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ImportanceMild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO.ObjectiveTo evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO.Design, Setting, and ParticipantsIn this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks.InterventionsParticipants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks.Main Outcomes and MeasuresThe primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded.ResultsA total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group.Conclusions and RelevanceThe results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort.Trial RegistrationClinicalTrials.gov Identifier: NCT02203682

Persistent inflammatory infiltration of skeletal muscle is a principal trigger for the loss of muscle mass and strength. Theaflavins, the main functional components of black tea, have effects on muscle health, but their biological effects on skeletal muscle inflammation are unclear. We constructed in vitro and in vivo models of muscle inflammation and found that theaflavins reduced the expression of inflammatory factors (IL-1β, IL-6, and TNF-α) by regulating the TLR4/MyD88/NF-κB signaling pathway to alleviate muscle inflammation. In addition, TF1 can regulate the metabolic function of skeletal muscle under inflammatory conditions, reduce the content of proinflammatory substances, improve the mechanical properties (stiffness and roughness) of the surface of inflammatory myotubes, and promote the recovery of muscle after an inflammatory injury. In conclusion, theaflavins may serve as a diet-derived anti-inflammatory factor with potential modulatory effects on skeletal muscle metabolism and mechanical properties in an inflammatory environment.

Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone.This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes.The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL.Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.

Epithelial-to-mesenchymal transition (EMT) is the process by which epithelial cells transform into mesenchymal cells, which plays a significant role in lung fibrotic disease. Transforming growth factor-β1(TGF-β1) is considered to be the most effective EMT inducer. The purpose of this study was to investigate the effect of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) on TGF-β1-induced EMT and the underlying mechanisms in the human bronchial epithelial cell line BEAS-2B.Human bronchial epithelial BEAS-2B cells were treated with TGF-β1 and TNF-α separately or in combination for 24 h, and qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to investigate the EMT process. Moreover, to further explore the effect of the NF-κB pathway on the EMT process, inhibitor assays (BAY-117082, NF-κB inhibitor), wound healing assays, and western blotting were performed.The results showed that both cytokines enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells. In addition, combined treatment with TNF-α and TGF-β1 further reduced E-cadherin expression, which conversely elevated α-SMA and vimentin mRNA and protein levels. Correspondingly, the migration rate of BEAS-2B cells was also increased. Furthermore, inhibiting the NF-κB signaling pathway blocked the expression of EMT-related markers and NOX4 induced by TGF-β1 and TNF-α, as well as cell migration.Taken together, TNF-α and TGF-β1 cooperatively promoted EMT and cell migration in BEAS-2B cells through the NF-κB/NOX4 signaling pathway.

ATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.One hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence.Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (HighHigh nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

A new species of the genus Neopheosia Matsumura, 1920, N. pseudofasciata sp. nov. is described and illustrated from Fujian province. The species resembles N. fasciata (Moore, 1888) but differs in a forewing pattern in M3 cell; diagnostic differences are observed in genitalia characters as well. DNA barcode data of the new species and its relatives are deposited in GenBank. A key to the Neopheosia species based on morphology is presented. The holotype is deposited in the Department of Entomology, College of Plant Protection, South China Agricultural University, Guangzhou.

We hypothesized that air pollution could cause oxidative damage and inflammation in the human body, which was linked to bone loss. Our result showed that long-term exposure to air pollution might decrease bone mineral density (BMD) T-score and increase the prevalence of osteoporosis in Hubei province.Osteoporosis is becoming an increasingly serious public health problem with the advent of global aging. Long-term exposure to air pollution has been linked to multitudinous adverse health outcomes, but evidence is still relatively limited and inconsistent for BMD T-score and osteoporosis. This study aimed at exploring the associations between long-term exposure to air pollution and BMD T-score and osteoporosis.The Hubei part of the China Osteoporosis Prevalence Study was extracted. Data on air pollutants were collected by the national air quality real-time release platform of China Environmental Monitoring Station. Linear mixed models and multilevel logistic regression analyses were performed to assess the associations between air pollution and BMD T-score and osteoporosis, respectively. Subgroup analyses were conducted to identify vulnerable populations.A total of 1845 participants were included in this cross-section study. Per 10 ug/mOur study provided evidence that long-term exposure to PM

Individualized instruction is a type of educational principle. On the one hand, it necessitates the creation of individualized teaching resources, courses, and methods. Students, on the other hand, require a high level of autonomy and the ability to make personalized plans based on their own cognitive characteristics and needs. The big data (BD) era opens up new possibilities for IE (ideological education) work in universities, but it also poses some challenges. IE development will be greatly aided by recognizing opportunities to meet challenges and optimizing and integrating PL (political lesson) resources. The LNN (Lagrange neural network) model has been established. The simulation results show that the LNN network can converge to the optimal solution quickly and effectively and then reconstruct sparse signals. Individualized college PL instruction using LNN and BD technology helps students communicate more effectively and improves the pertinence, immediacy, and positivity of IE.

Purpose. To develop and validate a radiomic nomogram based on texture features from out-of-phase T1W images and clinical biomarkers in prediction of liver fibrosis. Materials and Methods. Patients clinically diagnosed with chronic liver fibrosis who underwent liver biopsy and noncontrast MRI were enrolled. All patients were assigned to the nonsignificant fibrosis group with fibrosis stage

Immunosuppressive therapy (IST) is an effective treatment regimen for severe aplastic anaemia (SAA) patients without HLA-identical donors. This study further compared the outcomes between IST and IIST-UCB in SAA on the basis of research shown that IST combined with umbilical cord blood infusion (IIST-UCB) treated effectively. A total of 123 patients from 11 hospitals in China were enrolled. Sixty-nine patients in IIST-UCB group were treated with ATG + CsA + CTX combined with cord blood, while 54 patients in IST group with ATG + CsA. The overall remission rates (ORRs), complete remission (CR) rates and partial response (PR) rates of IIST-UCB group and IST group at 3 months were 69.67% vs 51.85% (P = .045), 21.74% vs 3.7% (P = .004) and 47.83% vs 48.15% (P = .972), respectively. After 6 months of treatment, they were 76.81% vs 57.41% (P = .022), 37.68% vs 11.11% (P = .001) and 39.13% vs 46.30% (P = .425), respectively. After 1 year of treatment, they were 85.51% vs 61.11% (P = .002), 59.42% vs 25.93% (P = .000) and 26.09% vs 35.19% (P = .275), respectively. The ORRs and CR rates of IIST-UCB group were both significantly higher than IST group after 3 months, 6 months and 1 year of treatment. The neutrophil granulocyte, platelet and haemoglobin recovery times of IIST-UCB group were significantly shorter than IST group. Compared with standard IST, IIST-UCB as an effective therapy for SAA patients without HLA-identical donors accelerated the haematopoietic reconstitution, resulting in higher early CR rates.

Scars are nearly impossible to avoid after a skin injury, but despite advancements in the treatment modalities, they remain a clinical problem, especially hypertrophic scars (HS). Many studies include the mechanism of formation and inhibition of HS, but it is not fully understood yet. Circular RNA HECTD1 (circHECTD1), for the first time, has been found to have roles in HS physiology. We determined the relative circHECTD1 levels in HS fibrous cells and tissues by RT-qPCR. Afterward, the effect of circHECTD1 knockdown on the proliferation, migration, invasion, fibrosis, and Transforming Growth Factor-beta/small mothers against decapentaplegic (TGF-β/Smad) signaling was studied using CCK-8, wound healing, Transwell, and western blot assays. After the role of circHECTD1 was clarified, its targeted micro RNA (miR) was predicted using the Starbase database, and we constructed a miR-142-3p mimic to study the details of its regulation mechanism. We used the TargetScan database to predict the downstream target high mobility group box 1 (HMGB1) of miR-142-3p, and the luciferase report assay verified the binding, and then its effect was determined by RT-qPCR. circHECTD1 is highly expressed in HS tissues and human skin hypertrophic scar fibroblasts (HSF); its loss of function inhibits cell proliferation, migration, invasion, fibrosis, and TGF-β/Smad signaling. However, miR-142-3p inhibitor reverses the effect of circHECTD1 on all the above-mentioned aspects, including HMGB1 expression. In conclusion, circHECTD1 knockdown interrupts TGF-β/Smad signaling through miR-142-3p/HMGB1 and suppresses scar fibrosis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Background Patients with a lateral femoral wall (LFW) fracture were reported to have high rates of re-operation and complication. Although the LFW thickness was a reliable predictor of post-operative or intra-operative LFW fracture, there was a paucity of literature evaluating the critical stress distributions on the femur and screws of intertrochanteric fractures treated with dynamic hip screw (DHS). This study aimed to investigate the biomechanical performance of intertrochanteric fractures with different LFW thickness treated with DHS device. Methods A three-dimensional model of the proximal femur was established by computed tomography images. The intertrochanteric fracture model with three different LFW thickness (10 mm, 20.5 mm and 30 mm, respectively) was created, which was fixed by DHS. The von Mises stress on the proximal femur, lateral femoral wall, DHS and the total displacement of the device components were evaluated and compared for three different LFW thickness model. Results The maximum von Mises stress in the proximal fragment of the 10 and 20.5 mm model increased by 80.56% and 57.97% when compared with the 30 mm model. The peek von Mises stress around the blade entry point of the 10 mm and 20.5 mm model increased by 89.26% and 66.39% when compared with the 30 mm model. The peek von Mises in the DHS located near the junction of the barrel and side plate of each model and the 30 mm model had the smallest von Mises stress compared with the other two models. Furthermore, the maximum displacement in the 30 mm model was much smaller than that in the10mm model and 20 mm model. Conclusions The intertrochanteric fracture with a thinner LFW tended to have a higher risk of LFW fracture stabilized by a DHS device. Thus, the intertrochanteric fractures with a thinner LFW should not be treated by DHS alone and the intramedullary nail or an addition of trochanteric stabilization plate(TSP) was recommended.

Herein, we report a new click-activated prodrug, CA4V, and a bioorthogonal nanoreactor, CA4V/ZIF-90@TzCOF@Apt, which consists of a ZIF-90 core, tetrazine-based covalent organic framework (COF) shells and an aptamer polymer coating. When targeting a tumor, the acid-causing collapse of ZIF-90 initiates a nanoconfined bioorthogonal reaction in defined COF cages, which boosts the click efficiency of CA4V activation and therapeutic effects

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission (

Background The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms, among which transcriptional regulation is one of the most important components. Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle. However, the patterns of transcript isoform expression in the cell cycle are unclear. Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies, but none of them have been designed or evaluated at the alternative splicing transcript level. The utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown, and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also rare. Methods To explore alternative splicing patterns during cell cycle progression, we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines, using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples, and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell cycle. Genomics of Drug Sensitivity in Cancer (GDSC) drug sensitivity datasets and Cancer Cell Line Encyclopedia (CCLE) transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug sensitivity. We identified transcripts associated with typical drugs targeting cell cycle by determining correlation coefficients. Cytotoxicity assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6 (CDK4/6) inhibitors. Finally, alternative splicing transcripts associated with mitotic (M) phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome analysis. Results We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT116 and breast cancer MDA-MB-231 cells. The results of the cell cycle assessment showed that 43,326, 41,578 and 29,244 transcripts were found to be periodically expressed in HeLa, HCT116 and MDA-MB-231 cells, respectively, among which 1280 transcripts showed this expression pattern in all three cancer cell lines. Drug sensitivity assessments showed that a large number of these transcripts displayed a higher correlation with drug sensitivity than their corresponding genes. Cell cycle-related drug screening showed that the level of the CDK4 transcript ENST00000547281 was more significantly associated with the resistance of cells to CDK4/6 inhibitors than the level of the CDK4 reference transcript ENST00000257904. The transcriptional inhibition assay following M phase arrest further confirmed the M-phase-specific expression of the splicing transcripts. Combined with the cell cycle-related drug screening, the results also showed that a set of periodic transcripts, for example, ENST00000314392 (a dolichyl-phosphate mannosyltransferase polypeptide 2 isoform transcript), was more associated with drug sensitivity than the levels of their corresponding gene transcripts. Conclusions In summary, we identified a panel of cell cycle-related periodic transcripts and found that the levels of transcripts of drug target genes showed different values for predicting drug sensitivity, providing novel insights into alternative splicing-related drug development and evaluation.

OBJECTIVE To examine the prevalence and factors associated with early resumption of sexual intercourse among postnatal women in China. METHOD We conducted a retrospective multicenter study of 15 834 postpartum women from 60 hospitals in 15 different locations across China. Data were obtained from questionnaires administered to the participants. All dates were analyzed using a one-way ANOVA and two-level Cox multiple linear regression models. RESULTS More than half of the participating women (55.9%) resumed sexual intercourse by 3 months postpartum. The independent variables associated with the postpartum resumption of sexual intercourse included sociodemographic characteristics (age, geographic location, educational attainment) and medical histories, including the previous abortion (incorporate with spontaneous and voluntary abortion) frequency, menstrual recovery, exclusive breastfeeding, and number of living children (p

Objective To reveal noteworthy characteristics of intramedullary (IM) nail breakage in pertrochanteric femur fractures. Materials and methods The data from 6 patients with IM nail breakage in our hospital between August 2008 and May 2018 were reviewed retrospectively. With an additional 64 cases reported in articles in the PubMed database prior to October 2019, a total of 70 cases were reviewed and analysed; epidemiological patient data and data on the initial trauma, fracture type, nail selected for the original surgery, time from surgery to breakage, mechanism and location of breakage, status of fracture healing, salvage treatment and prognosis were assessed. Results Seventy patients with pertrochanteric fractures, including 2 stable fractures and 68 unstable fractures, experienced IM nail breakage at a mean of 9.4 months after the initial surgery. Among them, 9 (12.9%) occurred within 3 months, 23 (32.9%) between 3 and 6 months and 38 (54.3%) after 6 months. The mean age was 72.3 years, and 16 (22.9%) patients were younger than 65 years old. When nail breakage occurred, 66 fractures (94.3%) exhibited delayed union/non-union. Self-dynamisation was found in 12 cases (17.1%). The salvage procedures included 4 partial/total implant removal procedures, 17 hemi/total hip arthroplasty procedures, 3 conservative treatment procedures, and 46 revised osteosyntheses, of which 7 cases (15.2%) sustained secondary implant failure. No significant differences were found between the failure rates of IM nails and extramedullary(EM) devices (odds ratio [OR], 3.429; 95% confidence interval [CI], 0.632–18.877; p = 0.330). Conclusion IM nail breakage is a rare complication lack of time regularity and mostly occurs in unstable pertrochanteric fractures in the presence of delayed union/non-union. Osteosynthesis revision can be conduct by a new IM nail or EM device but considerable secondary failure rate is noteworthy. Self-dynamisation may be a warning sign of nail breakage.

Few studies have specifically evaluated the comminution extent of lateral femoral wall (LFW) fracture and risk factors of implant failure in intertrochanteric fractures with LFW fracture. The aim of present study was to evaluate the influence of comminution extent of LFW fracture on implant failure and identify risk factors of implant failure in cases with LFW fracture after intramedullary fixation.This retrospective study included 130 intertrochanteric fracture with LFW fracture treated with intramedullary fixation at a teaching hospital over a 13-year period from January 2006 to December 2018. Demographic information, cortical thickness index, the reduction quality, status of medial support, position of the screw/blade and status of lateral femoral wall were collected and compared. The logistic regression analyzes was performed to evaluate risk factors of implant failure in intertrochanteric fractures with LFW fracture after intramedullary nail fixation.10 patients (7.69%) suffered from mechanical failure after intramedullary fixation. Univariate analyzes showed that comminuted LFW fracture (OR, 7.625; 95%CI, 1.437~40.446; p = 0.017), poor reduction quality (OR, 49.375; 95%CI, 7.217~337.804; p 0.001) and loss of medial support (OR, 17.818; 95%CI, 3.537~89.768; p 0.001) were associated with implant failure. After adjustment for confounding variables, the multivariable logistic regression analyzes showed that poor reduction quality (OR, 11.318; 95%CI, 1.126~113.755; p = 0.039) and loss of medial support (OR, 7.734; 95%CI, 1.062~56.327; p = 0.043) were independent risk factors for implant failure. Whereas, comminuted LFW fracture was not associated with implant failure (p = 0.429).The comminution extent of the LFW fracture might influence the stability of intertrochanteric fractures; and intramedullary fixation might be an effective treatment method. Furthermore, poor reduction quality and loss of medial support could increaze the risk of implant failure in intertrochanteric fractures with LFW fractures after intramedullary fixation. Therefore, we should pay great emphasis on fracture reduction quality in future.

Introduction There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs. Methods A total of 40 FNAs from 2014 to 2019 of HNSCC with p16 IHC were obtained. CB p16 staining was scored independently by 5 cytopathologists as interval percentages of tumor cell positivity. Receiver operating characteristic (ROC) curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values. Gwet’s coefficient (AC1) was calculated to assess inter-rater reliability. Results Greater than 10% was the lowest threshold to reach 100% specificity with high sensitivity (55%-84%) in all 5 raters. Rater performances were similar, with areas under the curve (AUCs) ranging from 0.89 to 0.95. Using the >10% threshold, Gwet’s AC1 = 0.72 (95% CI: 0.56-0.89). Diagnostic performance improved further when low-cellularity cases were excluded, with AUC ranging from 0.94 to 0.99 and Gwet's AC1 = 0.79 (95% CI: 0.61-0.98). Conclusion p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as “selective elimination of host cells capable of producing HIV” (SECH). Similar to the “shock and kill strategy,” the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

The detection of changes in the reactive oxygen species (ROS)/reactive sulfur species (RSS) couple is important for studying the cellular redox state. Herein, we developed a 1,8-naphthalimide-based fluorescence probe (NI) for the reversible detection of bisulfite (HSO3- ) and hydrogen peroxide (H2 O2 ) in vitro and in vivo. NI has been designed with a reactive ethylene unit which specifically reacts with HSO3- by a Michael addition reaction mechanism, resulting in the quenching of yellow fluorescence at 580 nm and the appearing of green fluorescence at 510 nm upon excitation at 500 nm and 430 nm, respectively. The addition product (NI-HSO3 ) could be specifically oxidized to form the original C=C bond of NI, recovering the fluorescence emission and color. The detection limits of NI for HSO3- and NI-HSO3 for H2 O2 were calculated to be 2.05 μM and 4.23 μM, respectively. The reversible fluorescence response of NI towards HSO3- /H2 O2 couple can be repeated for at least five times. NI is reliable at a broad pH range (pH 3.0-11.5) and features outstanding selectivity, which enabled its practical applications in biological and food samples. Monitoring the reversible and dynamic inter-conversion between HSO3- and H2 O2 in vitro and in vivo has been verified by fluorescence imaging in live HeLa cells, adult zebrafish and nude mice. Moreover, NI has been successfully applied to detect of HSO3- levels in food samples.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.

This study explored the impacts of matrine on hepatocellular carcinoma (HCC) cell growth, metastasis, epithelial-mesenchymal transition (EMT), and stemness through regulating the microRNA

IntroductionEmotional disorders are often observed in inflammatory bowel disease (IBD). IBD with emotional disorders leads to poor quality of life. This systematic review aims to assess the effectiveness of acupuncture in patients with IBD with emotional disorders.Methods and analysisNine electronic databases, including Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing & Allied Health Literature, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database, will be searched from inception to October 2021 without language restriction. The grey literature containing conference proceedings, as well as systematic reviews listed in the reference of definite publications, will also be retrieved. Randomised controlled trials either in English or Chinese reporting acupuncture therapy for IBD with emotional disorders will be included. The primary outcome is changes of emotional functioning outcomes. The Colitis Activity Index, Crohn’s Disease Activity Index, C reactive protein and adverse events will be assessed as the secondary outcomes. More than two assessors will conduct the study retrieval and selection, as well as the data extraction and evaluation of the risk of bias. Data synthesis will be performed using a random-effects model based on the results of heterogeneity. Data analysis will be performed using RevMan software (V.5.4). Moreover, the dichotomous data will be presented as risk ratios, and the continuous data will be calculated using weighted mean difference or standard mean difference.Ethics and disseminationThis systematic review contains no individual patient data; thus, ethical approval is not required. Moreover, this review will be disseminated in a peer-reviewed journal or relevant conference.PROSPERO registration numberCRD42020176340.

The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting.

Objective: The aim of this study is to validate the efficacy and reliability of two predictive models for postoperative fever after retrograde intrarenal surgery (RIRS) in pediatric patients Materi...

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Lung transplant is increasingly performed for the treatment of end-stage lung disease. As the number of lung transplants and transplant centers continues to rise, radiologists will more frequently participate in the care of patients undergoing lung transplant, both before and after transplant. Potential donors and recipients undergo chest radiography and CT as part of their pretransplant assessment to evaluate for contraindications to transplant and to aid in surgical planning. After transplant, recipients undergo imaging during the postoperative hospitalization and also in the long-term outpatient setting. Radiologists encounter a wide variety of conditions leading to end-stage lung disease and a myriad of posttransplant complications, some of which are unique to lung transplantation. Familiarity with these pathologic conditions, including their imaging findings and their temporal relationship to the transplant, is crucial to accurate radiologic interpretation. Knowledge of the surgical techniques and expected postoperative appearance prevents confusing normal posttransplant imaging findings with complications. A basic understanding of the indications, contraindications, and surgical considerations of lung transplant aids in imaging interpretation and protocoling and also facilitates communication between radiologists and transplant physicians. Despite medical and surgical advances over the past several decades, lung transplant recipients currently have an average posttransplant life expectancy of only 6.7 years. As members of the transplant team, radiologists can help maximize patient survival and hopefully increase posttransplant life expectancy and quality of life in the coming decades.

Epigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. m6A methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The m6A modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the m6A methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of m6A methylation are reviewed, especially the role of m6A methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of m6A deposition.

Key Summary points Aim RCT to evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in hospitalized older patients. Findings The multi-component interventions did not reduce hospital-acquired pneumonia but increased the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). This was likely due to the increased recognition of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). Message A multi-component intervention for nosocomial pneumonia may not significantly reduce the incidence of hospital-acquired pneumonia but significantly increases the frequency of diagnosis of oropharyngeal dysphagia, improves vaccination rates and can reduce future hospitalisations for respiratory infections in older adults., Aims To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. Methods A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. Results A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P

The advantages of face processing over processing items in other object categories have been found in conditions both with and without visual awareness. This study examined the possible mechanisms underlying the advantages of processing visible and invisible faces. Specifically, contributions from face-like configurations and face-specific local attributes were evaluated by comparing perceptual processes of three image types: genuine faces, face-like objects, and non-face-like objects. Illusory face perception induced from face-like objects largely depended on information from a global configuration level, with a high tolerance for variations in local features. Comparable processing advantages for real faces and face-like objects were observed in invisible conditions using interocular rivalry and crowding paradigms. However, the visible face advantage seemed to be exclusive to genuine faces. These results suggest that the face processing privilege is twofold: It is strongly triggered by global configuration without visual awareness, but with awareness, it relies on facial local attributes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objectives To investigate the sleep quality of women pregnant with a second child and the influencing factors and provide a scientific basis for health care guidance to clinically improve the sleep quality of pregnant women. Methods A total of 162 women pregnant with a second child at a first-class tertiary hospital in Changsha from January to August 2018 were selected as the research subjects. General demographic characteristics were collected, and the Pittsburgh Sleep Quality Index (PSQI) scale was used to assess their sleep quality. Multivariate logistic regression analysis was used to explore the influencing factors of the sleep quality of women pregnant with a second child. Results The PSQI score (except hypnotic drugs) and total score of pregnant women with second birth were higher than those of normal female population, and the difference was statistically significant (P P P = 0.001), low family monthly income (OR = 3.035, P = 0.014), expectation of gender (OR = 0.065, P = 0.038), and dissatisfaction with marital relationship (OR = 0.275, P = 0.001) were the primary risk factors of poor sleep quality of in women with second pregnant. Conclusions The overall sleep quality of women pregnant with a second child is poor, and 37.65% have sleep quality problems. Low education levels, low family monthly incomes, fetal gender expectations, and poor relationship between husband and wife are the main factors affecting the sleep quality of women pregnant with a second child. Pregnant women with the above factors should pay attention to their sleep quality and take necessary measures for intervention and guidance to improve the level of health care during pregnancy.

Abstract Purposes To identify the characteristics of the vertebral HU in the elderly patient with new osteoporosis vertebral compression fractures (OVCF) after treatment of percutaneous kyphoplasty (PKP), which may help us to preliminarily evaluate the risk of a new OVCF after the treatment of PKP. Methods We retrospectively analyzed the patients who received PKP treatments in our hospital to find out the patients suffered new OVCFs after the treatment of PKP and set an age-, sex-, first fracture vertebrae-, surgical segment-, and comorbidity-matched control group without new fractures. We measured the axial and sagittal L1-HU values to compare their differences. Results There were 32 patients who suffered new OVCFs and received another PKP surgery in our department. In the study group, the average L1 sagittal and axial HU values were 46.17 ± 21.31 HU and 47.77 ± 22.38 HU, and they had no statistical difference (P > 0.05). For the control group, the average L1 sagittal and axial HU values were 75.69 ± 29.72 HU and 80.23 ± 30.26 HU, and their difference was not significant (P > 0.05). No matter from the axial or sagittal evaluation, the L1 HU value in the study group was significantly lower than that in the control group (P Conclusions The lower the vertebral HU value is, the more likely the patients suffer new OVCFs after PKP treatment.

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Acquired drug resistance and epithelial-mesenchymal transition (EMT) mediated metastasis are two highly interacting determinants for non-small-cell lung cancer (NSCLC) prognosis. This study investigated the common mechanisms of drug resistance and EMT from the perspective of metabolic reprogramming, which may offer new ideas to improve anticancer therapy. Acquired resistant cells were found to grow faster and have a greater migratory and invasive capacity than their parent cells. Metabolomics analysis revealed that acquired resistant cells highly relied on glutamine utilization and mainly fluxed into oxidative phosphorylation energy production. Further mechanistic studies screened out glutamate dehydrogenase 1 (GLUD1) as the determinant of glutamine addiction in acquired resistant NSCLC cells, and provided evidence that GLUD1-mediated α-KG production and the accompanying reactive oxygen species (ROS) accumulation primarily triggered migration and invasion by inducing Snail. Pharmacological and genetic interference with GLUD1 in vitro significantly reversed drug resistance and decreased cell migration and invasion capability. Lastly, the successful application of R162, a selective GLUD1 inhibitor, to overcome both acquired resistance and EMT-induced metastasis in vivo, identified GLUD1 as a promising and druggable therapeutic target for malignant progression of NSCLC. Collectively, our study offers a potential strategy for NSCLC therapy, especially for drug-resistant patients with highly expressed GLUD1.

Timely diagnosis is essential in the management of cervical spine fracture (CSF) in ankylosing spondylitis (AS) patients. However, the value of simple plain X-ray in the early management of ASCSF has not been well-studied. This study aimed to explore the prediction ability of simple plain X-ray for CSF in AS patients who suffer from low-energy trauma (LET).From January 2010 to December 2020, AS patients who experienced LET were retrospectively reviewed. Clinical data including gender, age, body mass index, time interval between AS diagnosis and trauma, smoking or not, and a presence of continuous bony bridge between anterior margin of C1 and C2 body or not were collected. Morphological features including atlanto-occipital gap, Pavlov ratio of C2-7, Angle A-D, Borden's index, and Harrison's value were measured by the lateral cervical X-ray. All data was compared between patients who had CSF and those who did not. Binary logistic regression analysis and receiver operator characteristic (ROC) curves were applied to discriminate and assess the predictive parameters.A total of 129 AS patients were divided into Fracture group (41 cases) and Non-fracture group (88 cases) based on whether CSF existed. Twelve parameters showed significant differences between two groups (p 0.05). According to the binary logistic regression model, four of the 12 parameters showed a further correlation with the occurrence of CSF, namely, mean Pavlov ratio (p 0.001, OR = 0.067, 95% CI: 0.023 to 0.194), Angle D (p = 0.031, OR = 1.057, 95% CI: 1.005 to 1.112), Borden's index (p = 0.042, OR = 1.131, 95% CI: 0.994 to 1.287), the time interval between the AS diagnosis and the trauma (p 0.020, OR = 0.935, 95% CI: 0.883 to 0.990). The ROC curve further revealed the mean Pavlov ratio had the largest AUC (0.793) with the cut-off of 0.72. While the optimal cut-off value was 45.65° for Angle D (sensitivity = 61.0%, specificity = 78.4%), 9.79 for Borden's index (sensitivity = 87.8%, specificity = 37.5%), 15.50 years for the time interval between AS diagnosis and trauma (sensitivity = 70.7%, specificity = 56.8%).The time interval between the AS diagnosis and the trauma, mean Pavlov ratio, Angle D, and Borden's index showed predictive ability for the occurrence of CSF in AS patients who encounter LET. Surgeons should consider measuring these parameters in the management of AS patient.

Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss–related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss–related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs

BACKGROUND There is strong evidence of a genetic contribution to Wilms tumor, such as WT1 gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. Case report: A 4-year-old girl developed a Wilms tumor of the left isthmus of a horseshoe kidney. Chromosomal microarray analysis (CMA) of peripheral blood showed a 563 kb copy number gain at Xp22.11 that included PRDX4 and ZFX. PRDX4 has been shown to play an active role in the tumorigenesis of malignant neoplasms in various organs. Beckwith-Wiedemann methylation analysis and WT1 sequencing were negative. Whole exome sequencing of peripheral blood revealed pathogenic variant in PMS2 gene (c.765C > A), which is consistent with Lynch syndrome. Conclusion: We report a case of Wilms tumor with germline Xp22.11 duplication which further supports this locus as germline susceptibility alteration for Wilms Tumor.

Background : We conducted a survey to investigate the prevalence and factors associated with anxiety and depressive symptoms among patients hospitalized with hematological malignancies after chimeric antigen receptor T-cell (CAR-T) therapy. Methods : In total, 130 eligible patients completed the Self-Rating Anxiety Scale and Self-Rating Depression Scale at week 4 after CAR-T cell infusion. We collected sociodemographic information during the same period. We studied factors associated with anxiety and depressive symptoms using logistic regression analysis. Results : The prevalence of anxiety and depressive symptoms at week 4 after infusion were 13.8% and 40.0%, respectively. A cutoff value of 50 or above indicates significantly anxiety and depressive symptoms. Binary logistic regression analysis showed that high school education and above (OR = 0.22, 95% CI = 0.06–0.78) and middle age (OR = 0.16, 95% CI = 0.03–0.90) were associated with lower risk of anxiety symptoms, and increased odds of depressive symptoms was associated with old age (OR = 11.39, 95% CI = 2.50–51.88), non-manual occupations before illness (OR = 3.72, 95% CI = 1.20–11.58), and higher healthcare expenditure (OR = 3.93, 95% CI = 1.50–10.33), while lower risk of depressive symptoms was associated with rural household location (OR = 0.25, 95% CI = 0.08–0.76) and being cared for by spouse (OR = 0.12, 95% CI = 0.02–0.63). Conclusions : Patients receiving CAR-T therapy with lower education background, old ages, urban household location, or who used to work as non-manual workers require more attention and psychological care. Support from a spouse and medical expense deductions from the government may help patients develop positive attitudes.

Background The application of neoadjuvant docetaxel and androgen deprivation therapy before radical prostatectomy has been clinically recognized as beneficial for the overall and progression-free survival of patients with advanced prostate cancer. However, the mechanism underlying its clinical efficacy has not yet been reported. Methods We conducted a randomized comparative study on about 100 patients with high-risk localized prostate cancer. Through nontarget metabolomics and tissue microarray immunohistochemistry, we investigated the difference in the endogenous metabolism of tumors in patients with prostate cancer who received or did not receive the neoadjuvant therapy. Results Many endogenous metabolic pathways, especially nucleotide synthesis, glutathione metabolism, citric acid cycle, and lipid synthesis, in prostate cancer tissue were altered after the neoadjuvant treatment, and the levels of nearly 90% of the differentially regulated metabolites were significantly decreased. Moreover, the levels of key enzymes in the cellular energy pathways were downregulated in tumor tissues and upregulated in adjacent tissues after the treatment. The positive and negative effects of the neoadjuvant therapy on normal and tumor cells in the prostate, respectively, resulted in the activation of the former and inhibition of the latter, which helped in reducing the number of tumors and weakened their aggressiveness. Conclusions From the perspective of endogenous metabolism in tumors, we have confirmed that neoadjuvant therapy can significantly downregulate important pathways for biosynthesis and energy metabolism in prostate cancer tissue, and thereby, inhibit tumor growth and metastasis.

ObjectiveTo inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients.MethodsWe systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence.ResultsOf 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations.ConclusionOf available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies.Trial registration numberCRD42020168351.

Background The best treatment for acute Achilles tendon ruptures remains controversial. No cohort studies have compared different immobilisation durations after open surgery. This retrospective cohort study aimed to determine the optimal duration of immobilisation after this surgery. Methods A total of 266 patients with acute Achilles tendon rupture were divided into 4 groups (A, B, C, and D) according to immobilisation duration of 0, 2, 4, and 6 weeks, respectively. All patients underwent the same suture technique with a similar rehabilitation protocol and were examined clinically at 2, 4, 6, 8, 10, 12, 14, 16, 24, and 48 weeks, with a final follow-up at a mean of 22.3 months postoperatively. The primary outcome was the time of return to light sports activity (LSA). Secondary outcomes included range of motion (ROM) and single-legged heel rise height (SHRH). Data on operation time, complications, visual analogue pain scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, and Achilles tendon Total Rupture score (ATRS) were also collected. Demographic baseline data were analysed using one-way analysis of variance; outcome parameters were analysed using Kruskal-Wallis H test, and complications were analysed using Fisher’s exact test. Statistical significance was considered at P ≤ 0.05. Results VAS scores decreased significantly, reaching 0 in all groups after 12 weeks. The AOFAS and ATRS scores were significantly different between the groups from weeks 2 to 12 (P<0.001) and weeks 2 to 16 (P<0.001), respectively. All the mean scores showed better results in group B than in the other groups. In terms of recovery time of ROM, SHRH, and LSA, groups A and B were significantly faster than groups C and D (P<0.001). There were 13 (13/266, 4.9%) complications: 5 superficial infections, 3 deep venous thrombosis, and 5 trauma-related re-ruptures. On the last follow-up, all complications had recovered. There were no significant differences in complications between the groups. Conclusions Immobilisation for 2 weeks after this open surgery is the best choice for early rehabilitation and weight-bearing while minimising pain and other complications.

Purpose To investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML). Methods We searched published reports at the Medline, Embase, and Cochrane Databases as well as other databases from inception through July 2019. There was no restriction on date of publication or language (PROSPERO registration CRD42018095843). Results We enrolled 12 randomized controlled trials that included data of 4583 AML patients whose disease was untreated or relapsed/refractory, and compared the CR, death during induction therapy, DFS, and OS between mitoxantrone and daunorubicin. Mitoxantrone significantly increased the CR rate (relative risk = 1.07; 95% confidence interval [CI], 1.01, 1.14; P = .03) and DFS (hazard ratio = 0.87; 95% CI, 0.79, 0.96; P = .005) compared to daunorubicin. However, there was no significant difference in death during induction therapy (relative risk = 1.00; 95% CI, 0.81, 1.24; P = .99) and OS (hazard ratio = 0.94; 95% CI, 0.87, 1.01; P = .077) between the two drugs. Conclusion Although more studies are needed to compare mitoxantrone with higher-dose daunorubicin, the results showed that compared to daunorubicin, mitoxantrone can significantly improve CR and DFS in patients of all ages. These findings suggest that mitoxantrone may be a better choice than daunorubicin as an induction chemotherapy agent for AML patients, especially in developing countries.

Objective: Prepump arterial (Pa) pressure indicates the ease or difficulty with which the blood pump can draw blood from the vascular access (VA) during hemodialysis. Some studies have suggested that the absolute value of the Pa pressure to the extracorporeal blood pump flow (Qb) ratio set on the machine (|Pa/Qb|) can reflect the dysfunction of VA. This study was conducted to explore the impact of arteriovenous fistula (AVF) dysfunction and to explore the clinical reference value of |Pa/Qb|. Methods: We retrospectively identified adults who underwent hemodialysis at 3 hospitals. Data were acquired from electronic health records. We evaluated the pattern of the association between |Pa/Qb| and AVF dysfunction during 1 year using a Cox proportional hazards regression model with restricted cubic splines. Then, the patients were grouped based on the results, and hazard ratios were compared for different intervals of |Pa/Qb|. Results: A total of 490 patients were analyzed, with an average age of 55 (44, 66) years. There were a total of 85 cases of AVF dysfunction, of which 50 cases were stenosis and 35 cases were thrombosis. There was a U-shaped association between |Pa/Qb| and the risk of AVF dysfunction (p for nonlinearity 0.52 increased the risk of AVF dysfunction. Compared with the group with a |Pa/Qb| value between 0.30 and 0.52, the groups with |Pa/Qb| 0.52 had a 4.04-fold (p = 0.002) and 3.41-fold (p < 0.001) greater risk of AVF dysfunction, respectively. Conclusions: The appropriate range of |Pa/Qb| is between 0.30 and 0.52. When |Pa/Qb| is 0.52, the patient’s AVF function or Qb setting should be reevaluated to prevent subsequent failure.

BACKGROUND Ferroptosis involves in the development and therapeutic response of various types of tumors. This study aims to explore ferroptosis-related prognostic genes that could further accurately stratify AML patients. METHODS We investigated the prognosis significance of ferroptosis-related genes in AML by Univariate and multivariate Cox proportional hazards regression analyses. With the methylation data of TCGA samples, we looked for methylation sites associated with prognostic genes and compared the correlation between methylation and mRNA expression. R software and 'edgeR' packages were used to identify the DEGs between the high-and-low-risk groups divided by the FRPGs prognosis model and then run GO enrichment, KEGG pathway, and PPI network. RESULTS We found a prognostic risk model that included AKR1C2 and SOCS1 predicted outcomes in AML patients. Methylation analysis showed that AKR1C2 and SOCS1 are negatively regulated by their methylation, leading to their low expression in AML patients. Besides, both decreased SOCS1 expression and hypermethylation predicted favorable OS and PFS in AML patients. Finally, this prognostic risk model exhibited a close correlation with several clinical features, especially with age (P=0.005), cytogenetic type (P=0.031), risk_cytogenetic (P=0.001), and risk_molecular (P