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The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge.We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario.Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73.Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.

To explore the molecular biology of D variant blood group withA total of 6 samples from 3 generations of a family were analyzed. RHD blood group was identified by saline test tube and microcolumn gel card method. 10 exons ofThe proband was identified as D variant by serological identification,The first genetic lineage of the探讨分析一家系3代共6个标本，采用试管法及微柱凝胶卡法鉴定RHD血型，应用聚合酶链式反应-序列特异性引物法（PCR-SSP）对血清学鉴定先证者为D变异型，在中国人群中发现

To investigate the clinical effect of Kinesio Taping combined with electroacupuncture in the treatment of Bigliani typeⅠsubacromial impingement syndrome.From January 2019 to June 2021, 82 cases with Bigliani typeⅠsubacromial impingement syndrome were selected and divided into treatment group and control group. Treatment group included 41 cases, 23 males and 18 females, aged from 20 to 52 years old, with an average of (39.31±5.80)years old. There were 12 cases on left shoulder and 29 cases on right shoulder. The course of disease was from 3.2 to 35.4 months. The treatment group was treated with Kinesio Taping and electroacupuncture. In control group, there were 41 cases, including 22 males and 19 females, aged from 19 to 53 years old with an average of (40.67±6.13) years old, 30 cases on right shoulder, 11 cases on left shoulder. The courses of disease was from 3.0 to 36.0 months. The control group was treated with simple shoulder electroacupuncture. Patients in both groups were treated with electroacupuncture 3 times a week for 3 weeks. After each electroacupuncture treatment in the treatment group, the Kinesio Taping was applied immediately and kept for 2 days. Before treatment, immediately after treatment, and after 1, 3, 8 weeks, the shoulder joint Constant-Murley score, pain visual analogue scale (VAS), and shoulder joint range of motion were used to evaluate the treatment effect.After 1 week of treatment, there was 1 patient in treatment group refused treatment due to hypersensitivity to Kinesio Taping, 1 patient in control group was allergic to the metal needle and refused treatment. And the other 80 patients completed all treatment. Immediately after treatment, and 1, 3, and 8 weeks after treatment, VAS of treatment group were (2.06±1.03), (2.74±1.66), (3.28±1.04), and (3.90±0.12) points, respectively. The Constant-Murley scores of shoulder joint were(86.41±3.52), (82.44±3.14), (80.46±2.54), (76.97±2.01) points. VAS of control group were(3.35±0.41), (3.08±0.92), (3.77±0.67), (3.96±1.04) points, and the Constant-Murley scores of the shoulder joint were(75.82±2.73), (74.72±1.53), (73.66±1.53), (70.68±1.95) points respectively. Immediately after treatment, VAS, Constant-Murley score, and shoulder range of motion between two groups were better than those of before treatment (The treatment for bigliani typeⅠsubacromial impingement syndrome with Kinesio Taping combined with electroacupuncture can reduce pain, effectively improve the function of shoulder joint. In addition, with Kinesio Taping protection when motion, the patients sports ability can be improved obviously, with good immediate effect, and no trauma. If the patients are willing to accept it, it would be an immediate and effective treatment.

ObjectiveThe study aims to investigate the effect of metformin on Hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) who received transarterial chemoembolization (TACE) for the first time.MethodsFrom January 2016 to December 2019, T2DM patients diagnosed with HCC in Shandong Cancer Hospital and treated with TACE were included in this retrospective study. Overall survival (OS) and Progression-free survival (PFS) were compared between patients treated with metformin and other antidiabetics. Univariate and multivariate Cox regression models were used to evaluate the independent risk factors associated with OS and PFS. And sub-analysis was performed to investigate whether metformin could give a survival advantage in each Barcelona Clinic Liver Cancer (BCLC) stage of HCC. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted.ResultsA total of 123 HCC patients with T2DM underwent TACE, of which 50 (40.65%) received treatment with metformin. For the whole cohort, the median OS (42 vs 32 months, p=0.054) and PFS (12 vs 7 months, P=0.0016) were longer in the metformin group than that in the non-metformin group. Multi-analysis revealed that BCLC stage, BMI (Body Mass Index), and metformin use were independent predictors of OS. Metformin use was independently associated with recurrence. After PSM, 39 matched pairs were identified. The use of metformin was associated with a numerically longer m OS (43 vs 35 months, P=0.183) than the use of other anti-diabetics. And the difference in median PFS (13 vs 7 months, p=0.018) between the metformin group and non-metformin group remained significant.ConclusionThe combination of transarterial chemoembolization and metformin may be associated with better OS and PFS in HCC patients with T2DM.

A large human natural single‑chain fragment variable (scFv) phage library was constructed based on Cre‑LoxP recombination, and used to successfully identify antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). The library was derived from 400 blood samples, 30 bone marrow samples, and 10 cord blood samples from healthy donors. Lymphocytes were isolated from each sample and cDNA was synthesized using reverse transcription‑quantitative PCR. Two‑step overlap PCR was then used for scFv synthesis using a LoxP peptide as the linker. The scFv gene was inserted into the phagemid vector pDF by enzymatic digestion and ligation, and then transformed into Escherichia coli (E. coli) SS320 to establish a primary antibody library in the form of scFvs. A primary antibody library consisting of 5x107 peripheral blood and umbilical cord blood sources, as well as a primary antibody library of 5x107 bone marrow samples were obtained. By optimizing the recombination conditions, the primary phage library was used to infect E. coli BS1365 strain (which expresses the Cre enzyme), and a human scFv recombinant library with a size of 1x1011 was obtained through Cre‑LoxP enzyme‑mediated heavy and light chain replacement and recombination. This constructed recombinant library was employed to screen for antibodies against recombinant PCSK9. After four rounds of selection, a fully human antibody (3D2) was identified with a binding affinity of 1.96±1.56ⅹ10‑10 M towards PCSK9. In vitro, the PCSK9/low‑density lipoprotein receptor (LDLR) pathway of Hep‑G2 cells was inhibited by 3D2 treatment, thereby increasing LDL uptake in these cells. In addition, combination treatment with 3D2 and statin was more effective at increasing LDLR levels than treatment with 3D2 or statin alone. Furthermore, 3D2 resulted in a 3‑fold increase in hepatic LDLR levels, and lowered total serum cholesterol by up to 61.5% in vivo. Taken together, these results suggest that the constructed human Cre‑LoxP scFv phage display library can be used to screen fully human scFv, and that 3D2 may serve as a candidate hypolipidemic therapy.

Objective To explore the effect of air temperature on the hospitalization of rural residents with cardiovascular diseases and its lag effect in Dingxi city. Methods The meteorological data and air pollution data of Dingxi city from 2018 to 2019,as well as the daily hospitalization data of rural residents due to cardiovascular diseases,were collected.The distributed lag non-linear models were employed to analyze the relationship between daily mean air temperature and the number of inpatients with cardiovascular diseases.Meanwhile,stratified analysis was carried out according to gender,age,and disease. Results There was a non-linear relationship between air temperature and the number of hospitalized rural residents with cardiovascular diseases in Dingxi city.The exposure-response curve approximated a bell shape.The curves for different cardiovascular diseases appeared similar shapes,with different temperature thresholds.Low temperature(-7 ℃) and moderately low temperature(0 ℃) exhibited a cumulative lag effect on the number of patients hospitalized with cardiovascular diseases.With a cumulative lag of 7 days at -7 ℃ and 14 days at 0 ℃,the

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).

Our data suggest that Nuclear receptor corepressor (NCOR1) is involved in the maintenance of mitochondrial membrane potential in prostate cancer cells, and loss of NCOR1 may contribute to prostate cancer progression., Prostate cancer (PCa) is the most frequently diagnosed male cancer. An earlier study of a cohort of 333 primary prostate carcinomas showed that 74% of these tumors fell into one of seven subtypes of a molecular taxonomy defined by specific gene fusions (ERG, ETV1/4 and FLI1) or mutations (SPOP, FOXA1 and IDH1). Molecular subtypes may aid in distinguishing indolent cases from aggressive cases and improving management of the disease. However, molecular features of PCa outside the seven subtypes are still not well studied. Here we report molecular features of PCa cases without typical features of the established subtypes. We performed comprehensive genomic analysis of 91 patients, including 54 primary and 37 metastatic cases, by whole‐exome sequencing. TP53, SPOP, FOXA1, AR (androgen receptor) and a TMPRSS2–ERG fusion emerged as the most commonly altered genes in primary cases, whereas AR, FOXA1, PTEN, CDK12, APC and TP53 were the most commonly altered genes in metastatic cases. Nuclear receptor corepressor (NCOR1) genomic alterations have been identified in 5% of cases, which are nontypical molecular features of PCa subtypes. A novel NCOR1 c.2182G>C (p.Val728Leu) was identified in tumor. RT‐PCR was used to show that this mutation caused loss of NCOR1 exon 19 and might be oncogenic in PCa. NCOR1 is involved in maintenance of mitochondrial membrane potential in PCa cells, and loss of NCOR1 might contribute to PCa progression. Therefore, NCOR1 may be a potential molecular marker of a subtype of PCa.

Hepatic ischemic reperfusion injury (IRI) is a common complication of liver surgery. Although an imbalance between mitochondrial fission and fusion has been identified as the cause of IRI, the detailed mechanism remains unclear. Augmenter of liver regeneration (ALR) was reported to prevent mitochondrial fission by inhibiting dynamin-related protein 1 (Drp1) phosphorylation, contributing partially to its liver protection. Apart from phosphorylation, Drp1 activity is also regulated by small ubiquitin-like modification (SUMOylation), which accelerates mitochondrial fission. This study aimed to investigate whether ALR-mediated protection from hepatic IRI might be associated with an effect on Drp1 SUMOylation. Liver tissues were harvested from both humans and from heterozygous ALR knockout mice, which underwent IRI. The SUMOylation and phosphorylation of Drp1 and their modulation by ALR were investigated. Hepatic Drp1 SUMOylation was significantly increased in human transplanted livers and IRI-livers of mice. ALR-transfection significantly decreased Drp1 SUMOylation, attenuated the IRI-induced mitochondrial fission and preserved mitochondrial stability and function. This study showed that the binding of transcription factor Yin Yang-1 (YY1) to its downstream target gene UBA2, a subunit of SUMO-E1 enzyme heterodimer, was critical to control Drp1 SUMOylation. By interacting with YY1, ALR inhibits its nuclear import and dramatically decreases the transcriptional level of UBA2. Consequently, mitochondrial fission was significantly reduced, and mitochondrial function was maintained. This study showed that the regulation of Drp1 SUMOylation by ALR protects mitochondria from fission, rescuing hepatocytes from IRI-induced apoptosis. These new findings provide a potential target for clinical intervention to reduce the effects of IRI during hepatic surgery.

Breast cancer is a malignant tumor with the highest incidence in women of the world. CXCR4 and Skp2 are highly expressed in breast cancer cells and CXCR4 was positively correlated with Skp2 by interference or overexpression. The microRNA array was used to detect the differentially expressed spectrum of micro RNAs in breast cancer cells the changes of miR-7-5p after CXCR4 inhibitor (NT21MP) treatment to block the CXCR4/SDF-1 pathway was founded. MiR-7-5p has been found to be correlated with Skp2 in various tumors in the literature, and Skp2 expression can be regulated by transfection with miR-7-5p mimics or inhibitors. The expression level of miR-7-5p was upregulated or downregulated after CXCR4 interference or overexpression. Combined with the correlation between CXCR4 and miR-7-5p in the chip results, CXCR4 may regulate Skp2 through miR-7-5p. Epithelial cells have the morphological characteristics of mesenchymal cells for some reason called epithelial-mesenchymal transformation (EMT). Transfection of miR-7-5p mimics into drug-resistant cells reduced Skp2 levels, decreased the expression of Vimentin, Snail, and slug, and increased the expression of E-cadherin. CXCR4 inhibitor (NT21MP) can reverse the EMT changes caused by miR-7-5p inhibitor. Similarly, in vivo results suggesting that CXCR4 inhibitors can reverse the EMT phenotype of drug-resistant breast cancer cells through the CXCR4/miR-7-5p/Skp2 pathway. In summary, the CXCR4/miR-7-5p/Skp2 signaling pathway plays an important role in the progression of breast cancer. This study provides a theoretical basis for the treatment of breast cancer by targeting the CXCR4 pathway.

Microglial activation-induced neuroinflammation is closely associated with the development of Parkinson disease (PD). Macroautophagy/autophagy regulates many biological processes, but the role of autophagy in microglial activation during PD development remains largely unclear. In this study, we showed that deletion of microglial Atg5 caused PD-like symptoms in mice, characterized by impairment in motor coordination and cognitive learning, loss of tyrosine hydroxylase (TH) neurons, enhancement of neuroinflammation and reduction in dopamine levels in the striatum. Mechanistically, we found that inhibition of autophagy led to NLRP3 (NLR family pyrin domain containing 3) inflammasome activation via PDE10A (phosphodiesterase 10A)–cyclic adenosine monophosphate (cAMP) signaling in microglia, and the sequential upregulation of downstream IL1B/IL-1β in turn increased the expression of MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]), a pro-inflammatory cytokine. Inhibition of NLRP3 inflammasome activation by administration of MCC950, a specific inhibitor for NLRP3, decreased MIF expression and neuroinflammatory levels, and rescued the loss of TH neurons in the substantial nigra (SN). Interestingly, we found that serum MIF levels in PD patients were significantly elevated. Taken together, our results reveal an important role of autophagy in microglial activation-driven PD-like symptoms, thus providing potential targets for the clinical treatment of PD. Abbreviations: ATG: autophagy related; cAMP: cyclic adenosine monophosphate; cKO: conditional knockout; NOS2/INOS: nitric oxide synthase 2, inducible; IL1B: interleukin 1 beta; ITGAM/CD-11b: integrin alpha M/cluster of differentiation molecule 11B; MAP1LC3: microtubule-associated protein 1 light chain 3; MIF: macrophage migration inhibitory factor (glycosylation-inhibiting factor); NLRP3: NLR family pyrin domain containing 3; PBS: phosphate-buffered saline; PD: parkinson disease; PDE10A: phosphodiesterase 10A; SN: substantial nigra; TH: tyrosine hydroxylase; TNF: tumor necrosis factor; WT: wild type.

Although pre-treatment paroxysmal nocturnal hemoglobinuria (PNH) clone has been reported in a fraction of aplastic anemia (AA) for a long time, its predictive value on response to immunosuppressive therapy (IST) remained debatable. Therefore, we conducted a meta-analysis to elaborate this issue.The identified articles were retrieved from five English databases PubMed, EMBASE, Web of Science, Medline, the Cochrane Library, and four Chinese databases Weipu, Wangfang, China National Knowledge Infrastructure (CNKI), and SinoMed. We extracted odds ratios (ORs) and the corresponding 95% confidential intervals (CIs) for response to IST in AA patients with pre-treatment PNH clone versus those without from the available studies.Twelve studies covering 1787 patients were included this meta-analysis. The pooled ORs indicated that the pre-treatment PNH clone had no impact on 3-month response (pooled OR: 1.323, 95% CI: 0.260-6.735,Pre-treatment PNH clone is associated with favorable 12-month response to IST in AA, the underlying mechanism needs further exploring.

Rationale: It is known that neuroinflammation plays a critical and detrimental role in the development of cerebral ischemia/reperfusion (I/R), but the regulation of the cyclic GMP-AMP synthase (cGAS)-mediated innate immune response in I/R-induced neuroinflammation is largely unexplored. This study aimed to investigate the function and regulatory mechanism of cGAS in I/R-induced neuroinflammation and brain injury, and to identify possible strategies for the treatment of ischemic stroke. Methods: To demonstrate that microglial histone deacetylase 3 (HDAC3) regulates the microglial cGAS-stimulator of interferon genes (cGAS-STING) pathway and is involved in I/R-induced neuroinflammation and brain injury, a series of cell biological, molecular, and biochemical approaches were utilized. These approaches include transient middle cerebral artery occlusion (tMCAO), real-time polymerase chain reaction (PCR), RNA sequencing, western blot, co-immunoprecipitation, chromosome-immunoprecipitation, enzyme-linked immunosorbent assay (ELISA), dual-luciferase reporter assay, immunohistochemistry, and confocal imaging. Results: The microglial cGAS- STING pathway was activated by mitochondrial DNA, which promoted the formation of a pro-inflammatory microenvironment. In addition, we revealed that HDAC3 transcriptionally promoted the expression of cGAS and potentiated the activation of the cGAS-STING pathway by regulating the acetylation and nuclear localization of p65 in microglia. Our in vivo results indicated that deletion of cGAS or HDAC3 in microglia attenuated I/R-induced neuroinflammation and brain injury. Conclusion: Collectively, we elucidated that the HDAC3-p65-cGAS-STING pathway is involved in the development of I/R-induced neuroinflammation, identifying a new therapeutic avenue for the treatment of ischemic stroke.

OBJECTIVE: To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD). METHODS: A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks. RESULTS: Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P0.05). CONCLUSIONS: Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

BRAF138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFEight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914-0.990], AUC 0.792 [95% CI, 0.703-0.882], and AUC 0.985 [95% CI, 0.965-1.000] in the training dataset, AUC 0.931 [95% CI, 0.841-1.000], AUC 0. 725 [95% CI, 0.569-0.880], and AUC 0.938 [95% CI, 0.851-1.000] in the test dataset, respectively.The radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAF

The major hurdle in glioblastoma therapy is the low efficacy of drugs crossing the blood-brain barrier (BBB). Neisseria meningitidis is known to specifically enrich in the central nervous system through the guidance of an outer membrane invasion protein named Opca. Here, by loading a chemotherapeutic drug methotrexate (MTX) in hollow manganese dioxide (MnO

Shennongjia is one of the most important ecological function areas and ecologically vulnerable zones in the world. With the rapid development of social economies, especially tourism, the ecological environment of Shennongjia has experienced profound changes. Exploring the characteristics and changing trends of ecological environment in Shennongjia will help to analyze the causes of the damage to the ecological environment, and build a vulnerability analysis framework with multi-scale, multi-element, multi-flow, and multi-circulation characteristics, which provides an effective research paradigm and analysis tool for the study of regional ecological vulnerability. With the support of RS and GIS technology, this study uses spatial principal component analysis (SPCA) and the vulnerability scoring diagram (VSD) model to comprehensively and quantitatively analyze the spatial and temporal evolution characteristics and driving forces of ecological vulnerability in Shennongjia from 1996 to 2018. The VSD model was selected to decompose the vulnerability into three components of "exposure-sensitivity-adaptation", and 16 indicators were selected to construct an ecological vulnerability evaluation system in Shennongjia, and the evaluation data were organized in a progressive and detailed way. (1) During the study period, the overall ecological vulnerability of Shennongjia is in a mild vulnerability level, exhibiting differentiation characteristics of high in the northeast and low in the southwest. High vulnerability zones are mainly distributed in the main towns and roads. (2) The risk of ecological vulnerability of the entire region presents the characteristics of continuous decline. (3) Land-use types, population density, and vegetation coverage are the main factors driving the evolution of ecological vulnerability. (4) A high level of coupling coordination exists between ecological vulnerability and landscape patterns. Analyses of the ecological vulnerability of Shennongjia shows that the entire region is in a mild vulnerability level. The extreme vulnerability risk of the ecological environment shows polarization. The evolution of ecological environment in Shennongjia is the result of the interaction between human activities and natural environment. This study offers an effective way to assess ecological vulnerability and provides some strategies and guidance for improving ecological security.

To evaluate the clinical efficacy of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children.From January to December 2020, we treated 116 children with distal hypospadias in the Department of Urology, Department of Pediatrics and the Seventh Medical Center of the PLA General Hospital, 58 by primary Snodgrass urethroplasty only (the control group) and the other 58 with Compound Chamomile and Lidocaine Hydrochloride Gel smeared on the penis postoperatively in addition (the trial group). We compared the operation time and postoperative pain score, edema regression and incidence of infection between the two groups, followed by statistical analysis using T test and Chi-square test.All the operations were successfully completed by the same surgeon under general anesthesia. There were no statistically significant differences between the trial and control groups in age (［2.5 ± 0.8］ vs ［2.4 ± 0.6］ yr, P0.05) or operation time (［95.6 ± 14.5］ vs ［97.1 ± 15.2］ min, P0.05). No incision infection occurred in any of the cases. The pain scores at dressing removal were remarkably lower in the trial than in the control group at 2 hours (1.4 ± 1.0 vs 2.6 ± 1.3, P0.05), 24 hours (2.2 ± 1.3 vs 3.9 ± 1.6, P0.05), 48 hours (1.2 ± 0.7 vs 1.6 ± 0.9, P0.05) and 72 hours after surgery (2.5 ± 0.8 vs 3.7 ± 1.8, P0.05). Significantly more cases of edema regression were achieved in the trial than in the control group at 2 weeks postoperatively (35 vs 19, P0.05).Compound Chamomile and Lidocaine Hydrochloride Gel can effectively relieve pain, reduce edema and accelerate edema regression after surgery in children with hypospadias, and therefore deserves wide clinical application.、.

This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms.Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol.Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer.In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.

Objective. To investigate the expression and clinical significance of serum heparin-binding protein (HBP), C-reactive protein (CRP), and white blood cell count (WBC) in an acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods. A prospective research model was used to select 63 patients with acute exacerbation of chronic obstructive pulmonary disease who were hospitalized in Xuzhou First People’s Hospital from January 2020 to June 2020, and among the chronic obstructive pulmonary disease patients who were followed up in our hospital during the same period, 18 patients were in the stable phase, and 43 healthy patients in our hospital during the same period were selected as the healthy control group. 18 patients with stable chronic obstructive pulmonary disease were selected as the observation group, and 43 healthy people who underwent examination at the same time as the control group. For patients with acute COPD recombination, 5 ml of venous blood was collected according to whether the condition of COPD patients with acute exacerbation was stable or not. 5 ml of venous blood was collected for acute exacerbation. According to their clinical symptoms (such as cough, sputum, and asthma), dyspnea score (MRC score), and pulmonary function (FEV1 and FEV1/FVC), it is determined whether the patient’s condition is stable. Patients in the stable COPD group will collect 5 ml of venous blood during the outpatient follow-up, and those in the healthy physical examination group will collect veins on the day of the physical examination. In 5 ml of blood, the levels of HBP and CRP in the blood were measured by the enzyme-linked immunosorbent method and the immunoturbidimetric method, respectively, and the peripheral blood WBC was measured by a blood cell analyzer and its supporting reagents. The differences of the three indicators in each group were statistically analyzed. Normally distributed measurement data were compared using t-test, homogeneity of variance of nonnormally distributed measurement data were compared using one-way analysis of variance, uneven variance of nonnormally distributed measurement data were compared using a rank-sum test, and Pearson linear analysis was used for correlation test. Subject working characteristic curve (ROC) was drawn, P < 0.05 means the difference is statistically significant, the receiver working characteristic curve was established, and the area under the curve (AUC) was calculated to analyze blood HBP. The value of blood CRP and peripheral blood WBC counts alone or in combination in the diagnosis of acute exacerbations of chronic obstructive pulmonary disease. Results. The level of blood heparin-binding protein in the acute exacerbation phase was significantly higher than that in the stable phase and healthy controls ( P < 0.05 ). In the acute exacerbation stage and stable stage group, the blood heparin binding protein, the percentage of leukocytes, neutrophils, and CRP were detected. There is a correlation between ( P < 0.05 ) and a correlation with lung function (FEV1) ( P < 0.05 ). The predictive value of heparin-binding protein, white blood cells, neutrophil percentage, CRP, etc. for the acute exacerbation of chronic obstructive pulmonary disease, with the area under the heparin-binding protein curve, is the largest, and compared with the stable phase, the comparison of heparin-binding protein, white blood cells, and CRP is statistically significant ( P < 0.05 ). Conclusion. Heparin-binding protein increases in the stable phase and acute exacerbation phase and is related to other inflammatory factors. It is one of the important inflammatory factors in chronic obstructive pulmonary disease. Heparin-binding protein, white blood cells, CRP, etc. have diagnostic and predictive value for acute exacerbation of chronic obstructive pulmonary disease. Heparin-binding protein has the best predictive result, and the combined index test has a better diagnostic predictive value, which is better than single index detection.

To analyze the clinical characteristics of patients with POEMS syndrome and explore its effective treatment strategies.The clinical data of 75 patients with POEMS syndrome treated in The First Affiliated Hospital of Zhengzhou University from June 2012 to June 2018 were collected and retrospectively analyzed. The clinical characteristics, treatment regimes and outcomes of the patients were summarized.The median age of 75 diagnosed patients was 50 (30-81) years old and 100% (75/75) of the patients were accompanied with peripheral neuropathy, 77.3% (58/75) with organ enlargement, 82.7% (62/75) with endocrine abnormality, 93.3% (70/75) with monoclonal plasma cell diseases and 64.0% (48/75) with skin changes. Among the 75 patients, 5 cases gave up treatment, while the others showed varying degrees of improvement after treatment. The hematological complete remission (CRThe clinical manifestations of POEMS syndrome are complex and diverse, the clinicians therefore should be vigilant to reduce the misdiagnosis and missed diagnosis. Bortezomib or Lenalidomide can be recommended as the first-line medicines and autologous HSCT should be considered for appropriate patients.POEMS综合征患者的临床特征及疗效分析.分析POEMS综合征患者的临床特征，并探讨有效的治疗策略。.对2012年6月至2018年6月本院收治的75例POEMS综合征患者的病历资料进行收集并回顾性分析，总结患者的临床特点、治疗方法及疗效。.75例POEMS患者诊断时中位年龄50（30-81）岁，100%（75/75）见周围神经病变，77.3%（58/75）合并器官肿大，82.7%（62/75）伴有内分泌功能异常，93.3%（70/75）存在单克隆性浆细胞疾病，64.0%（48/75）伴有皮肤改变。75例患者中，5例放弃治疗，剩余70例患者经治疗后症状得到不同程度的改善，血液学完全缓解（CRPOEMS综合征临床表现复杂多样，临床医师应提高警惕，减少误诊、漏诊。硼替佐米或来那度胺等药物可用于一线治疗，有条件者建议行自体造血干细胞移植。.

Aims Post-acute coronary syndrome (ACS) P2Y12 inhibitor non-adherence is common and associated with greater risk of major adverse cardiovascular events (MACEs). Non-adherence can follow different trajectories from an inability to initiate, implement, or continue therapy for the intended duration. We aimed to evaluate P2Y12 inhibitor adherence trajectories among ACS patients treated with percutaneous coronary intervention (PCI), their frequency, and association with MACE. Methods and results We conducted a cohort study of adults discharged alive after PCI for ACS (2012–16) using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry linked with administrative data. The primary outcome was P2Y12 inhibitor adherence trajectory in the year after PCI assessed using group-based trajectory modelling. We used logistic regression and Cox proportional-hazards regression to assess associations of trajectories with risk factors and MACE, respectively. We included 12 844 patients (mean age 62.4 years, 23.6% female). Five trajectories were identified: early consistent non-adherence (11.0%), rapid decline (7.7%), delayed initiation (6.0%), gradual decline (20.5%), and persistent adherence (54.8%). Compared with persistent adherence, rapid decline [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01–1.49] and delayed initiation (HR 1.41, 95% CI 1.12–1.78) were associated with higher MACE in the overall cohort, whereas early consistent non-adherence was associated with higher MACE only in the subgroup receiving a drug-eluting stent (HR 2.44, 95% CI 1.60–3.71). Conclusion After PCI for ACS, patients followed one of five distinct P2Y12 inhibitor adherence trajectories. Rapid decline and delayed initiation were associated with a higher risk of MACE, whereas early consistent non-adherence was only associated with higher MACE risk in patients with a drug-eluting stent. Key questions Key findings Take-home message

Seven in absentia homolog 1 (Siah1) has been shown plays important roles in the pathogenesis and development of multiple cancers. However, the functions and mechanisms of Siah1 in non-small cell lung cancer (NSCLC) remain unclear. In our study, we found that knock down of Siah1 could inhibit the proliferation of NSCLC cells, while over-expression of Siah1 had the opposite effects. Molecularly, the bioinformatics analysis determined that notch receptor 1 (Notch1) might be the potential target of Siah1. Subsequently, we identified that Siah1 acted as an E3 ligase to promote the ubiquitination and stabilization of Notch1 through the proteasome pathway. Furthermore, the results showed that the Siah1 expression was directly correlated with CTR9 in human NSCLC tissues. Finally, Siah1 could promote Akt phosphorylation through regulating Notch1, thus promoting the proliferation of NSCLC cells. In conclusion, our study demonstrated that Siah1 acts as an oncogene, can ubiquitinate and stabilize Notch1 by proteasome pathway, which promotes Akt phosphorylation and ultimately leads to NSCLC cell proliferation.

Claudin 6 (CLDN6) is an important component of tight junctions. Through the PDZ binding motif, CLDN6 binds to a variety of signaling proteins that contain the PDZ domain to regulate different signaling pathways, and plays an important role in the occurrence and development of tumors. Our previous work showed that CLDN6 was expressed at low levels in breast cancer cells, and overexpression of CLDN6 inhibited breast cancer cell proliferation, migration and invasion. However, the mechanism of how CLDN6 works remains unclear. In this study, we aimed to explore the mechanism by which CLDN6 inhibits breast cancer cell malignant behavior. As a result, overexpression of CLDN6 inhibited the proliferation of breast cancer cells along with the downregulation of cyclin D1, which plays an important role in regulating cell proliferation. After overexpression of Sp1 in CLDN6-overexpressing cells, the expression of cyclin D1 was upregulated. On the other hand, CLDN6 inhibited breast cancer cell migration and invasion along with the downregulation of IL-8, CXCR2 and FAK. When treated with IL-8, the migration and invasion ability were promoted along with the upregulation of CXCR2 and p-FAK, and the cytoskeleton was rearranged in CLDN6-overexpressing cells. Furthermore, when treated with the ERK signaling activator PMA, the proliferation, migration and invasion abilities were promoted along with the upregulation of Sp1, cyclin D1 and IL-8 in CLDN6-overexpressin cells. In conclusion, CLDN6 suppressed ERK/Sp1/cyclin D1 and ERK/IL-8 signaling to inhibit proliferation, migration and invasion in breast cancer cells. The mechanism may provide experimental evidence for the treatment of breast cancer targeting CLDN6.

Objective We previously highlighted the problem of frequent false positives in 24 hour urine normetanephrine(UNM) measurements owing to reference intervals that are inappropriately low for the population being screened for pheochromocytoma. Using a large population database, we devised new age-stratified reference intervals for the 24 hour UNM test that were higher compared to previous. However, it was uncertain as to whether this would compromise test sensitivity for true pheochromocytoma cases. Design and Methods: Retrospective analysis of all pheochromocytoma cases from a recently constructed provincial registry. All confirmed cases had their diagnostic UNM results retrospectively re-analysed according to the newly proposed UNM reference intervals to determine the percentage and phenotype of cases that might have been theoretically missed with the new reference range. Results After excluding pediatric and non-secretory head and neck paragangliomas, there were 60 confirmed pheochromocytoma cases. Using prior reference intervals, 51/60 (85%) had an abnormally high UNM. Of the 9 with normal UNM, 4 had a high urine metanephrine(UMN), 5 had normal levels of both UNM and UMN such that 55/60 had abnormal test results, representing the historical combined test sensitivity of 92%. Using the proposed reference interval, 43/60 (72%) had high UNM results. Of the 17 with normal UNM, 12 had high UMN, 5 had normal levels of both UNM and UMN. Therefore, 55/60 patients had had elevations in either UNM or UMN, corresponding to an identical combined test sensitivity of 92%. Conclusions Reference intervals for UNM derived from actual clinical population screening data are higher than in traditional healthy volunteers. Use of these more appropriate reference intervals can significantly reduce the false positive rate without compromising test sensitivity for true pheochromocytoma.

Understanding the mechanisms of structural organization of corneal stroma is scientifically interesting and may lead to advances in corneal tissue engineering. In the past, we used the combination of second harmonic generation and fast Fourier transform to study a number of topics including the structural alteration of human keratoconus. Recently, we applied this approach to studying changes of chick embryonic cornea during development. As numerous studies were performed with ex vivo specimens, a thorough understanding of the parameters associated with the development process cannot be achieved until experiments are performed in living chick embryos.

Objective To explore the effect of air pollution on the number of emergency room visits for respiratory diseases in residents at different ages and its seasonal changes in Lanzhou,so as to provide a scientific basis for the early prevention of respiratory diseases in Lanzhou. Methods The daily number of emergency room visits for respiratory diseases in three class A hospitals in Lanzhou from January 1,2013 to December 31,2017,as well as the air pollutants and meteorological data of Lanzhou in the same period,was collected.After controlling the confounding factors including long-term trend of time,meteorological factors and day-of-week effect using a generalized additive model,we analyzed the relationships between air pollutants and the daily number of emergency room visits for respiratory diseases,and explored whether there was a lag effect of air pollutants.Results From 2013 to 2017,the emergency room visits for respiratory diseases in Lanzhou had a total number of 124 871,with an average of 69(1-367)visits per day.The single pollutant model showed that among the six conventional air pollutants monitored in Lanzhou,PM

To observe the clinical efficacy of Kinesio Taping combined with electroacupuncture in the treatment of patellofemoral disorder in middle-aged and elderly exercise enthusiasts.From April 2018 to April 2020, 62 middle-aged and elderly exercisers with patellofemoral disorder were selected and divided into observation group and control group. In the observation group, there were 30 cases:12 males and 18 females, aged from 35 to 66 years old, with an average age of (48.32±6.80) years old. The observation group was treated with Kinesio Taping and electroacupuncture . In the control group, there were 32 cases:12 males and 20 females, aged from 35 to 67 years old, with an averageage of (48.67±8.13) years old. The patients in the control group was treated with knee electroacupuncture. All the patients in both groups were treated once every other day, 3 times a week, for a total of 4 weeks. The VAS pain score and knee Lysholm score before and after treatment were compared between the two groups before and after treatment, and statistical analysis was conducted.In the control group, 2 patients were not satisfied with the curative effect after 2 weeks of treatment and gave up treatment, while the remaining 60 patients completed all the treatments. After 4 weeks of treatment, the VAS and Lyshlom scores of the control group were 2.73±1.46 and 75.63±8.62 respectively;the VAS and Lyshlom scores of the observation group were 2.02±1.85 and 83.31±5.53 respectively;the VAS and Lyshlom scores of the observation group and the control group were better than those before treatment, and the Lyshlom scores of the observation group were better than those of the control group.Kinesio Taping combined with electroacupuncture is aimed at patellofemoral disorderof middle-aged and elderly sports enthusiasts. It has little trauma, can relieve pain and has a fast onset speed, which is readily accepted by patients, and promotes the rehabilitation of knee joint function of patients, thus providing a favorable reference for the promotion in clinical application.

We hypothesized that PD-1expressed by regulatory T cells (Tregs) would be functional and their expression levels may associate with activation status of CD4+ T and CD8+ T cells and the disease progression of HIV-1-infected patients. To prove it, we dynamically examined PD-1 expression levels by Tregs in peripheral blood of HIV-1-infected individuals not receiving antiretroviral therapy. Eighty-one HIV-1-infected individuals not undergoing antiretroviral therapy and 22 HIV-1-seronegative donors were enrolled in our study. Tregs were defined as CD4+CD25+CD127lo/- by flow cytometry. Expression of PD-1 and the activation markers CD38, HLA-DR, and Ki67 by Tregs and CD4+ T and CD8+ T cells was also determined by flow cytometry. TGF-β and IL-10 were measured to evaluate the suppressive function of Tregs. In all Tregs, the proportion of PD-1+ Tregs observed in HIV-1-infected persons was significantly greater than that seen in HIV-1-seronegative donors, and correlated with the activation of Tregs and CD4+ T and CD8+ T cells. This increased proportion of Tregs was also statistically associated with the disease progression. Blockade of PD-1/PD-L1 pathway with anti-PD-L1 mAb profoundly increased the level of intracellular TGF-β and IL-10 in CD4+CD25+CD127lo/- Tregs. Our data not only support that PD-1 plays a critical role to predict the activation status of cellular immunity and disease progression during HIV-1 infection but also indicate that blockade of PD-1/PD-L1 pathway represents a novel therapeutic approach to AIDS.

The oncolytic reovirus (RV) has demonstrated clinical efficacy and minimal toxicity in a variety of cancers, including multiple myeloma (MM). MM is a malignancy of plasma cells that is considered treatable but incurable because of the 90% relapse rate that is primarily from drug resistance. The systemic nature of MM and the antitumor immunosuppression by its tumor microenvironment presents an ongoing therapeutic challenge. In the present study, we demonstrate that RV synergizes with the standard-of-care MM drug bortezomib (BTZ) and, importantly, enhances its therapeutic potential in therapy-resistant human MM cell lines in vitro. Using the syngeneic Vk*MYC BTZ-resistant immunocompetent transplantable MM murine model, we also demonstrate that mice harboring BTZ-insensitive MM tumors respond to the RV/BTZ combination treatment in terms of decreased tumor burden and improved overall survival (P < .00001). We demonstrate that BTZ augments RV replication in tumor-associated endothelial cells and myeloma cells, leading to enhanced viral delivery and thereby stimulating cytokine release, immune activity, apoptosis, and reduction of the MM-associated immune suppression. We conclude that combined RV/BTZ is an attractive therapeutic strategy with no safety signals for the treatment of MM.

Background Radiofrequency ablation and microwave ablation are frequently prescribed for thoracic cancer. However, few writers have been able to draw on any systematic research into the differences between the two ablation methods. Methods A literature search was carried out using Embase, PUBMED, Web of Science, Cochrane Library, and CNKI databases, with additional searches carried out manually using terms associated with thoracic cancer and thermal ablation. Then we used Google Scholar for a complementary search. Data were extracted from studies of patients that underwent radiofrequency ablation or microwave ablation, and the investigator carried out efficacy evaluation and follow up. The data obtained from the literature were summarized and analyzed using Cochrane Revman software Version 5.3 and SPSS 22.0. Results There were seven comparative studies, but no randomized studies identified for data extraction; 246 patients received radiofrequency ablation therapy and 319 controls received microwave ablation. There was no significant difference in the six-month, one-year, two-year, and three-year survival rates, and adverse reactions were found in the two treatments. For patients' long-term survival rate, the two treatments can achieve a similar survival time. Conclusion In the treatment of thoracic cancer, microwave ablation can achieve the same efficacy as radiofrequency ablation.

Background Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size. Purpose To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference. Material and Methods A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland–Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC). Results Correlation between the MR images and pathology was high for both readers (0.899–0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, P≤0.012; reader 2, P≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971–0.997). Conclusion The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.

Infectious diseases continue to inflict a high global disease burden. The consensus is that vaccination is the most effective option against infectious diseases. Oral vaccines have unique advantages in the prevention of global pandemics due to their ease of use, high compliance, low cost, and the ability to induce both systemic and mucosal immune responses. However, challenges of adapting vaccines for oral administration remain significant. Foremost among these are enzymatic and pH-dependent degradation of antigens in the stomach and intestines, the low permeability of mucus barrier, the nonspecific uptake of antigens at the intestinal mucosal site, and the immune suppression result from the elusive immune tolerance mechanisms. Innovative delivery techniques promise great potential for improving the flexibility and efficiency of oral vaccines. A better understanding of the delivery approaches and the immunological mechanisms of oral vaccine delivery systems may provide new scientific insight and tools for developing the next-generation oral vaccine. Here, an overview of the advanced technologies in the field of oral vaccination is proposed, including mucus-penetrating nanoparticle (NP), mucoadhesive delivery vehicles, targeting antigen-presenting cell (APC) nanocarriers and enhanced paracellular delivery strategies and so on. Meanwhile, the mechanisms of delivery vectors interact with mucosal barriers are discussed.

The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer's disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.

Background Risk factors that predispose the development of severe community-acquired pneumonia (CAP) among pediatric CAP patients of different age ranges are yet to be identified. Methods We retrospectively analyzed pediatric in-patients ( Results A total of 20,174 cases were initially included. Among them, 3309 (16.40%) cases were identified as severe CAP, and 2824 (14.00%) cases required ICU admission. Potential risk factors for severe CAP and ICU admission identified by univariate analysis included younger age, rural residency, premature birth, low birth weight (LBW), formula feeding, congenital heart disease (CHD), history of pneumonia or neonatal jaundice, patients with other health issues, certain symptoms (manifesting wheezing, dyspnea, cyanosis, but have no cough or fever), abnormal laboratory findings (abnormal levels of white blood cells, albumin, and C-reactive protein and RSV infection), and chest X-ray (odds ratio [OR] > 1 for all). CHD, low albumin, proteinuria, abnormal chest x-ray were independent risks factors across different age groups, whereas birth or feeding history, history of pneumonia, cyanosis or dyspnea on admission, and RSV infection were independent risk factors for only younger kids ( Conclusions Risk factors predicting disease severity among children hospitalized with CAP vary with age. Risk factor stratification of pediatric CAP based on age-specific risk factors can better guide clinical practice. Trial registration This study has been registered in China, with the registration number being ChiCTR2000033019.

Purpose To evaluate the value of preoperative computed tomography (CT) features including morphologic and quantitative features for predicting the Ki-67 labeling index (Ki-67LI) of gastric gastrointestinal stromal tumors (GISTs). Methods We retrospectively included 167 patients with gastric GISTs who underwent preoperative contrast-enhanced CT. We assessed the morphologic features of preoperative CT images and the quantitative features including the maximum diameter of tumor, total tumor volume, mean total tumor CT value, necrosis volume, necrosis volume ratio, enhanced tissue volume, and mean CT value of enhanced tissue. Potential predictive parameters to distinguish the high-level Ki-67LI group (>4%, n = 125) from the low-level Ki-67LI group (≤4%, n = 42) were compared and subsequently determined in multivariable logistic regression analysis. Results Growth pattern (p = 0.036), shape (p = 0.000), maximum diameter (p = 0.018), total tumor volume (p = 0.021), mean total tumor CT value (p = 0.009), necrosis volume (p = 0.006), necrosis volume ratio (p = 0.000), enhanced tissue volume (p = 0.027), and mean CT value of enhanced tissue (p = 0.004) were significantly different between the two groups. Multivariate logistic regression analysis indicated that lobulated/irregular shape (odds ratio [OR] = 3.817; p = 0.000) and high necrosis volume ratio (OR = 1.935; p = 0.024) were independent factors of high-level Ki-67LI. Conclusions Higher necrosis volume ratio in combination with lobulated/irregular shape could potentially predict high expression of Ki-67LI for gastric GISTs.

BACKGROUND It is unclear whether vitamin D status is related to cardiovascular risk beyond that explained by conventional risk markers. We examined the relationship between serum 25-hydroxy (OH) vitamin D and incident cardiovascular disease (CVD; heart attack/stroke) after adjusting for individual- and community-level covariates from laboratory, administrative and survey data. METHODS Patients receiving their first 25-OH vitamin D test in Calgary, Alberta from 2009 to 2013 without a past CVD diagnosis but an electrocardiogram and body mass index (BMI) +/- 3 months from testing were included. The following was merged to this data: first results for laboratory-measured CVD risk markers (lipid profile, fasting plasma glucose, and HbA1c) measured +/- 3 months from testing; Census Dissemination Area (CDA)-level indicators of socioeconomic status (SES) in 2011; and CVD diagnoses > 3 months from testing between 2009 and 2016. Linear and Poisson regression were used to examine associations between 25-OH vitamin D quartile and covariates, and Cox proportional hazard models were used to examine associations with incident CVD before and after adjusting for covariates. RESULTS Among 72 348 patients, there were 1898 CVD events over a median of 6.0 years. Increasing quartile of 25-OH vitamin D was associated with improved lipid and glycemic profiles (p

MicroRNAs (miRNAs/miRs) are small, non-coding RNAs that are reported to serve numerous important regulatory functions; however, the role of miRNAs in regulating breast cancer cell biology remains poorly understood. Accumulating evidence has demonstrated that miRNAs orchestrate multiple cellular functions and serve crucial roles in cell differentiation and cancer development, either by acting as tumor suppressors or oncogenes. In particular, miR-155-5p expression levels have been found to be upregulated and serve as a prognostic marker in numerous types of solid cancer, including human breast cancer. More than half of patients with breast cancer benefit from treatment with adjuvant paclitaxel chemotherapy following the early postoperative period. Despite the initial response to intensive combination chemotherapy, the majority of most patients will eventually acquire resistance to the drug and succumb to their disease. Therefore, further investigations into the association between miRNAs and the mechanism of paclitaxel resistance are required. The results of the present study revealed a strong positive association between miR-155-5p expression levels and the paclitaxel resistance, as the expression levels of miR-155-5p were upregulated in resistant cells. MiR-155-5p was further validated to regulate paclitaxel resistance using gain- and loss-of-function experiments. TP53INP1 was identified as a direct target gene of miR-155-5p by combining the results from the prediction algorithm based on free energy minimization and reverse transcription-quantitative PCR (qRT-PCR) analysis. Also, miR-155-5p was suggested to be a key regulator of paclitaxel resistance in tumor cells, as it increased cell viability and motility, and promoted resistance to paclitaxel-induced apoptosis. The transfection with miR-155-5p inhibitors re-sensitized the paclitaxel-resistant breast cancer cells, while the overexpression of miR-155-5p led to an increase in the resistance to paclitaxel. Furthermore, the overexpression of the target gene, TP53INP1, contributed to the re-sensitivity of drug-resistant cells to paclitaxel. The subsequent combination of the knockdown of miR-155-5p and the overexpression of TP53INP1 conferred paclitaxel sensitivity in resistant cells. These results may enhance the understanding of the molecular mechanisms underlying breast cancer progression and resistance to chemotherapy, and suggested that miR-155-5p or TP53INP1 may serve as novel therapeutic approaches to combat resistance to therapy, as well as the proliferation and evasion of apoptosis in breast cancer.

Objective: This study aimed to investigate if CT-detected extramural venous invasion (ctEMVI) was associated with the presence of lymph node metastasis (LNM) and survival outcomes in patients with gastric cancer. Methods: We retrospectively reviewed 105 patients with pathologically proved gastric cancer who underwent pre-operative CT examinations and received radical gastrectomy with extended lymphadenectomy. Differences in CT characteristics between the LNM-positive and -negative groups were assessed by two observers. Binary logistic regression analysis was performed to determine the risk factors of lymph node metastasis in gastric cancer. Progression-free survival analysis was performed by Kaplan–Meier method. Results: Two observers reached good inter-reader agreements in ctEMVI and ctN status with κ values of 0.711 and 0.751, respectively. The frequency of ctEMVI-positive status was 58.1% (61/105) in patients with gastric cancer. The LNM-positive group showed higher possibility of ctEMVI-positive status (81.7% vs 26.7%, p＜0.001), larger tumor volume (mean volume, 40.77 vs 22.09 mL, p＜0.001), poor tumor margin (45.0% vs 26.7% , p = 0.054) and high enhancement on arterial phase (43.3% vs 26.7%, p = 0.023) and venous phase (60.0% vs 44.4%, p = 0.048), than LNM-negative group. In multivariate analysis, ctEMVI status and tumor volume were identified as independent risk factors for lymph node metastasis with odds ratio (OR) of 9.804 (95% CI, 3.076－31.246; p＜0.001) and 1.030 (95% CI, 1.001－1.060; p = 0.044). CT-detected EMVI presented better diagnostic efficiency for lymph node metastasis than CT-defined N status, with sensitivity (81.7% vs 70.0%), specificity (73.3% vs 71.1%), accuracy (78.1% vs 70.5), PPV (80.3% vs 76.4%), and NPV (75.0% vs 64.0%), respectively. Kaplan–Meier curves showed that patients with positive ctEMVI findings has lower PFS rate than patients with negative ctEMVI findings (Log-rank test, p = 0.007). Conclusion: CT-detected EMVI was significantly associated with lymph node metastasis and progression free survival in patients with gastric cancer. Compared to CT-defined N status, ctEMVI provided superior diagnostic performance to predict pathologic Nstatus. Advances in knowledge: Our study proved that CT-detected EMVI is a promising imaging marker to predict lymph node metastasis and poor prognosis, which may contribute to the precise evaluation of gastric cancer before surgery.

A new meroterpene, chrysomutanin (

Penicimutanin C, a new alkaloidal compound, was isolated from the neomycin-resistant mutant strain 3-f-31 of the marine-derived fungus, Penicillium purpurogenum G59, together with four known compounds. The structure of penicimutanin C, including the absolute configuration, was determined by spectroscopic and chemical methods. The absolute configuration of penicimutanin A was also re-confirmed by Marfey's and chiral HPLC analyses of the hydrolyzed products. Penicimutanins C and A inhibited the proliferation of five human cancer cell lines to some extent. Penicimutanin C is the third dimer of diketopiperazine and penicimutanolone, which are only produced by mutants of P. purpurogenum G59 isolated to date, and it showed cytotoxic activity against human cancer cell lines. The neomycin-resistant screening strategy has been previously successfully used to discover new compounds by activating silent metabolites in fungi, and the present results provide an additional example of the effectiveness of this method.

To observe the clinical effects of zheng's massage combined with electroacupuncture in the treatment ofreflex sensory dystrophy syndrome of the wrist.From October 2016 to September 2018, 48 cases of reflex sensory dystrophy syndrome of the wrist were divided into the observation group and the control group. In the observation group, there were 24 cases, including 10 males and 14 females, ranging in age from 54 to 76 years old, with an average age of (61.41 ±7.90) years old. The patients in the observation group were treated withAfter 6 weeks of treatment, VAS in the control group was 4.9±1.8, and Cooney wrist score was 74.63±1.72; VAS in the observation group was 2.2±1.4, and Cooney wrist score was 86.31±2.53. The comprehensive scores of VAS and Cooney wrist joint between two groups were improved after treatment, and the observation group was better than control group(Zheng's massage combined with electroacupuncture has the following advantages in the treatment of reflex sympathetic dystrophy syndrome of the wrist, such as small trauma, patients' willingness promoting functional rehabilitation, which is worthy of clinical promotion.

Background: The standard treatment for esophageal carcinoma is extensive resection of the tumor and esophagogastric anastomosis despite the high incidence of related anastomotic complications, such...

Background and objectives The atherogenic index of plasma (AIP) is elevated in fatty liver disease, but its value in non-obese people with non-alcoholic fatty liver disease (NAFLD) is unclear. This study aimed to investigate the relationship between AIP and NAFLD as well as to determine whether AIP might be used as an indicator of NAFLD in non-obese individuals. Methods The present study involved non-obese Chinese and Japanese participants. Risk factors are evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic curve. Results In the unadjusted model, the odds ratio (OR) for every 1 standard deviation (SD) increase in AIP was 52.30. In adjusted models I and II, the OR for every 1 SD increase in AIP was 36.57 and 50.84, respectively. The area under the receiver operating characteristic curve for AIP was 0.803 and 0.802 in the development and validation groups, respectively. The best cut-off value of AIP for discrimination between NAFLD and non-NAFLD was 0.005 in the Chinese group and − 0.220 in the Japanese group. Conclusions AIP and NAFLD are positively correlated in Chinese and Japanese populations. Therefore, AIP can be used as a new screening indicator for non-obese people with NAFLD in different nations.

To evaluate the efficacy and safety of acupuncture combined with modified Xiangfu Decoction in the treatment of menopausal insomnia case by liver Qi stagnation. Totally 120 cases were randomly divided into the control group(60 cases) and the treatment group(60 cases). Estazolam and acupuncture combined with modified Xiangfu Decoction were given for 16 weeks. Before and after treatment, Epworth sleepiness scale(ESS), Pittsburgh sleep quality index(PSQI), Hamilton anxiety scale(HAMA) and traditional Chinese medicine(TCM) syndrome score were compared between the two groups. Polysomnography monitor was used to monitor sleep progress and sleep structure. Serum LH, FSH and E_2 were determined. The clinical efficacy and incidence of adverse reactions were observed. Four cases were lost during the study. The total effective rate in the treatment group was 91.5%, which was higher than that in the control group 75.4%(Plt;0.05). After treatment, the scores of clinical symptoms(ESS, PSQI, HAMA, TCM symptoms) in the treatment group were significantly reduced(Plt;0.05), and lower than that in the control group(Plt;0.05). TST, SE in the treatment group were increased(Plt;0.05), while AWT, SL, AT in the treatment group were decreased(Plt;0.05), and the improvement was more significant than that in the control group(Plt;0.05). S_1 in the treatment group was decreased(Plt;0.05), whereas S_2, S_(3+4), REM in the treatment group were increased(Plt;0.05), and the improvement was more significant than that in the control group(Plt;0.05). The contents of LH and FSH in the treatment group were significantly reduced(Plt;0.05), while the content of E_2 was significantly increased(Plt;0.05), and the changes were more significant than those in the control group(Plt;0.05). The incidence of adverse reactions in the control group was 8.8%, which was higher than 1.7% in the treatment group(Plt;0.05). Acupuncture combined with modified Xiangfu Decoction could significantly improve the sleep status of menopausal insomnia cases caused by liver Qi stagnation, with a lower incidence of adverse reactions, and so is worthy of clinical promotion and application.

T‑2 toxin is a type A trichothecene mycotoxin. In order to reduce the side effects of T‑2 toxin and increase the tumor targeting ability, a pH‑sensitive liposome of T‑2 toxin (LP‑pHS‑T2) was prepared and characterized in the present study. The cytotoxicity of LP‑pHS‑T2 on A549, Hep‑G2, MKN‑45, K562 and L929 cell lines was tested by 3‑(4,5‑dimethylthiazolyl‑2)‑2,5‑diphenyltetrazolium bromide assay, with T‑2 toxin as the control. The apoptotic and migratory effects of LP‑pHS‑T2 on Hep‑G2 cells were investigated. The preparation process of LP‑pHS‑T2 involved the following parameters: Dipalmitoyl phosphatidylcholine: dioleoylphosphatidylethanolamine, 1:2; total phospholipid concentration, 20 mg/ml; phospholipid:cholesterol, 3:1; 4‑(2‑hydroxyethyl)‑1‑piperazineethanesulfonic acid buffer (pH 7.4), 10 ml; drug:lipid ratio, 2:1; followed by ultrasound for 10 min and extrusion. The encapsulation efficiency reached 95±2.43%. The average particle size of LP‑pHS‑T2 after extrusion was 100 nm; transmission electron microscopy showed that the shape of LP‑pHS‑T2 was round or oval and of uniform size. The release profile demonstrated a two‑phase downward trend, with fast leakage of T‑2 toxin in the first 6 h (~20% released), followed by sustained release up to 48 h (~46% released). From 48‑72 h, the leakage rate increased (~76% released), until reaching a minimum at 72 h. When LP‑pHS‑T2 was immersed in 0.2 mol/l disodium phosphate‑sodium dihydrogen phosphate buffers (pH 6.5), the release speed was significantly increased and the release rate reached 91.2%, demonstrating strong pH sensitivity. Overall, antitumor tests showed that LP‑pHS‑T2 could promote the apoptosis and inhibit the migration of Hep‑G2 cells. The present study provided a new approach for the development of T‑2 toxin‑based anti‑cancer drugs.