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The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years. In particular, viral mutation like delta strain has led to third- or fourth-wave transmission among the countries in Asia, Europe, and North America. Although large-scale vaccination has been carried out in many countries, the incidence of reinfection and vaccine-past breakthrough infection is becoming an emerging challenge to humans worldwide. The related mechanisms underlying the reinfection and breakthrough infection remain unknown. In this review, we summarized the challenge and related reasons for severe acute respiratory syndrome coronavirus 2 reinfection and breakthrough infection. Simultaneously, we addressed some critical contents of the study in future.

Congenital hyperinsulinism (CHI), a major cause of persistent and recurrent hypoglycemia in infancy and childhood. Numerous pathogenic genes have been associated with 14 known genetic subtypes of CHI. Adenosine triphosphate-sensitive potassium channel hyperinsulinism (KATP-HI) is the most common and most severe subtype, accounting for 40–50% of CHI cases. Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism (SCHAD-HI) is a rare subtype that accounts for less than 1% of all CHI cases that are caused by homozygous mutations in the hydroxyacyl-coenzyme A dehydrogenase (HADH) gene. This review provided a systematic description of the genetic pathogenesis and current progress in the diagnosis and treatment of SCHAD-HI to improve our understanding of this disease.

Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/β-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role.PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA).Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients.RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.HINTERGRUND: Für Sclerostin, ein Regulator des Knochenstoffwechsels und der Gefäßkalzifizierung, der an der Regulierung des Wnt/β-Catenin-Signalwegs beteiligt ist, wurde nachgewiesen, dass es auch in der Pathogenese der rheumatoiden Arthritis (RA) eine Rolle spielt. Jedoch sind die aktuellen Ergebnisse in Bezug auf die Werte für zirkulierendes Sclerostin bei RA-Patienten umstritten. Ziel der vorliegende Studie war es, die Werte für zirkulierendes Sclerostin bei RA-Patienten zu untersuchen und dessen Rolle kurz zusammenzufassen.Die Datenbanken PubMed, EMBASE und der Cochrane Library wurden systematisch bis 27. Mai 2021 auf infrage kommende Artikel hin durchsucht. Nützliche Daten aus allen geeigneten Arbeiten wurden systematisch erfasst und mittels der Software Stata 12.0 analysiert (Stata Corp LP, College Station, TX, USA).In dieser aktualisierten Metaanalyse wurden 13 geeignete Studien mit 1030 Fällen und 561 normalen Kontrollen ausgewertet. Das Walddiagramm dieser Metaanalyse zeigte, dass RA-Patienten höhere Werte für Werte für zirkulierendes Sclerostin aufwiesen als die normalen Kontrollen (p 0,001; standardisierte mittlere Differenz, SMD: 0,916; 95%-Konfidenzintervall, 95%-KI: 0,235–1,597). Untergruppenanalysen ergaben, dass Alter, Region und Bestimmungsmethode mit dem Sclerostinwert bei RA-Patienten in Zusammenhang standen.Bei RA-Patienten fanden sich höhere Werte für zirkulierendes Sclerostin auf als bei normalen Kontrollen. Dieser Zusammenhang wurde durch die Faktoren Alter, Region und Bestimmungsmethode beeinflusst.

Background The nonspecific clinical, radiological and pathological characteristics of gastric syphilis can establish it as an imitator of other gastric diseases. The absence of primary or secondary lubricating lesions should not prevent consideration of gastric syphilis. Case summary A 63-year-old female patient presented to the hospital with dull pain in the middle and upper abdomen without apparent cause for one week, which was aggravated for two days. The patient had been sexually active with the same male partner for the past years, but her partner was promiscuous. Abdominal contrast-enhanced computed tomography (CT) and positron emission tomography/CT suggested gastric cancer. The gastroscopy revealed an antral gastric ulcer with gastric retention, and also suggested gastric cancer. But no cancer cells were found in the biopsies taken during the two gastroscopies. Treponema pallidum (T. pallidum) antibodies: ELISA positive, rapid plasma reagin titer 1:16. Hematoxylin and eosin (HE) stain showed macrophage infiltration in the lamina propria. Numerous spirochetes were observed by immunohistochemical staining using a monoclonal antibody against T. pallidum. The patient was finally diagnosed with gastric syphilis. Conclusion Only a few cases of gastric syphilis have been misdiagnosed as gastric cancer. Penicillin can relieve symptoms of gastric syphilis.

Purpose Henagliflozin is a highly selective and effective sodium glucose co-transporter (SGLT)-2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of meal intake on the pharmacokinetic properties of henagliflozin, and to understand the excretion pathways of henagliflozin in humans. Methods In this Phase I, randomized, open-label, single-dose, two-period crossover study, 12 healthy male Chinese volunteers were randomized to receive either henagliflozin 10 mg in the fasted condition followed by henagliflozin 10 mg in the fed condition, or the reverse schedule, with the two administrations separated by a washout period of at least 7 days. Samples of blood, urine, and feces were collected and analyzed for the investigation of the pharmacokinetic profile and excretion pathways in the fasted and fed conditions. Any adverse events that occurred throughout the study were recorded for tolerability assessment. Findings After the administration of a single oral dose of henagliflozin, mean (SD) plasma AUC0–∞ and Cmax were 1200 (274) h · ng/mL and 179 (48.8) ng/mL, respectively, in the fasted state and were decreased to 971 (245) h · ng/mL and 115 (34.2) ng/mL in the fed state. The fed/fasted ratios (90% CIs) of the geometric mean values of Cmax, AUC0–t, and AUC0–∞ were 64% (54%–76%), 80% (76%–85%), and 80% (76%–85%), respectively. The median (range) Tmax was prolonged from 1.5 (1–3) hours in the fasted condition to 2 (1.5–6) hours in the fed condition. Mass-balance testing revealed that henagliflozin was eliminated primarily as the parent drug in feces and as glucuronide metabolites in urine. In the fasted state, the cumulative excretion percentages of the parent drug and its metabolites to dose in feces and urine were 40.6% and 33.9%, respectively. The values in the fed condition were changed to 50.4% and 25.5%, respectively. These findings suggest that postprandial administration decreases the absorption rate and the extent of henagliflozin exposure in humans, but has no effect on the metabolism or elimination of the drug. Implications In the present study, the consumption of a high-fat meal prior to henagliflozin administration was associated with reductions in AUC0–∞ and Cmax of 19.4% and 36.4%, respectively. However, based on the analysis of the pharmacokinetic/pharmacodynamic findings on henagliflozin, this slight change may not have clinical significance. Mass balance of henagliflozin in humans was achieved with ∼75% of the administered dose recovered in excretions within 4 days after administration whether in the fasted or fed state. These findings suggest that henagliflozin tablets can be administered with or without food.

Objective The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals. Methods This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension. Results In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10–1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01–0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99–1.06; P = 0.098) was not significantly associated with hypertension incidence. Conclusion Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.

Total knee replacement (TKR) is one of the most common orthopaedic procedures performed, and enhanced recovery after surgery (ERAS) has been developed and incorporated into inpatient surgical pathways to improve patient outcomes. Under ERAS recommendations, multimodal prophylaxis has been used to help manage postoperative nausea and vomiting (PONV) following TKR. Dexamethasone is one of the commonly used for this and the anti-inflammatory properties could depress vagal activity, reducing postural hypotension (PH). The hypothesis of this study is that postoperative dexamethasone use is associated with lower rates of early postoperative PH following TKR surgery. In our institution, patients who undergo elective primary TKR are admitted on the day of surgery and follow a standardized ERAS protocol. Data on patients who underwent elective primary TKR under a single adult reconstruction team from September 2017 to March 2020 were reviewed and analyzed. A review of demographic characteristics, surgical data, postoperative medications, and postoperative notes was performed. Binary logistic regression was used to assess the effect of the use of dexamethasone on PH, with an adjusted odds ratio (OR) calculated after accounting for potential confounders. Of the 149 patients were included in the study, 78 had dexamethasone postoperatively, and 71 did not. Patients who had received dexamethasone were statistically less likely to suffer from PH (OR = 0.31, p = 0.03) and less likely to develop PONV (OR = 0.21, p = 0.006). Patients who had received dexamethasone were more likely able to participate in early physiotherapy (OR = 2.42, p = 0.14), and this result was statistically insignificant. The use of postoperative intravenous dexamethasone is significantly associated with lower rates of postoperative PH after TKR. However, more studies are required to assess the optimal dosing amount and frequency, as well as to assess other factors which can enhance early postoperative patient mobilization as part of our goals for ERAS. This therapeutic study reflects level of evidence III.

Background/purpose Effective regulation of the inflammatory process is essential for pulp repair and regeneration. Meloxicam has anti-inflammatory activity in systemic administration. The purpose of this study is to observe effects of topically applied meloxicam on inflamed pulp and to explore its potential value in the treatment of pulpitis. Materials and methods The coronal pulp tissues of rat molars were stimulated with 10 mg/mL lipopolysaccharide (LPS group) and then treated with 500 μmol/L meloxicam (meloxicam group). The untreated pulp tissues were used as the control group. After 3 h of incubation in vitro, the gene expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in each group was detected by real-time RT-PCR. The pulp tissues of each group were randomly subcutaneously implanted into nude mice, and 500 μmol/L meloxicam was injected into the subcutaneous pocket of the meloxicam group. Haematoxylin eosin staining, Masson staining and immunohistochemical staining were performed on samples after 3 days and 4 weeks retrieval, respectively. Results Compared with the LPS group, the mRNA expression levels of TNF-α and IL-6 of the meloxicam group were significantly reduced in vitro. The inflammatory response and cyclooxygenase-2 expression of the meloxicam group were decreased, and osteodentin-like tissue was generated in the pulp cross section of the meloxicam group in vivo. Conclusion The topical application of meloxicam inhibits the inflammatory response of inflamed pulp and further promotes the formation of osteodentin-like tissues but fails to induce the formation of the pulp–dentin complex. Topically applied meloxicam has the potential to regulate pulp inflammation.

OBJECTIVE To investigate whether continuous infusion of propofol at a subhypnotic dose prevents nausea and vomiting following carboprost administration at cesarean delivery. METHODS A prospective, randomized, double-blind, placebo-controlled trial conducted at West China Second University Hospital, from June 28, 2017 to January 30, 2018. Pregnant women were randomly allocated to propofol or saline infusion immediately before receiving carboprost at cesarean delivery under combined spinal-epidural (CSE) anesthesia. Propofol was given at an infusion rate of 1.0 mg/kg/h following a loading dose of 0.3 mg/kg. Primary outcome was incidence of intraoperative nausea and vomiting (IONV). Potential sedative effect of propofol infusion was assessed using Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scoring and continuous Bispectral Index (BIS) monitoring. RESULTS The incidence of IONV was lower in patients who received propofol compared with saline (46.7% vs 76.7%, OR 0.27; 95% CI, 0.092-0.78, P = 0.016 for nausea; 26.7% vs 53.3%, OR 0.50; 95% CI, 0.25-0.95, P = 0.032 for retching; 10.0% vs 50.0%, OR 0.11; 95% CI, 0.03-0.44, P

BACKGROUND N-Methyl-d-aspartate receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) plays critical roles in regulating sympathetic outflow. Studies showed that acute application of the antagonists of NMDAR or its subunits would reduce sympathetic nerve discharges. However, little is known about the effect of long-term management of NMDAR in hypertensive animals. METHODS PEAQX, the specific antagonist of NMDAR subunit 2A (GluN2A) was injected into both sides of the PVN of two-kidney, one-clip (2K1C) renal hypertensive rats and control (normotensive rats) for 3 weeks. RESULTS Three weeks of PEAQX infusion significantly reduced the blood pressure of the 2K1C rats. It managed to resume the balance between excitatory and inhibitory neural transmitters, reduce the level of proinflammatory cytokines and reactive oxygen species in the PVN, and reduce the level of norepinephrine in plasma of the 2K1C rats. PEAQX administration also largely reduced the transcription and translation levels of GluN2A and changed the expression levels of NMDAR subunits 1 and 2B (GluN1 and GluN2B). In addition, NMDAR was known to function through activating the extracellular regulated protein kinases (ERK) or phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways. In our study, we found that in the PVN of 2K1C rats treated with PEAQX, the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), ERK1/2, and cAMP-response element-binding protein (CREB) significantly reduced, while the phosphorylation level of PI3K did not change significantly. CONCLUSIONS Chronic blockade of GluN2A alleviates hypertension through suppression of MEK/ERK/CREB pathway.

Apatinib, a competitive inhibitor of VEGFR2, has anti-angiogenesis and anticancer activities through different mechanisms, but it still cannot fully explain the drug efficacy of apatinib. Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in cancer biology, however, the exact role of ferroptosis in apatinib-mediating anticancer treatment are still not clear. The effects of (1S, 3R)-RSL3 and apatinib were evaluated in different GC cell lines and in normal human gastric epithelial cells. Further, the effects of apatinib and inhibition of antioxidant defense enzyme glutathione peroxidase (GPX4) on cell viability, cell death, glutathione (GSH) levels, lipid ROS production, cellular malondialdehyde (MDA) levels and protein expression were evaluated in vitro as well as in a mouse tumor xenograft model. The expression level of GPX4 in GC tissues and paracancerous tissues was measured by immunohistochemistry. (1S, 3R)-RSL3 selectively killed GC cells, but not normal cells. Apatinib induced ferroptosis in GC cells by decreasing cellular GSH levels and increasing lipid peroxidation levels. This effect was blocked by co-incubation with ferrostatin-1, liproxstatin-1, GSH, or vitamin E. Further investigation revealed that apatinib down-regulated GPX4 expression via inhibition of the transcription factors Sterol regulatory element-binding protein-1a (SREBP-1a). Besides, we found that multi-drug resistant GC cells were vulnerable to apatinib-induced GPX4 inhibition. In summary, we show that apatinib could induce the lipid peroxidation through GPX4 mediated by SREBP-1a, then negatively regulate the GC cell, even the multi-drug-resistant GC cell, ferroptosis.

To analyze clinical characteristics and potential predictors of disease severity in patients with COVID-19.Clinical data from 64 patients with COVID-19 were retrospectively analyzed. Of the 64 patients, 37 were male and 27 were female. Their mean age was 47.8 years, 43 (67.2%) cases were non-severe, 21 (32.8%) were severe, and 2 patients (3.1%) died. Age and serum ferritin were significantly associated with COVID-19 severity. Repeated monitoring of ferritin, interleukin-6, C-reactive protein, lactic acid dehydrogenase, and erythrocyte sedimentation rate during COVID-19 treatment may assist the prediction of disease severity and evaluation of treatment effects. There were no significant differences in the duration of severe illness or the number of days on high-level respiratory support between a low-dose methylprednisolone group and a high-dose methylprednisolone group. The mean number of days in hospital in the high dose group was higher than that in the low-dose group. Repeated monitoring of ferritin, interleukin-6, C-reactive protein, lactic acid dehydrogenase, and erythrocyte sedimentation rate during COVID-19 treatment may assist the prediction of disease severity and evaluation of treatment effects.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

A chlorine e6 (Ce6) and curcumin (Cur) based self-delivery nanomedicine (CeCu) is prepared for chemotherapy sensitized photodynamic therapy (PDT). The chemotherapeutic agent of Cur could inhibit the TrxR activity to destroy the cellular ROS-defence system for enhanced PDT, which provides synergistic effects for tumor precision therapy in consideration of the unfavorable tumor microenvironments.

A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.

Objective: Due to the inconsistent results of current studies on the association between urinary and blood vascular cell adhesion molecule-1 (VCAM-1) and systemic lupus erythematosus (SLE) disease activity, we conducted this study and analyzed its influencing factors. Methods: A literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library. Data were extracted from eligible studies to calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Cochrane Q test and I2 statistics were used to examine heterogeneity. The sources of heterogeneity were assessed through sensitivity analysis and subgroup analysis. Publication bias was evaluated by funnel plots and Egger's test. Results: A total of 15 studies met the inclusion criteria, including 473 active SLE patients and 674 inactive SLE patients. The random effects model was used for data analysis. In both urine and blood samples, VCAM- 1 level in active SLE patients was significantly higher than those in inactive SLE patients (urine: SMD: 0.769; 95% CI: 0.260-1.278; blood: SMD=0.655, 95% CI: 0.084-1.226). No publication bias was found in this study. Conclusion: Compared with inactive SLE patients, patients with active SLE have higher levels of VCAM-1 in both urine and blood. VCAM-1 may be a potential indicator of SLE disease activity.

Objectives To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and possible reasons among guidelines. Methods A systematic search was performed in the database to obtain guidelines for the management of MPE and ascites. The AGREE IIGtool was used to assess the quality of these guidelines. The Measurement Scale of Rate of Agreement (MSRA) was introduced to assess the scientific agreement of formulated recommendations for the management of MPE and ascites among guidelines, and evidence supporting these recommendations was extracted and analyzed. Results Nine guidelines were identified. Only 4 guidelines scored more than 60% and are worth recommending. Recommendations were also heterogeneous among guidelines for the management of MPE, and the main reasons were the different emphases of the recommendations for the treatment of MPE, the contradictions in recommendations, and the unreasonably cited evidence for MPE. Conclusions The quality of the management guidelines for patients with MPE and malignant ascites was highly variable. Specific improvement of the factors leading to the heterogeneity of recommendations will be a reasonable and effective way for developers to upgrade the recommendations in the guidelines for MPE.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE‐like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT‐PCR and Western blotting. In PE‐like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)‐1β, tumor necrosis factor alpha (TNF‐α), IL‐6 and IL‐18, as well as IL‐4, IL‐10, PIGF, VEGF and sFlt‐1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL‐1β and IL‐6 in PE rats model, and AsIV treatment inhibited the activation of TLR‐4, NF‐κB, and sFlt‐1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE‐like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF‐κB signaling pathway.

Qingqing Wu,1,2 Xiaodong Wang,3 Qian Chen,1,2 Yang Zou,1,2 Xiaoyan Xu,1,2 Tingting Li,1,2 Chen Yu,1,2 Fu Zhu,1,2 Kanyin E Zhang,4 Jingying Jia,1,2 Yanmei Liu1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Changzhou Siyao Pharmaceuticals Co., Ltd, Jiangsu, People’s Republic of China; 4ViaClinical Ltd, Shanghai, People’s Republic of ChinaCorrespondence: Yanmei LiuCenter Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, People’s Republic of ChinaTel/Fax +86-21-54030254Email ymliu@shxh-centerlab.comPurpose: To compare the bioequivalence of two formulations of valsartan (80 mg capsules) under fasting and fed conditions in healthy Chinese volunteers using a full-replicate study design.Methods: A total of 78 Subjects were randomly assigned to fasting cohort (n = 48) or fed cohort (n = 30). Each cohort includes 4 single-dose observation periods and 3-day washout periods. Blood samples were collected at designed time point. Plasma concentration of valsartan was analyzed by a validated LC-MS/MS method. Noncompartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation (SWR) of the reference formulation, either reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was used to evaluate the bioequivalence of the two formulations.Results: Under fasting conditions, the RSABE method was used to evaluate the bioequivalence of Cmax (SWR> 0.294), while ABE method was used to evaluate the bioequivalence of AUC0-t and AUC0-∞. The geometric mean ratio (GMR) of the test/reference for Cmax was 99.52%, and the 95% upper confidence bound was < 0. For AUC0-t and AUC0-∞ comparisons, GMRs were 102.07% and 101.92%, and the 90% CIs of the test/reference were 96.28%– 108.21%, 96.28%– 107.88%, respectively. Under fed conditions, the SWR value of Cmax, AUC0-t and AUC0-∞ all exceeded the cutoff value of 0.294 and therefore, the RSABE method was used. The GMRs for Cmax, AUC0-t and AUC0-∞ were 98.78%, 103.33% and 103.08%, respectively, while the 95% upper confidence bound values were all < 0. These results all met the bioequivalence criteria for highly variable drugs. All adverse events were mild and transient.Conclusion: In this study, the generic formulation of valsartan 80 mg capsule was considered to be bioequivalent to the reference product under both fasting and fed conditions, and satisfied the requirements for marketing in China.NMPA Registration No: CTR20181422.Keywords: valsartan, bioequivalence, replicate, pharmacokinetics, safety

Introduction: COVID-19 has become a global health security issue, it has caused more than half a million deaths worldwide so far, the treatment strategies are the most concerned issues for clinicians. In this study, the treatments and outcomes in 40 pediatric patients diagnosed with COVID-19 and treated with different drugs were evaluated. Methodology: All cases were diagnosed with COVID-19 nucleic acid positive by using RT-PCR or clinical manifestations, imaging specific characteristics and epidemiological clinical diagnosis. The biological information and first symptom of all cases were collect. A variety of treatments were employed and the outcomes were evaluated by Cox regression analysis. Multivariable analysis was performed to evaluate cure rate at 14 days with different drug treatment. Results: The average length of hospital stay was 10.4 days. The cure rate was increased with the treatment time extended and 90% of pediatric patients were cured and discharged after 14 days’ treatment. And multivariable analysis results proved that none of the covariates were related to the cure rate at 14 days with different drug treatment since p values were over 0.05. Conclusions: Multivariable analysis suggested that the present drug treatments cannot significantly shorten the clinical cure time and improve the cure rate of children with COVID-19.

Healthcare workers (HCWs) are at high risk of occupational exposure to the new pandemic human coronavirus, SARS-CoV-2, and are a source of nosocomial transmission in airborne infectious isolation rooms (AIIRs). Here, we performed comprehensive environmental contamination surveillance to evaluate the risk of viral transmission in AIIRs with 115 rooms in three buildings at the Shanghai Public Health Clinical Center, Shanghai, during the treatment of 334 patients infected with SARS-CoV-2. The results showed that the risk of airborne transmission of SARS-CoV-2 in AIIRs was low (1.62%, 25/1544) due to the directional airflow and strong environmental hygiene procedures. However, we detected viral RNA on the surface of foot-operated openers and bathroom sinks in AIIRs (viral load: 55.00–3154.50 copies/mL). This might be a source of contamination to connecting corridors and object surfaces through the footwear and gloves used by HCWs. The risk of infection was eliminated by the use of disposable footwear covers and the application of more effective environmental and personal hygiene measures. With the help of effective infection control procedures, none of 290 HCWs was infected when working in the AIIRs at this hospital. This study has provided information pertinent for infection control in AIIRs during the treatment of COVID-19 patients. Electronic supplementary material The online version of this article (10.1007/s12250-020-00301-7) contains supplementary material, which is available to authorized users.

Purpose Surufatinib is a potent and orally active small-molecule tyrosine kinase inhibitor targeting VEGFRs 1 to 3, FGFR-1, and CSF-1R, and thus may exert antitumor and antiangiogenic effects. The objective of this study was to determine the tolerability and effects of food intake on the pharmacokinetic properties of surufatinib in healthy Chinese subjects. Methods A total of 24 healthy Chinese male subjects aged between 18 and 55 years were enrolled. Subjects were administered a single dose of surufatinib 250–mg capsules in the fasted and fed states in succession. Pharmacokinetic analysis was performed through the collection of blood samples at predose and at several time points after surufatinib administration. Tolerability assessments comprised physical examination including vital sign measurements, laboratory testing, and ECG to determine adverse events (AEs). Findings The 90% CIs of the geometric mean ratios of AUC0–t and AUC0–∞ in the fasted and fed states was within 0.80 to 1.25; and for Cmax, within 0.70 to 1.43, indicating that food had no effect on the bioavailability of surufatinib in these healthy Chinese male subjects. Food intake delayed the time to peak absorption of surufatinib, as the median Tmax in the fed state was longer than that in the fasted state (4.0 vs 2.0 h). Surufatinib was marginally excreted from urine (mean [SD] cumulative excretion fraction, 1.2% [0.4%]). AEs occurred in 7 of the 24 subjects (29.2%) and included upper respiratory tract infection, dizziness, merycism, intervertebral disc protrusion, influenza-like disease, hematuria, prostatitis, and elevated blood urea nitrogen. All AEs were grade 1 or 2. Implications The bioavailability of surufatinib was not affected by food intake prior to dosing. However, food intake led to delated Tmax of surufatinib. The tolerability of a single oral dose of surufatinib 250 mg in the fasted and fed states was favorable in these healthy Chinese male subjects. These results indicate that surufatinib capsules could be administered before or after meals. ClinicalTrials.gov identifier: NCT02320409.

The vigorous development of rural E‐commerce reveals a powerful pattern of economic clustering. Recently, many Taobao Villages have formed in more than 80% of the provinces in rural China, and increasingly households are using E‐commerce for entrepreneurial innovation in Taobao Villages. However, the effect and mechanism of the Taobao Village model on households' entrepreneurship behavior remain unclear. Using survey data and structural equation modeling, we analyzed the factors of households' entrepreneurship behavior and investigated the mechanism of rural E‐commerce clustering on the households' entrepreneurship behavior in Taobao Villages. The results show that: (1) rural E‐commerce clusters stimulated entrepreneurial enthusiasm and increased entrepreneurial behavior; (2) local resource endowment, entrepreneurial atmosphere and culture, threshold for entrepreneurship, and demonstrative leadership had significant positive effects on households' entrepreneurship behavior; (3) external environmental support, including government, and external business environment support had significant positive effects on E‐commerce development. All these results indicate that rural E‐commerce clusters promote households' entrepreneurship behavior.

Searching for two-dimensional (2D) group V materials with ferromagnetism, elastic anisotropy, and carrier mobility and tunable band structure is one key to developing constantly developing nanodevices. The 2D monolayers SnxPy with x/y (1/1, 1/2, 1/3, and so on) coordination number are studied based on the particle-swarm optimization technique combined with the density functional theory optimization. Its thermal stability can be confirmed by molecular dynamics at 70K and 300K, indicating that the novel 2D materials have a stable existence. The electronic band structures of four stable structures suggest that all the monolayers of SnxPy are fully adjustable and flexible tunable band gaps semiconductors under the biaxial strain. The monolayer of P$$ \overline{4}{2}_1 $$ 4 ¯ 2 1 m-SnP2 with unique valence band structure can go from nonmagnetic to ferromagnetic by the hole doping because of the “Stoner criterion,” and Pmc21-SnP2 is a direct-like gap semiconductor with in-plane elastic anisotropy to possess a high electron mobility as high as 800 cm2V−1 s−1 along the kb direction, which is much higher than that of MoS2 (∼ 200 cm2V−1 s−1). The optical absorption peak of the material is in the ultraviolet region. These discoveries expand the potential applications of the emerging field of 2D SnxPy structures in nanoelectronics.

Distant metastasis is the major cause of short survival in ccRCC patients. However, the development of effective therapies for metastatic ccRCC is limited. Herein, we reported that ETV4 was selected from among 150 relevant genes with in vivo evidence of promoting metastasis. In this study, we identified that ETV4 promoted ccRCC cell migration and metastasis in vitro and in vivo, and a positive correlation between ETV4 and FOSL1 expression was found in ccRCC tissues and cell lines. Further investigation suggested that ETV4 increase FOSL1 expression through direct binding with the FOSL1 promoter. Furthermore, ETV4/FOSL1 was proved as a novel upstream and downstream causal relationship in ccRCC in an AKT dependent manner. In addition, both ETV4 and FOSL1 serve as an independent, unfavorable ccRCC prognostic indicator, and the accumulation of the ETV4 and FOSL1 in ccRCC patients result in a worse survival outcome in ccRCC patients. Taken together, our results suggest that the ETV4/FOSL1 axis acts as a prognostic biomarker and ETV4 directly up-regulates FOSL1 by binding with its promoter in a PI3K-AKT dependent manner, leading to metastasis and disease progression of ccRCC.

Background Ovarian endometrioid carcinoma resembling sex cord-stromal tumor (ECSCSs) is rare. Case summary We present a rare case of primary ECSCSs in the left ovary. A 39-year-old female patient had persistent dull pain in the lower abdomen for more than 1 mo, and she was initially diagnosed with pelvic inflammatory disease at a hospital. The patient received transabdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node dissection at our hospital and finally diagnosed with ECSCSs. After the operation, the patient received eight courses of cisplatinum + etoposide + bleomycin chemotherapy treatment and no evidence of tumor recurrence or metastasis was found in a 2-year follow-up period. Conclusion Ovarian endometrioid carcinoma is similar to the ovary sex cord-stromal tumor, especially when the cord-like structure is obvious. The clinical diagnosis for this tumor is difficult before surgery and pathology examination. The necessary immunohistochemical markers are of positive significance for assisting diagnosis and differential diagnosis.

Background Atherosclerosis is one of the most common cardiovascular and cerebrovascular diseases. This study aimed to explore the correlation between gene polymorphism of human apolipoprotein E (ApoE) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Methods A total of 220 patients with atherosclerotic cardiovascular disease who were treated in our hospital from June 2016 to March 2017 were enrolled in this study and assigned as the atherosclerotic cardiovascular disease group and 193 patients who were treated contemporaneously in our hospital but had no atherosclerotic cardiovascular disease were enrolled and assigned as the control group. Gene polymorphism of ApoE was detected by PCR-fluorescent probe technique and the level of Lp-PLA2 was detected by ELISA. Results There were a total of 5 genotypes of ApoE in these two groups, which were E2/3, E3/3, E3/4, E2/4, and E4/4. E2/2 was not found in any of the patients. E3/3 made up the majority in both groups. There was no significant difference between the proportion of genotypes and frequencies of alleles in the two groups (P>0.05). There was no difference between LP-PLA2 among the different genotypes in these two groups (P>0.05). Conclusions We cannot conclude that ApoE gene polymorphism is related to atherosclerotic cardiovascular and cerebrovascular diseases. And it cannot be concluded that ApoE gene polymorphism is related to Lp-PLA2 level.

The thermal lens problem of optical system caused by high temperature environment is a common problem. Athermal design of lenses based on optical calculation software is an effective passive compensation method. But it is difficult to determine its accuracy and measure it experimentally. We describe an athermal design technology and propose a simulated scheme to verify the accuracy of this design. Three materials with negative dn/dT have been selected to compensate for the thermal lenses produced by a fused silica lens. The results show that the compensation effect of N-PSK53A is the best.

Older adults undergoing emergency abdominal surgery have significantly poorer outcomes than younger adults. For those who survive, the level of care required on discharge from hospital is unknown and such information could guide decision-making. The ELF (Emergency Laparotomy and Frailty) study aimed to determine whether preoperative frailty in older adults was associated with increased dependence at the time of discharge.The ELF study was a UK-wide multicentre prospective cohort study of older patients (65 years or more) undergoing emergency laparotomy during March and June 2017. The objective was to establish whether preoperative frailty was associated with increased care level at discharge compared with preoperative care level. The analysis used a multilevel logistic regression adjusted for preadmission frailty, patient age, sex and care level.A total of 934 patients were included from 49 hospitals. Mean(s.d.) age was 76·2(6·8) years, with 57·6 per cent women; 20·2 per cent were frail. Some 37·4 per cent of older adults had an increased care level at discharge. Increasing frailty was associated with increased discharge care level, with greater predictive power than age. The adjusted odds ratio for an increase in care level was 4·48 (95 per cent c.i. 2·03 to 9·91) for apparently vulnerable patients (Clinical Frailty Score (CFS) 4), 5·94 (2·54 to 13·90) for those mildly frail (CFS 5) and 7·88 (2·97 to 20·79) for those moderately or severely frail (CFS 6 or 7), compared with patients who were fit.Over 37 per cent of older adults undergoing emergency laparotomy required increased care at discharge. Frailty scoring was a significant predictor, and should be integrated into all acute surgical units to aid shared decision-making and discharge planning.Los adultos mayores sometidos a cirugía abdominal de urgencia tienen resultados significativamente peores que los adultos jóvenes. Para aquellos pacientes que sobreviven, el nivel de atención que requieren tras el alta hospitalaria se desconoce y esta información podría servir de guía en la toma de decisiones. El estudio ELF (Emergency Laparotomy and Frailty) tenía como objetivo determinar si la fragilidad preoperatoria en adultos mayores se asociaba con un aumento de la dependencia en el momento del alta. MÉTODOS: El estudio ELF era un estudio multicéntrico extenso efectuado en el Reino Unido (n = 49) que incluyó una cohorte prospectiva de 934 pacientes mayores ( 65 años) sometidos a laparotomía de urgencia durante marzo-junio de 2017. El objetivo fue establecer si la fragilidad preoperatoria aumentaba el nivel de asistencia en el momento del alta en comparación con el nivel de asistencia preoperatorio. Para el análisis se utilizó una regresión logística multinivel ajustada a características previas al ingreso: fragilidad, edad del paciente, género, y nivel de asistencia.La edad media de los pacientes fue 76,2 años (DE = 6,83), con un 57% de mujeres, un 20,2% de pacientes frágiles y un 37,4% de adultos mayores que presentaron un aumento en el nivel de asistencia en el momento del alta. Un aumento de la fragilidad se asoció con un incremento en el nivel de asistencia en el momento del alta (y mayor poder predictivo que la edad). La razón de oportunidades (odds ratio, OR) ajustada por el aumento del nivel de asistencia fue 4,48 (i.c. del 95% 2,03-9,91) para pacientes aparentemente vulnerables (Clinical Frailty Scale, CFS 4); 5,94 (i.c. del 95% 2,54-13,90) para aquellos ligeramente frágiles (CFS 5); y 7,88 (i.c. del 95% 2,97-20,79) para aquellos con fragilidad moderada o grave (CFS 6 and 7) en comparación con pacientes en buenas condiciones. CONCLUSIÓN: Este es el primer estudio que documenta que más del 37% de adultos mayores sometidos a laparotomía de urgencia precisaron un aumento en el nivel de asistencia en el momento del alta. La evaluación de la fragilidad debería integrarse en todas las unidades quirúrgicas de agudos para ayudar a compartir la toma de decisiones y los planes de tratamiento.

Background Access to antibiotics without a prescription from retail pharmacies has been described as a major contributor to anti-microbial resistance (AMR) globally. In the context of high rates of AMR, the Chinese government has recently introduced strict policies regarding hospital antibiotic use, but the existing ban on antibiotic sales without prescription in retail pharmacies has not been strongly enforced. In 2016, a goal of prescription-only antibiotics by 2020 was announced. The objective of the study was to determine progress towards the 2020 goal, through estimating the proportion of retail pharmacies selling antibiotics without prescription across the three regions of mainland China. Methods Using the Simulated Patient method, we conducted a cross-sectional survey across purposively-sampled retail pharmacies in urban and rural areas of 13 provinces in eastern, central and western China. Medical students presented a scenario of a mild upper respiratory tract infection, following a strict three-step protocol. They recorded the pharmacy characteristics, and details of their experience, including at which step antibiotics were offered. Results Complete data were obtained from 1106 pharmacies. Antibiotics were obtained in 925 (83.6, 95% CI: 81.5, 85.8%) pharmacies without a prescription, 279 (25.2%) at Stage 1 (symptoms only described), 576 (52.1%) at stage 2 (asked for antibiotics), and 70 (6.3%) at Stage 3 (asked for penicillin or cephalosporins). There were significant differences between provinces, with antibiotic access (at any stage) ranging from 57.0% (57/100) in Zhejiang (81/82) to 98.8% in Guizhou. However, there were no significant differences in access to antibiotics by level of city, county, township or village (P = 0.25), whether the pharmacy was part of a chain or independent (P = 0.23), whether a licensed pharmacist was attending (P = 0.82) or whether there was a sign saying that prescriptions were required for antibiotics (P = 0.19). Conclusions It is easy to obtain antibiotics without a prescription in retail pharmacies in China, despite the fact it is against the law. This must be addressed as part of the wider anti-microbial stewardship effort which could include intense enforcement of the existing law, supported by a public education campaign.

Background: This study investigated the differences in clinicopathologic features and surgical treatment between an Italian and a Chinese cohort of premenopausal women with breast cancer, and highlighted the potential advantages of international medical exchange projects. Methods: Premenopausal women who underwent surgical treatment between 2012 and 2016 at one Italian and one Chinese institution participating in a medical exchange program were compared. Factors associated with the probability to receive mastectomy were determined via logistic analysis. Changes in surgical management at the Chinese institution in the period 2018–2019, after the exchange program, were also evaluated. Results: A total of 505 patients, 318 from Italy and 187 from China, were evaluated. The Chinese patients had more frequently advanced-stage tumours, large tumour size (30.9 vs. 18.1 mm, p < 0.01), invasive carcinoma (92.5 vs. 83.3%, p < 0.01), positive axillary lymph nodes (54.5 vs. 27.4%, p < 0.01), Her-2 positivity (36.4 vs. 22.0%, p < 0.01), and high proliferative index (55.1 vs. 30.2%, p < 0.01). Positive oestrogen receptor status and rates of triple-negative breast cancer did not differ (77.0 vs. 69.5%, p = 0.09 and 14.2 vs. 16%, p = 0.56, respectively). Mastectomy rates were higher among Chinese women (85 vs. 41%, p < 0.001), whereas use of sentinel node biopsy was more frequent among Italian women (77 vs. 33%, p < 0.001). Chinese women had more than 4-fold higher risk of receiving mastectomy. In the last 2 years, the rates of breast-conserving surgery and sentinel node biopsy at the Chinese institution increased from 15 to 23%, and from 33 to 42%, respectively. Conclusions: Tumour features and surgical strategies for premenopausal breast cancer may differ significantly between Italy and China. Since the international exchange program, patients from the Chinese institution have been offered more frequently less invasive surgery. International exchange programs can help in designing epidemiological studies which may be useful for strategies to improve breast cancer management and control.

Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM.Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA.Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM.Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

Aims: A high proportion of all tuberculosis (TB) cases present with extrapulmonary tuberculosis (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site within the body. However, previous reports only characterised lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. Methods: An observational multi-centre study was carried out in China from Jan 2011 to Dec 2017 that included a total of 208,214 patients with EPTB lesions. Multivariable logistic regression analysis was used to identify associations between gender and age with concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. Results: The most prevalent form of EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial tuberculosis (14.8%) and tuberculous meningitis (7.6%). The most predominant concurrent EPTB case type was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). Altogether 22 association rules were identified that included 20 strong association rules, among which highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis and sacral TB concurrent with lumbar vertebral TB. Moreover, association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males and highest in patients of ages 25-34 years (87.50%). Conclusions: Many types of concurrent EPTB were found. Thus, greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

BackgroundMultimodal CT, including CT angiography (CTA) and CT perfusion (CTP), was increasingly used in stroke triage. This study was to determine the relationship between a new integrated parameter—both collateral circulation and relative permeability surface (PS)—and the hemorrhagic transformation (HT) in acute ischemic stroke (AIS) with middle cerebral artery occlusion (MCAO).MethodsWe retrospectively reviewed consecutive AIS patients with MCAO who underwent baseline CTA/CTP within 4 h of symptom onset and follow-up susceptibility-weighted imaging (SWI) within 3 weeks. Collateral circulation was assessed on the baseline CTA. Baseline CTP data were postprocessed to generate PS parameter. The patients with poor collateral circulation and at the same time with high relative PS were classified as the group of both poor collateral circulation and high relative PS. HT was defined according to European Cooperative Acute Stroke Study II criteria on follow-up SWI imaging. Multivariate logistic regression analysis was performed using HT as an outcome variable.ResultsThe group of patients with both poor collateral circulation and high relative PS was thirteen and thirty-three (52%) developed HT of the final cohort sixty-three AIS patients with MCAO. Multivariate logistic analysis revealed the new integrated parameter—both collateral circulation and relative PS (odds ratio, 16.59; 95% confidence interval, 13.09–19.10; P < 0.001) was independent predictor of HT. The area under the curve was 0.85 (95% confidence interval, 0.81–0.89). The sensitivity was 57%, specificity 97% and positive predictive value 92%, negative predictive value 58%.ConclusionsFor AIS patients with MCAO, these with poor collateral circulation on CTA and at the same time with high relative PS on CTP were at high risk for HT.

Ischemic stroke is a leading cause of mortality and disability. Diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood-brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague-Dawley rats. Treatment with selenium and the autophagy inhibitor 3-methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy-related proteins (P

Li-Ping Zhu,1,&ast; Wei-Lan Yin,2,&ast; Lei Peng,1,&ast; Xiao-Hong Zhou,3 Peng Zhou,1 Shu-Xia Xuan,1 Ying Luo,1 Chen Chen,1 Bin Cheng,1 Jin-Duan Lin,1 Yan-Mei Liu,1 Feng-Jun Tan,4 Wei-Guo Yin1,&ast; 1Department of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China; 2Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, 421001, Hunan, People’s Republic of China; 3Kingmed Diagnostic Center for Clinical Laboratory, Guangzhou, 510330, Guangdong, People’s Republic of China; 4Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, 511518, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Guo YinDepartment of Molecular Diagnosis Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, No. B24, Xincheng Yinquan Road, Qingcheng District, Qingyuan, 511518, Guangdong, People’s Republic of ChinaTel +86 763 311 3890Email wgy09dr_mn@163.comObjective: This study explored the correlation between myocardial infarction (MI) and the Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene in the Qingyuan area.Methods: The Glu504Lys polymorphism of the ALDH2 gene was analyzed using the polymerase chain reaction and deoxyribonucleic acid microarray analysis for 468 patients diagnosed with MI for the first time and 132 healthy subjects.Results: There was a significant difference in the distribution of the ALDH2 genotype between the MI group and the control group (P = 0.0492), but there was no significant difference in allele frequency between the two groups (P = 0.1363). The clinical data showed that there were statistically significant differences (P < 0.05) in the two groups’ gender and age distributions, rates of diabetes and hypertension, levels of alcohol and tobacco use, serological levels of heart markers, blood lipids and glucose. The subgroup analysis of ALDH2 genotypes found that alcohol consumption, high levels of myoglobin, and low levels of high-density lipoprotein cholesterol were significantly associated with a higher incidence of MI (P < 0.05). After adjusting for gender, hypertension, diabetes, and other related influencing factors, logistic regression analysis showed that the ALDH2 genotype GA/AA was an independent risk factor for MI (P < 0.05, OR = 1.479, 95% CI = 1.003– 2.179).Conclusion: The presence of risk alleles with the genetic effect (ALDH2 genotype GA/AA) is an independent risk factor for MI.Keywords: myocardial infarction, aldehyde dehydrogenase 2, polymorphism

Background. Pneumonia is a serious global health problem. In traditional Chinese medicine, acupuncture or moxibustion is used to directly stimulate select acupoints on the surface of the human body and produce physical stimulation to further stimulate regulatory functions in the body, strengthening bodily resistance, eliminating disease, and adjusting the viscera. However, this Chinese medicine knowledge does not include the specific mechanisms of action or targets of acupoints. Therefore, an in-depth research is needed. Methods. An acupoint-element database was constructed, and the target elements of the Feishu point were screened. The UniProt-Swiss-Prot sublibrary was used to obtain correct gene name information. The National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database and GEO2R were used to analyze differentially expressed genes in pneumonia. The STRING database was used to analyze interactions, construct a network of the Feishu point efficacy system in pneumonia, and elucidate the mechanisms of action. Results. The Feishu point comprises 34 elements in total. The protein interaction analysis has 38 nodes and 115 edges. The Feishu point efficacy system-pneumonia system network shows that cytokine signaling in the immune system, signaling by interleukins (ILs), IL-4 and IL-13 signaling, and the immune system may be related to immunity and inflammation. The Feishu point efficacy system regulating pneumonia showed that FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1 are the main targets. Conclusion. From the perspective of systematic acupuncture and moxibustion, the Feishu point regulates cytokine signaling in the immune system, signaling by ILs, IL-4 and IL-13 signaling, and the immune system by targeting FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1, thereby regulating pneumonia.

Taking the modern service industry as the research object, this paper uses the existing decision-making information to sort a limited number of alternatives, establishes a multi-attribute decision-making model of value-added tax, enterprise income tax and other taxes, and analyzes the relationship between tax burden and various influencing factors. The flexible application and practice of the unified scheduling model can realize the maximization of taxpayers' after tax interests and the minimization of tax payment, which is helpful for enterprises to reduce tax costs, improve the level of business management and financial management, and enhance the competitiveness of enterprises.

Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.

Background: Inflammation and oxidative stress play important roles in energy imbalance and its complications. Recent research indicates that hypothalamic inflammation may contribute to the pathogenesis of metabolic syndrome and cardiac dysfunction, but the mechanisms remain unclear. We hypothesized that suppression of the proinflammatory IKKβ/NF-κB pathway in the hypothalamus can improve energy balance and cardiac function in type 2 diabetic (T2D) rats. Methods: Normal and T2D rats received bilateral hypothalamic arcuate nucleus (ARC) infusions of the IKKβ inhibitor SC-514 or vehicle via osmotic minipump. Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were used to investigate the outcomes of inhibition of the hypothalamic IKKβ. Echocardiography and glucometer were used for measuring cardiac function and blood glucose, respectively. Blood samples were collected for the evaluation of circulating proinflammatory cytokines. Heart was harvested for cardiac morphology evaluations. The ARC was harvested and analyzed for IKKβ, NF-κB, proinflammatory cytokines, reactive oxygen species (ROS), and NAD(P)H (gp91phox, p47phox) oxidase activity levels and neuropeptides. Results: Compared with normal rats, T2D rats were characterized by hyperglycemia, hyperinsulinemia, glucose intolerance, cardiac dysfunction, as well as higher ARC levels of IKKβ, NF-κB, proinflammatory cytokines, ROS, gp91phox, and p47phox. ARC infusion of the IKKβ inhibitor SC-514 attenuated all these changes in T2D rats, but not in normal rats. Conclusions: Our results indicate that the hypothalamic IKKβ/NF-κB pathway plays a key role in modulating energy imbalance and cardiac dysfunction, suggesting its potential therapeutic role during type 2 diabetes mellitus.

Objective Although patients with psoriasis frequently report seasonal changes in their symptoms, the seasonality of psoriasis has rarely been explored. This study aims to investigate the seasonal pattern of and global public interest in psoriasis using Google search data. Methods Internet search data were collected from Google Trends. Data on the relative search volume (RSV) from January 2004 to December 2018 were retrieved using the term psoriasis. Cosinor analyses were conducted to examine the seasonality of psoriasis using data from two southern hemisphere countries (Australia and New Zealand) and four northern hemisphere countries (USA, Canada, UK and Ireland). Results Overall, searches for psoriasis steadily decreased between 2004 and 2010, and then rose from 2011 to 2018. On cosinor analyses, RSV of ‘psoriasis’ displayed a significant seasonal variation worldwide (p Conclusion There was a significant seasonal pattern for psoriasis, with peaks in the late winter/early spring and troughs in the late summer/early autumn. Further studies are warranted to confirm the seasonal pattern of psoriasis using clinical data and to explore the underlying mechanisms.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.

The indicators for measuring vitamin D are various, and 25-hydroxyvitamin D (25(OH)D) is considered as the optimal indicator of total vitamin D levels. In this study, we aim to deeply explore the 25(OH)D status in systemic lupus erythematosus (SLE) patients, and evaluate its relation to SLE risk and disease severity.Literature about 25(OH)D status and its associations with SLE were searched in Pubmed, Embase and Cochrane Library databases. Standardized mean difference (SMD), odds ratio (OR) and corresponding 95% confidence interval (95% CI) were illustrated by forest plots, and correlation coefficients (r) were combined by generic inverse variance method. Heterogeneity and publication bias were quantified by I-squared (INineteen articles were included into our meta-analysis. The overall results showed that compared with the healthy controls, the circulating 25(OH)D levels were significantly lower in SLE patients (pooled SMD = -1.63, 95% CI: -2.51 to -0.76). Subgroup analysis revealed that compared with the healthy controls, SLE patients of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 10, Arab and European ethnicity, all 4 seasons, no vitamin D supplement, had significantly lower circulating 25(OH)D levels; no significant differences were observed in SLE patients of SLEDAI 10, mixed ethnicity, spring, summer, vitamin D supplement, respectively; no matter the changes of age, disease duration, and the therapy of corticosteroid or immunosuppressive or neither, circulating 25(OH)D levels were significantly reduced in SLE patients. The deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease (not significantly), significantly decrease SLE risk, respectively (pooled OR = 4.37, 95% CI: 1.49 to 12.84; pooled OR = 0.52, 95% CI: 0.22 to 1.26; pooled OR = 0.31, 95% CI: 0.15 to 0.63). Circulating 25(OH)D levels were inversely associated with SLEDAI (pooled correlation coefficient = -0.50, 95% CI: -0.8278 to -0.1689).Compared with healthy controls, 25(OH)D levels are significantly lower in SLE patients, which is influenced by disease activity, ethnicity, seasons and vitamin D supplement; no matter the change of age, diseases duration and therapy of corticosteroid or immunosuppressive or neither, 25(OH)D levels are significantly decreased in SLE patients; the deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease, and significantly decrease SLE risk, respectively; and 25(OH)D levels inversely correlate with SLEDAI.

The deniable authentication and designated verifier signature protocol can achieve the property of deniability by a transcript simulation algorithm, so two protocols are similar in the concepts and application scenarios. In this paper, we will avoid the research ideas of classical cryptography and research how to convert quantum deniable authentication protocol into quantum designated verifier signature in this universal case that the owner of the signature and the signer isn’t the same user in quantum designated verifier signature scheme such as electronic ID cards and e-passports. A mode on converting quantum deniable authentication into quantum designated verifier signature is firstly proposed by introducing quantum signature with public verifiability, including the entities and the implementation process converting, and then a real quantum designated verifier signature scheme is proposed, which satisfies all security requirements of a designated verifier signature scheme and can withstand intercept-resend attack and impersonation attack and entangle-measure attack.

The in-plane nonlinear elastic stability of single arches has been investigated by many researchers, however, a similar research of multi-span continuous arches is not available even though they are extensively used in arch bridge engineering. This paper proposes an analytical method for the in-plane nonlinear elastic buckling and post-buckling of pin-ended parabolic multi-span continuous arches. There are four key parts in the proposed method. Firstly, the in-plane nonlinear equilibrium differential equations of each arch were derived based on the strain expression in the Cartesian coordinate system of non-circular arches and the virtual work principle. Secondly, the nonlinear equilibrium equation of continuous arches was proposed based on the deformation compatibility condition of each arch end, and three key coefficients were obtained. Thirdly, the buckling requirements were deduced according to the force balance condition in each arch end. Lastly, analytical solutions for buckling and post-buckling predictions were derived. Comparisons with the results of finite element method, including the load-displacement curve, buckling behavior and buckling predictions, demonstrate that the proposed analytical solution is equipped with high accuracy. The results of theoretical and parametric analysis show that the deformation shape of symmetric and asymmetric buckling of multi-span continuous arches is thoroughly different from the single arches, the mechanical effect of the unloaded arches is a nonlinear horizontal spring support acting on the loaded arch, and the stability parameter ratio has a significant influence on the buckling behavior of multi-span continuous arches.

Optical lenses used in high temperature environment are usually affected by thermal lenses problems, but it is difficult to evaluate their focal shifts in practical applications. A three-dimensional single-lens model based on finite element solver was built to evaluate the focal shift in this study, when the temperature of surface was raised from the initial temperature to the specified temperature. An experimental method based on a Hartmann-Shack wavefront sensor was proposed to verify the rationality of the model. The nearly same results between simulations and experiments for N-BK7 and fused silica were obtained, which proves that it is feasible to analyze focal shifts of optical lenses by simulation methods.