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Family conflict is a risk factor for suicidal behaviors among adolescents. However, few longitudinal studies have investigated this association and explored the mediation effect of behavioral and emotional problems. This study aimed to examine the longitudinal association between family conflict, internalizing and externalizing problems, and suicidal behaviors in a large sample of Chinese adolescents.This longitudinal study of 7,072 adolescents was based on the Shandong Adolescent BehaviorHealth Cohort (SABHC). Participants completed a self-administrated questionnaire to assess family conflict, internalizing and externalizing problems, suicidal behaviors, and family demographics at baseline. Excluding adolescents with any suicidal behavior at baseline (N = 839), others (N = 6,233) were allowed to report their internalizing and externalizing problems and suicidal behaviors one-year later. Path analyses were conducted to examine the mediation relationship of internalizing and externalizing problems between family conflict and suicidal behaviors.Of 6,233 participants, mean age was 14.52 at baseline and 51.2% were males. Adolescents with subsequent suicidal behaviors reported higher scores in family conflict, internalizing and externalizing problems (Ps 0.01). Path analyses showed that internalizing and externalizing problems played a significant mediating role in the associations of family conflict with suicidal behaviors after adjusting for covariates.Family conflict is associated with suicidal behaviors in adolescents, which is partially mediated by internalizing and externalizing problems. Internalizing problems is the major mediator between family conflict and suicidal thought or suicide plan; however, internalizing and externalizing problems play similar mediating roles in the family conflict-suicide attempt link.

Community solidarity is increasingly important in public health. However, few studies have examined solidarity in relation to health outcomes. The purpose of this study was to develop a psychometric tool to measure solidarity among Chinese men who have sex with men (MSM) and assess whether community solidarity relates to differences in sexually transmitted infection testing.We used data from the pay-it-forward randomized controlled trial of 301 men from Beijing and Guangzhou, China. Men who have sex with men were randomized into pay-it-forward (participants receive free gonorrhea/chlamydia testing as gifts and choose to donate toward subsequent MSM's tests), pay-what you-want, and standard payment arms. After testing decision, participants completed a cross-sectional questionnaire to assess community solidarity. Factor analysis was conducted to identify dimensions of solidarity. The solidarity factors were compared across study arms and assessed against gonorrhea/chlamydia test uptake in multivariable logistic regression.Two hundred eighty-eight participants responded to the survey. We identified 3 latent community solidarity factors: engagement, social network support, and sense of belonging. Several items related to belonging were significantly greater among participants in the pay-it-forward scenario compared with those assigned to other scenarios. Higher sense of belonging was associated with higher odds of gonorrhea and chlamydia test uptake.Community solidarity among MSM in China can be characterized by 3 factors: engagement, social network support, and sense of belonging. Sense of belonging was higher in the pay-it-forward intervention arm and may be associated with the uptake of gonorrhea/chlamydia test. Future studies are warranted to confirm the psychometric structure of community solidarity and further investigate behavioral mechanisms of pay it forward.

The shortage of donor liver restricts liver transplantation (LT). Nowadays, donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor liver. Although it is now possible to perform ABO-incompatible (ABO-I) LT, antibody-mediated rejection (AMR) has been recognized as the primary cause of desperate outcomes after ABO-I LT. Anti-A/B antibody is the trigger of immune response to ABO-I LT graft injury. Therapeutic plasma exchange (TPE) can quickly reduce the titer of plasma antibodies and effectively inhibit humoral immunity.We searched PubMed and CNKI databases using search terms "therapeutic plasma exchange", "ABO-incompatible liver transplantation", "ABO-I LT", "liver transplantation", "LT", "antibody-mediated rejection", and "AMR". Additional publications were identified by a manual search of references from key articles. The relevant publications published before September 30, 2020 were included in this review.Different centers have made different attempts on whether to use TPE, when to use TPE and how often to use TPE. However, the control standard of lectin revision level is always controversial, the target titer varies significantly from center to center, and the standard target titer has not yet been established. TPE has several schemes to reduce antibody titers, but there is a lack of clinical trials that provide standardized procedures.TPE is essential for ABO-I LT. Hence, further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

Background Observational studies have shown promising therapeutic effects of long-pulsed neodymium-doped yttrium aluminum garnet (LP-Nd:YAG) laser on warts. Objective To evaluate whether LP-Nd:YAG laser was superior to cryotherapy for cutaneous warts. Methods In this study, 150 adult patients with warts were randomized equally to receive laser or cryotherapy every 3–4 weeks, a maximum of 4 sessions. The primary outcomes were cure rate at 16 weeks and 6 months; secondary outcomes included time to clearance of warts and treatment-related adverse effects. Results There was no difference in the cure rate for laser versus cryotherapy at 16 weeks (54.1% vs. 46.7%) and 6 months (59.5% vs. 57.3%). However, time to clearance of warts, up to 16 weeks and 6 months, tended to be shorter for laser versus cryotherapy ( P = .04 and .08, respectively). Post-hoc analyses showed a significantly higher cure rate for laser versus cryotherapy in 3 subgroups of HPV 2/27/57-induced recalcitrant warts, but not in their counterpart subgroups. Laser had more mild adverse effects. Limitations Single-center. Conclusions The overall therapeutic effects of LP-Nd:YAG laser were similar to cryotherapy, but laser may be more effective to relatively recalcitrant warts and may associate with shorter time to clearance of warts.

HIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) have been implicated in the “Shock and Kill” strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps to develop efficient LRAs. In this study, we demonstrate that the Wnt downstream β-catenin/TCF1 pathway is a crucial modulator for HIV-1 latency. The pharmacological activation of the β-catenin/TCF1 pathway with glycogen synthase kinase-3 (GSK3) inhibitors promoted transcription of HIV-1 proviral DNA and reactivated latency in CD4+ T cells; the GSK3 kinase inhibitor 6-bromoindirubin-3′-oxime (6-BIO)-induced HIV-1 reactivation was subsequently confirmed in resting CD4+ T cells from cART-suppressed patients and SIV-infected rhesus macaques. These findings advance our understanding of the mechanisms responsible for viral latency, and provide the potent LRA that can be further used in conjunction of immunotherapies to eradicate viral reservoirs., GRAPHICAL ABSTRACT

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.

Objective This study aimed to investigate the demographic and clinicopathological characteristics, and survival outcomes of subglottic Squamous Cell Carcinoma (SCC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods Demographic and clinicopathological information, including age, sex, race, tumor size, histologic grade, clinical/TNM stage, tumor invasion extent, Lymph Node Metastasis (LNM) extent, size of metastatic lymph nodes, LNM ratio and treatment data, of 842 subglottic SCC patients diagnosed between 1996 and 2016 were acquired. Kaplan-Meier survival analyses were performed to assess the effects of clinicopathological characteristics, treatment modalities, surgical procedures, and adjuvant therapies on overall survival and cancer-specific survival. Results Subglottic SCC was more frequent among males aged 60-70 years, with low-grade but locally advanced lesions without local or distant metastases. Age and several primary tumor/LNM related variables were independent risk factors for overall survival and cancer specific survival. Advanced-stage and high-grade disease led to unfavorable prognosis. The most common treatment modality and surgical procedure were surgery plus radiotherapy and total laryngectomy, respectively. Surgery plus radiotherapy provided favorable 5-year survival outcomes, while total laryngectomy had the worst. Surgery plus adjuvant therapy showed better survival outcomes than surgery alone. Conclusion This study confirmed the rarity of subglottic SCC. Patients with subglottic SCCs suffered poor prognosis especially for those with advanced-stage or high-grade lesions. The prognosis of subglottic SCC remained poor over the years, despite recent progress in cancer therapies. Surgery plus adjuvant therapy improved the survival outcome. Although larynx preservation surgery was beneficial for early-stage disease, total laryngectomy was favored for patients with advanced tumors. Level of evidence Level 4.

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.

Although there are current studies on breast cancer brain metastasis, population-level analysis is still lacking. As treatment for metastatic breast cancer has improved, an updated population-level analysis is necessary. Our aim was to use the SEER database to characterize the incidence and survival of patients with brain metastases at the initial diagnosis of breast cancer.Patients with breast cancer from 2010 to 2018 were identified using the SEER database. The stratified incidence and median survival of patients with BM at diagnosis were described. Multivariate logistic and Cox regression were performed to determine the covariates associated with brain metastasis and survival outcomes, respectively. Multiple comparisons based on Cox proportional hazards model were performed for the analysis of interactive effects on overall survival.A total of 2,248 patients with brain metastases at the initial diagnosis of breast cancer were identified, accounting for 0.40% of all patients with breast cancer, and 7.26% of patients with metastatic disease. Incidence proportions were highest, and survival outcomes were worst among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes. For patients with brain metastases, the prognostic differences among different molecular subtypes have been gradually narrowing, and the survival benefits from various treatment methods have been all increased over time.Our study provides an updated population-level estimate of the incidence and survival for patients with brain metastases at the diagnosis of breast cancer, thus may help early identification, prognostic stratification and treatment planning for such patients.

Compared to the activation of acquired immunity by the immune checkpoint blockade, the activation of innate immunity via anti-phagocytosis checkpoint blockade could significantly increase the beneficiary population of immunotherapy. However, the activation of innate immunity and the occurrence of phagocytosis are only accomplished when the interaction between pro-phagocytosis signals and anti-phagocytosis signals is realized. Herein, a versatile nanoplatform (DHMR) based on mesoporous silicon nanoparticles (MSNPs) has been constructed. Two drugs, doxorubicin, a chemotherapeutic drug which could initiate tumor cells to release pro-phagocytosis signals, and RRx-001, an immunoadjuvant that could effectively implement the anti-phagocytosis checkpoint blockade, were loaded in MSNPs. Further decoration of hyaluronic acid encapsulation endows DHMR with the function of tumor targeting and long circulation. Ultimately, the DHMR system could efficiently and accurately target tumor tissue, release the drugs in the tumor microenvironment, achieve the activation of innate immunity, and finally dramatically inhibit the growth and metastasis of tumor cells.

The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage.Ten recreationally active male runners (VOThere was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L,Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.

Because of the availability of highly active antiretroviral therapy, individuals infected with human immunodeficiency virus (HIV) are enjoying greater longevity with chronic conditions including abnormal adipose distribution. However, prior data on postoperative outcomes of liposuction in HIV-positive patients were limited by small sample size. Therefore, the authors aimed to compare differences in temporary trend, clinical characteristics, and outcomes between patients with and without HIV who underwent liposuction.The National Inpatient Sample database from 2010 to 2017 was queried to identify patients who underwent liposuction. Univariate, multivariate logistic regression and 1:4 propensity score-matched analyses were used to assess the primary outcomes (i.e., in-hospital mortality and postoperative outcomes) and secondary outcomes (i.e., discharge disposition, prolonged length of stay, and total cost).Overall, 19,936 patients who underwent liposuction were identified, among whom 61 patients (0.31%) were infected with HIV. Patients with HIV were more likely to be male, insured by Medicare, and had more comorbidities and lower income. Unadjusted length of stay was longer among patients with HIV (OR, 1.81; 95% CI, 1.09 to 2.99; P = 0.020); nevertheless, multivariable models and propensity score-matched analysis demonstrated that patients with HIV were no more likely to have complications than the general population. This was also the case for length of stay and total costs.The authors' findings indicated that patients with HIV who underwent liposuction did not experience an increased risk of major complication or mortality. Liposuction could be safely considered as a surgical treatment for HIV-positive patients with local fat deposition.Risk, II.

Prolonged mobile phone use has been demonstrated to be associated with mental health problems and suicidal behavior in adolescents. This study examined the mediating role of depressive symptoms in the association between duration of mobile phone use (DMPU) and suicidal behavior in adolescents.A total of 6,923 participants from the Shandong Adolescent BehaviorHealth Cohort (SABHC) were included in the analysis. Participants completed a self-administered questionnaire to assess DMPU on weekdays and weekends, mental disorders, insomnia symptoms, depressive symptoms, suicidal behavior (thought, plan, or attempt), and family demographics in November-December 2015. One year later, a follow-up survey was conducted to ask participants to report their depressive symptoms and suicidal behavior. Path analyses with logistic regressions were performed to examine the mediating role of depressive symptoms in the DMPU-suicidal behavior link.Of the sample, mean age was 14.58 (SD = 1.45) and 3,455 (49.9 %) were female at baseline. 12.12 % of participants reported having ever suicidal behavior during the past 12 months at baseline, and 10.63 % reported having ever suicidal behavior during 1-year follow-up. Path analyses showed that the depressive symptoms played a partial mediating role in the association of DMPU on weekdays and weekends with subsequent suicidal behavior. After controlling for covariates, depressive symptoms accounted for 33.6 % and 58.6 % of the total effect of DMPU on weekdays and weekends on suicidal behavior, respectively.All variables were measured based on self-report.The link between DMPU and suicidal behavior was partially mediated by depressive symptoms. Prolonged mobile phone use and depressive symptoms should be assessed and intervened to prevent suicidal behavior in adolescents.

There are several treatment options for patients with concomitant carotid and coronary artery disease, and it is difficult to identify an optimal treatment strategy that has consensus. Here, we performed a meta-analysis to compare the early and long-term outcomes of staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches.We performed a meta-analysis that compared staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches between July 1976 and September 2021. PubMed, EMBASE, and the Cochrane Library were systematically searched for related articles.Nineteen studies were identified with a total of 39,269 and 30,066 patients in the synchronous and staged groups, respectively. Early mortality was lower in the staged group than in the synchronous group (odds ratio OR 1.256, 95% confidence interval CI 1.006-1.569, P= P 0.05, IPatients treated with the synchronous approach had a significantly higher risk of early mortality, stroke, TIA, wound infection, and reoperation and a lower risk of myocardial ischemia than those treated with the staged approach. There was no significant difference in the long-term results between the 2 groups.

Objective: The study aimed to investigate the value of pulmonary function test (PFT) in evaluating and predicting pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Methods: This was a prospective observational study recruiting patients diagnosed with CTD-PAH. Patients with interstitial lung disease and pulmonary hypertension induced by other causes were not eligible for enrollment. All patients were assessed for PAH every 1–3 months. A patient was considered to have clinical improvement if the grade of risk stratification declined or at least two parameters improved during follow-up, otherwise no improvement. Results: A total of 31 patients with CTD-PAH were recruited in this study. Nearly 70% of patients had declined forced vital capacity (FVC), 60% had declined total lung capacity and maximum expiratory flow at 50% of vital capacity, and 95% had normal or mild decline in forced expiratory volume in 1 second (FEV1)/FVC. A decline in diffusing capacity of the lung for carbon monoxide (DLCO) was present in 96% of patients, and 60% were moderate to severe. Furthermore, 50% of patients had an FVC/DLCO ratio of less than 1.4. Univariate analysis showed that FEV1/FVC, DLCO, and FVC/DLCO were associated with disease prognosis. After adjusting for age as a confounding factor, multivariate logistic regression analysis revealed that DLCO was an independent predictive factor for the prognosis of CTD-PAH. Conclusion: The pulmonary function of patients with CTD-PAH is abnormal in parameters such as lung volume, small airway, and gas exchange. PFT can reveal complex pathophysiological changes in the lungs of CTD-PAH patients and predict prognosis.

Immune checkpoint blockade (ICB) has been hailed as the hope for conquering cancer as ICB could produce a significant and durable response to tumor cells. However, the high cost and severe side effects of ICB drugs limited their application for further anticancer therapy. Here, we developed a photoactivated immunotherapy nanoplatform (Apt@AuNC). This nanoplatform could target tumor tissues via enhanced penetration retention (EPR) effect and the aptamer (Apt) could be released from Apt@AuNC in tumor sites via illumination. The immune system in the tumor area was then activated after the combination of Apt and PD-1 protein. The heat generated from AuNC was able to continue killing tumor cells. This nanoplatform could not only achieve the precise immunotherapy but also significantly facilitate the anticancer efficacy.

Doxorubicin (DOX) is a class of effective chemotherapeutic agents widely used in clinical practice. However, its use has been limited by cardiotoxicity. The mechanism of DOX-induced cardiotoxicity (DIC) is complex, involving oxidative stress, Ca2+ overload, inflammation, pyroptosis, ferroptosis, apoptosis, senescence, etc. Exosomes (EXOs), as extracellular vesicles (EVs), play an important role in the material exchange and signal transmission between cells by carrying components such as proteins and RNAs. More recently, there has been a growing number of publications focusing on the protective effect of EXOs on DIC. Here, this review summarized the main mechanisms of DIC, discussed the mechanism of EXOs in the treatment of DIC, and further explored the value of EXOs as diagnostic biomarkers and therapeutic strategies for DIC.

We aimed to investigate the clinical features, prognosis and predictive factors for the non-small cell lung cancer (NSCLC) patients with uncertain resection [R(un)].Kaplan-Meier method with a log-rank test was used to compare overall survival (OS) and disease-free survival (DFS) between groups. The least absolute shrinkage and selection operator (LASSO)-penalized Cox multivariable analysis was used to identify the prognostic factors. Random forest was used to determine the important predictive factors of R(un) resection.A total of 2,782 eligible cases (R0 group: 1,897 cases; R(un) group: 885 cases) were included in this study. The rate of conventional R0 to R(un) reclassification was 31.8%. Patients with R(un) resection were more likely to have left-sided tumors, receive open surgery, and be diagnosed with advanced tumors. The survivals of the patients with R(un) resection were inferior to those of the patients with R0 resection in the entire cohort and in the nodal category, histology and adjuvant therapy subgroups. The LASSO-penalized multivariable Cox analysis confirmed that R(un) resection was an adverse prognostic factor for both OS and DFS. At last, surgical extent, surgical approach and tumor location were proven as the predictive factors for R(un) resection.NSCLC patients with R(un) resection was not rare. R(un) had an adverse impact on the survivals of resected patients. Patients received non-lobectomy and open surgery, and patients with left-sided tumors were more likely to be suffered from R(un) resection.

Senescence is an effective barrier to tumor progression. Mutations that inhibit senescence and promote cell division are mandatory for the development of cancer. Therefore, it is particularly important to explore the differences between cutaneous melanoma (CM) patients with severe and mild degrees of senescence. We clustered all the patients with CM in the Cancer Genome Atlas (TCGA) database based on all the genes of the senescence pathway in the CellAge and MSigDB database. The prognosis, immunotherapy effect, tumor microenvironment score, NRAS mutation rate, expression of CD274, CTLA4, and PDCD1, and abundance of CD8

The ideological and political collaborative education mechanism is an important course teaching method that uses all courses as a carrier to cultivate students' all-round development in morality, intelligence, physique, and beauty. The purpose of this paper is to conduct a better research on the construction of the ideological and political collaborative education mechanism by building models based on edge computing and neural network algorithm. This paper first gave a general introduction to edge computing and neural network algorithm and then analyzed the current situation of ideological and political courses in a certain school. Then, edge computing and neural network algorithm were introduced into the analysis of an important course teaching method that used all courses as a carrier to cultivate students’ comprehensive development in morality, intelligence, physique, and beauty. The BP neural network model was established. Through analysis and comparison, the experimental results showed that 56.47% of the students believed that the impact of personal morality on the future development of college students was the first in the relationship between “virtue” and “talent.” More than half of the students believed that the “virtue” of building morality and cultivating people was mainly civic morality, and about 30% of the students thought that the main value was loving the party and patriotism, which meant that most students believed that the main value of building morality and cultivating people was to establish morality.

Dysregulation of Sonic hedgehog (SHH) signaling drives the growth of distinct cancer subtypes, including medulloblastoma (MB). Such cancers have been treated in the clinic with a number of clinically relevant SHH inhibitors, the majority of which target the upstream SHH regulator, Smoothened (SMO). Despite considerable efficacy, many of these patients develop resistance to these drugs, primarily due to mutations in SMO. Therefore, it is essential to identify druggable, signaling components downstream of SMO to target in SMO inhibitor resistant cancers. We utilized an integrated functional genomics approach to identify epigenetic regulators of SHH signaling and identified a novel complex of Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), DNA methyltransferase 1 (DNMT1), and GLI proteins. We show that this complex is distinct from previously described UHRF1/DNMT1 complexes, suggesting that it works in concert to regulate GLI activity in SHH driven tumors. Importantly, we show that UHRF1/DNMT1/GLI complex stability is targeted by a repurposed FDA-approved therapy, with a subsequent reduction in the growth of SHH-dependent MB ex vivo and in vivo. Implications: This work describes a novel, druggable UHRF1/DNMT1/GLI complex that regulates SHH-dependent tumor growth, and highlights an FDA-approved drug capable of disrupting this complex to attenuate tumor growth.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare mesenchymal tumor that is primarily treated with surgery. Targeted therapy is a promising approach to help reduce the high rate of recurrence. This study aims to identify the potential target genes and explore the candidate drugs acting on them effectively with computational methods. Methods: dentification of genes associated with DFSP was conducted using the text mining tool pubmed2ensembl. Further gene screening was carried out by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-Protein Interaction (PPI) network was constructed by using the Search Tools for the Retrieval of Interacting (STRING) database and visualized in Cytoscape. The gene candidates were identified after a literature review. Drugs targeting these genes were selected from Pharmaprojects. The binding affinity scores of Drug-Target Interaction (DTI) were predicted by a deep learning algorithm Deep Purpose. Results: total of 121 genes were found to be associated with DFSP by text mining. The top 3 statistically functionally enriched pathways of GO and KEGG analysis included 36 genes, and 18 hub genes were further screened out by constructing a PPI networking and literature retrieval. A total of 42 candidate drugs targeted at hub genes were found by Pharmaprojects under our restrictions. Finally, 10 drugs with top affinity scores were predicted by DeepPurpose, including 3 platelet-derived growth factor receptor beta kinase (PDGFRB) inhibitors, 2 platelet-derived growth factor receptor alpha kinase (PDGFRA) inhibitors, 2 Erb-B2 receptor tyrosine kinase 2 (ErbB-2) inhibitors, 1 tumor protein p53 (TP53) stimulant, 1 vascular endothelial growth factor receptor (VEGFR) antagonist, and 1 prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitor. Conclusion: Text mining and bioinformatics are useful methods for gene identification in drug discovery. DeepPurpose

Injuries of the bone-to-tendon interface, such as rotator cuff and anterior cruciate ligament tears, are prevalent musculoskeletal injuries, yet effective methods for repair remain elusive. Tissue engineering approaches that use cells and biomaterials offer a promising potential solution for engineering the bone-tendon interface, but previous strategies require seeding multiple cell types and use of multiphasic scaffolds to achieve zonal-specific tissue phenotype. Furthermore, mimicking the aligned tissue morphology present in native bone-tendon interface in three-dimensional (3D) remains challenging. To facilitate clinical translation, engineering bone-tendon interface using a single cell source and one continuous scaffold with alignment cues would be more attractive but has not been achieved before. To address these unmet needs, in this study, we develop an aligned gelatin microribbon (μRB) hydrogel scaffold with hydroxyapatite nanoparticle (HA-np) gradient for guiding zonal-specific differentiation of human mesenchymal stem cell (hMSC) to mimic the bone-tendon interface. We demonstrate that aligned μRBs led to cell alignment in 3D, and HA gradient induced zonal-specific differentiation of mesenchymal stem cells that resemble the transition at the bone-tendon interface. Short chondrogenic priming before exposure to osteogenic factors further enhanced the mimicry of bone-cartilage-tendon transition with significantly improved tensile moduli of the resulting tissues. In summary, aligned gelatin μRBs with HA gradient coupled with optimized soluble factors may offer a promising strategy for engineering bone-tendon interface using a single cell source. Impact statement Our 3D macroporous microribbon hydrogel platform with alignment cues zonally integrated with hydroxyapatite nanoparticles enables differentiation across the bone-tendon interface within a continuous scaffold. While most interfacial scaffolds heretofore rely on composites and multilayer approaches, we present a continuous scaffold utilizing a single cell source. The synergy of niche cues with human mesenchymal stem cell (hMSC) culture leads to an over 45-fold enhancement in tensile modulus in culture. We further demonstrate that priming hMSCs towards the chondrogenic lineage can enhance the differential osteogenesis. Relying on a single cell source could enhance zone integration and scaffold integrity, along with practical benefits.

Bachkground: The risk factors of Posttraumatic Stress Symptoms (PTSS) and depressive symptoms have been well-established, but whether the network structure of their symptoms changes over time remains unclear. This study aims to examine the six-year changes of network structure of PTSS and depressive symptoms among Wenchuan earthquake adult survivors in China.Methods: In this pooled cross-sectional study, respondents were sampled from the same population at each of the five waves (N = 1343, 1205, 1177, 1376, and 1339). The network structure of them was investigated using network analyses.Results: The study shows network connections stable across waves were the positive connections between hyperarousal and intrusions, hyperarousal and somatic symptoms, and two dimensions of positive effects. Stable negative connections were those between depressed affects and positive effects, avoidance and depressed affects, avoidance with interpersonal symptoms and avoidance with somatic symptoms. Across waves, fearful emotion consistently was the strongest bridge symptom connecting with PTSS symptoms. However, for PTSS the strongest bridge symptom varied across time as it was avoidance in wave 1 but were hyperarousal in other four waves.Limitations: This study was based on a pooled cross-sectional survey, which inhibits conclusions regarding causal influences between symptoms at the individual patient level.Conclusions: The network structure of PTSS and depressive symptoms was partly stable, yet also varied across survey waves. Core symptom clusters for PTSS and depressive symptoms were avoidance and depressed affect, respectively. The central role of these clusters in PTSS and depressive symptoms has important implications to future psychiatric programs.

To compare short-term follow-up outcomes after primary arthroscopy in femoroacetabular impingement syndrome (FAIS) patients with untreated central acetabular osteophytes (CAO) to a control group without CAO.A retrospective analysis was performed using data from FAIS patients who had primary arthroscopy between 2017 and 2018. The presence of CAO was confirmed arthroscopically, and there were 2 groups created. The CAO group was 1:1 propensity-score matched to a control group (without CAO) based on age, gender, body mass index (BMI), Tӧnnis grade, symptom duration before surgery, and follow-up time. Patient-reported outcomes (PROs), such as the Hip Outcome Score-Activities of Daily Living (HOS-ADL), International Hip Outcome Tool 12-component form (iHOT-12)，modified Harris Hip Score (mHHS), and visual analog scale (VAS) scores were used to evaluate the level of function included. The minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) were also calculated to determine meaningful outcome improvement. Radiographic measures, performed procedures, complications, and revision surgery were also compared and analyzed for both groups. P values less than .05 were considered statistically significant.A total of 46 hips with CAO and 46 hips without CAO were propensity matched. At the minimum final follow-up of 2 years, the CAO group had significantly lower HOS-ADL (78.8 vs 85.5; P = .008), iHOT-12 (74.8 vs 79.3; P = .019), and mHHS (78.9 vs 87.2; P = .002) scores, as compared to the CAO group. Furthermore, patients in the CAO group were significantly less likely to achieve the MCID and PASS for the mHHS score (78.3% vs 93.5%; P = .036, 58.7% vs 78.2%; P = .043, respectively). There was no change in the rate of complications (4.3% vs 0%) and revision hip arthroscopy (4.3% vs 2.2%) between the two groups at the final follow-up.This study demonstrated that surgically treated FAIS patients with CAO might experience worse short-term, patient-reported outcomes, as compared with propensity-matched patients without CAO.III, case-control study.

The nuclear import receptor karyopherin β1 (KPNB1), a member of the Karyopherin protein family, is reported to be overexpressed in various cancers and promote carcinogenesis. By analyzing the correlation between the expression of KPNB1 and the overall survival rate of melanoma patients, we found that melanoma patients with higher expression of KPNB1 had worse survival. Furthermore, the database analyzed that the KPNB1 mRNA level was higher in melanoma samples than that in skin nevus tissues. We thus proposed that KPNB1 played a role in promoting melanoma development, and conducted gain-of- and loss-of-function experiments to test our hypothesis. We found that KPNB1 knockdown significantly retarded the growth and metastasis of melanoma cells in vitro and in vivo, and increased their sensitivity towards the anti-tumor drug cisplatin. KPNB1 overexpression had opposite effects. Notably, in melanoma cells, KPNB1 overexpression significantly decreased Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) protein level, which was also overexpressed in melanoma samples and enhanced malignant behaviors of melanoma cells. We further demonstrated that KPNB1 overexpression induced deubiquitination of G3BP1, and prevented its degradation. However, KPNB1 overexpression hardly affected the nuclear translocation of G3BP1. Additionally, alterations induced by KPNB1 overexpression were partly reversed by G3BP1 inhibition. Therefore, the results suggest that KPNB1 may promote melanoma progression by stabilizing the G3BP1 protein. KPNB1-G3BP1 axis represents a potential therapeutic targetable node for melanoma.

Two important considerations in clinical research studies are proper evaluations of internal and external validity. While randomized clinical trials can overcome several threats to internal validity, they may be prone to poor external validity. Conversely, large prospective observational studies sampled from a broadly generalizable population may be externally valid, yet susceptible to threats to internal validity, particularly confounding. Thus, methods that address confounding and enhance transportability of study results across populations are essential for internally and externally valid causal inference, respectively. These issues persist for another problem closely related to transportability known as data-fusion. We develop a calibration method to generate balancing weights that address confounding and sampling bias, thereby enabling valid estimation of the target population average treatment effect. We compare the calibration approach to two additional doubly-robust methods that estimate the effect of an intervention on an outcome within a second, possibly unrelated target population. The proposed methodologies can be extended to resolve data-fusion problems that seek to evaluate the effects of an intervention using data from two related studies sampled from different populations. A simulation study is conducted to demonstrate the advantages and similarities of the different techniques. We also test the performance of the calibration approach in a motivating real data example comparing whether the effect of biguanides versus sulfonylureas - the two most common oral diabetes medication classes for initial treatment - on all-cause mortality described in a historical cohort applies to a contemporary cohort of US Veterans with diabetes.

Purpose Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement. Materials and methods CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry. Results Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%. Conclusion Anti-CD19 CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.

Objective. This study focused on mood regulations and their association with sociodemographic status, exercise pattern, and physical conditions of adults and older adults in China who did not undergo interventions. Method. Data were based on the 2016 to 2018 Guangdong National Physique Monitoring data, in which 5242 participants aged 20-69 years were recruited. Multiple statistical analysis methods, such as descriptive and logistic regression analyses, were used to study each exercise motivation and its association with influencing factors, including sociodemographic characteristics, exercise measurements, and physical conditions. An exercise index for mental health was also used to investigate the number and types of people who were more likely to meet the index. Results. We observed that 44.9% (2355/5242) of participants did not engage in physical exercise in this study. Only older participants (40 to 69 years old) and those with an average level of education (high school/technical secondary school) showed a significant association with exercising for mood regulation. Few people met the index that is good for mental health (16.64% [872/5242] met index 1, and 2.84% (149/5242) met index 2), and higher education showed a significant association with a reduction in the mental health burden and the prevention of depression. Conclusion. This study found that motivating people to be more active and educating them on the potential mental health benefits of exercise could help them to exercise more.

Fear of cancer recurrence (FCR), anxiety, and depression are common psychological disturbances that frequently occur together among cancer patients. This study investigated network connectivity between FCR, anxiety, and depressive symptoms in a large representative sample of breast cancer patients.This was a multicenter, cross-sectional study of 803 women with breast cancer. All participants completed the 4-item FCR scale, Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire (PHQ-9). Network analysis was conducted to investigate the network structure, central symptoms, bridge symptoms, and network stability of these disturbances.The generated network model indicated that anxiety and depression symptom communities were well-connected with each other, while FCR emerged as a distinct cluster with only a few weak links to anxiety and depression communities. Depressive and anxiety symptoms were more central than FCR symptoms were in the model. 'Having trouble relaxing' (#GAD4, strength = 1.147) was the most central node within the whole network, and 'strong feelings about recurrence' (#FCR4, strength = 0.531) was the least central node. Several anxiety symptoms (e.g., 'feeling afraid', 'uncontrollable worry', and 'restlessness') acted as important bridging symptoms connecting FCR, depression and anxiety communities. 'Uncontrollable worry' (#GAD2) had the highest node-specific predictive betweenness value. The network stability of this model was high.Depression and anxiety symptoms are highly interactive with each other among women with breast cancer. Conversely, FCR may have attenuated relations with anxiety and depression communities and emerged as a relatively independent, unique experience. Anxiety symptoms, particularly 'uncontrollable worry', acted as important trans-diagnostic symptoms that connected different communities. Findings suggested interventions to alleviate excessive worries and enhance feelings of personal control might be helpful in preventing or reducing related symptoms of FCR, anxiety and depression.

BACKGROUND AND OBJECTIVES: There have been only several studies on the correlation between glomerular exostosin expression and membranous lupus nephritis. In this study, we validate the previous findings in Chinese patients with class 5 lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASURE: One hundred sixty-five patients with class 5 lupus nephritis and varying numbers of control patients were included. Exostosin1/exostosin2 staining was performed by immunohistochemistry, and the staining intensity was quantified using an imaging analysis system. Between-group comparisons were tested for statistical significance using the Pearson chi-squared test, the Fisher exact test, the unpaired t test, the Mann–Whitney U test, or one-way ANOVA. RESULTS: In total, 46% of patients with class 5 lupus nephritis, 9% of patients with class 5 + 3/4 lupus nephritis, and none of the other classes of lupus nephritis were exostosin positive. Only three patients were exostosin positive among the 61 patients with other secondary membranous nephropathy. The exostosin-positive rate in nephrotic patients was significantly higher than that in patients without nephrotic syndrome (P

Objective. This study intends to construct an error distribution prediction model and analyze its parameters and analyzes the boundary size of CTV extension to PTV, so as to provide a reference for lung cancer patients to control clinical set-up errors and radiotherapy planning. Methods. The prior SBRT set-up error data of 50 patients with lung cancer treated by medical linear accelerator were selected, the Gaussian mixture model was adopted to construct the error distribution prediction model, and the model parameters were solved, based on which the emission boundary from CTV to PTV was calculated. Results. According to the analysis of the model parameters, the spatial distribution of set-up errors is mainly concentrated in the direction of four central points (μ1 ~ μ4), and the error is smaller in the Vrt direction (-0.991~2.808 mm) and Lat direction (-0.447~1.337 mm) and larger in the Lng direction (-1.065~4,463 mm). The possibility of offset of set-up errors in μ2 and μ3 direction (0.4440, 02198) is greater than that of μ1 and μ4 (0.1767, 0.1595). The standard deviation of set-up errors can reach 0.538 mm. The theoretical expansion boundary of CTV to PTV in Vrt, Lng, and Lat can be calculated as 1.7963 mm, 2.3749 mm, and 0.6066 mm. Conclusion. The GMM Gaussian mixture model can quantitatively describe and predict the set-up errors distribution of lung cancer patients and can obtain the emission boundary of CTV to PTV, which provides a reference for radiotherapy set-up errors control and tumor planning target expansion of lung cancer patients without SBRT.

In order to improve the detection function of wearable intelligent devices in the Internet of things and facilitate people to control a variety of information such as heart rate, exercise state, blood oxygen saturation, and so on, the scientific detection of human physical health based on wearable devices based on Internet of things technology is proposed. Through the combination of software- and hardware-related functional modules, the real-time detection of human physical health information can be effectively realized. Firstly, the detection principle of optical capacitance product pulse wave signal and the waveform characteristics of pulse wave are introduced, and then the application scenarios and advantages of wearable devices are further introduced; then, the convolutional neural network for pulse wave signal denoising and the basic principle of self-encoder are introduced; finally, the regression prediction method and support vector machine method for pulse wave signal feature extraction are introduced in detail. The pulse wave based on optical capacitance product is removed to improve the waveform quality of pulse wave signal. Firstly, the system software development environment is briefly described. Then, the software design of watch terminal master device based on MSP432 and belt terminal slave device based on MSP430 are described in detail, and the detailed program implementation flow of each key technology in the system is given. In addition, the fall detection algorithm based on threshold discrimination is studied, and the program implementation of the algorithm is also described in detail. Finally, the system is tested. The results show that normal state mainly include normal walking, jogging, and fast sitting, and the accuracy rate is 97%, 95%, and 93%, respectively. For fall state, the experimenter needs to simulate various possible fall states, and the accuracy rate is 95%, 93%, and 95%, respectively, which verifies the detection accuracy of the algorithm. The system can automatically turn on the satellite positioning function when the user’s physical sign parameters are abnormal or the user’s current fall dangerous situation occurs, and send the current position information and alarm content information through the GSM module, so that the dangerous situation can be found and handled at the first time.

The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body weight in Jing Hong laying hens. Blood samples were collected at predetermined time points. Plasma meloxicam concentrations were determined using a validated high-performance liquid chromatography (HPLC) assay method and then subjected to a non-compartmental analysis. After IV administration, meloxicam had a mean (±SD) volume of distribution at steady-state (Vd

Due to shortage of childcare facilities while high social expectations for mothering, becoming a mother is a big life challenge for most women in urban China. The understandings on Chinese postpartum women's affective well-being and its relation with spousal support and maternal role adaptation remain limited. This study aims to investigate the affective well-being (including both positive and negative affect) of Chinese urban postpartum women and how it is associated with spousal support and maternal role adaptation. A cross-sectional survey was conducted in Shanghai, China, between June and July 2019. A total of 498 urban mothers whose babies were 0 to 1 year old participated in this survey. They completed the Postpartum Social Support Questionnaire (PSSQ), the Maternal Role Adaptation Scale, and the Positive and Negative Affect Scale (PANAS), and reported socio-demographic information. Results showed that positive and negative affect of postpartum women were not significantly associated with each other. Positive affect had a positive correlation with spousal support and maternal role adaptation. Negative affect was negatively associated with maternal role adaptation, while not significantly associated with spousal support. Maternal role adaptation partially mediated the relationship between spousal support and positive affect of the participants, controlling for age, household income, education, birth order, and inter-generational support. The findings indicate that intervention programs towards mental health of postpartum women should focus more on positive affect cultivation; moreover, clinical services should help postpartum women to adapt to maternal role by encouraging new fathers' or partners' involvement in daily childcare-giving.

Background: Direct oral anticoagulants (DOACs) are the guideline-recommended therapy for some hypercoagulable diseases but are used off-label for left ventricular thrombus (LVT) owing to a paucity of evidence. We performed a meta-analysis to assess the safety and efficacy of DOACs compared with vitamin K antagonists (VKAs) for LVT treatment. Methods: We comprehensively searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for studies that compared DOACs with VKAs for LVT treatment. Outcome indicators included stroke or systemic embolism (SSE), thrombus resolution, bleeding, and death. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Data were analyzed using Review Manager 5.3, and the meta-analysis is registered at PROSPERO (CRD 42020211376). Results: We included 12 observational studies (n = 2262 patients). SSE was similar for DOACs and VKAs groups (odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.66-1.54, P = 0.95). For thrombus resolution, DOACs were not significantly different to VKAs (OR = 1.15, 95% CI 0.54-2.45, P = 0.71). DOACs and VKAs had a similar bleeding risk (OR = 0.78, 95% CI 0.45-1.35, P = 0.37). DOACs and VKAs groups had a comparable mortality (OR = 0.91, 95% CI 0.50-1.65, P = 0.76). Subgroup analysis showed that post-acute myocardial infarction (AMI) patients using DOACs had a lower risk of SSE (OR = 0.24, 95% CI 0.07-0.87, P = 0.03) and bleeding (OR = 0.38, 95% CI 0.18-0.81, P = 0.01). Conclusion: DOACs and VKAs showed no difference in the safety and efficacy of patients with LVT. DOACs might be superior to VKAs for LVT treatment in post-AMI patients. Registration No: A review protocol (number: CRD 42020211376) was registered in the PROSPERO International prospective register of systematic reviews.

Molecular diagnostics devoted to discover and monitor new biomarkers is gaining increasing attention in clinical diagnosis. In this work, a programmable DNA-fueled electrochemical analysis strategy is designed for the determination of an emerging biomarker in lung cancer, PD-L1-expressing exosomes. Specifically, PD-L1-expressing exosomes are first enriched onto magnetic beads functionalized with PD-L1 antibody and are able to interact with cholesterol-modified hairpin templates. Then, programmable DNA synthesis starts from the hairpin template-triggered primer exchange reaction and generates a large number of extension products to activate the trans-cleavage activity of CRISPR-Cas12a. After that, CRISPR-Cas12a-catalyzed random cleavage boosts the degradation of methylene blue-labeled signaling strands, so electro-active methylene blue molecules can be enriched onto a cucurbit[7]uril-modified electrode for quantitative determination. Our method demonstrates high sensitivity and specificity toward electrochemical analysis of PD-L1-expressing exosomes in the range from 10

It was to investigate the regulation of motigen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathways mediated by epithelial cell adhesion molecules (EpCAM) N-glycosylation on epithelial-mesenchymal transition (EMT) in breast cancer cells. Breast cancer cells MCF-7 and MDA-MB-231 were taken in the control group; the blank vector plasmid transfection (blank plasmid group) and EpCAM N-glycosylation mutant plasmid transfection (Mutant-EpCAM group) were analyzed. The EpCAM in breast cancer cells was localized by immunofluorescence technique, the proliferation activity of cells in each group was detected by methyl thiazolyl tetrazolium (MTT) assay, and the clonality of cells was detected by plate cloning. and apoptosis-related proteins (Caspase-3, Bcl-2, and Bax), EMT-related molecular markers (E-cadherin, N-cadherin, and Vimentin), as well as MAPK and PI3K/Akt pathway-related proteins (p38, PI3K, and Akt) in cells were detected by western blotting (WB). EpCAM N-glycosylation mutations did not alter the expression localization of EpCAM in breast cancer cells. Compared with the control group and the blank plasmid group, the cell proliferation activity and the number of colonies formed were decreased in the Mutant-EpCAM group (P0.05). The protein expressions of Caspase-3, Bax, and E-cadherin were up-regulated significantly, and the expressions of Bcl-2, N-cadherin, Vimentin, p-p38, p-PI3K, and p-Akt were greatly down-regulated (P0.05). EpCAM N-glycosylation could regulate the EMT in breast cancer cells through MAPK and PI3K/Akt pathways.

Objectives The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. Methods Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. Results The anthropometric data and hormone indicators between CPP and PT were statistically different (p Conclusions IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

The objective of the study was to characterize the longitudinal, dynamic intracranial pressure (ICP) trajectory in acute brain injury (ABI) patients admitted to intensive care unit (ICU) and explore whether it added sights over traditional thresholds in predicting outcomes.ABI patients with ICP monitoring were identified from two public databases named Medical Information Mart for the Intensive Care (MIMIC)-IV and eICU Collaborative Research Database (eICU-CRD). Group-based trajectory modeling (GBTM) was employed to identify 4-h ICP trajectories in days 0-5 post-ICU admission. Then, logistic regression was used to compare clinical outcomes across distinct groups. To further validate previously reported thresholds, we created the receiver operating characteristic (ROC) curve in our dataset.A total of 810 eligible patients were ultimately enrolled in the study. GBTM analyses generated 6 distinct ICP trajectories, differing in the initial ICP, evolution pattern, and number/proportion of spikes20/22 mmHg. Compared with patients in "the highest, declined then rose" trajectory, those belonging to the "lowest, stable," "low, stable," and "medium, stable" ICP trajectories were at lower risks of 30-day mortality (odds ratio [OR] 0.04; 95% confidence interval [CI] 0.01, 0.21), (OR 0.04; 95% CI 0.01, 0.19), (OR 0.08; 95% CI 0.01, 0.42), respectively. ROC analysis demonstrated an unfavorable result, for example, 30-day mortality in total cohort: an area under the curve (AUC): 0.528, sensitivity: 0.11, and specificity: 0.94.This study identified three ICP trajectories associated with elevated risk, three with reduced risks for mortality during ICU hospitalization. Notably, a fixed ICP threshold should not be applied to all kinds of patients. GBTM, a granular method for describing ICP evolution and their association with clinical outcomes, may add to the current knowledge in intracranial hypertension treatment.

Ischemic heart disease (IHD) is currently one of the leading causes of death among cardiovascular diseases worldwide. In addition, blood reflow and reperfusion paradoxically also lead to further death of cardiomyocytes and increase the infarct size. Multiple evidences indicated that mitochondrial function and structural disorders were the basic driving force of IHD. We summed up the latest evidence of the basic associations and underlying mechanisms of mitochondrial damage in the event of ischemia/reperfusion (I/R) injury. This review then reviewed natural plant products (NPPs) which have been demonstrated to mitochondria-targeted therapeutic effects during I/R injury and the potential pathways involved. We realized that NPPs mainly maintained the integrality of mitochondria membrane and ameliorated dysfunction, such as improving abnormal mitochondrial calcium handling and inhibiting oxidative stress, so as to protect cardiomyocytes during I/R injury. This information will improve our knowledge of mitochondrial biology and I/R-induced injury’s pathogenesis and exhibit that NPPs hold promise for translation into potential therapies that target mitochondria.

Increasing attention to serious environmental problems has caused the public to put forth more pressure on firms to fulfill their responsibilities to society at large. The establishment of a strict and mandatory environmental information disclosure (EID) mechanism has become particularly urgent. This study takes A-share listed firms in China's pharmaceutical manufacturing industry from 2011 to 2019 as a case. Considering the impact of the quality of EID on financial performance (FP), the moderating effects of internal and external factors, such as environmental regulation (ER), media pressure (MP), and executive compensation (EC), are analyzed. The results showed that the quality of EID had a negative effect on FP. It is difficult for EC to have a moderating effect on the relationship between the two. ER and MP, which are intended to exert strong external means of governance, cannot have a positive impact. Differences in regional marketization and ownership affect the moderators. This study highlights the difficulty of improving the environmental behavior of firms even while under the direct pressure from internal and external stakeholders and provides a reference for regulatory authorities to improve the EID mechanism.

Following the approval of the T cell engaging bispecific antibody blinatumomab, immune cell retargeting with bispecific or multispecific antibodies has emerged as a promising cancer immunotherapy strategy, offering alternative mechanisms compared to immune checkpoint blockade. As we gain more understanding of the complex tumor microenvironment, rules and design principles have started to take shape on how to best harness the immune system to achieve optimal anti-tumor activities.In the present review, we aim to summarize the most recent advances and challenges in using bispecific antibodies for immune cell retargeting and to provide insights into various aspects of antibody engineering. Discussed herein are studies that highlight the importance of considering antibody engineering parameters, such as binding epitope, affinity, valency, and geometry to maximize the potency and mitigate the toxicity of T cell engagers. Beyond T cell engaging bispecifics, other bispecifics designed to recruit the innate immune system are also covered.Diverse and innovative molecular designs of bispecific/multispecific antibodies have the potential to enhance the efficacy and safety of immune cell retargeting for the treatment of cancer. Whether or not clinical data support these different hypotheses, especially in solid tumor settings, remains to be seen.

For NSCLC patients with complete resection, the prognostic role of EGFR mutation for recurrence, especially for CNS metastasis, is still controversial. In this study, we aimed to identify the characteristics of the recurrence pattern of lung adenocarcinoma based on EGFR mutation status.Overall, 888 patients with completely surgically resected LUAD who underwent EGFR mutation status analysis from two Chinese institutions were included. Sites and data of initial recurrence were recorded. The recurrence patterns according to EGFR mutation status were estimated by Kaplan-Meier analysis, and hazard rate curves were generated.245 (27.6%) of 888 patients suffered from recurrence. Before and after PSM, there were no statistically significant differences between the EGFR mutation and EGFR WT groups for all types of recurrence, including CNS metastasis. Multivariable Cox analysis revealed that EGFR status was not a risk factor for all types of recurrence, including CNS metastasis (HR 0.88, 95% CI 0.54-1.46, p = 0.632). The CNS metastasis hazard curve in the EGFR mutation group showed that the first peak occurred at approximately 24-26 months after surgery, which was 10 months later than that in the EGFR WT group. In addition, the second peak time in the EGFR mutation group was approximately 2 years later than that in the EGFR WT group.EGFR mutation was not an independent prognostic factor for postoperative recurrence. EGFR-mutated LUADs did not have a clinical course with a higher incidence of CNS metastasis. However, the peak hazards for recurrence of CNS metastasis occur at a later time point in the EGFR mutant group compared with the EGFR wild type group.

Interfacial DNA self-assembly is fundamental to solid nucleic acid biosensors, whereas how to improve the signal-to-noise ratio has always been a challenge, especially in the charge-based electrochemical DNA sensors because of the large noise from the negatively charged DNA capture probes. Here, we report a DNA framework-reversed signal-gain strategy through background-to-signal transition for ultrasensitive and highly specific electrical detection of microRNAs (miRNAs) in blood. By using a model of enzyme-catalyzed deposition of conductive molecules (polyaniline) targeting to DNA, we observed the highest signal contribution per unit area by the highly charged three-dimensional (3D) tetrahedral DNA framework probe, relative to the modest of two-dimensional (2D) polyA probe and the lowest of one-dimensional (1D) single-stranded (ss)DNA probe, suggesting the positive correlation of background DNA charge with signal enhancement. Using such an effective signal-transition design, the DNA framework-based electrochemical sensor achieves ultrasensitive miRNAs detection with sensitivity up to 0.29 fM (at least 10-fold higher than that with 1D ssDNA or 2D polyA probes) and high specificity with single-base resolution. More importantly, this high-performance sensor allows for a generalized sandwich detection of tumor-associated miRNAs in the complex matrices (multiple cell lysates and blood serum) and further distinguishes the tumor patients (e.g., breast, lung, and liver cancer) from the normal individuals. These advantages signify the promise of this miRNA sensor as a versatile tool in precision diagnosis.

Radiotherapy is one of the major approaches to cancer treatment. Artificial intelligence in radiotherapy (shortly, Intelligent radiotherapy) mainly involves big data, deep learning, extended reality, digital twin, radiomics, Internet plus and Internet of Things (IoT), which establish an automatic and intelligent network platform consisting of radiotherapy preparation, target volume delineation, treatment planning, radiation delivery, quality assurance (QA) and quality control (QC), prognosis judgment and post-treatment follow-up. Intelligent radiotherapy is an interdisciplinary frontier discipline in infancy. The review aims to summary the important implements of intelligent radiotherapy in various areas and put forward the future of unmanned radiotherapy center.

Little is known about the association between perceived social support (PSS) and suicidal ideation in Chinese adolescents. This study was to examine the association of perceived social support and suicidal ideation (SI) and the mediating role of depressive symptoms in a large sample of adolescents in China.A total of 11,831 adolescents who participated in the baseline Shandong Adolescent BehaviorHealth Cohort were included for analysis. Perceived social support, depressive symptoms, and other variables were assessed by a self-administrated questionnaire. Path analysis was used to estimate the association between PSS, depressive symptoms, and suicidal ideation.The prevalence rate of SI in the past year was 12.5%. Suicidal ideation and depressive symptoms were significantly associated with low PSS from family, friends, and significant others. Path analysis revealed that depressive symptoms partially mediated the relationship between PSS from family, friends, and significant others and suicidal ideation. After controlling for covariates, the mediation effect proportion of depressive symptoms on the associations between perceived social support from family, friends, and significant others and SI ranged from 19.20% to 62.12%.As this is a cross-sectional study, no causal relationship could be made.Depressive symptoms partially mediated the association between perceived social support and suicidal ideation. Longitudinal research is needed to better understand the association between social support and suicidal ideation in adolescents.

This study aimed to investigate the effect of N6-methyladenosine (m