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The beneficial role of social support on posttraumatic growth (PTG) has been assumed by theoretical models and established in some studies. However, there are inconsistent findings and little knowledge on moderators. The present study aims to investigate the overall effect size of the relationship and identify factors affecting the association.Six electronic databases were searched. Newcastle-Ottawa Quality Assessment Scale (NOS) were used to evaluate the quality of studies. Study quality, study design, trauma type, PTG measure, social support measure, continent, publishing language, sample size, gender, religion, and age were analyzed as moderators. Meta-regression was conducted with the significant differential predictors in moderator analysis.The meta-analysis included 217 samples and a total of 47,940 participants from both longitudinal and cross-sectional studies. There was a medium positive effect size between social support and PTG in random effect model, r = 0.418, p .001. The meta-regression analysis indicated that the association between social support and PTG was stronger among caregivers (vs. other traumatized samples), Chinese, older individuals and studies with smaller sample size.Only survey results were included in the analysis. The retrospective self-report may limit a more objective assessment of the relations. In addition, 87 % of the studies were cross-sectional, which may influence the estimation of a valid effect size.Regarding the medium positive association between social support and PTG, it is important to enhance social support for trauma survivors. It will be especially effective for caregivers, Chinese, and older people.

The increasing morbidity of oral diseases, such as dental caries, periodontitis and oral cancer, has greatly compromised the life quality of humans. With the rapid development of biomaterials and nanotechnology, various biomaterials-based systems have been reported to treat oral diseases. As the biocompatible, biodegradable and bioadhesive polysaccharide biomaterials, chitosan and its derivatives have also been widely used for the oral disease therapy, either as the antibacterial agents, drug delivery carriers or tissue engineering scaffolds. It has been well demonstrated that chitosan can significantly enhance the therapy efficacy for various oral diseases, due to its intrinsic antibacterial activity and controlled drug release feature. Herein, we aim to provide a comprehensive understanding of the biological functions of chitosan, such as antimicrobial, anticancer and remineralization activity, and summarize the applications of chitosan-based therapeutic systems in treating the typical oral diseases, including dental caries, endodontic diseases, periodontal diseases, oral cancer, oral and maxillofacial surgery, and oral mucosal diseases. In addition, the concerns and possible solutions of the clinical use of chitosan are also discussed.

P53 protein tumor suppressor gene plays a guiding role in the treatment and prognosis of colorectal cancer (CRC). This paper aimed at proposing a feature selection method based on variable clustering to improve positive and negative discrimination of P53 protein in CRC patients. In this approach, we cluster the preprocessed dataset with variables, and then find the features with the largest information value (IV) for each cluster to form a feature subset. We call this method as IV_Cluster. In the actual medical data test, compared with the information value feature selection method, the accuracy of the 10-fold cross-validation logistic regression model increased by 4.4%, 2.0%, and 5.8%, and Kappa values increased by 21.8%, 8.6%, and 22.4%, respectively, under 5, 10, and 15 feature sets.

We aimed to determine prognostic factors and develop an effective and practical nomogram for predicting cancer-specific survival in gastrointestinal stromal tumor (GIST) patients. Postoperative data were obtained from the SEER database (2000-2018). Patients were divided into training and validation cohorts at random (7 : 3). Prognostic factors were screened, and a prognostic nomogram was established using log-rank testing and Cox regression. We used DCA, ROC curves, C-index, and calibration curves to evaluate our model’s predictive performance. The clinical value of the nomogram and the modified National Institute of Health (M-NIH) classification were compared using the NRI and IDI. The Kaplan-Meier method was applied to examine survival by risk group, and log-rank tests were applied to compare variations in survival curves. Independent prognostic risk factors associated with cancer-specific survival on multivariate Cox proportional hazards regression analysis were age, race, and tumor location, size, grade, and stage. Clinically relevant variables need to be considered in addition to statistically significant variables when developing prognostic models to aid clinical decision-making. We included two additional variables (mitotic rate and chemotherapy) when constructing the prognostic model. The C-index was 0.766 (95% confidence interval (CI): 0.737-0.794) in the training cohort and 0.795 (95% CI: 0.754-0.836) in the internal validation group suggesting robustness. The areas under the ROC curve for three-year and five-year survival were >0.700, indicating satisfactory discrimination. The calibration curves showed good agreement between the predictions of the nomogram and the actual results. The NRI (0.346 for 3-year and 0.265 for 5-year cancer-specific survival for patients with GIST (GSS) prediction; validation cohort: 0.356 for 3-year and 0.246 for 5-year GSS prediction) and IDI values (0.047 for 3-year and 0.060 for 5-year GSS prediction; validation cohort: 0.071 for 3-year and 0.084 for 5-year GSS prediction) suggested that the established nomogram performed significantly better than the M-NIH classification. The DCA indicated that the nomogram was clinically useful and had a high discriminative ability in identifying patients who were at high risk of poor outcomes. According to nomogram findings, patients were divided into three groups (high, moderate, and low risk), with significantly different prognoses in both cohorts. Our nomogram satisfactorily predicted survival in postsurgical GIST patients, which may assist clinicians to evaluate the postoperative status and guide subsequent treatments.

N6-methyladenosine (m6A) is the most abundant epigenetic modification. Although the dysregulation of m6A regulators has been associated with cancer progression in several studies, its relationship with cancer prognosis and clinicopathology is still controversial. Therefore, we evaluated the prognostic and clinicopathological value of m6A regulators in cancers by performing a comprehensive meta-analysis.The PubMed, Cochrane Library, Web of Science, and Embase databases were searched up to April 2022. Hazard ratios were used to analyze the association between m6A with prognosis. We also analyze the relationship between m6A and clinicopathology using odds ratios.METTL3 overexpression predicted poor overall survival and disease-free survival in cancer patients (High expression of METTL3 predicted poor outcome. In contrast, high expression of METTL14 was associated with better outcome. Thus, we suggest that among all the m6A regulators, METTL3 and METTL14 could be potential prognostic markers in cancers.

Endoscopic submucosal dissection (ESD) is an established technique for the treatment of early gastrointestinal neoplasia. Generally, multi-day (M-D) admission is required for patients undergoing ESD due to potential complications.To evaluate the feasibility of a same-day (S-D) discharge strategy for ESD of the esophagus or stomach.The data of patients who underwent esophageal or gastric ESD were retrospectively collected from January 2018 to December 2021 at Peking University Cancer Hospital. The propensity score matching (PSM) method was applied to balance the unevenly distributed patient baseline characteristics between the S-D and M-D groups. Intraoperative and postoperative parameters were compared between the matched groups.Among the 479 patients reviewed, 470 patients, including 91 in the S-D group and 379 in the M-D group, fulfilled the inclusion and exclusion criteria. Following PSM, 78 patients in each group were paired using the 1:1 nearest available score match algorithm. No significant difference was found between groups with respect to intraoperative and postprocedural major adverse events (AEs). Tumor size, complete resection rate, and procedural duration were comparable between the groups. The S-D group demonstrated a significantly shorter length of hospital stay (The S-D discharge strategy may be feasible and effective for esophagogastric ESD, and the procedural-related AEs can be managed successfully.

The fibular myocutaneous flap is a classic flap used to reconstruct oral and maxillofacial defects. This study aimed to evaluate the effectiveness of high-frequency color Doppler ultrasound in detecting the blood vessels in the fibular myocutaneous flap, analyze the influence of variations in the peroneal vessels and perforating peroneal arteries on the surgical design, and explore the value of this technology in preoperatively assessing the blood vessels of the fibular myocutaneous flap.Twenty-five patients with mandibular disease or defect underwent preoperative evaluation of the blood vessels of the calf by high-frequency color Doppler ultrasound. The inner diameter and peak systolic velocity (PSV) of the peroneal arteries and veins and the perforating peroneal arteries were compared between different groups. The consistency between the perforating peroneal arteries marked by ultrasonography and the intraoperative findings was analyzed.The initial segment of the peroneal artery had a larger inner diameter (p0.001) and lower PSV (p0.05) than the middle segment. The perforating peroneal arteries were mainly distributed in the middle of the fibula. The inner diameter of the perforating peroneal artery was larger in men than in women (p0.05). In comparison with surgical exploration as the gold standard, high-frequency color Doppler ultrasound results showed good consistency (Kappa=0.684, 95% CI: 0.512-0.856, p0.001), with a sensitivity of 89.36%, specificity of 78.57%, and accuracy of 85.33%.High-frequency color Doppler ultrasound can detect, quantitatively evaluate, and accurately mark the peroneal artery and vein and perforating peroneal artery before fibular myocutaneous flap transplantation.

The results of best medical treatment (BMT), endovascular based treatment (EBT), and total arch replacement (TAR) with frozen elephant trunk (FET) treatment in a single centre experience were reported in non-A non-B aortic dissection patients.From January 2016 to May 2020, 215 consecutive patients with acute or subacute non-A non-B aortic dissection were enrolled. The primary endpoints were all cause death. Secondary endpoints included follow up adverse aortic event (AE), a composite of the outcomes of dissection related death, rupture, retrograde type A aortic dissection, stent graft induced new entry tear, secondary endoleak, and follow up re-intervention. Kaplan-Meier curves were used to evaluate associations between different treatments and outcomes.Among the 215 dissection patients, 127 (59.1%) received EBT, 42 (19.5%) received TAR + FET, and the remaining 46 (21.4%) received BMT. Thirty day mortality was higher in patients receiving TAR + FET (7.1%) than in those treated with EBT (1.6%) or BMT (2.2%) (p = .12). However, after a median follow up of 39.1 (27.0 - 50.7) months, no additional death was recorded in the TAR + FET group, while nine (7.3%) patients died in the EBT group and 14 (31.8%) died in the BMT group (p.001). Specifically, EBT and TAR + FET showed no significant difference in midterm mortality rate, follow up AE, and re-intervention for complicated or uncomplicated dissection patients involving zone 2. For patients with uncomplicated non-A non-B aortic dissection involving zone 2, EBT could profoundly decrease the mortality rate, follow up AE and re-intervention when compared with BMT (p.010 for all), although this difference was not statistically significant between TAR + FET and BMT. No statistical comparison was performed in patients with zone 1 involvement because of the limited number of patients.It was demonstrated that EBT or TAR + FET might be a viable strategy for non-A non-B aortic dissection patients.

The treatment of chronic osteomyelitis (COM) is extremely challenging for physicians and patients. It is of great significance to explore the research status, development trend and future research hotspots in the field of COM to promote the development of this field. This study is aimed to explore the global research status of COM and predict its future research hotspots based on bibliometric and visualized analysis.Web of Science core collection database was used to search the related literature of COM from 1994 to 2020. All data were imported into Microsoft Excel 2019 for collation. Additionally, the literature quality of countries, authors, journals, and institutions is evaluated. The VOS viewer software was used for conducting co-analysis, co-citation analysis, and keyword co-occurrence analysis of literature to analyze the global status and predict the future hotspots of the COM field.A total of 726 articles were retrieved in this study. The number of global publications shows a trend of wave growth, but the increase is not significant. It is expected that the number of COM articles will remain at more than 50 per year in the next decade. The COM literature published in the United States (Publications = 160, H index = 37, average citations per item = 28.63) is of the highest quality. Girschick HJ (Publications = 16, H index = 14, average citations per item = 52.25) is the most contributed scholar in the field of COM. UNIV IOWA (Publications = 15, H index = 11, average citations per item = 57.27) and UNIV WURZBURG (Publications = 18, H index = 15, average citations per item = 47.5) are influential institutions in the field of COM. The results of co-occurrence analysis show that the field of COM can be roughly divided into the following five modules: COM surgical research, COM basic research, COM diagnosis-related research, chronic recurrent multifocal osteomyelitis (CRMO)-related research, risk factors of COM. Risk factors of COM are the module with the highest concentration of hot words.COM-related research will continue to develop further in the next decade. The diagnosis research and risk factors of COM are the most popular research modules in recent years. Some controversial or troubled issues including the efficacy of perforator flap and fascia flap covering soft tissue, searching exclusive detection methods for the diagnosis of COM and bisphosphonates and biological agents in the treatment of CRMO may lead to the development of the COM field.

We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC).Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared.The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] μg vs. 5.6 [±10.6] μg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%).TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial.

The aim of this systematic review and network meta-analysis was to comprehensively evaluate and compare the effectiveness of diverse therapies for disc displacement (DD) of the temporomandibular joint (TMJ). An electronic search of PubMed, Embase, the Cochrane Library, the China Academic Journals full-text database (CNKI), and Wanfang databases was performed to identify relevant studies available up to 31 July 2021. Study selection, data extraction, and quality assessment were performed for all included studies, while the outcomes of interest contained post-therapeutic maximum mouth opening and pain intensity. Interventions consisted of arthrocentesis, injections with diverse drugs, occlusal splints, or a combination of two to three of the above. Controls were regarded as oral analgesics, self-exercise, massage, or health instruction. Twenty-six studies appeared to meet the inclusion criteria and were subjected to further examination. Our data of the entire network showed that the most invasive therapies performed better than non-invasive therapies, while arthrocentesis + platelet-rich plasma injection and platelet-rich plasma injection in Grade I performed well in both mouth opening improvement and pain alleviation. Platelet-rich plasma injection is probably the best treatment overall for patients with DD owing to its anti-inflammatory, analgesic, and lubricating effects.

Human industrial activities have caused environmental uranium (U) pollution, resulting in uranium(VI) had radiotoxicity and chemical toxicity. Here, a cellulase-producing Penicillium fungus was screened and characterized by X-ray fluorescence (XRF), and Fourier transform infrared reflection (FT-IR), as well as by GC/MS metabolomics analysis, to study the response to uranium(VI) stress. The biomass of Penicillium decreased after exposure to 100 mg/L U. Uranium combined with carboxyl groups, amino groups, and phosphate groups to form uranium mineralized deposits on the surface of this fungal strain. The α-activity concentration of uranium in the strain was 2.57×10

Objective. To comprehensively explore the survival characteristics of primary esophageal small-cell carcinoma (PSCCE) and identify the main factors affecting the prognosis. Methods. The clinical and follow-up data of PSCCE patients admitted to the Fourth Hospital of Hebei Medical University from 2006 to 2010 were retrospectively analyzed. The primary endpoint was five-year survival. Survival curves were drawn using the Kaplan-Meier method, and log-rank test was used to compare the differences in survival rates among the groups. Cox regression models were used to analyze prognostic factors. Results. A total of 119 eligible patients were retrieved. Median survival was 27 months (3-100 months). Changes in overall survival (OS) in PSCCE patients were associated with TNM stage ( P = 0.007 ), T stage ( P = 0.049 ), and lymph node metastasis ( P = 0.004 ). When TNM was in stage I-IIb, lymph node metastasis ( P = 0.003 ) or combined adjuvant therapy ( P = 0.004 ) was an independent factor affecting OS. Survival analysis showed that TNM staging had no predictive value for 5-year survival time or disease-free survival (DFS) of PSCCE ( P > 0.05 ). Conclusion. TNM stage, T stage, and lymph node metastasis were related to the survival of patients. Negative lymph node metastasis and treatment are independent prognostic factors in PSCCE TNM stage I-IIb patients.

Pelvic incidence (PI) is a key morphological parameter that reflects the relation between the sacrum and iliac wings. It is well accepted that PI remains constant after reaching maturity. However, recent studies indicated that PI might be altered after lumbosacral fusion. Additionally, it remains uncertain on the long-term influence of long fusion to pelvis with S2-alar-iliac screw on PI in patients with adult spinal deformity (ASD).A retrospective study.To investigate whether and how PI would change during the follow-up in ASD patients who underwent S2AI fixation and to identify factors associated with the change in PI.We retrospectively reviewed all ASD patients who underwent spinal surgery using S2AI screws between November 2014 and January 2017 at our institution. Patients with minimum follow-up of two years were included. The following sagittal radiographic parameters were measured: PI, Lumbar lordosis (LL), pelvic tilt (PT), PI-LL, sagittal vertical axis (SVA) at pre-op, post-op and 2-year follow-up. According to the changes in PI at immediate post-operation, patients were classified into two groups; Group A: Changes of PI less than or equal 5° and Group B: Changes of PI greater than 5°.A total of 82 ASD patients (Group A: 32, Group B: 50; mean age of 53.5 ± 12.6 years) with a mean follow-up period of 30.2 ± 9.2 months were included in this study. At immediate post-operation, Group A showed no significant change in PI (45.7° ± 11.4° to 45.3° ± 11.2°, p = 0.749); while Group B had a significant decrease in PI (51.6° ± 14.5° to 40.9° ± 14.0°, p 0.001). At the last follow-up, 48% patients (24/50) in Group B had a significant increase in PI (32.8° ± 6.4° to 45.8° ± 11.2°, p 0.001). Intergroup analysis showed that ΔPI, post-op PI, post-op PT and age were significantly different between both groups. In addition, pre-op PI, post-op PI, post-op PT, post-op PI-LL were significantly correlated with ΔPI at last follow-up. Also, logistic regression analysis showed that post-op PI was the associated risk factor (OR = 0.865, p = 0.024) for PI-LL mismatch.Our study showed that PI decreased in more than half of ASD patients immediately after spinal surgery using S2AI screws. Approximately 48% of them were able to recover during the 2-year follow-up. Lower pre-op PI, post-op PI and PT were found to be strongly associated with the return of PI. Thus, these current findings indicated that patients with a high PI at pre-operation should not be over-corrected to avoid PI-LL mismatch postoperatively.

Background: There are relatively few data on the genetic spectrum of Chinese frontotemporal dementia (FTD) population. Objective: With the dementia cohort of Peking Union Medical College Hospital, we aim to illustrate the genetic spectrum of FTD patients, as well as the phenotypic heterogeneity of FTD-gene variant carriers. Methods: 204 unrelated, clinically diagnosed FTD patients of Chinese ancestry were enrolled. All the participants received demographic survey, history inquiry, physical examination, cognitive assessment, blood biochemical test, brain CT/MRI, and gene sequencing. Results: 56.4% (115/204) participants were clinically diagnosed with behavioral variant of FTD, 20.6% (42/204) with nonfluent/agrammatic variant primary progressive aphasia (PPA), 20.1% (41/204) with semantic variant PPA, and 2.9% (6/204) with mixed variant PPA. 11.8% (24/204) subjects harbored the potential causative variants in FTD-related genes, including the MAPT (n = 7), TBK1 (n = 7), GRN (n = 2), TBK1+GRN (n = 1), VCP (n = 1), TARDBP (n = 1), UBQLN2 (n = 1), SQSTM1 (n = 1), DCTN1 (n = 1), HNRNPA1 (n = 1), and C9orf72 GGGGCC repeats (n = 1). The TBK1 T31fs, T457fs, K622fs, c.359-1G>A, the VCP P188T, and the GRN P50fs, P439fs were novel pathogenic/likely pathogenic variants. The TBK1 carriers showed a later disease onset and a higher incidence of parietal atrophy relative to the MAPTcarriers. Conclusion: There is genetic and clinical heterogeneity among Chinese FTD population. The TBK1 has a high mutation frequency in Chinese FTD patients.

Arsenene, a two-dimensional (2D) monoelemental layered nanosheet composed of arsenic, was recently reported to feature outstanding anticancer activities. However, the specific biological mechanism of action remains unknown. In this work, we extensively analyzed the mechanism of arsenene

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. This study aimed to determine whether chronic alcohol inhibits type-H vessel-dependent bone formation. Two-month-old mice were fed with 5% (v/v) alcohol liquid diet (28% of calories) or normal liquid diet every day for 2 months. The tibias were isolated and detected with X-ray and microcomputed tomography. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining, respectively. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of alcohol, including 0 mM (0%), 8.7 mM (0.5%), 52 mM (3%), or 87 mM (5%) alcohol for 12 h. The conditioned medium of the above HUVEC cells was collected to culture human bone marrow-mesenchymal stem cells (BM-MSCs), which were induced to differentiate into osteoblasts in vitro. The alcoholic diet retarded the bone growth and led to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31

Establishing tolerance remains a central, if elusive, goal of transplantation. In solid-organ transplantation, one strategy for inducing tolerance has been cotransplantation of various forms of thymic tissue along with another organ. As one of the biological foundations of central tolerance, thymic tissue carries with it the ability to induce tolerance to any other organ or tissue from the same donor (or another donor tissue-matched to the thymic tissue) if successfully transplanted. In this review, we outline the history of this approach as well as work to date on its application in organ transplantation, concluding with future directions. We also review our experience with allogeneic processed thymus tissue for the treatment of congenital athymia, encompassing complete DiGeorge syndrome and other rare genetic disorders, and consider whether allogeneic processed thymic tissue implantation may offer a novel method for future experimentation with tolerance induction in organ transplantation.

The effects of transcranial direct current stimulation (tDCS) on post-stroke executive impairment (PSEI) remain controversial. Resting stateelectroencephalogram (EEG) can assist in the diagnosis and assessment of executive dysfunction.We aimed to use EEG to explore the effect of tDCS on executive function among stroke patients.Twenty-four patients with PSEI were randomly divided into experimental and control groups, which received real and sham stimulation, respectively. Anodal electrical stimulation was applied to the left dorsolateral prefrontal lobe (F3). The stimulation intensity was 2 mA for 20 min once daily for 7 days. Executive function was monitored using neuropsychological scales.The experimental group outperformed the control group in clinical scale results, with significant differences in the following scores: symbol digital modalities test, TMT-A, TMT-B, and digital span test. In the left central zone, theta band power was significantly higher after anodal electrical stimulation than before. Analysis of the correlation between EEG power and psychometric scores revealed that the power change was positively correlated with the scores on the symbol digital modality test (r = 0.435, p 0.05).Anodal tDCS can enhance executive function in patients with PSEI, and tDCS-related improvements are related to the enhancement of theta power in the affected region.

Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS).An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated.The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16).Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Impairment of pulmonary function was evaluated in chronic bronchitis patients with preserved ratio impaired spirometry (PRISm). We retrospectively collected clinical data from 157 chronic bronchitis (CB) and 186 chronic obstructive pulmonary disease (COPD) patients between October 2014 and September 2017. These patients were assigned to three groups: control (normal pulmonary function), PRISm (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ≥ 0.7, FEV1 p < 0.001 , maximal expiratory flow (MEF) 25% p < 0.001 , MEF50% p < 0.001 , maximal midexpiratory flow (MMEF) 25–75% p < 0.001 , residual volume (RV)/total lung capacity (TLC; p < 0.001 ), FVC% p < 0.001 , total respiratory resistance and proximal respiratory resistance (R5-R20; p < 0.001 ), respiratory system reactance at 5 Hz (X5; p < 0.001 ), resonant frequency (Fres; p < 0.001 ), and area of reactance (Ax; p < 0.001 ). However, the predicted FEV1% and RV/TLC were similar between the PRISm and COPD groups ( p = 0.992 and 0.122, respectively). PRISm is a nonspecific pattern of pulmonary function that indicates small airway dysfunction and may increase the risk of transformation to obstructive ventilation dysfunction. This trial is registered with ChiCTR-OCH-14004904.

Excessive fluoride ions (F

Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor outcomes in patients with PDAC. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NF-κB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NF-κB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an antitumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NF-κB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC. Significance: Inhibition of Plk1 induces upregulation of PD-L1 expression in pancreatic ductal adenocarcinoma, stimulating antitumor immunity and sensitizing tumors to immunotherapy.

Background and Hypothesis Multisite massive schizophrenia neuroimaging data sharing is becoming critical in understanding the pathophysiological mechanism and making an objective diagnosis of schizophrenia; it remains challenging to obtain a generalizable and interpretable, shareable, and evolvable neuroimaging biomarker for schizophrenia diagnosis. Study Design A Morphometric Integrated Classification Index (MICI) was proposed as a potential biomarker for schizophrenia diagnosis based on structural magnetic resonance imaging data of 1270 subjects from 10 sites (588 schizophrenia patients and 682 normal controls). An optimal XGBoost classifier plus sample-weighted SHapley Additive explanation algorithms were used to construct the MICI measure. Study Results The MICI measure achieved comparable performance with the sample-weighted ensembling model and merged model based on raw data (Delong test, P > 0.82) while outperformed the single-site models (Delong test, P Conclusions In summary, the proposed MICI biomarker may provide a simple and explainable way to support clinicians for objectively diagnosing schizophrenia. Finally, we developed an online model share platform to promote biomarker generalization and provide free individual prediction services (http://micc.tmu.edu.cn/mici/index.html).

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

Background: Lacunar stroke accounts for a quarter of all strokes, but little is known about the underlying pathological mechanisms. Analysis of serum metabolites may allow better understanding of the underlying biological processes. Mendelian randomization (MR) can provide information on the causality of associations. Aims: To identify causal relationships between serum metabolites and lacunar stroke. Methods: We applied a two-sample MR analysis to evaluate relationships between 486 serum metabolites and lacunar stroke. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of the exposure on the outcome, while sensitivity analyses were performed using MR-Egger, weighted median, and MR-PRESSO to eliminate the pleiotropy. We also performed a metabolic pathway analysis to identify potential metabolic pathways. Results: We identified 15 known (8 risk and 7 protective) and 14 unknown serum metabolites associated with lacunar stroke. Among the known risk metabolites, two were lipids (1-linoleoylglycerophosphoethanolamine and dihomo-linolenate (20:3n3 or n6)), five amino acids (kynurenine, isobutyrylcarnitine, aspartate, trans-4-hydroxyproline, and 3-methyl-2-oxovalerate), and one peptide (ADSGEGDFXAEGGGVR). The known protective metabolites included four lipids (4-androsten-3beta,17beta-diol disulfate 1, 1-palmitoleoylglycerophosphocholine, adrenate (22:4n6), and glycodeoxycholate), one amino acid (methionine), and two exogenous metabolites (homostachydrine and 2-methoxyacetaminophen sulfate). Metabolic pathway analysis identified several pathways that might be involved in the disease. Conclusion: We identified eight risk and seven protective human serum metabolites associated with lacunar stroke. Isobutyrylcarnitine was positively associated with an increased risk of lacunar stroke. In addition, 3-methyl-2-oxovalerate and aspartate may be involved in the disease pathogenesis through metabolic pathways.

OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline from the Women’s Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. RESULTS In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (hazard ratio in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24–1.37]) and plant protein with decreased risk (0.82 [0.78–0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (0.79 [0.74–0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG. CONCLUSIONS Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.

Fluid shear stress (FSS) regulates the metastasis of hepatocellular carcinoma (HCC), but the role of the RhoA-YAP1-autophagy pathway in HCC remains unclear. Due to the core role of liver cancer stem cells (LCSCs) in HCC metastasis and recurrence, we explored the RhoA-YAP1-autophagy pathway in LCSCs under FSS. Our results indicate that LCSCs have stronger proliferation and cell spheroidization abilities. FSS (1 dyn/cm

Although most studies believe that systematic biopsy (SB) and targeted biopsy (TB) should be performed simultaneously in patients with suspected prostate cancer, we believe that patients with the Prostate Imaging-Reporting and Data System (PI-RADS) score of 4/5 may be able to perform TB only.We retrospectively analyzed the pathological results of patients undergoing transperineal prostate biopsy with PI-RADS 4 and 5 in our center. We use the data from 2019 to 2020 as the training set to establish the prediction model and the data from 2021 as the verification set to test the effectiveness. Through stepwise logistics regression analysis, we integrate statistically significant clinical factors and establish a model to further predict whether the target area is tumor.The results showed that age (O), total number of lesions (T), histological region (R), PI-RADS score (S), and PSA density (P) were significantly correlated with the results of TB, and the formula was: p = 1/[1 + e^(- 11.387 + 0.058 × O + (- 0.736 × T) + 0.587 × R + 1.574 × S + 7.338 × P)]. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the prediction model was 0.840 (95% CI 0.802-0.877), with the optimal threshold of 0.762. And the corresponding specificity and sensitivity were 0.765 and 0.752. In the validation set, the AUC of the prediction model was 0.816 (95% CI 0.759-0.874), which means that it has good prediction efficiency.The P.R.O.S.T score can effectively screen PI-RADS 4/5 lesions, which may help physicians shunt patients who need prostate biopsy to reduce unnecessary systematic biopsies.

Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.

This study aimed to investigate the prognostic value of C-reactive protein to albumin ratio (CAR) in hepatocellular carcinoma (HCC) patients after transcatheter chemoembolization (TACE).Totally, 958 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B were incorporated into the secondary analysis. X-Tile software was applied to determine the optimal cutoff point for CAR, and the total patients were divided into two groups. Cox proportional hazard regression models and Kaplan-Meier analyses were used to estimate the relationship between CAR and overall survival (OS). Stratified analyses were performed to evaluate the prognostic role of CAR in subgroups of major confounding factors, such as alpha-fetoprotein (AFP), diameter of the main tumor, Glasgow prognostic score (GPS) and modified GPS (mGPS).The optimal cutoff level for the CAR was 0.06. There was a direct correlation between an elevated CAR (≥ 0.06) and shorter OS after adjustment (HR:1.580; 95%CI:1.193-2.092). Kaplan-Meier analysis and log-rank test showed a significant difference in OS curves between the two groups (P 0.001). CAR showed the distinct value of prognostic stratification in most subgroups, especially in the subgroup of GPS-0 (HR:1.966; 95%CI:1.453-2.660), mGPS-0 (HR:1.984; 95%CI:1.509-2.608) and AFP ≤ 400 ng/ml (HR:1.925; 95%CI:1.393-2.659).The CAR was one of the prognostic factors for HCC patients undergoing TACE treatment. CAR could also provide further prognostic stratification for HCC patients who appear to have a good prognosis, such as patients with AFP-negative, GPS-0 or mGPS-0 to identify patients at a higher risk of death for closer follow-up or more aggressive treatment.Level 3, Cohort Study.

Background: Quantitative measures of atrophy on structural MRI are sensitive to the neurodegeneration that occurs in AD, and the topographical pattern of atrophy could serve as a sensitive and specific biomarker. Ojective: We aimed to examine the distribution of cortical atrophy associated with cognitive decline and disease stage based on quantitative structural MRI analysis in a Chinese cohort to inform clinical diagnosis and follow-up of AD patients. Methods: One hundred and eleven patients who were clinically diagnosed with probable AD were enrolled. All patients completed a systemic cognitive evaluation and domain-specific batteries. The severity of cognitive decline was defined by MMSE score: 1-10 severe, 11-20 moderate, 21-30 mild. Cortical volume and thickness determined using 3D-T1 MRI data were analyzed using voxel-based morphometry and surface-based analysis supported by the DR. Brain Platform. Results: The male:female ratio was 38:73. The average age was 70.8±10.6 years. The mild:moderate:severe ratio was 48:38:25. Total grey matter volume was significantly related to cognition while the relationship between white matter volume and cognition did not reach statistical significance. The volume of the temporal-parietal-occipital cortex was most strongly associated with cognitive decline in group analysis, while the hippocampus and entorhinal area had a less significant association with cognitive decline. Volume of subcortical grey matter was also associated with cognition. Volume and thickness of temporoparietal cortexes were significantly correlated with cognitive decline with a left predominance observed. Conclusion: Cognitive deterioration was associated with cortical atrophy. Volume and thickness of the left temporal-parietal-occipital cortex were most important in early diagnosis and longitudinal evaluation of AD in clinical practice. Cognitively relevant cortices were left predominant.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

The COVID-19 pandemic could increase the number of older adults who are socially isolated including community-dwelling older adults, and result in the secondary damage of mental health. This study aimed to examine the longitudinal association between social isolation transitions and psychological distress among the community-dwelling older adults before and during the COVID-19 pandemic in rural China.A total of 2749 community-dwelling older adults aged 60 years and older in rural Shandong, China were included. We used the generalized estimating equations (GEE) model to estimate the impact of social isolation transitions on psychological distress before and during the COVID-19 pandemic.The percentage of high and very high psychological distress (K10 ≥ 22) was 23.54% and 31.36% before and during the COVID-19 pandemic, respectively, indicating a 7.82% increase (P 0.001). Compared with the group remaining nonisolated, "became socially isolated" and "remained isolated" groups were more likely to have a deterioration of psychological distress after experiencing the COVID-19 pandemic (became socially isolated: b = 0.92, P 0.001; remained isolated: b = 0.98, P 0.001).The main variables in this study were measured by self-report information, which might result in recall bias.During the COVID-19 pandemic, psychological distress increased among the community-dwelling older adults in rural China. There was a significant risk of psychological distress among those who had transitioned from nonisolation before the pandemic to social isolation after experiencing the pandemic, thus intervention on social isolation process during the pandemic may be important to protect older adults' mental health.

Fei-Ran Yang,1,&ast; Si-Yi Li,1,&ast; Xi-Wen Hu,1 Xiu-Rong Li,2 Hui-Jie Li2 1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui-Jie Li; Xiu-Rong Li, Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, Jinan, Shandong, 250014, People’s Republic of China, Email 2008lihuijie@163.com; szylxr2012@126.comBackground: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin.Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein–protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells.Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes.Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.Graphical Abstract: Keywords: lung adenocarcinoma, curcumin, antitumor effect, bioinformatics analysis, TCGA

Background: The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer’s disease (AD) patients. Of the identified variants, the PSEN2 mutations are even less common. Objective: With the genetic study from the dementia cohort of Peking Union Medical College Hospital (PUMCH), we aim to illustrate the PSEN2 mutation spectrum and novel functionally validated mutations in Chinese AD patients. Methods: 702 AD participants, aged 30–85, were identified in PUMCH dementia cohort. They all received history inquiry, physical examination, biochemical test, cognitive evaluation, brain CT/MRI, and next-generation DNA sequencing. Functional analysis was achieved by transfection of the HEK293 cells with plasmids harboring the wild-type PSEN2 or candidate mutations. Results: Nine PSEN2 rare variants were found, including two reported (M239T, R62C) and seven novel variants (N141S, I368F, L396I, G117X, I146T, S147N, H220Y). The HEK293 cells transfected with the PSEN2 N141S, M239T, I368F plasmids showed higher Aβ42 and Aβ42/Aβ40 levels relative to the wild-type PSEN2. The PSEN2 L396I, G117X, S147N, H220Y, and R62C did not alter Aβ42, Aβ40 levels, or Aβ42/Aβ40 ratio. 1.9%,(13/702) subjects harbored rare PSEN2 variants. 0.4%,(3/702) subjects carried pathogenic/likely pathogenic PSEN2 mutations. The three subjects with the functionally validated PSEN2 mutations were all familial early-onset AD patients. The common symptoms included amnesia and mental symptom. Additionally, the M239T mutation carrier presented with dressing apraxia, visuospatial agraphia, dyscalculia and visual mislocalization. Conclusion: The PSEN2 N141S, M239T, and I368F are functionally validated mutations.

Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear.The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University.A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 10Mononuclear cells dose (MNC, cut off: 8.53 × 10We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

This study systematically reviewed the effect of DNA methylation in the promoter region of the coagulation factor vWF gene on the risk of unexplained recurrent hemophilia. PubMed, Medline, Web of Science, and other computers were used to search the database, and the statistical randomized controlled trials of coagulation factor vWF in the risk analysis of unknown recurrent hemophilia were collected. The Cochrane systematic evaluation method was used to evaluate the quality of the included kinds of literature, and Revman5 software was used to sort out and analyze the kinds of literature. Meta-analysis showed that there was a statistical difference between the experimental group and the control group in case fatality rate (OR = 1.76, 95% CI (1.29, 2.39), P = 0.0003 , I2 = 0%, Z = 3.58), adverse events (OR = 2.38, 95% CI (1.65, 3.45), P < 0.00001 , I2 = 0%, Z = 4.60), incidence of joint hemorrhage (OR = 2.52, 95% CI (1.62, 3.91), P < 0.00001 , I2 = 0%, Z = 4.12), incidence of subcutaneous stasis (OR = 1.76, 95% CI (1.26, 2.45), P = 0.0009 , I2 = 5%, Z = 3.33), and hematoma volume (OR = 1.78, 95% CI (1.32, 2.40), P = 0.0001 , I2 = 23%, Z = 3.80). DNA methylation in the promoter region of the coagulation factor vWF gene was significantly associated with the risk of unexplained recurrent hemophilia. Whether demethylation can improve the bleeding index of patients with recurrent hemophilia remains to be further explored.

Thyroid nodules are one of the most common nodular lesions. The incidence of thyroid cancer has increased rapidly in the past three decades and is one of the cancers with the highest incidence. As a non-invasive imaging modality, ultrasonography can identify benign and malignant thyroid nodules, and it can be used for large-scale screening. In this study, inspired by the domain knowledge of sonographers when diagnosing ultrasound images, a local and global feature disentangled network (LoGo-Net) is proposed to classify benign and malignant thyroid nodules. This model imitates the dual-pathway structure of human vision and establishes a new feature extraction method to improve the recognition performance of nodules. We use the tissue-anatomy disentangled (TAD) block to connect the dual pathways, which decouples the cues of local and global features based on the self-attention mechanism. To verify the effectiveness of the model, we constructed a large-scale dataset and conducted extensive experiments. The results show that our method achieves an accuracy of 89.33%, which has the potential to be used in the clinical practice of doctors, including early cancer screening procedures in remote or resource-poor areas.

The correlation between dietary inflammation index (DII) and rheumatoid arthritis (RA) has been found, but the effect of confounding factors is not considered. This study aims to further explore the association between DII and RA risk by taking the Americans as the research object.The data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) database included 1819 self-reported RA individuals and 8602 non-RA individuals. The analytical methods include logistic regression, additive model, smooth curve fitting, and the recursive algorithm.There was a positive correlation between DII and RA in Americans (β = 1.068, 95% CI = 1.026 to 1.111, P = 0.001). This result was still presented in the subgroup analysis, including age less than 50 years, female, other Hispanics, BMI ≥ 25, and federal poverty rate 185%, and it was more pronounced in smokers. The results show that the superposition of DII and other risk factors would increase the risk of RA (β 1.068). In addition, individuals with RA are inadequate in intake of anti-inflammatory foods, in line with the Mediterranean diet.The inflammatory potential of the diet is positively correlated with the risk of RA, and has a superimposed effect with other risk factors, increasing the probability of the risk of disease. These results emphasize that reducing the intake of pro-inflammatory foods may be an effective measure to prevent the onset of rheumatoid arthritis. However, eating anti-inflammatory foods exclusively is not the best option. Intaking some pro-inflammatory foods like protein, energy, and total saturated acids may be necessary to maintain the physiological function of the human body. Key Points • Dietary inflammation index (DII) is positively correlated with RA risk. • When DII and other risk factors appear at the same time, the effects of the two will be superimposed on each other, increasing the risk of RA. • When the DII is the same, Hispanic has a higher incidence of RA. • Among the pro-inflammatory foods, the intake of protein, energy, and saturated fatty acids is still required by RA patients.

Parabens are widely used as preservatives, which have been found to affect thyroid function in toxicological studies. However, population studies on whether they are associated with thyroid tumors remain unclear. This study aims to investigate the relationship between environmental paraben exposure and thyroid cancer and benign nodules. We recruited participants from the Department of Thyroid and Breast Surgery at Wuhan Central Hospital, Wuhan, China. The detectable percentages of methyl paraben, ethyl paraben, and propyl paraben in the urinary samples of 425 study subjects were 99.1%, 95.3%, and 92.0%, respectively. All uncorrected and creatinine-corrected parabens were moderately correlated with one another. After adjusting for possible confounders, all three parabens were associated with an increased risk of thyroid cancer. Furthermore, the mixture pollutant analysis of parabens found positive associations with risk of thyroid cancer (OR = 0.24, 95% CI: 0.18, 0.31) and benign nodules (OR = 1.33, 95% CI: 0.86, 1.80). We observed that individual exposure to paraben mixtures may be associated with the risk of thyroid cancer and benign nodules.

Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti-allergic effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.

Objectives: The influence of radiotherapy on implants placed before diagnosed as head and neck cancer (HNC) is a potentially informative but poorly explored topic. The aims of this study were to investigate the influence of implant-bed-specific radiation dose on dental implants and to evaluate the impact of these implants on radiation dosimetry. Material and methods: We conducted a retrospective study with 58 irradiated patients that received dental implant restorations before undergoing radiation treatment for HNC. The radiological success rate and the peri-implant bone resorption values were measured radiographically at 1 and 3 years after radiotherapy. Patients with no implants matching tumor site and stage served as a control group (n = 58). Results: The median implant-bed-specific radiation dose was 40.3 Gy, which was significantly lower than tumor bed 62.4 Gy. An implant-bed-specific radiation dose higher than 40.0 Gy showed a significantly decreased radiologic success rate when compared to lower doses. Finally, evaluation of the radiation treatment plans revealed similar radiation hot spots in the test group of patients with implants and those of the control group. Conclusion: Our study confirms that radiotherapy negatively worsens peri-implant bone resorption, especially for implant-bed-specific dose more than 40 Gy, and the presence of implants within the radiation fields does not alter radiation dosimetry. The findings could be clinically informative to both surgeons and radio-oncologists. Clinical relevance: The interactions between radiotherapy and implants placed prior to radiotherapy treatment remain a largely unexplored topic. Based on the analysis of 3-dimensional modulated radiation plans, this study demonstrates the impact of implant-bed-specific radiation dose on marginal bone resorption of implants placed pre-radiation and considers the influence of these implants on radiation dosimetry. Registration number: ChiCTR2100051923: (http://www.chictr.org.cn/usercenter.aspx).

Background: We conducted a trial to evaluate the efficacy and safety of apatinib, a tyrosine inhibitor against vascular endothelial growth factor receptor 2, combined with neoadjuvant chemotherapy ...

Acute kidney injury (AKI) is a life-threatening condition that is one of most common side effects of cisplatin therapy. Fatty acid oxidation (FAO) is the main source of energy production in kidney proximal tubular epithelial cells (PTECs) but it is inhibited in AKI. Recent work demonstrated that activation of the farnesoid X receptor (FXR) protects against AKI, but the underlying mechanism remains elusive. Using a model of cisplatin-induced AKI, we found that FXR and FAO-related genes were remarkably downregulated while kidney lipid accumulated. Proximal tubule-specific or whole body FXR knockout worsened, while pharmacological activation attenuated these effects. Conversely, FXR knockout in non-proximal tubules did not. RNA-sequencing of PTECs demonstrated increased transcripts involved in metabolic pathways in cells overexpressing FXR versus control after cisplatin treatment, specifically transcripts associated with FAO and peroxisome proliferator-activated receptor-γ (PPARγ) signaling. Furthermore, FXR overexpression or activation improved FAO and inhibited intracellular lipid accumulation in cisplatin-treated cells. In vivo studies have shown that pharmacological activation of PPARγ can prevent cisplatin-induced lipid accumulation, kidney tubule injury and kidney function decline. However, inhibition of PPARγ eliminated the protective effects of FXR compared to control mice during the cisplatin treatment phase and after ischemia-reperfusion injury. Consistent with findings in vivo, FXR/PPARγ reduced lipid accumulation by improving FAO in cisplatin-treated cells. Furthermore, the inhibition of carnitine palmitoyltransferase 1α abolished the protective effect of FXR in cisplatin-treated mice. Thus, FXR improves FAO and reduced lipid accumulation via PPARγ in PTECs of the kidney. Hence, reconstruction of the FXR/PPARγ/FAO axis may be a novel therapeutic strategy for preventing or treating AKI.

Background: Retroperitoneal approach and segmental renal artery clamping in partial nephrectomy are techniques that facilitate postoperative recovery and renal function preservation. This study aimed to compare the renal function preservation and perioperative outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) with these techniques. Materials and Methods: Clinical parameters of 43 patients who had undergone retroperitoneal RAPN from March 2017 to December 2019 were retrospectively collected and compared with those of 52 patients who had undergone retroperitoneal LPN at the same period in our institution. Differences in operating time, warm ischemia time, estimated blood loss, complications, postoperative hospital stay, as well as renal function loss were compared between the two groups. Results: Background characteristics between RAPN and LPN groups such as age, gender, BMI, and tumor characteristics were comparable. All RAPNs and LPNs were successfully completed without conversion to open surgery or nephrectomy. No significant difference in operating time, estimated blood loss, complications, and postoperative hospital stay was observed between RAPN and LPN groups. The warm ischemia time in RAPN group was slightly shorter than that of LPN groups (P = .054). Compared with the LPN group, the RAPN group was significantly associated with less glomerular filtration rate reduction and renal volume loss rate (P = .042 and P = .013, respectively). Conclusions: The perioperative outcomes were comparable between the two groups. However, compared with LPN, RAPN had superiority in preserving renal function in our series.

The effect of single- and dual-limb circuits on aerosol delivery during noninvasive ventilation (NIV) in adult models is unclear.A noninvasive ventilator equipped with a single-limb circuit or an ICU ventilator equipped with a dual-limb circuit was connected to a simulated lung. Ventilator parameters were adjusted to maintain a tidal volume at ∼500 mL. Aerosol deposition with different placements of a vibrating mesh nebulizer and humidification conditions were compared. Additional experiments by using a non-vented mask or a vented mask were compared in the single-limb circuit only. Aerosol was collected by a disposable filter placed between the simulated lung and the head model (n = 3), and measured by ultraviolet spectrophotometry (276 nm).The aerosol deposition varied between 4.12 ± 0.22% and 20.75 ± 0.95%. The greatest aerosol delivery during NIV when using a non-vented mask was found when a vibrating mesh nebulizer was placed between the mask and 15 cm from the exhalation port in the humidified single-limb circuit, and 15 cm from the Y-piece in the inspiratory limb of the humidified dual-limb circuit, and no significant difference of aerosol deposition was found between the two optimal positions (20.03 ± 1.48% vs 18.04 ± 0.93%, respectively;During NIV, the aerosol delivery was optimal when a vibrating mesh nebulizer was placed between the non-vented mask and 15 cm from the exhalation port in the single-limb circuit or 15 cm from the Y-piece in the inspiratory limb of the dual-limb circuit; no significant difference was found between the two optimal placements. Humidification had little effect on aerosol delivery. Aerosol delivery was poor in the single-limb circuit with a vented mask.

Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival ( P < 0.0001 ). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA–mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumour. Hepatectomy is an effective treatment for early ICC, but postoperative recurrence greatly affects patient survival. Studies on recurrent ICC after hepatectomy are lacking.To investigate the clinical characteristics of patients with recurrent ICC after hepatectomy, analyse prognostic factors and explore diagnosis and treatment strategies.A retrospective analysis was performed on all ICC patients undergoing hepatectomy from January 2013 to August 2021. Patients with postoperative recurrence were selected according to the inclusion and exclusion criteria. Cumulative overall survival was plotted by the Kaplan-Meier method, and differences were assessed by univariate survival analysis using the log-rank test. Multivariate analysis of cumulative survival was performed using the Cox proportional risk model.During the 8-year study period, 103 patients underwent ICC-related hepatectomy, and 54 exhibited postoperative recurrence. The median disease-free survival (DFS) was 6 mo, the median overall survival (OS) was 9 mo, and the cumulative OS rates at 1, 2 and 3 years after the operation were 40.7%, 14.8% and 7.4%, respectively. The median OS after recurrence was 4 mo, and the cumulative OS rates at 1, 2 and 3 years after recurrence were 16.1%, 6.7% and 3.4%, respectively. Multivariate analysis showed that alcohol consumption [hazard ratio (HR) = 4.64, 95% confidence interval (CI): 1.53-14.04,The prognosis of patients with recurrence after ICC-related hepatectomy is poor. Alcohol consumption and DFS6 mo are independent risk factors in terms of the cumulative survival of patients with recurrence, while treatment after recurrence is an independent protective factor. Multimodality therapy can effectively improve the prognosis of patients.

Bone marrow cell morphology has always been an important tool for the diagnosis of blood diseases. Still, it requires years of experience from a suitable person. Furthermore, the outcomes of their recognition are subjective and there is no objective quantitative standard. As a result, developing a deep learning automatic classification system for bone marrow cells is extremely important. However, typical classification machine learning systems only produce classification answers, and will not refuse to generate predictions when the prediction reliability is low. It will pose a big problem in some high-risk systems such as bone marrow cell recognition. This paper proposes a bone marrow cell classification method with rejected option (CMWRO) to classify 11 bone marrow cells. CMWRO is based on convolutional neural networks, ICP and SoftMax (CNN-ICP-SoftMax), containing a classifier with rejected option. When the rejected rate (RR) of tested samples is 0.3143, it can ensure that the precision, sensitivity, accuracy of the accepted samples reach 0.9921, 0.9917 and 0.9944 respectively. And the rejected samples will be handled by other ways, such as identified by doctors. Besides, the method has a good filtering effect on cell types that the classifier is not trained, such as abnormal cells and cells with less sample distribution. It can reach more than 82% in filtering efficiency. CMWRO improves the doctors’ trust in the results of accepted samples to a certain extent. They only need to carefully identify the samples that CMWRO refuses to recognize, and finally combines the two results. It can greatly improve the efficiency and accuracy of bone marrow cell recognition.