Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Alfalfa xeno-miR159a regulates bovine mammary epithelial cell proliferation and milk protein synthesis by targeting PTPRF.

Milk protein content is an important index to evaluate the quality and nutrition of milk. Accumulating evidence suggests that microRNAs (miRNAs) play important roles in bovine lactation, but little is known regarding the cross-kingdom regulatory roles of plant-derived exogenous miRNAs (xeno-miRNAs) in milk protein synthesis, particularly the underlying molecular mechanisms. The purpose of this study was to explore the regulatory mechanism of alfalfa-derived xeno-miRNAs on proliferation and milk protein synthesis in bovine mammary epithelial cells (BMECs). Our previous study showed that alfalfa miR159a (mtr-miR159a, xeno-miR159a) was highly expressed in alfalfa, and the abundance of mtr-miR159a was significantly lower in serum and whey from high-protein-milk dairy cows compared with low-protein-milk dairy cows. In this study, mRNA expression was detected by real-time quantitative PCR (qRT-PCR), and casein content was evaluated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis were detected using the cell counting kit 8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, western blot, and flow cytometry. A dual-luciferase reporter assay was used to determine the regulation of Protein Tyrosine Phosphatase Receptor Type F (PTPRF) by xeno-miR159a. We found that xeno-miR159a overexpression inhibited proliferation of BMEC and promoted cell apoptosis. Besides, xeno-miR159a overexpression decreased ß-casein abundance, and increased α-casein and κ-casein abundance in BMECs. Dual-luciferase reporter assay result confirmed that PTPRF is a target gene of xeno-miR159a. These results provide new insights into the mechanism by which alfalfa-derived miRNAs regulate BMECs proliferation and milk protein synthesis.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis.

RATIONALE AND OBJECTIVES: To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). MATERIALS AND METHODS: Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600 s/mm2) examinations using a 3.0 T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n = 65 kidneys) and LN with moderate to severe (LNms, n = 31 kidneys) groups according to the threshold of 30 ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. RESULTS: Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p < 0.05). ROC curve analysis demonstrated that split medullary FA (AUC = 0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC = 0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r = 0.534, p < 0.001). CONCLUSION: Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis.

OBJECTIVE: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s). METHODS: FLS were separated from synovial tissues obtained from patients with RA. Protein expression was measured by Western blot or immunohistochemistry. Gene expression was detected by quantitative RT-PCR. The EdU incorporation was used to measure cell proliferation. Migration and invasion were determined by Boyden chamber assay. RNA sequencing analysis was used to seek for the target of coptisine. The in vivo effect of coptisine was evaluated in collagen-induced arthritis (CIA) model. RESULTS: Treatment with coptisine reduced the proliferation, migration, and invasion, but not apoptosis of RA FLS. Mechanistically, we identified PSAT1, an enzyme that catalyzes serine/one-carbon/glycine biosynthesis, as a novel targeting gene of coptisine in RA FLS. PSAT1 expression was increased in FLS and synovial tissues from patients with RA compared to healthy control subjects. Coptisine treatment or PSAT1 knockdown reduced the TNF-α-induced phosphorylation of p38, ERK1/2, and JNK MAPK pathway. Interestingly, coptisine administration improved the severity of arthritis and reduced synovial PSAT1 expression in mice with CIA. CONCLUSIONS: Our data demonstrate that coptisine treatment suppresses aggressive and proliferative actions of RA FLS by targeting PSAT1 and sequential inhibition of phosphorylated p38, ERK1/2, and JNK MAPK pathway. Our findings suggest that coptisine might control FLS-mediated rheumatoid synovial proliferation and aggression, and be a novel potential agent for RA treatment.

Widespread incomplete lineage sorting and introgression shaped adaptive radiation in the Gossypium genus.

Cotton (Gossypium) stands as a crucial economic crop, serving as the primary source of natural fiber for the textile sector. However, the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved. In this investigation, we leveraged 25 Gossypium genomes and introduced four novel assemblies-G. harknessii, G. gossypioides, G. trilobum, and G. klotzschianum (Gklo)-to delve into the speciation history of this genus. Notably, we encountered intricate phylogenies potentially stemming from introgression. These complexities are further compounded by incomplete lineage sorting (ILS), a factor likely to have been instrumental in shaping the swift diversification of cotton. Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution. For a recently diverged lineage comprising G. davidsonii, Gklo, and G. raimondii, we constructed a finely detailed ILS map. Intriguingly, this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome. Moreover, we identified signs of robust natural selection influencing specific ILS regions. Noteworthy variations pertaining to speciation emerged between the closely related sister species Gklo and G. davidsonii. Approximately 15.74% of speciation structural variation genes and 12.04% of speciation-associated genes were estimated to intersect with ILS signatures. These findings enrich our understanding of the role of ILS in adaptive radiation, shedding fresh light on the intricate speciation history of the Gossypium genus.

Insights to Gossypium defense response against Verticillium dahliae: the Cotton Cancer.

The soil-borne pathogen Verticillium dahliae, also referred as "The Cotton Cancer," is responsible for causing Verticillium wilt in cotton crops, a destructive disease with a global impact. To infect cotton plants, the pathogen employs multiple virulence mechanisms such as releasing enzymes that degrade cell walls, activating genes that contribute to virulence, and using protein effectors. Conversely, cotton plants have developed numerous defense mechanisms to combat the impact of V. dahliae. These include strengthening the cell wall by producing lignin and depositing callose, discharging reactive oxygen species, and amassing hormones related to defense. Despite the efforts to develop resistant cultivars, there is still no permanent solution to Verticillium wilt due to a limited understanding of the underlying molecular mechanisms that drive both resistance and pathogenesis is currently prevalent. To address this challenge, cutting-edge technologies such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), host-induced gene silencing (HIGS), and gene delivery via nano-carriers could be employed as effective alternatives to control the disease. This article intends to present an overview of V. dahliae virulence mechanisms and discuss the different cotton defense mechanisms against Verticillium wilt, including morphophysiological and biochemical responses and signaling pathways including jasmonic acid (JA), salicylic acid (SA), ethylene (ET), and strigolactones (SLs). Additionally, the article highlights the significance of microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) in gene expression regulation, as well as the different methods employed to identify and functionally validate genes to achieve resistance against this disease. Gaining a more profound understanding of these mechanisms could potentially result in the creation of more efficient strategies for combating Verticillium wilt in cotton crops.

Clinical value of radiography after transnasal ileus intubation for the surgical timing of small bowel obstruction.

OBJECTIVE: To explore the guiding value of radiography after transnasal ileus intubation for the treatment of small bowel obstruction and the selection of surgical timing. METHODS: This retrospective study analyzed the clinical data of 133 patients with small bowel obstruction who were admitted to Gongli Hospital from January 2013 to December 2020. The patients were included in a nasogastric intubation group (n=65) or a transnasal ileus intubation + radiography group (n=68), according to different treatment methods. The response rate of non-surgical treatment, bowel function, observation time before surgery, postoperative complications and the recurrence rate were observed in both groups. RESULTS: There was no significant difference in the response rate of non-surgical treatment and the incidence of postoperative complications between the two groups (P=0.257 and P=0.959, respectively). The observation time before surgery was shorter and the recurrence rate of obstruction was lower in the transnasal ileus intubation + radiography group than those in the nasogastric intubation group. The pain relief time, first flatus time and hospital stay were shorter in the transnasal ileus intubation + radiography group than those in the nasogastric intubation group, with statistically significant differences (all P<0.05). It was found that ascites and observation time before surgery were the influencing factors of surgical timing in patients with small bowel obstruction. CONCLUSION: Transnasal ileus intubation is an effective treatment for small bowel obstruction. Radiography after transnasal ileus intubation is helpful to determine the optimal surgical timing for small bowel obstruction, shorten the postoperative recovery time and reduce the recurrence rate in patients, so it is recommended in clinical practice.

Evolutionary divergence of duplicated genomes in newly described allotetraploid cottons.

Allotetraploid cotton (Gossypium) species represents a model system for the study of plant polyploidy, molecular evolution, and domestication. Here, chromosome-scale genome sequences were obtained and assembled for two recently described wild species of tetraploid cotton, Gossypium ekmanianum [(AD)6, Ge] and Gossypium stephensii [(AD)7, Gs], and one early form of domesticated Gossypium hirsutum, race punctatum [(AD)1, Ghp]. Based on phylogenomic analysis, we provide a dated whole-genome level perspective for the evolution of the tetraploid Gossypium clade and resolved the evolutionary relationships of Gs, Ge, and domesticated G. hirsutum. We describe genomic structural variation that arose during Gossypium evolution and describe its correlates-including phenotypic differentiation, genetic isolation, and genetic convergence-that contributed to cotton biodiversity and cotton domestication. Presence/absence variation is prominent in causing cotton genomic structural variations. A presence/absence variation-derived gene encoding a phosphopeptide-binding protein is implicated in increasing fiber length during cotton domestication. The relatively unimproved Ghp offers the potential for gene discovery related to adaptation to environmental challenges. Expanded gene families enoyl-CoA δ isomerase 3 and RAP2-7 may have contributed to abiotic stress tolerance, possibly by targeting plant hormone-associated biochemical pathways. Our results generate a genomic context for a better understanding of cotton evolution and for agriculture.

Ultrasound imaging features of bronchial anthracofibrosis: A case-control study.

To determine the ultrasound imaging characteristics of patients with bronchial anthracofibrosis (BAF) and identify clinical markers for prevention and treatment. We randomly selected 1243 participants (113 with BAF) who underwent bronchoscopy and received treatment at our institution between April 2018 and October 2019. BAF was classified as flat, deep-seated retracted, or black mucosal protruding based on microscopic findings. Ultrasound probes were used to determine the maximum thickness of the tube walls and submucosa. The average values of the submucosal and bony tissue areas in the BAF subtypes were compared. The BAF group included 13 participants with a history of tuberculosis (11.5%) and 57 participants with biofuel exposure (50.4%). The average exposure time was 17.4 ± 6.2 years; BAF accounted for 10% of the bronchoscopies performed. The maximum tube-wall thicknesses of the deep-seated retracted (17.3 ± 5.7) and black mucosal protruding (19.3 ± 5.4) groups were significantly greater than those of the flat group (12.5 ± 5.0; P < .05). The maximum thicknesses of the submucosa in the deep-retracted (9.8 ± 3.0) and black mucosal protruding (14.5 ± 5.0) groups were significantly greater than that of the flat group (6.6 ± 3.5; P < .05). The ratios of bone tissue in the flat and black mucosal protruding groups were 33.3 ± 9.3% and 34.9% ± 12.1%, respectively. The ratio in the deep-seated retracted group (65.2% ± 8.7%) was significantly reduced (P < .05). The flat group showed no significant change (P > .05). Differences in BAF airway remodeling among different subtypes may lead to varying clinical symptoms. Analyzing the characteristics of BAF airway remodeling and the regulatory pathway may provide new clues for treatment.

Genome-Wide Identification and Expression Analysis Elucidates the Potential Role of PFK Gene Family in Drought Stress Tolerance and Sugar Metabolism in Cotton.

Drought has been identified as a major threat for global crop production worldwide. Phosphofructokinase (PFK) is vital for sugar metabolism. During phosphorylation, plants have two enzymes: ATP-dependent phosphofructokinase (PFK) and pyrophosphate-dependent fructose-6-phosphate phosphotransferase (PFP). Genome-wide identification led to the identification of 80 PFK genes, 26 genes in G. hirsutum and G. barbadense, and 14 genes in G. arboreum and G. raimondii. Phylogenetic, gene structure, and motif analyses showed that PFK genes were grouped into two main categories, namely, PFK and PFP, with 18 and 8 genes in the allotetraploid species and 10 PFK and 4 PFP genes in the diploid species, respectively. Using the RNA-seq expressions of 26 genes from GhPFK, a co-expression network analysis was performed to identify the hub genes. GhPFK04, GhPFK05, GhPFK09, GhPFK11, GhPFK13, GhPFK14, and GhPFK17 in leaves and GhPFK02, GhPFK09, GhPFK11, GhPFK15, GhPFK16, and GhPFK17 in root tissues were found as hub genes. RT-qPCR analysis validated the expressions of identified hub genes. Interestingly, GhPFK11 and GhPFK17 were identified as common hub genes, and these might be the true candidate genes involved in the drought stress tolerance. In the KEGG enrichment analysis, amino acids such as L-valine, L-histidine, L-glutamine, L-serine, L-homoserine, L-methionine, L-cysteine, and gluconic acid were significantly upregulated, whereas sugars, mainly fructose-1-phosphate, D-mannitol, D-sorbitol, dulcitol, and lactose, were significantly downregulated during drought stress. Genome-wide analysis paves the way for a deeper understanding of the PFK genes and establishes the groundwork for future research into PFK's role in enhancing drought stress tolerance and sugar metabolism in cotton.

Elevated serum cholesterol levels are associated with proteinuria over 0.5 g/day in premenopausal women with systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) commonly occurs in premenopausal women and is associated with elevated estrogen levels. Patients with SLE may have abnormal serum triglyceride (TG) levels, and lipid reportedly promotes kidney damage in patients with nephrosis. Since estrogen regulates lipid levels, we investigated the serum lipid levels of premenopausal women with SLE and their relationship with proteinuria. Methods: This cross-sectional study included 123 premenopausal women with SLE (SLE group), who were classified into 24-h urine protein exceeding 0.5 g (24 h-UPRO > 0.5 g, n = 22) and 24 h-UPRO ≤ 0.5 g (n = 101) subgroups, and 100 similarly aged healthy women (control group). Clinical characteristics and biomarker levels were compared between these groups. The associated factors of proteinuria over 0.5 g/day were evaluated using multivariate logistic regression. A receiver operating characteristic (ROC) curve was plotted to assess the cholesterol (CH) cut-off associated with increased development of proteinuria over 0.5 g/day. Results: The SLE group had significantly higher serum TG levels than that of control group. 24 h-UPRO were significantly correlated with serum creatinine, CH, TG, and uric acid levels. Serum CH level was the greatest associated factor for proteinuria over 0.5 g/day. The area under the ROC curve was 0.843, with a CH cut-off of 4.58 mmol/L. Patients with serum CH above 4.58 mmol/L had a higher proportion of type IV LN, but with no statistical difference. Conclusions: In premenopausal SLE patients, serum TG levels were higher than in healthy women, and serum CH levels were the primary associated factor for proteinuria over 0.5 g/day. Proteinura over 0.5 g/day may occur in women with SLE with serum CH levels >4.58 mmol/L. CH levels may be useful for predicting proteinuria.

Clostridium perfringens and Escherichia coli Bacteremia in a Patient with Acute Obstructive Suppurative Cholangitis: A Case Report and Review of the Literature.

BACKGROUND Clostridium perfringens (CP), one of several clostridial species gram-positive bacteria, is a major cause of animal necrosis enteritis and traumatic gangrene. In some reports, CP can cause acute emphysematous cholecystitis in patients with biliary tract infections. However, C. perfringens combined with other aerobic bacteria (eg, E. coli) in bloodstream co-infection is extremely rare and often fatal. Herein, we present a case of co-infection to underscore this unusual situation so that clinicians can adequately evaluate and treat patients in time. CASE REPORT A 74-year-old man presented to the Emergency Department half a day after the onset of acute abdominal pain accompanied by nausea, vomiting, and chills. The patient was admitted, following development of jaundice, chills, high fever, confusion, and shock. Computed tomography (CT) revealed that the patient had cholangiectasis with acute obstructive suppurative cholangitis (AOSC). We subsequently performed percutaneous transhepatic gallbladder drainage surgery combined with antibiotics, including ceftriaxone, levofloxacin, and metronidazole. C. perfringens and Escherichia coli infections were identified by in vitro blood culture. Fortunately, the patient responded favorably to treatment in our hospital and was cured within 1 week. CONCLUSIONS We report a rare case of C. perfringens and E. coli bloodstream co-infection in a patient with AOSC. We suggest that anaerobic and aerobic co-infection should be considered in future clinical diagnoses. Effective antibiotic treatment combined with surgical drainage is crucial if mixed infection occurs.

Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression.

To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.

Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Objective: Aggressive phenotype and abnormal glycolytic metabolism of fibroblast-like synoviocytes (FLSs) are essential to joint inflammation and damage in rheumatoid arthritis (RA). Eukaryotic elongation factor-2 kinase (eEF2K) is a negative regulator of protein synthesis and has been shown to play an important role in regulating various cellular processes and promoting glycolysis in tumor cells. However, the role of eEF2K in regulating the pathogenic FLS behaviors is unknown. Methods: A specific inhibitor of eEF2K, NH125, and siRNA were used to evaluate the role of eEF2K on RA FLSs in vitro. Collagen-induced arthritis (CIA) mice were used to evaluate the in vivo effect of eEF2K. Cell migration, invasion of RA FLSs were assessed by transwell or wound healing assays. Relative changes of cytokines were analyzed by quantitative real-time PCR, western blot and ELISA. Results: Herein, we found an increased expression of eEF2K in synovial tissues and FLSs of RA patients. eEF2K knockdown by siRNA or treatment with NH125, an inhibitor of eEF2K, significantly reduced inflammation, migration/invasion, glucose uptake and lactate productions. eEF2K knockdown suppressed TNF-α-induced activation of NF-κB and AKT pathways in RA FLSs. Lactate reversed the inhibitory effect of eEF2K knockdown on inflammation and migration of RA FLSs. Moreover, lactate was also involved in eEF2K-mediated activation of NF-κB and AKT. NH125 treatment attenuated the severity of arthritis in collagen-induced arthritis mice. Conclusion: eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.

Standard-Intensity Induction and Intermediate/High-Dose Cytarabine Consolidation Can Improve Survival for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Cohort Study.

BACKGROUND: There is great uncertainty in the treatment of elderly patients with acute myeloid leukemia (AML), which leads to great challenges in treatment decision. The aim of this study is to find more suitable induction therapy and consolidation therapy for elderly AML patients. METHODS: A total of 149 consecutive newly diagnosed elderly AML patients (aged ≥60 years) who received induction chemotherapy in our medical center from January 2015 to December 2019 were retrospectively analyzed. RESULTS: After the first induction treatment, the complete remission/or complete remission with incomplete hematologic recovery (CR/CRi) rates in the standard-intensity chemotherapy group was significantly higher than that in the low-intensity chemotherapy group (58.2% vs 32.9%, p = 0.003). Compared with the low-intensity chemotherapy, the incidence of severe infection in the standard-intensity chemotherapy was significantly increased (p < 0.001), but the early mortality was comparable. One hundred and seven patients received minimal residual disease (MRD) examination after the first induction treatment; and MRD was negative accounting for 51.9% in the standard-intensity chemotherapy group, while only 32.7% in the low-intensity group (p = 0.05). The 2-year-overall survival (OS) of patients in standard-intensity induction chemotherapy group (37.2%) was slightly higher than that in low-intensity induction chemotherapy group (23.4%) (p = 0.075). Eighty-one CR/CRi patients received intermediate or high dose cytarabine (n = 35) or sequential chemotherapy regimens (n = 46) as consolidation treatment. The 2-year OS and event-free survival (EFS) of patients in the intermediate or high-dose cytarabine group were significantly higher than those in the sequential chemotherapy regimens group (73.0% vs 38.5%, p = 0.002; 54.8% vs 35.0%, p = 0.035). CONCLUSION: Our results showed that standard-intensity induction chemotherapy can significantly improve the CR rate for elderly AML patients, and does not increase the early mortality; consolidation therapy with intermediate or high-dose cytarabine can significantly improve EFS and OS for elderly AML patients achieved CR.

Effects of statins in primary and secondary prevention for venous thromboembolism events: A meta analysis.

OBJECTIVE: The associations between statins use and incidence or recurrence of venous thromboembolism (VTE) are controversial. We aimed to conduct a meta-analysis to reconcile the conflicting results. METHODS: We searched PubMed, Embase and Cochrane Library for studies published from database inception until May 31, 2021. Cohort studies and Randomized Controlled Trials that reported incidence or recurrence of VTE using statins compared with placebo or non-statins were included for meta-analysis. RESULTS: A total of 43 studies comprising over 8.6 million participants were included for analysis. The median follow-up duration was 38.1 months. Compared with no statins treatment, statins appeared to have a protective effect in primary prevention of VTE (RR 0.78, 95% CI 0.72-0.85), but significant heterogeneity was found among included studies (I2 = 81%). Statins was also associated with a 26% reduced risk of recurrent VTE (RR 0.74, 95% CI 0.70-0.78), even in patients receiving anticoagulant therapy (RR 0.77, 95% CI 0.65-0.92). In patients with a history of VTE, statins was associated with a reduced risk of bleeding and all cause mortality. The NNT of statins to prevent one case of VTE in the cancer population, and one case of recurrent VTE in patients with a history of VTE was 103.1 and 90.7 person-years respectively. CONCLUSION: In high-risk patients, statins treatment may reduce the incidence of VTE. Statins can also reduce the risk of recurrent VTE and all-cause mortality in patients with a history of VTE.

Total endoscopic sublay mesh repair for umbilical hernias.

ABSTRACT: Umbilical hernias constitute some of the most common surgical diseases addressed by surgeons. Endoscopic techniques have become standard of care together with the conventional open techniques for the treatment of umbilical hernias. Several different approaches were described to achieve laparoscopic sublay repair.We prospectively collected and reviewed the medical records of 10 patients with umbilical hernias underwent total endoscopic sublay repair (TES) at our institution from November 2017 to November 2019. All operations were performed by a same surgical team. The demographics, intraoperative details, and postoperative complications were evaluated.All TES procedures were successfully performed without conversion to an open operation. No intraoperative morbidity was encountered. The average operative time was 109.5 minutes (range, 80-140 minutes). All the patients resumed an oral diet within 6 hours after the intervention. The mean time to ambulation was 7.5 hours (range, 4-14 hours), and mean postoperative hospital stay was 2.2 day (range, 1-4 days). One patient developed postoperative seroma. No wound complications, chronic pain, or recurrence were registered during the follow-up.Initial experiences with this technique show that the TES is a safe, and effective procedure for the treatment of umbilical hernias.

Post-operative chemotherapy improves the survival of patients with well differentiated widespread metastatic appendiceal non-mucinous adenocarcinomas.

BACKGROUND: Appendiceal adenocarcinoma is a very rare type of tumor, often asymptomatic in the early stages of development. Surgical resection is the most preferred intervention against appendiceal non-mucinous adenocarcinoma, but the efficacy of post-operative adjuvant chemotherapy is still unclear because the cancer is rare. Accordingly, we sought to characterize appendiceal non-mucinous adenocarcinoma profile that confers a better survival advantage for post-operative chemotherapy. METHODS: We analyzed patients with appendiceal non-mucinous adenocarcinoma in the Surveillance, Epidemiology and End Results database, histologically diagnosed for the cancer between 2004 and 2015. Nearly half of the patients first underwent surgery and thereafter received post-operative chemotherapy. Logistic regression, Kaplan-Meier, univariate and multivariate Cox analysis were performed to evaluate the odds ratio for the propensity of patients underweening chemotherapy, whereas hazard ratios were used to evaluate the overall as well as cancer-specific survival. RESULTS: Of the 724 patients with appendiceal non-mucinous adenocarcinoma who underwent surgery, 301 (41.6%) received post-operative chemotherapy. Notably, patients with metastatic appendiceal non-mucinous adenocarcinoma were more likely to receive chemotherapy (OR =7.42, 95% CI: 5.34-10.39, P<0.001), similar to those with poor pathologically differentiated cancer types (OR =2.10, 95% CI: 1.49-3.00, P<0.001). However, univariate and multivariable Cox regression analyses found no significant overall survival and cancer-specific survival advantage for patients put on postoperative post-operative chemotherapy. In the disease stage and pathological differentiation groups, only patients with widespread metastatic (Stage IV) but well differentiated tumors displayed better 3-year (11.9% in overall survival, 11.5% in cancer-specific survival) and 5-year survival rate (7.8% in overall survival, 6.8% in cancer-specific survival) to post-operative chemotherapy. CONCLUSIONS: Staging and grading of appendiceal non-mucinous adenocarcinoma is invaluable in guiding the rationale of post-operative chemotherapy. Findings of this research support the view that only patients with both of widespread metastatic but well differentiated appendiceal non-mucinous adenocarcinoma should be considered for post-operative chemotherapy. Nonetheless, further prospective multidisciplinary clinical trials are necessary to further discern the use chemotherapy after surgery in appendiceal non-mucinous adenocarcinoma patients.

Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study.

OBJECTIVE: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. METHODS: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. RESULTS: 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS: The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03185793.