolled.The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg group.Compared with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein level.Compared with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine protein.With a superiority threshold of 15%,neither was statistically significant.eGFR,serum creatinine and serum albumin from the baseline did not change statistically significant.The average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any group.Conclusion:SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients,with no change in the rate of decrease in the eGFR.SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.Trial registration number:NCT02063100 on ClinicalTrials.gov.展开更多
The healing of large skin defects remains a significant challenge in clinical settings.The lack of epidermal sources,such as autologous skin grafting,limits full-thickness skin defect repair and leads to excessive sca...The healing of large skin defects remains a significant challenge in clinical settings.The lack of epidermal sources,such as autologous skin grafting,limits full-thickness skin defect repair and leads to excessive scar formation.Skin organoids have the potential to generate a complete skin layer,supporting in-situ skin regeneration in the defect area.In this study,skin organoid spheres,created with human keratinocytes,fibroblasts,and endothelial cells,showed a specific structure with a stromal core surrounded by surface keratinocytes.We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid.Moreover,the 3D bioprinted skin organoid was customized to match the size and shape of the wound site,facilitating convenient implantation.When applied to full-thickness skin defects in immunodeficient mice,the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration,epithelialization,vascularization,and inhibition of excessive inflammation.The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes,offering a novel treatment strategy to address large-area skin defects.展开更多
Aims To analyse whether heart rate may affect the efficacy of adenosine , verap amil and carotid sinus massage in terminating symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) in adults. Methods a...Aims To analyse whether heart rate may affect the efficacy of adenosine , verap amil and carotid sinus massage in terminating symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) in adults. Methods and results The study po pulation was selected among 175 adult patients, affected by symptomatic PSVT. On e hundred and six of them were considered eligible for the study. Each subject r eceived one of the following treatments: verapamil, 5 mg intravenously (IV) in 5 -10 min, followed by 1-5 μg/kg/min; adenosine, 6 mg IV, followed by 12 mg IV after 2-3 min; carotid sinus massage. Adenosine and verapamil were similarly ef fective in terminating PSVT (74.4%vs 81.8%, P=0.45). The efficacy of carotid s inus massage was significantly lower in comparison with the other two groups (32 .4%, P=0.00032 vs adenosine and P=0.000044 vs verapamil group). At logistic reg ression, PSVT rate showed a positive association with the percentage of sinus rh ythm restoration in the group who received adenosine (P=0.0004). The probability of success in resolving the tachycardia following treatment with adenosine was >75%for heart rates over 166 beats per minute (bpm), but rapidly decreased at l ower frequencies, reducing to 25%at 138 bpm. In the verapamil group, PSVT rate was negatively related to the percentage of sinus rhythm restoration (P=0.018). The probability of success in terminating PSVT following administration of verap amil was >75%for heart rates lower than 186 bpm, but tended to decrease at fast er rates, reducing to 25%at 241 bpm. No significant effects of heart rate were observed in the carotid sinus massage group (P=0.17). The probability curves obt ained in the adenosine and verapamil group crossed at a point corresponding to 1 73 bpm, which may represent a cut-off value to predict which treatment could en sure higher rate of success. Conclusions Heart rate predicts restoration of sinu s rhythm in adult subjects with symptomatic episodes of PSVT treated with adenos ine and verapamil. Adenosine is highly effective in PSVT characterised by fast r ates, whereas the efficacy of verapamil is increased in patients with low-frequ ency PSVT.展开更多
To the Editor:Angiosarcoma(AS)is a rare and highly malignant mesenchymal tumor that accounts for 2%of adult soft tissue sarcomas.The prognosis of AS is poor due to the high rate of metastasis and reoccurrence.Accordin...To the Editor:Angiosarcoma(AS)is a rare and highly malignant mesenchymal tumor that accounts for 2%of adult soft tissue sarcomas.The prognosis of AS is poor due to the high rate of metastasis and reoccurrence.According to a retrospective study by Lahat et al and Fayette et al,[1,2]31 of 121(19%)patients had metastases upon initial diagnosis,and 90(74%)had relapse and progression.The median survival of AS was 3.4 years,declining to 10 months in patients with metastasis.To attempt to improve AS treatment outcomes,a multimodality approach is advocated,including surgical resection combined with radiation,chemotherapy,immunotherapy,and/or anti-angiogenetic therapy.Herein,we present a man who previously underwent resection of a mesorectal-derived intermediate hemangioendothelioma(HAE)and developed pulmonary metastasis of AS within a year.The history is remarkable because of(1)the rare primary location:only 2 cases were mesenteric-related;(2)the uncharacteristic clinical course:the primary diagnosis of intermediate hemangioendothelioma later progressed to pulmonary metastatic AS;and(3)a successful series of multidisciplinary therapeutic procedures,especially selective arterial infusion(SAI)chemotherapy before metastases resection.展开更多
Immunotherapy has demonstrated the potential to cure melanoma,while the current response rate is still unsatisfactory in clinics.Extensive evidence indicates the correlation between the eficacy and pre-existing T-cell...Immunotherapy has demonstrated the potential to cure melanoma,while the current response rate is still unsatisfactory in clinics.Extensive evidence indicates the correlation between the eficacy and pre-existing T-cell in tumors,whereas the baseline T-cell infiltration is lacking in low-response melanoma patients.展开更多
文摘Objective: To identify the principal factors associated with the occurrence and development of medical device-related pressure injuries (MDRPI) in adults admitted to hospitals. MDRPI, a peculiar subtype of pressure injuries (PI), result from the pression exerted by devices (or their fixation systems) applied for diagnostic and therapeutic purposes. MDRPI represent a serious problem for patients and healthcare systems. Understanding potential risk factors is an important step in implementing effective interventions. Methods: In this study, we will perform a systematic review;if possible, also a meta-analysis will be performed. The review will follow the preferred reporting items for systematic reviews and meta-analyses (PRISMA) reporting guidelines for systematic reviews. A rigorous literature search will be conducted both in electronic databases (Medline/PubMed, Embase, CINAHL, Web of Science, Scopus, Cochrane Library) to identify studies published since 2000 and in gray literature for unpublished studies. Pairs of researchers will identify relevant evidence, extract data, and assess risk of bias independently in each eligible study. Factors associated with the occurrence of MDRPI are considered the primary outcome. Secondary outcomes are prevalence and incidence of MDRPI, length of hospital stay, infections, and death. The evidence will be synthesized using the GRADE methodology. Results: Results are not currently available as this is a protocol for a systematic review. Conclusions: This systematic review will identify evidence on risk factors for developing MDRPI. We are confident that the results of this review will help to improve clinical practice and guide future research.
基金supported by the National Natural Science Foundation of China(Nos.81273816,81774379,and 81370974)the Natural Science Foundation of Hunan Province,China(Nos.2017JJ2338 and 2020JJ4860)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(No.502211706)the Fund for the Key Laboratory of Hunan Province,China(No.2017TP1004).
文摘Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning millennia.It enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced pain.Despite its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain unexplored.In this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and osteoclastogenesis.Eight-week-old female mice underwent ovariectomy and were treated with CEE for eight weeks.Micro-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical properties.Enzyme-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)levels.Osteoclastogenesis-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB assay.Compared with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric parameters.Serum E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE group.CEE downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein expression.In bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast differentiation.Compared with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK),NF-kappa B-p65(p65)phosphorylation in osteoclasts.In conclusion,CEE significantly inhibits OVX-induced osteoporosis and RANKL-induced osteoclastogenesis,potentially through modulating the Estrogen Receptor(ER)/RANK/NFATc1 signaling pathway.
文摘BACKGROUND Total mesorectal excision remains the gold standard for the management of rectal cancer however local excision of early rectal cancer is gaining popularity due to lower morbidity and higher acceptance by the elderly and frail patients.AIM To investigate the results of local excision of rectal cancer by transanal endoscopic microsurgery(TEMS)approach carried out at three large cancer centers in the United Kingdom.METHODS TEMS database was retrospectively reviewed to assess demographics,operative findings and post operative clinical and oncological outcomes.This is a retro-spective review of the prospective databases,which included all patients operated with TEMS approach,for early rectal cancer(Node-negative T1-T2),selected T3 in unfit/frail patients.RESULTS Two hundred and twenty-two patients underwent TEMS surgery.This included 144 males(64.9%)and 78 females(35.1%),Median age was 71 years.The median distance of the tumours from the anal verge 4.5 cm.Median tumour size was 2.6 cm.The most frequent operative position of the patient was lithotomy(32.3%),Full-thickness rectal wall excision was done in 204 patients.Median operating time was 90 minutes.Average blood loss was minimal.There were two 90-day mortalities.Complete excision of the tumour with free microscopic margins by>1mm were accomplished in 171 patients(76.7%).Salvage total mesorectal excision was performed in 42 patients(19.8%).Median disease-free survival was 65 months(range:3-146 months)(82.8%),and median overall survival was 59 months(0-146 months).CONCLUSION TEMS provides a promising option for early rectal cancers(Large adenomas-cT1/cT2N0),and selected therapy-responding cancers.Full-thickness complete excision of the tumour is mandatory to avoid jeopardising the oncological outcomes.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2023A1515010194)Shanghai Hospital Development Commission(SHDC2020CR1037B)+6 种基金National Key R&D Program of China(2017YFC0908100)the National Science and Technology Major Project(2018ZX10302206,2018ZX10723203,2017ZX10202202)Shanghai Municipal Education Commission-Guofeng Clinical Medicine Grant Support,the National Natural Science Foundation of China(82170629,81930061,81900579,81970550,82070613,82070650,81972265)the Chongqing Natural ScienceFoundation(CSTC2019jcyj-zdxmX0004)Beijing Municipal Science&Technology Commission(Z191100006619033)Local Innovative and Research TeamsProject of Guangdong Pearl River Talents Program(2017BT01S131)the Foundation for Innovative Research Groups of Hubei Provincial Natural ScienceFoundation(2018CFA031).
文摘Aims Increased serum creatinine(sCR)is associated with increased mortality in cirrhotic patients,while there remains a lack of evidence-based sCR cutoffs for indicating disease deterioration and predicting 90-day liver transplantation(LT)-free mortality in the cirrhotic Chinese population.We aimed to investigate the quantitative relationship between sCR on admission and 90-day mortality in hospitalized patients with cirrhosis in the Chinese population.Methods Data were prospectively collected from two multicenter cohorts,which enrolled hospitalized patients with chronic liver disease.After screening,2582 patients with cirrhosis from January 2015 to December 2016 and from July 2018 to January 2019 were included in the primary analysis.Creatinine values were collected on admission.Patients were regularly followed up at the end of 90 days.The univariate and multivariate Cox proportional hazard model was conducted to explore the relationship between sCR and 90-day LT-free mortality.A generalized additive model and second derivative(acceleration)were used to plot“creatinine-mortality correlation curves”,adjusting for potential confounders.Results Among 2582 hospitalized patients with cirrhosis,428(16.6%)experienced deaths at the end of 90 days.sCR levels on admission were significantly associated with 90-day LT-free mortality in both univariate and multivariate analyses(hazard ratio[HR],1.77,p<0.001;HR,1.22,p=0.003).sCR of 1.1 mg/dL was identified as the starting point(stage 1a)of disease deterioration of acute kidney injury(AKI)in hospitalized patients with cirrhosis.Patients with 1.1 mg/dL<sCR≤1.8 mg/dL had significantly higher 90-day mortality compared to those with sCR≤1.1 mg/dL(HR,1.90,p<0.001).The corresponding 28-day and 90-day LT-free mortality to sCR 1.1 mg/dL were 11%and 18%,respectively.Conclusions sCR was an independent risk factor for 90-day LT-free mortality in hospitalized cirrhotic patients.sCR of 1.1 mg/dL is the starting point of disease deterioration and serves as an important supplement for the diagnostic threshold of AKI stage 1a in the Chinese cirrhotic population without baseline sCR.
基金Supported by Heber Biotec,Havana(for providing products and reagents)and the Ministry of Public Health of Cuba(for hospital facilities and general medical care of patients)
文摘AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P < 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P < 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P < 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P < 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P < 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.
基金Supported by The Mexican Council for Science and Technology,CONACyT, grant 43928
文摘AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histological and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema （E）, polymorphonuclear neutrophU （pIVlN） infiltration, cytoplasmic vacuolization （V）, zymogen granule depletion （ZD） and acinar disorganization （AD） were microscopically evaluated. Accumulation of pancreatitis- associated protein （PAP） and L13A mRNAs were quantified by real-time PCR. RESULTS： The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d. CONCLUSION： From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pan- creas occur and PAP expression is exclusively an acute response of pancreatitis.
文摘Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects.Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years.Despite high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health Initiative.Subsequently,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes prolonged.Subsequent analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal women.Regarding cognitive function,the timing hypothesis is consistent with observations from basic and animal studies.There is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women.It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural tissues.In the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.
基金Supported by Central Level Public Welfare Scientific Research Institute"Advantageous Diseases-Hospital Preparations-New Drug Preparation Research and Development Project"(ZZZ15-XY-CT-01)Major Gynecology Program of Science and Technology Innovation Project,China Academy of Chinese Medical Sciences(CI2021A02408).
文摘[Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of ovarian pathological morphological changes, apoptosis and expression of Wnt/β-β catenin signaling pathway protein. [Methods] Ten of 40 female SD rats were randomly selected as the normal group, and the other 30 rats were treated with letrozole combined with high-fat diet to establish the PCOS rat model. After successful modeling, the model group was randomly divided into Qigongwan group, positive Daying-35 (Ethinylestradiol and Cyproterone Acetate Tablets) group and model group, with 10 rats in each group. Qigongwan group was given 14.7 g/(kg·d) by gavage, Daying-35 group was given 0.21 mg/(kg·d) by oral gavage, and normal group and model group were given the same amount of distilled water, and the intervention lasted for 21 d. ELISA method was used to detect the levels of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E 2) and progesterone (P) in serum. HE staining was used to observe the pathological morphological changes of ovarian tissues;TUNEL staining was used to observe apoptosis of ovarian tissue granule cells;the expression of Wnt, β-catenin protein in rat ovarian tissue was detected by immunohistochemistry. [Results] (i) Compared with the model group, Qigongwan group and Daying-35 group could significantly increase serum E 2 and P levels, significantly reduce serum T levels ( P <0.01), significantly reduce serum LH levels and LH/FSH ratio ( P <0.01), and increase serum FSH levels ( P <0.05) in different degrees. (ii)The results of HE staining showed that compared with the model group, Qigongwan and Daying-35 groups could improve follicular development and reduce atretic follicles in different degrees. Compared with Daying-35 group, the number of GC layers in Qigongwan group was significantly increased. (iii) The results of TUNEL staining showed that compared with the model group, the rate of TUNEL-positive cells in the Qigongwan group and Daying-35 group decreased significantly ( P <0.01). (iv) The immunohistochemical results showed that compared with the model group, the expression levels of wnt and β-catenin in the Qigongwan group and the Daying-35 group increased in different degrees ( P <0.05), and the expression range increased. [Conclusions] Qigongwan can regulate the secretion level of sex hormones such as FSH and LH, improve the pathological damage of ovarian tissue, and inhibit apoptosis of ovarian granule cells, and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.
基金This work was funded by Instituto de Salud Carlos III and FEDER founds(Exp.JR/21/00041)。
文摘In recent decades,life expectancy has been increasing significantly.In this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease.However,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific re-commendations.This document aims to review prevention recommendations focused in patients≥75 years with high or very high cardiovascular risk,regarding objectives,medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs.Also,we will show why geriatric syndromes such as frailty,dependence,cognitive impair-ment,and nutritional status,as well as comorbidities,ought to be considered in this population regarding their important pro-gnostic impact.
文摘Introduction: Human immunodeficiency virus infec- tion is associated with several different types of peripheral neuropathy: distal predominantly sensory axonal polyneuropathy, like Guillain Barre syndrome. Case presentation: A 55-year-old Caucasian woman with Human immunodeficiency virus infection, diag- nosed with Guillain Barre syndrome was studied. Serum and CSF immunoglobulin G and Albumin levels were quantified by using an immunodiffusion technique. She had preceding viral symptoms. The clinical diagnosis of the illness in this patient was pa-resthesias or sensory loss, tendon reflexes. It was also observed cranial nerves abnormalities, acute mo- tor and sensory axonal neuropathy and ophthalmoplegia. The mean CD4 count was 367/mm3, CSF white blood cell 25 wbc/mm3. The serum sodium concentration was significantly low (133 mmol/L). She had a respiratory compromise as a result of their neuropa- thy and developed congestive heart failure and hy- potension and died of a cardiac arrest. The neuro-immunological response described by our patient was a blood/CSF barrier dysfunction without IgG intra-thecal synthesis. Conclusion: There is no doubt that this study is of great importance because will help clinicians increase their knowledge of the immune response in patients with this autoimmune disorder on the basis of this case report, in which, for first time, could be seen the neuroimmunological response through the reibergram in a patient with HIV- asso-ciated Guillain-Barre syndrome.
基金supported by the National Key Research and Development Projects(2019YFE0103800)Sichuan Science and Technology Program(2019YFH0113,2021YFH0060,2021YFH0072,2021ZHFP0045,2021YFN0092)the Fundamental Research Funds for the Central Universities(2018CDLZ-07,2018CDPZH-9,2019CDPZH-23,2020CDLZ-17)。
文摘This study explored the antibiofilm efficacy of 3,3’-diindolylmethane(DIM)on Staphylococcus aureus and its disinfection on common food-contact surfaces.The minimum biofilm inhibitory concentration(MBIC)of DIM on S.aureus was 62.5μmol/L,while it did not impede the bacterial growth evaluated by growth curve and XTT reduction assay.DIM in the concentration range of 31.2-62.5μmol/L demonstrated a dose-dependent antibiofilm activity to S.aureus,as confirmed by light microscopic(LM),confocal laser scanning microscopic(CLSM),and scanning electron microscopic(SEM)analyses.At DIM of62.5μmol/L,the biomass of S.aureus biofilm was significantly reduced by 97%and its average thickness by 58%(P<0.05).DIM of 62.5μmol/L inhibited the bacterial initial adhesion and proliferation,as well as cell motility;the release of extracellular DNA(eDNA)and extracellular polysaccharide(EPS)were reduced by 75%and 69%,respectively.DIM exhibited a strong inhibition to S.aureus biofilm formation on common food-contact surfaces,including 304 stainless steel,glass,and polyvinyl chloride(PVC)but not disperse the mature biofilm.Overall,our investigation identified DIM as a promising antibiofilm agent and its suitability to prevent the biofilm formation of S.aureus on common food-contact surfaces utilized during food processing.
文摘Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated with AHF cases found in patients hospitalized in STP. Methods: Descriptive and quantitative analysis of AHF cases hospitalized in STP in the period December 2021 to May 19, 2022 through the variables: demographic data;clinical data;laboratory data and clinical outcome. Results: Analyzed 18 of 22 AHF cases, 50% of them male, mean age 33.7 years, 85.7% residing in the 2 largest districts of the country, 66.7% rural workers, administrative near maritime areas, sailors and domestics. 66.7% were healthy individuals. ≥50% had a fever, asthenia/weakness, myalgia, headache, lethargy, nausea, vomiting, and diarrhea. 22.2% to 33.3% had retro-orbital pain, abdominal pain, decreased consciousness, dyspnea/hypoxia, and cough. In a smaller register (5.6% - 11.1%), exanthema, convulsion, arthralgia, low back pain, chills, and chest pain. Bleeding from the digestive tract was found in 72.2%, followed by vaginal (33.3%), urethral (27.8%), nasal (22.2%), and oral (16.7%). 50% had laboratory confirmation for dengue, and another 50% with suspected clinical diagnosis without laboratory confirmation of the etiologic agent. Despite hemorrhage, 66.7% of confirmed cases were hemodynamically non-severe, and 88.9% of suspected cases were severe. Coinfection with malaria is evidenced in 11.1% of cases. 72.2% recovered and 27.8% died (deaths in 55.5% of suspected cases). Case deaths were male (100%), resident foreigners (40%), tool store employees, sailors and students, healthy (80%), and residing in the largest district in the country (60%). All deaths were hospitalized in serious condition, 80% were hospitalized for hemorrhage and shock, with bleeding arising between day 4 - 5 of illness in 60% and hospitalization on day 5 of illness. 60% died within ≤24 hours of hospitalization. 80% died from shock and multi-organ dysfunction and 20% from respiratory failure. Deaths had thrombocytopenia (100%), renal dysfunction (100%) and significantly increased transaminases (100%), anemia (75%) and leukocytosis (66.7%). 20% had a radiological change of pulmonary infiltrates. Conclusion: Our data reveal the complexity of the pathogens causing AHF and suggest the possible presence of other human pathogens usually unknown in the Santomean geographical territory.
基金supported by the National Science and Technology Major Projects of China(No.2014ZX09201021)Beijing Municipal Science and Technology Commission Major Projects(No.D181100000118002)。
文摘Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan potassium.Design,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical trial.Primary glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 mg.Main outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of treatment.Results:A total of 735 participants were enrolled.The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg group.Compared with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein level.Compared with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine protein.With a superiority threshold of 15%,neither was statistically significant.eGFR,serum creatinine and serum albumin from the baseline did not change statistically significant.The average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any group.Conclusion:SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients,with no change in the rate of decrease in the eGFR.SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.Trial registration number:NCT02063100 on ClinicalTrials.gov.
基金Science Foundation of China(NO.92249303,NO.82230071,No.82172098,No.82371603)Jiangsu Province Natural Science and Technological Project(No.BK20231218)+4 种基金Experimental Animal Research Field Project Shanghai Science and Technology Commission(No.23141900600)Research Physician Innovation and Transformation Ability Training Project from Shanghai Health Commission(No.SHDC2023CRT013)Basic Medical Innovation Project of Changhai Hospital(No.20237Y38)Deep Blue Talent Project of Naval Medical University(Jin Cui)Shanghai Oriental Talent Program(Xiao Chen,Yuanyuan Liu).
文摘The healing of large skin defects remains a significant challenge in clinical settings.The lack of epidermal sources,such as autologous skin grafting,limits full-thickness skin defect repair and leads to excessive scar formation.Skin organoids have the potential to generate a complete skin layer,supporting in-situ skin regeneration in the defect area.In this study,skin organoid spheres,created with human keratinocytes,fibroblasts,and endothelial cells,showed a specific structure with a stromal core surrounded by surface keratinocytes.We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid.Moreover,the 3D bioprinted skin organoid was customized to match the size and shape of the wound site,facilitating convenient implantation.When applied to full-thickness skin defects in immunodeficient mice,the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration,epithelialization,vascularization,and inhibition of excessive inflammation.The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes,offering a novel treatment strategy to address large-area skin defects.
文摘Aims To analyse whether heart rate may affect the efficacy of adenosine , verap amil and carotid sinus massage in terminating symptomatic episodes of paroxysmal supraventricular tachycardia (PSVT) in adults. Methods and results The study po pulation was selected among 175 adult patients, affected by symptomatic PSVT. On e hundred and six of them were considered eligible for the study. Each subject r eceived one of the following treatments: verapamil, 5 mg intravenously (IV) in 5 -10 min, followed by 1-5 μg/kg/min; adenosine, 6 mg IV, followed by 12 mg IV after 2-3 min; carotid sinus massage. Adenosine and verapamil were similarly ef fective in terminating PSVT (74.4%vs 81.8%, P=0.45). The efficacy of carotid s inus massage was significantly lower in comparison with the other two groups (32 .4%, P=0.00032 vs adenosine and P=0.000044 vs verapamil group). At logistic reg ression, PSVT rate showed a positive association with the percentage of sinus rh ythm restoration in the group who received adenosine (P=0.0004). The probability of success in resolving the tachycardia following treatment with adenosine was >75%for heart rates over 166 beats per minute (bpm), but rapidly decreased at l ower frequencies, reducing to 25%at 138 bpm. In the verapamil group, PSVT rate was negatively related to the percentage of sinus rhythm restoration (P=0.018). The probability of success in terminating PSVT following administration of verap amil was >75%for heart rates lower than 186 bpm, but tended to decrease at fast er rates, reducing to 25%at 241 bpm. No significant effects of heart rate were observed in the carotid sinus massage group (P=0.17). The probability curves obt ained in the adenosine and verapamil group crossed at a point corresponding to 1 73 bpm, which may represent a cut-off value to predict which treatment could en sure higher rate of success. Conclusions Heart rate predicts restoration of sinu s rhythm in adult subjects with symptomatic episodes of PSVT treated with adenos ine and verapamil. Adenosine is highly effective in PSVT characterised by fast r ates, whereas the efficacy of verapamil is increased in patients with low-frequ ency PSVT.
文摘To the Editor:Angiosarcoma(AS)is a rare and highly malignant mesenchymal tumor that accounts for 2%of adult soft tissue sarcomas.The prognosis of AS is poor due to the high rate of metastasis and reoccurrence.According to a retrospective study by Lahat et al and Fayette et al,[1,2]31 of 121(19%)patients had metastases upon initial diagnosis,and 90(74%)had relapse and progression.The median survival of AS was 3.4 years,declining to 10 months in patients with metastasis.To attempt to improve AS treatment outcomes,a multimodality approach is advocated,including surgical resection combined with radiation,chemotherapy,immunotherapy,and/or anti-angiogenetic therapy.Herein,we present a man who previously underwent resection of a mesorectal-derived intermediate hemangioendothelioma(HAE)and developed pulmonary metastasis of AS within a year.The history is remarkable because of(1)the rare primary location:only 2 cases were mesenteric-related;(2)the uncharacteristic clinical course:the primary diagnosis of intermediate hemangioendothelioma later progressed to pulmonary metastatic AS;and(3)a successful series of multidisciplinary therapeutic procedures,especially selective arterial infusion(SAI)chemotherapy before metastases resection.
基金This work was supported by National Natural Science Foundation of China(Nos.U1903125,31800979)Natural ScienceFoundationof HunanProvinceinChina(2021JJ20084,2021J20092)+6 种基金the Science and Technology Innovation Program of Hunan Province(2021RC3020,2020RC2010)This study was also supported by National Key Research and Development Program of China(2019YFA0111600 and 2019YFE0120800)the Natural Science Foundation of China for Outstanding Young Scholars(82022060)the Youth Talent Program of Hunan Province(2019RS2009)the Natural Science Foundation of Hunan Province for Outstanding Young Scholars(2019JJ30040)Innovation-Driven Project of Central South University(2020CX043)China Postdoctoral Science Foundation Funded Project(2021M693558,2022T150741).
文摘Immunotherapy has demonstrated the potential to cure melanoma,while the current response rate is still unsatisfactory in clinics.Extensive evidence indicates the correlation between the eficacy and pre-existing T-cell in tumors,whereas the baseline T-cell infiltration is lacking in low-response melanoma patients.
