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Background and Aims. Mean platelet volume to platelet count ratio (MPV/PC) has been found to be an independent risk factor for mortality in various diseases, including cardiovascular disease, cancer, and hemodialysis. We aimed to evaluate the association between MPV/PC and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods and Results. We conducted a retrospective cohort study at a single center and enrolled 1473 PD patients who were catheterized at our PD center from January 1, 2006, to December 31, 2013. All patients were divided into four groups according to the quartiles of baseline MPV/PC levels and followed up until December 31, 2018. A total of 453 patients died, and 221 deaths were caused by cardiovascular disease during a median follow-up time of 48.0 (21.9-82.2) months. There was a significant interaction by age of association between MPV/PC level and all-cause mortality ( P = 0.009 ), and multivariate Cox regression analysis showed that higher MPV/PC level was related to a decreased risk of all-cause and CV mortality in PD patients aged < 60 years ( HR = 0.62 , 95 % CI = 0.40 − 0.96 , P = 0.032 ; HR = 0.49 , 95 % CI = 0.26 − 0.93 , P = 0.029 , respectively), rather than in patients aged ≥ 60 years ( HR = 1.37 , 95 % CI = 0.84 − 2.22 , P = 0.208 ; HR = 1.50 , 95 % CI = 0.77 − 2.92 , P = 0.237 , respectively). Conclusion. Our results indicated that low MPV/PC level was an independent risk factor for all-cause and CV mortality in PD patients aged less than 60 years.

This study aimed to investigate the prevalence characteristics of human papillomavirus (HPV) infections in 29,508 female cases in Jinshan District, Shanghai.The current research represents a retrospective study that included 29,508 women who received cervical screening in the Jinshan Branch of Shanghai Sixth People's Hospital from 2010 to 2020. The overall prevalence, distribution types, age-specific prevalence and annual trends were analysed.The overall HPV infection rate among the patients was 21.97%. They were primarily high-risk HPV (HR-HPV) infections (20.30%) and single HPV infections (15.91%). A general decline in HPV and HR-HPV prevalence was observed with time from 33.52% to 25.45% in 2011 to 21.47% and 20.18% in 2020. The most common HPV genotypes were HPV52, HPV16, HPV58, HPV51, HPV53 and HPV68. The infection rates of HPV genotypes, including HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV66 and HPV68, showed overall declines across different years. The age-specific prevalence of total HPV and HR-HPV infections formed an approximate U-shaped curve with two peaks, one in the ≥55 age group (29.75%, 28.43%) and the other in the25 age group (22.93%, 20.85%). Both total HPV and HR-HPV infection rates decreased to their lowest in the 25-34-year age groups.The prevalence of HPV infections showed a downward tendency with time. Single HPV genotype infections and HR-HPV infections were predominantly detected. The after prevalent characteristics of HPV can help to guide HPV vaccinations and cervical cancer screenings: 1) non-HPV16/HPV18 H R-HPV genotypes were prevalent; 2) non-vaccine-covered HPV53, HPV51 and HPV68 were also prevalent; 3) women above the age of 55 years had the highest HPV and HR-HPV infection rates.

Arginase is a ubiquitous enzyme in the urea cycle (UC) that hydrolyzes L-arginine to urea and L-ornithine. Two mammalian arginase isoforms, arginase1 (ARG1) and arginase2 (ARG2), play a vital role in the regulation of β-cell functions, insulin resistance (IR), and vascular complications via modulating L-arginine metabolism, nitric oxide (NO) production, and inflammatory responses as well as oxidative stress. Basic and clinical studies reveal that abnormal alterations of arginase expression and activity are strongly associated with the onset and development of diabetes mellitus (DM) and its complications. As a result, targeting arginase may be a novel and promising approach for DM treatment. An increasing number of arginase inhibitors, including chemical and natural inhibitors, have been developed and shown to protect against the development of DM and its complications. In this review, we discuss the fundamental features of arginase. Next, the regulatory roles and underlying mechanisms of arginase in the pathogenesis and progression of DM and its complications are explored. Furthermore, we review the development and discuss the challenges of arginase inhibitors in treating DM and its related pathologies.

The Dispositional Flow Scale-2 (DFS-2) is an instrument for measuring the flow experiences of the general population while participating in daily activities. This study aimed to examine the equivalence in the measurement structure of Traditional Chinese DFS-2 (TCDFS-2) between the schizophrenic patients and healthy subjects.We recruited 100 adults with schizophrenia or schizoaffective disorder from the psychiatric clinics or the centers for daycare or rehabilitation and 104 healthy adults. Each participant finished the TCDFS-2 by recalling the most important and meaningful daily activity.We conducted two two-group confirmatory factor analyses (CFA) with the healthy subjects and schizophrenic patients as the reference group respectively in LISREL. When the healthy subjects as the reference standard, 43 items of the TCDFS-2 were added to this constrained two-group CFA model for the schizophrenic patients, but the cross-group equivalence was still unsatisfactory. By contrast, when the schizophrenic patients as the reference standard, only 6 items were added for the healthy subjects, and the cross-group equivalence was barely acceptable.Thus, the measurement structures of the TCDFS-2 were quite different between the schizophrenic patients and healthy subjects. The flow states experienced by the schizophrenic patients might not entirely be the same as those of the healthy subjects.

Sepsis is a life-threatening condition, and treatment for sepsis in clinic is often not available, partially due to insufficient understanding of the pathogenesis of sepsis. Extensive study to elucidate the pathogenesis is required to improve the clinical management and outcome of sepsis. In this study, we investigated the pathogenesis of sepsis using peripheral blood mononuclear cells (PBMCs) from septic patients and studied the underlying mechanism of miR-16-5p on aerobic glycolysis in lipopolysaccharide (LPS)-treated THP1 and Raw264.7 cells. The levels of RNA and protein were determined by real-time quantitative PCR and immunoblotting assay, respectively. The production of high mobility group box 1 (HMGB1) was measured by enzyme-linked immunosorbent assay. The levels of succinate and lactate were determined using colorimetric kits. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by extracellular flux analyzer. The results showed that the expression of miR-16-5p was elevated, while sirtuin 3 (SIRT3) was decreased in PBMCs from septic patients and LPS-treated cells, along with accumulation of acetylated succinate dehydrogenase complex, subunit A. Concomitantly, an increase in HMGB1, succinate, lactate, as well as ECAR and a decrease in OCR were observed. Knockdown of miR-16-5p upregulated SIRT3 expression, facilitated SDHA deacetylation, and attenuated sepsis-related aerobic glycolysis. Further study identified that SIRT3 is targeted by miR-16-5p, and overexpression of SIRT3 rescued LPS-induced responses via deacetylation of SDHA. Our findings revealed a novel miR-16-5p-regulated SIRT3-SDHA axis in sepsis and provided novel insights for sepsis treatment.

Renal fibrosis is the pathological hallmark of chronic kidney disease that is influenced by numerous factors. Arrest of renal tubular epithelial cells (RTECs) in G2/M phase is closely correlated with the progression of renal fibrosis; however, the mechanisms mediating these responses remain poorly defined. In this study, we observed that human leukocyte antigen-F adjacent transcript 10 (FAT10) deficiency abolished hypoxia-induced upregulation of checkpoint kinase 1 (CHK1) expression in RTECs derived from FAT10

Artificial intelligence is developing rapidly, bringing increasing numbers of intelligent products into daily life. However, it has little progress in dry eye, which is a common disease and associated with meibomian gland dysfunction (MGD). Noninvasive infrared meibography, known as an effective diagnostic tool of MGD, allows for objective observation of meibomian glands. Thus, we discuss a deep learning method to measure and assess meibomian glands of meibography.We used Mask R-CNN deep learning (DL) framework. A total of 1878 meibography images were collected and manually annotated by two licensed eyelid specialists with two classes: conjunctiva and meibomian glands. The annotated pictures were used to establish a DL model. An independent test dataset that contained 58 images was used to compare the accuracy and efficiency of the deep learning model with specialists.The DL model calculated the ratio of meibomian gland loss with precise values by achieving high accuracy in the identification of conjunctiva (validation loss 0.35, mAP 0.976) and meibomian glands (validation loss 1.0, mAP 0.92). The comparison between specialists' annotation and the DL model evaluation showed that there is little difference between the gold standard and the model. Each image takes 480 ms for the model to evaluate, almost 21 times faster than specialists.The DL model can improve the accuracy of meibography image evaluation, help specialists to grade the meibomian glands and save their time to some extent.

The purpose of this study was to investigate the effect of intracytoplasmic sperm injection (ICSI) on the normal fertilization rate of oocytes and the clinical pregnancy rate of cycles in male infertility. Eighty cases of male infertility patients attending our hospital from March 2020 to March 2021 were selected and divided into observation group and control group using the random number table method, with 40 cases in each group. The control group was treated with in vitro fertilization (IVF), and the observation group was treated with ICSI. The normal fertilization rate of oocytes and the clinical pregnancy rate of the cycle were compared between the two groups, and the adverse pregnancy outcome and obstetric and perinatal complications were compared between the two groups The rate of normal fertilization and clinical pregnancy in the cycle was higher in the observation group ( P P > 0.05) when comparing adverse pregnancy outcomes between the two groups. The difference was not statistically significant ( P > 0.05) when comparing obstetrics (5.41%, 10.34%) and perinatal complications (8.33%, 14.81%) between the two groups. ICSI in male infertility is significantly effective in improving the rate of normal oocyte fertilization and the clinical pregnancy rate of the cycle. It also has a low impact on adverse pregnancy outcomes and obstetric and perinatal complications and has a high safety profile.

Background Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. Methods We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. Results Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. Conclusion Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

Objective. The present study is aimed at investigating the biochemical and clinical effects of electroacupuncture in patients with sepsis. Methods. Patients with sepsis treated at Guangdong Provincial Hospital of Chinese Medicine from July 2019 to December 2020 were included. Patients were randomly assigned to treatment with routine Western medicine (WM group) or treatment with Western medicine plus electroacupuncture based on Western medicine (EA group). Indices associated with immune function and clinical efficacy were determined before and at 3 and 5 days after treatment. Indicators of immune function included the percentage of T lymphocyte subsets, natural killer (NK) cells, and soluble programmed death protein 1 (sPD-1) levels. Indicators of clinical efficacy included infection-related indicators in whole blood; levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interferon-γ (INF-γ); and assessments using acute physiology and chronic health evaluation-II (APACHE-II) and sequential organ failure assessment (SOFA) scores. Results. Baseline data were not different between WM ( N = 30 ) and EA groups ( N = 30 ). At day 5 following treatment, the level of sPD-1 in the EA group was lower than that in the WM group. Proportions of CD3 + T lymphocytes, CD4 + T lymphocytes, and NK cells, the percentage of lymphocytes, and INF-γ levels in the EA group were significantly higher than those in the WM group. Compared with the WM group, the white blood cell count (WBC), percentage and count of neutrophils, ratio of neutrophils to lymphocytes, and levels of CRP and TNF-α were significantly decreased in the EA group 5 days after treatment. The APACHE-II score of the EA group was significantly lower than that of the WM group 5 days after treatment. Conclusion. Electroacupuncture may regulate the immune function of patients with sepsis through the PD-1 pathway to achieve an anti-inflammatory state and improve clinical symptoms.

Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM.The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients.The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660).Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Objective. To investigate the effects of nutritious meal combined with online publicity and education on postoperative nutrition and psychological state in patients with low rectal cancer after colostomy. Methods. The clinic data of 88 patients with low rectal cancer who received the colostomy in our hospital (August 2020-August 2021) were retrospectively reviewed. Among them, 44 patients received nutritious meal combined with online publicity and education and they made up the study group, and the others were given conventional care and they made up the reference group. The nutrition indicators, scores of the World Health Organization Quality of Life (WHOQOL)-BREF, and other materials of the patients in the two groups were compared. Results. After intervention, the various nutrition indicators, immune indexes, and WHOQOL-BREF score of the study group were all prominently higher than those of the reference group ( P < 0.001 ). Compared with the reference group, the study group after intervention achieved markedly lower self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) score ( P < 0.001 ) and obviously lower total incidence of complications ( P < 0.05 ). Conclusion. Combining nutritious meal with online publicity and education can effectively improve the postoperative nutrition and immune function of the patients with low rectal cancer after colostomy, and this intervention contributes to releasing the patients’ adverse emotions. Further study helps to provide these patients with favorable solutions.

The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.

More couples worldwide, delay their childbearing years. The increase in age causes a gradual decrease in female ovarian function and fertility, leading to an exponential decrease in women over 35 years of age having children. Although promising for some, assisted reproductive technology (ART) is not promising for older women. Decreased fertility in advanced age has become a growing concern in the field of reproduction. In this study, high-throughput transcriptome sequencing was used to identify the differentially expressed genes (DEGs) in the ovarian granulosa cells (GCs) of older women (aged 35-44) with infertility and younger women (aged 25-34). The enriched functions and signaling pathways of DEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The function of DEGs were analyzed and predicted combined with clinical ART data. Sequencing results were verified by quantitative reverse transcription-polymerase chain reaction. Retrospective clinical data and bioinformatics analyses revealed marked reductions in the retrieved oocyte, metaphase II oocyte, 2PN fertilization, and effective embryo numbers in older women. Although the clinical pregnancy and live birth rates did not differ notably between the groups, the miscarriage rate increased significantly in older women. In total, 620 DEGs were identified, of which 246 were upregulated, and 374 were downregulated in the older group. GO, and KEGG analyses indicated that the mechanism of fertility decline in older women was probably related to chronic inflammation, cytokine receptor interaction, and oxidative stress. In conclusion, combined with basic clinical ART data and pregnancy outcomes, we tried to provide a more intuitive and in-depth understanding of age-related reduction in ovarian function and pathogenesis of infertility with regard to chronic inflammation and oxidative stress.

Copy number alterations (CNAs) are pivotal genetic events in triple-negative breast cancer (TNBC). Here, our integrated copy number and transcriptome analysis of 302 TNBC patients reveals that gene alpha-endosulfine (ENSA) exhibits recurrent amplification at the 1q21.3 region and is highly expressed in TNBC. ENSA promotes tumor growth and indicates poor patient survival in TNBC. Mechanistically, we identify ENSA as an essential regulator of cholesterol biosynthesis in TNBC that upregulates the expression of sterol regulatory element-binding transcription factor 2 (SREBP2), a pivotal transcription factor in cholesterol biosynthesis. We confirm that ENSA can increase the level of p-STAT3 (Tyr705) and activated STAT3 binds to the promoter of SREBP2 to promote its transcription. Furthermore, we reveal the efficacy of STAT3 inhibitor Stattic in TNBC with high ENSA expression. In conclusion, the amplification of ENSA at the 1q21.3 region promotes TNBC progression and indicates sensitivity to STAT3 inhibitors.

Objective This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. Methods A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. Results In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529–0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775–0.886) and a specificity of 30.02% (95% CI = 0.257–0.346). Conclusion Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.

An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8+ T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.

Sarcoplasmic calcium-binding protein is a stable allergen in Scylla paramamosain and named Scy p 4. To explore the importance of linear epitopes in the immunoglobulin G (IgG)/immunoglobulin E (IgE)-binding capacity of Scy p 4, chemical denaturants were used to destroy the structure. Scy p 4 was reduced with dithiothreitol and subsequently alkylated with iodoacetamide (IAA). Furthermore, the structural analysis indicated that IAA-Scy p 4 was an unstructured protein. The inhibition enzyme-linked immunosorbent assay showed that IAA-Scy p 4 could inhibit the binding of Scy p 4 to sensitize serum, with inhibition rates reached 55%. Moreover, the linear mimotopes of Scy p 4 were predicted in silico. Three linear epitopes were verified by serological tests and named L-Scy p 4-1 (AA76-91), L-Scy p 4-2 (AA111-125), and L-Scy p 4-3 (AA137-146). Overall, these data provide an understanding of the relationship between the structure and allergenicity about Scy p 4, and the identified linear epitopes can be used for diagnosis and food processing of shellfish allergy.

Background: Overexpression of LSD1 is associated with the occurrence of many diseases, including cancers, which makes LSD1 a significant target for anticancer drug research. Methodology & Results: With the aid of 3D quantitative structure–activity relationship models established with 34 reported resveratrol derivative LSD1 inhibitors, derivatives 35–40 were designed. Absorption, distribution, metabolism and excretion calculations showed that they may have good bioavailability and drug likeness. Additionally, 35 and 37 presented good antitumor effects in an in vitro antiproliferative assay. Molecular docking and molecular dynamics simulation results indicated that 35 and 37 can establish extensive interactions with LSD1. Conclusion: The results of computational prediction and experimental validation suggest that 35 and 37 are effective antitumor inhibitors, which provides some ideas and directions for the development of new anticancer LSD1 inhibitors.

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Background Enteral nutrition is a major pathway of nutrition for patients requiring critical care. However, it remains unclear whether intermittent or continuous feeding is the better approach, especially after nasogastric enteral nutrition via a gastric tube. Therefore, this randomized controlled clinical study was designed to observe the effects of different methods on critically ill patients. Methods Different Feeding Methods on Gastrointestinal Function of Critical patients (DFM-GFC) is a randomized clinical study that will be performed to assess the effects of three feeding methods on critically ill patients. A total of 90 critically ill patients will be equally randomized into three groups: continuous feeding, cyclic feeding, and intermittent feeding. The patients will be administered a gastrointestinal nutrition preparation over 24 h via a gastric tube or over 16 h via an intermittent pump. The primary outcome is the mean duration (days) to reach the caloric goal in each group. Secondary outcomes include the rate of onset of gastric residual, abdominal pressure, the rate of onset pneumonia, and the proportion of individuals achieving the caloric goal. Additionally, the length of intensive care unit (ICU) stay and mortality rate at 28 days post-enrolment will be evaluated. Discussion This study will observe the effects of different feeding methods on various parameters, such as the energy target and gastrointestinal motility, in critically ill patients to improve quality of life and reduce the case fatality rate. The purpose of this study is to explore whether there is a more effective, safer and cost-efficient feeding method for the clinical treatment of critically ill patients. Trial registration ID: NCT04224883, ClinicalTrials.gov, registered January 9, 2020

To review the clinical features, diagnosis, and treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and to report a case with the use of ultra-widefield fluorescein angiography (UWFA) for confirming the precise staging of IRVAN and aid in early treatment. The patient improved after being treated with intravitreal aflibercept injection.A 26-year-old female complained of progressive blurred vision OD for one week. Her BCVA was 0.6 OD and 1.0 OS. Fundus examination showed vitritis, retinal hemorrhage, and vasculitis over bilateral eyes. Fluorescein angiography (FA) with a 55 degree of view revealed aneurysmal dilations of the peripapillary arteriole, peripapillary focal leakage, venous leakage, and capillary nonperfusion area. Stage 2 IRVAN was impressed OU. Oral prednisolone was administered. After four months, she experienced decreased visual acuity OS. Optical coherence tomography (OCT) revealed subretinal and intraretinal fluid with hyperreflective material. One posterior subtenon triamcinolone and one intravitreal aflibercept injection were performed OS, and macular edema subsided. A 105-degree ultra-widefield fluorescein angiography (UWFA) showed multiple peripheral background hypofluorescence areas corresponding to capillary nonperfusion. Retinal neovascularization (NV) was found OS, which had not been revealed by the previous 55-degree FA. Stage 3 IRVAN was made OS and panretinal laser photocoagulation (PRP) was performed. Oral prednisone and cyclosporine were prescribed. Her vision improved to 1.0 OU.UWFA provides visualization of peripheral retinal pathology and for precise staging. It also had direct implications in the follow-up and treatment strategy.

Background To compare the surgical effects of coronary intervention through the transradial intervention (TRI) versus distal transradial intervention (dTRI) approach. Methods From September 2020 to April 2021, 302 patients undergoing coronary artery angiography (CAG) or percutaneous coronary intervention in our hospital were retrospectively included. Patients were divided into the TRI group and dTRI group with 151 cases in each group. The technique features, lesion features, and cannulation process were compared between the two groups. Results The number of patients who underwent CAG in the dTRI group (35.1%) was significantly greater compared with the TRI group (12.6%) (P P P P P P > 0.05). RAD at the puncture site was a predictor of the overall cannulation success rate with an AUC of 0.747 (95% CI 0.663–0.860; P Conclusions Despite a steep learning curve, the dTRI approach had a shorter hemostasis time, reduced RAO rates, and notable preliminary safety results compared with the TRI approach. The dTRI approach can be used as a supplemental method to the TRI approach.

Background Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. Methods We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. Results Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. Conclusions Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks.

The oncogenic function of circ-ATAD1 has been characterized in gastric cancer, while its role in cervical squamous cell carcinoma (CSCC) is unclear. This study explored the role of circ-ATAD1 in CSCC. To evaluate the differential expression of circ-ATAD1, mature miR-218, and premature miR-218 in CSCC, a total of 62 CSCC patients were subjected to biopsies to collect CSCC and paired normal tissues. Gene expression levels were quantified by RT-qPCRs. Nuclear fractionation assay was performed to analyze the subcellular location of circ-ATAD1. CSCC cells were used to perform cell transfections to explore the crosstalk between circ-ATAD1 and miR-218. The roles of circ-ATAD1 and miR-218 in CSCC cell behaviors were explored by BrdU assay, Transwell assay, cell apoptosis assay, and cell stemness assay. CSCC tissues exhibited upregulated expression of circ-ATAD1, which was localized to both nucleus and cytoplasm. Mature miR-218 was downregulated in CSCC tissues and was inversely correlated with circ-ATAD1, while premature miR-218 was not differentially expressed in CSCC. Upregulation of circ-ATAD1 in CSCC cells decreased the expression levels of mature miR-218, but not that of premature miR-218. In addition, overexpression of circ-ATAD1 increased cell proliferation and decreased cell apoptosis, while overexpression of miR-218 decreased cell proliferation and increased cell apoptosis, and it also attenuated the effects of overexpression of circ-ATAD1 on cell proliferation. However, CSCC cell invasion, migration, and stemness were not affected by circ-ATAD1 and miR-218. Circ-ATAD1 is upregulated in CSCC and may regulate cell proliferation and apoptosis by suppressing the maturation of miR-218.

CONTEXT: Pioneering empirical studies show that people bereaved due to COVID-19 experience elevated acute grief, posttraumatic stress, anxiety, and depressive symptom levels, which relate to functional impairment. However, studies focused on Western samples and multivariate analyses of relations between potential risk factors and mental health in this population are lacking. OBJECTIVES: To assess the mental health of Chinese adults bereaved due to COVID-19. To elucidate the associations of demographic and loss-related characteristics with mental health after COVID-19 bereavement. METHODS: Four hundred twenty-two Chinese adults (56% male; Mean age: 32.73 years) recently bereaved due to COVID-19 completed an online survey. Demographic and loss-related characteristics and prolonged grief, posttraumatic stress, anxiety, and depressive symptoms were assessed. RESULTS: Clinically relevant prolonged grief (49%, n = 207), posttraumatic stress (22%, n = 92), depressive (70%; n = 294), and anxiety symptoms (65%; n = 272) were reported by a substantial group of participants. In four multiple regressions predicting each mental health indicator, Fs(15,406) = 5.08-7.74, Ps < 0.001, loss-characteristics (i.e., a shorter time since loss, ss =  -.12-.11, loss of a first-degree relative, ss =  .18-.37) and subjective loss experiences (i.e., feeling traumatized by the loss, ss =  .13-.18, or a close and/or conflictual relation with the deceased, ss =  .12-.23) related most consistently to mental health problems. CONCLUSION: Many Chinese adults bereaved due to COVID-19 experience severe mental health problems. The recent loss of first-degree relatives, feeling traumatized by the loss, and having a close and/or conflictual relationship with the deceased may elevate risk for these mental health problems, which could require indicated psychological treatment.

To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea.Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group.In the observation group, the scores of VAS and CMSS were all decreased after treatment (The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.

To explore the effect of personalized digital analog assisted acetabular prosthesis precise implantation in hip dysplasia.From February 2017 to July 2019, 11 patients(12 hips) with hip dysplasia underwent total hip arthroplasty, including 4 males(5 hips) and 7 females(7 hips), aged from 27 to 61 years old, with an average of (46.64±12.93) years old;Crowe classification:8 hips in typeⅠ and 4 hips in typeⅡ. The preoperative thin-layer CT scan was imported into Mimics 10.01 software. The appropriate size and placement angle of acetabular prosthesis were selected through preoperative simulation, and the acetabular bone defect was understood to determine whether structural bone grafting was needed during the operation. The length of both lower limbs, the anteversion angle of acetabular prosthesis, the abduction angle, the height of acetabular rotation center and the horizontal distance of hip joint center before and after the operation were measured, and the postoperative dislocation, bone graft healing and acetabular cup loosening were observed. The hip Harris score was used to evaluate the joint function.All patients were followed up for 18 to 30 months with an average of (23.45±3.70) months. There was no prosthesis dislocation, loosening and bone graft healing after operation. One case had numbness in the innervation area due to the traction of sciatic nerve during operation, and was treated with neurotrophic drugs and recovered one month after operation. The length difference of both lower limbs decreased from (31.73±5.98) mm before operation to (4.73±1.90) mm 3 months after operation (Through preoperative personalized digital analog reconstruction of acetabulum in patients with hip dysplasia, we can better understand the acetabular defect, help to evaluate the size and placement angle of acetabular prosthesis and whether structural bone grafting is needed, and obtain satisfactory clinical curative effect.

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Currently, there is a significant unmet need for novel analgesics with fewer side effects. In this study, we carried out structural modification of a hit compound previously identified in an artificial-intelligence (AI) virtual screening and discovered the potent analgesic, benzo[b]thiophene-2-carboxamide analog (compound 25) with new structural scaffold. We investigated the signaling pathways of opioid receptors mediated by compound 25, and found this racemic compound activated mu-opioid receptor through the cyclic adenosine monophosphate (cAMP) and β-arrestin-2-mediated pathways with strong potency and efficacy, and accompanying nociceptin-orphanin FQ opioid peptide and delta-opioid receptors through the cAMP pathway with weak potencies. Compound 25 elicited potent antinociception in thermal-stimulated pain (ED

Hepatitis B virus(HBV) is the pathogen causing hepatitis B, which is characterized by strong infectivity, high incidence, and widespread prevalence and has seriously threatened human health and affected their quality of life. Anti-HBV drugs in western medicine mainly include nucleosides(nucleic acids) and interferons, among which nucleosides(nucleic acids) are used more often. Due to the easy development of drug resistance, their therapeutic effects are not remarkable. Interferons can easily cause serious adverse reactions such as liver injury. Anti-HBV drugs in traditional Chinese medicine mainly include single Chinese herbs(Artemisiae Scopariae Herba, Artemisiae Annuae Herba, Salviae Miltiorrhizae Radix et Rhizoma, etc.) and Chinese herbal compounds(Yinchenhao Decoction, Xiaochaihu Decoction, Tiaogan Huaxian Pills, etc.), whose chemical compositions and action targets have not been fully identified. The combined medication is better than single medication, in that the former can improve drug resistance, make up each other's deficiencies, reduce adverse reactions, and prolong the action time. This study reviewed the anti-HBV activities and mechanisms of western drugs, Chinese herbs, and combined medications, in order to provide reference for the development and research of new anti-HBV drugs.

The combined procedure of catheter ablation and left atrial appendage closure (LAAC) aims to simultaneously control the heart rhythm and reduce the risk of strokes in patients with atrial fibrillation (AF). The study aims to evaluate the procedural safety and long-term outcome of the combined procedure in a large patient cohort.Clinical data of AF patients who underwent the combined procedure was retrospectively analyzed. Procedural and imaging follow-up parameters were compared between the transesophageal echocardiography-guided standard process and fluoroscopy-guided modified process, and between the single-seal WATCHMAN and dual-seal LACBES devices. Long-term outcomes included all-cause mortality, thromboembolic events, major bleeding, and recurrence of atrial tachyarrhythmias.A total of 1114 patients were included. The rates of procedure-related major complications were comparable between the standard and modified processes (3.7% vs. 2.2%, p = 0.219), except for a higher incidence of respiratory depression in standard process group (0.9% vs 0%, p = 0.037), and between WATCHMAN and LACBES devices (2.4% vs. 3.3%, p = 0.535). The follow-up imaging evaluation revealed a high rate of satisfactory seals (99.7%) and a low rate of device related thrombus (1.9%), which were similar between two process groups and devices. The follow-up of over 1960 patient-years revealed low rates of mortality, thromboembolism, and nonprocedural major bleeding (1.8, 3.2, and 0.9 per 100 patient-years, respectively). Recurrent atrial tachyarrhythmias was observed in 23.9% patients.The results supported the safety and long-term efficacy of the combined procedure of catheter ablation and LAAC. Fluoroscopy-guided LAAC device implantation may be considered in experienced centers.

Currently, breast cancer (BRCA) has become the most common cancer in the world, whose pathological mechanism is complex. Among its subtypes, triple-negative breast cancer (TNBC) has the worst prognosis. With the increasing number of diagnosed TNBC patients, the urgent need of novel biomarkers is also rising. Cyclin-dependent kinase inhibitor 2A (CDKN2A) has recently emerged as a key regulator associated with ferroptosis and cuproptosis (FAC) and has exhibited a significant effect on BRCA, but its detailed mechanism remains elusive. Herein, we conducted the first converge comprehensive landscape analysis of FAC-related gene CDKN2A in BRCA and disclosed its prognostic value in BRCA. Then, an unsupervised cluster analysis based on CDKN2A-correlated genes unveiled three subtypes, namely cold-immune subtype, IFN-γ activated subtype and FTL-dominant subtype. Subsequent analyses depicting hallmarks of tumor microenvironment (TME) among three subtypes suggested strong association between TNBC and CDKN2A. Given the fact that the most clinically heterogeneous TNBC always displayed the most severe outcomes and lacked relevant drug targets, we further explored the potential of immunotherapy for TNBC by interfering CDKN2A and constructed the CDKN2A-derived prognostic model for TNBC patients by Lasso-Cox. The 21-gene–based prognostic model showed high accuracy and was verified in external independent validation cohort. Moreover, we proposed three drugs for TNBC patients based on our model via targeting epidermal growth factor receptor. In summary, our study indicated the potential of CDKN2A as a pioneering prognostic predictor for TNBC and provided a rationale of immunotherapy for TNBC, and offered fresh perspectives and orientations for cancer treatment via inducing ferroptosis and cuproptosis to develop novel anti-cancer treatment strategies.

Coronavirus is an enveloped RNA virus that causes mild to severe respiratory diseases in humans, including HKU1-CoV, 229E-CoV, NL63-CoV, OC43-CoV, SARS-CoV, MERS-CoV, and SARS-CoV-2. Due to the outbreak of SARS-CoV-2, it is important to identify the patients and investigate their immune responses. Protein microarray is one of the best platforms to profile the antibodies in the blood because of its fast, multiplexed, and sensitive nature. To fully understand the immune responses and biological specificities, this study developed a human coronavirus (HCoV) protein microarray and included all seven human coronaviruses and three influenza viruses. Each protein was printed in triplicate and formed 14 identical blocks per array. The HCoV protein microarray showed high reproducibility and sensitivity to the monoclonal antibodies against spike and nucleocapsid protein with detection limits of 10-200 pg. The HCoV proteins that were immobilized on the array were properly folded and functional by showing interactions with a known human receptor, e.g., ACE2. By profiling the serum IgG and IgA from 32 COVID-19 patients and 36 healthy patients, the HCoV protein microarray demonstrated 97% sensitivity and 97% specificity with two biomarkers. The results also showed the cross-reactivity of IgG and IgA in COVID-19 patients to spike proteins from various coronaviruses, including that from SARS-CoV, HKU1-CoV, and OC43-CoV. Finally, an innate immune protein named surfactant protein D showed broad affinities to spike proteins in all human coronaviruses. Overall, the HCoV protein microarray is multiplexed, sensitive, and specific, which is useful in diagnosis, immune assessment, biological development, and drug screening.

The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound 13 was identified, which potently (IC50 < 200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of 13 by prodrug strategies resulted in orally bioavailable 25, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of 25 showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of 25 for the treatment of MYC-amplified cancers including SCLC.

OBJECTIVES To evaluate the effect of zoledronic acid (ZA) on human umbilical vein endothelial cells (HUVECs) attached to different surfaces. MATERIALS AND METHODS A total of three groups were evaluated in this study: sandblasting and acid etching (SLA) + HUVECs; mechanically polished (MP) + HUVECs; and plastic cell culture plates + HUVECs. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, surface roughness and water contact angle were tested for titanium surface characterisation. ZA was added at different concentrations (0, 1, 10, 50 and 100 μM). Cell adhesion, proliferation, viability, apoptosis and gene expression were evaluated. RESULTS Mechanically polished and SLA surfaces showed negative effects on cell adhesion and proliferation and promoted cell apoptosis with 100 μM ZA (p

Objective: Traditional breast ultrasound relies too much on the operation skills of diagnostic doctors, and the repeatability in different doctors was low. This study aimed to evaluate the assistant diagnostic value of S-Detect artificial intelligence (AI) system in differentiating benign from malignant breast masses. Methods: The ultrasound images of 40 patients who underwent ultrasound examination in our hospital were collected. The conventional ultrasound images, elastic images, and S-Detect mode of breast lesions were analyzed. The breast imaging reporting and data system recommended by the American Society of Radiology (BI-RADS) classification for each breast mass was evaluated both by the doctor and AI. The receiver operator characteristics (ROC) curves were drawn to compare the diagnostic efficiency. Result: Among the 40 lesions, 16 were benign, and 24 were malignant. The S-Detect AI system had a high diagnostic efficiency for malignant mass, with sensitivity, specificity, and accuracy of 95.8%, 93.8%, and 89.6%. The accuracy of AI was higher than the elastic image and then than the conventional gray-scale image. With the assistance of the S-Detect AI system, the accuracy of BI-RADS classification was improved significantly. Conclusion: The S-Detect AI system will enhance breast cancer diagnostic accuracy and improve ultrasound examination quality.

BACKGROUND Le Fort I maxillary repositioning influences nasal morphology. In Asian cultures, upward nasal tip rotation with increased nostril exposure is considered aesthetically unpleasant and can have psychosocial consequences. This three-dimensional imaging-based study evaluated the effect of different Le Fort I maxillary movements on nasal tip rotation. METHODS Consecutive patients who underwent two-jaw orthognathic surgery (n = 107) were enrolled. To achieve a standard head orientation, preoperative and 1-week and 12-month postoperative cone-beam computed tomography-derived three-dimensional craniofacial models were superimposed. Tip rotation angle was calculated according to the Frankfort horizontal plane for all three-dimensional digital models. The final tip rotation angle change was defined as 12-month postoperative value minus preoperative value. Translational maxillary movement types (advancement versus setback and intrusion versus extrusion), postoperative maxillary segment locations (anterosuperior, anteroinferior, posterosuperior, or posteroinferior), and actual linear maxillary changes were noted. RESULTS Advancement (1.79 ± 5.20 degrees) and intrusion (2.23 ± 4.96 degrees) movements demonstrated significantly larger final tip rotation angle changes than setback (-0.88 ± 5.15 degrees) and extrusion (0.09 ± 5.44 degrees) movements (all p < 0.05). Postoperative anterosuperior location (2.95 ± 4.52 degrees) of the maxillary segment demonstrated a significantly larger final tip rotation angle change than anteroinferior (0.48 ± 5.65 degrees), posterosuperior (-1.08 ± 4.77 degrees), and posteroinferior (-0.64 ± 5.80 degrees) locations (all p < 0.05). Translational maxillary movement and actual linear maxillary change were not correlated with final tip rotation angle change. CONCLUSION Effects of Le Fort I maxillary repositioning on nasal tip rotation depend on movement types and maxillary segment location. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

In our earlier study, we showed that the expression of microRNA‐221‐3p (miR‐221‐3p) was significantly lower in women of advanced age with diminished ovarian reserve (DOR) compared with young women with normal ovarian reserve (NOR). Therefore, in this study, we aimed to explore how miR‐221‐3p regulates apoptosis of granulosa cells and the pathogenesis of DOR. Bioinformatics prediction and dual‐luciferase reporter assay were conducted to identify the target gene of miR‐221‐3p. miR‐221‐3p expression was manipulated by transfecting KGN cells with miR‐221‐3p mimics, inhibitor, and negative control. Following transfection, apoptosis of granulosa cells was determined by flow cytometry, and the expression of the target gene was measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis (WB). In addition, the expression of the target gene in granulosa cells of DOR patients and NOR patients was measured. miR‐221‐3p were found to directly bind the 3ʹ untranslated region of Forkhead box O1 (FOXO1). Transfection with miR‐221‐3p mimics significantly decreased the apoptosis rate of KGN cells compared with transfection with miR‐221‐3p inhibitors. The expression level of miR‐221‐3p was negatively correlated with the messenger RNA and protein levels of the FOXO1 gene. Besides, FOXO1 expression was upregulated in DOR patients. In conclusion, these results provide evidence that downregulation of miR‐221‐3p expression promotes apoptosis of granulosa cells by upregulating FOXO1 expression, thus serving an important role in DOR pathogenesis.

Background This study analyzed the influence of implant protrusion length (IPL) on the possible factors that affect the long-term outcomes utilizing non-grafting osteotome sinus floor elevation (OSFE) with simultaneous implant placement, and to explore the optimal range of IPL. Materials and methods A retrospective study design was adopted. The clinical and radiographic data of 105 implants in 65 patients were collected after 3–9 (mean 5.04) years follow-up. IPL was divided into three groups (group1, IPL Results A total of 102 implants in 62 patients fulfilled the survival criteria, giving the cumulative survival rates of 96.4% and 94.1% for implant-based analysis and patient-based analysis, respectively. The mean ESBG, MBL, and BICL at the latest follow-up were 1.95±0.88 mm, 0.58±0.68 mm, and 5.51±1.47 mm. ESBG was found to be positively correlated to IPL. A significant decreased bone formation efficiency was found when IPL was over 4 mm (P=0.02). Conclusions An optimal range of IPL within 4 mm was recommended for better long-term outcomes when applying non-grafting OSFE with simultaneous implant placement.

AIMS To examine the relationship between leisure-time physical activity, sitting time and prefrailty in community-dwelling older adults. DESIGN Cross-sectional study. METHODS Between February and July 2019, 539 individuals over age 60 were recruited in northern Taiwan. Demographic, medical history, physical activity and frailty data were analysed using descriptive statistics, chi-square tests and logistic regression. RESULTS The prevalence of prefrailty was 24.4%; 33.2% had regular leisure-time physical activity, and 14.7% reported >6 hrs daily sitting time. Compared with individuals having regular leisure-time physical activity and shorter sitting times (daily average ≤6 hrs), those having no regular leisure-time physical activity and also shorter sitting times (adjusted OR, 1.80; 95% CI, 1.12, 2.92), or those also having regular leisure-time physical activity but longer sitting times (adjusted OR, 4.42; 95% CI, 2.22, 8.79) had an increased prefrailty risk. CONCLUSIONS Having no regular leisure-time physical activity or longer sitting times is associated with a higher risk of prefrailty. For sedentary older adults to prevent prefrailty, they can become more active, sit less or better yet, commit to both.

Le Fort I maxillary movements affect nasal width, but nasal width changes with specific movement types have not been formally addressed to date.The purpose of this study was to analyze and compare the changes in nasal width with different maxillary movements.A retrospective study was performed among consecutive patients who underwent bimaxillary orthognathic surgery (n = 138) and who were grouped based on the type of maxillary movement (ie, maxillary advancement with intrusion [MAI], maxillary advancement with extrusion [MAE], and maxillary setback with intrusion [MSI]). Preoperative and 12-month postoperative nasal widths were analyzed photogrammetrically by 2 blinded evaluators.Maxillary advancement with intrusion and MAE presented a significantly (P0.05) higher alar base widening than MSI did, with no significant (P0.05) differences between MAI and MAE. Maxillary advancement movements (MAI and MAE) showed significantly (P0.05) higher alar base widening than maxillary setback movement (MSI). However, no significant (P0.05) difference was observed between maxillary intrusion (MAI and MSI) and maxillary extrusion (MAE) movements.This study shows that the nasal width varies distinctly depending on the type of Le Fort I maxillary surgical movement.

Background: Liver fibrosis leads to loss of liver function. Xiaoyaosan decoction (XYS) as a classical Traditional Chinese Medicine (TCM) formula is used to treatment liver fibrosis in clinical and alleviated CCl4-induced liver fibrosis in our previous study.Xiaoyaosan decoction was composed of many ingredients, and the active ingredients is not clear. The Aim of this study is to explore the clarified compounds or compound combinations to treat liver fibrosis.Methods: Network pharmacology combined with transcriptomics analysis were used to analyze the Xiaoyaosan decoction (XYS) and liver depression and spleen deficiency syndrome liver fibrosis. This consisted constructed XYS-Syndrome-liver fibrosis network, the predict formula named LLAAF was develop from the network by topological analysis according to network stability. The anti-fibrosis effect was evaluated by in vitro and in vivo study.Results: According to the network XYS-Syndrome-liver fibrosis network, luteolin, licochalcone A, aloe-emodin, and acacetin formula (LLAAF) was predicted from 8 key compounds and 255 combinations in XYS, and LLAAF had a synergistic effect on the proliferation inhibition of hepatic stellate cells (HSCs) compared to each individual compound alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rat. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signaling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signaling in vitro and in vivo.Conclusions: This study developed a novel anti-liver formula, LLAAF from XYS demonstrated the anti-liver fibrotic activity may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signaling.

BACKGROUND Infantile-onset inflammatory bowel disease (IO-IBD) occurs in very young children and causes severe clinical manifestations, which has poor responses to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. AIM To search for valuable indicators for early identifying IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into a monogenic IBD group (M-IBD) and a non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included in a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD, respectively. RESULTS Among the 44 M-IBD patients, 35 carried IL-10RA mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and the c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely to have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, P = 0.013], while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, P = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in IL-10RA in IO-IBD patients was strongly suggested. CONCLUSION Serum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.