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Hyperuricemia is a metabolic disease caused by the accumulation of uric acid in the body. Allopurinol, benzbromarone, and febuxostat, which are available in the market, have reduced the circulating urate levels; however, they exhibit serious side effects. Therefore, it is reasonable to develop a new active antihyperuricemia drug with few side effects. With the deepening of research, numerous kinds of literature have shown that natural active substances are effective in the treatment of hyperuricemia with a variety of sources and few side effects, which have become the focus of research in recent years. This review focuses on natural active substances with uric-acid-reducing activity and discusses their pharmacological effects. More specifically, the bioactive compounds of natural active substances are divided into five categories: natural extracts, monomer compounds extracted from plants, natural protease hydrolysates, peptides, and probiotic bacteria. In addition, the mechanisms by which these bioactive compounds exhibit hypouricemic effects can be divided into four classes: inhibition of key enzyme activities, promotion of uric acid excretion and inhibition of reabsorption in the kidney, promotion of decomposing uric acid precursors, and promotion of decomposing uric acid. Overall, this current and comprehensive review examines the role of natural active substances in the treatment of hyperuricemia.

With the rapid development of biopharmaceuticals and the outbreak of COVID-19, the world has ushered in a frenzy to develop gene therapy. Therefore, therapeutic genes have received enormous attention. However, due to the extreme instability and low intracellular gene expression of naked genes, specific vectors are required. Viral vectors are widely used attributed to their high transfection efficiency. However, due to the safety concerns of viral vectors, nanotechnology-based non-viral vectors have attracted extensive investigation. Still, issues of low transfection efficiency and poor tissue targeting of non-viral vectors need to be addressed. Especially, pulmonary gene delivery has obvious advantages for the treatment of inherited lung diseases, lung cancer, and viral pneumonia, which can not only enhance lung targeting and but also reduce enzymatic degradation. For systemic diseases therapy, pulmonary gene delivery can enhance vaccine efficacy via inducing not only cellular, humoral immunity but also mucosal immunity. This review provides a comprehensive overview of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery. First of all, the characteristics and therapeutic mechanism of DNA, mRNA, and siRNA are provided. Thereafter, the advantages and challenges of pulmonary gene delivery in exerting local and systemic effects are discussed. Then, the inhalation dosage forms for nanoparticle-based drug delivery systems are introduced. Moreover, a series of materials used as nanocarriers for pulmonary gene delivery are presented, and the endosomal escape mechanisms of nanocarriers based on different materials are explored. The application of various non-viral vectors for pulmonary gene delivery are summarized in detail, with the perspectives of nano-vectors for pulmonary gene delivery.

Background Extremely preterm (EP) birth is associated with higher risks of perinatal white matter (WM) injury, potentially causing abnormal neurologic and neurocognitive outcomes. MRI biomarkers distinguishing individuals with and without neurologic disorder guide research on EP birth antecedents, clinical correlates, and prognoses. Purpose To compare multiparametric quantitative MRI (qMRI) parameters of EP-born adolescents with autism spectrum disorder, cerebral palsy, epilepsy, or cognitive impairment (ie, atypically developing) with those without (ie, neurotypically developing), characterizing sex-stratified brain development. Materials and Methods This prospective multicenter study included individuals aged 14-16 years born EP (Extremely Low Gestational Age Newborns-Environmental Influences on Child Health Outcomes Study, or ELGAN-ECHO). Participants underwent 3.0-T MRI evaluation from 2017 to 2019. qMRI outcomes were compared for atypically versus neurotypically developing adolescents and for girls versus boys. Sex-stratified multiple regression models were used to examine associations between spatial entropy density (SE

The control of harmful cyanobacterial blooms has been becoming a global challenge. The development of eco-friendly algicides with strong specificity is urgently needed. The photosynthetic apparatus is a promising target site for algicides to minimize the possible harmful effects on animals and humans. In this study, biologically derived 2-hydroxychalcone efficiently inhibited the growth of bloom-forming

To perform a prospective cohort study to investigate whether night shift work is associated with incident hypertension and whether this association is modified by genetic susceptibility to hypertension because evidence on the association between night shift work and hypertension is insufficient.A total of 232,665 participants of UK Biobank who were recruited from 2006 to 2010 and observed to January 31, 2018, were included in this study. A Cox proportional hazards model with covariate adjustment was performed to assess the association between night shift work exposure and hypertension risk. We constructed a polygenic risk score (PRS) for genetic susceptibility to hypertension, which was used to explore whether genetic susceptibility to hypertension modified the effect of night shift work. The robustness of the results was assessed by sensitivity analysis.Night shift workers had a higher hypertension risk than day shift workers, which increased with increasing frequency of night shift work (PNight shift work exposure was associated with increased hypertension risk, which was modified by the genetic risk for hypertension, indicating that there is a joint effect of night shift work and genetic risk on hypertension.

Aims: The purpose of this paper is to prospectively evaluate the performance of an artificial intelligence (AI) system in diagnosing thyroid nodules and to assess its potential value in comparison with the performance of radiologists with different levels of experience, as well as the factors affecting its diagnostic accuracy. Background: In recent years, medical imaging diagnosis using AI has become a popular topic in clinical application research. Objective: This study aimed to evaluate the performance of an AI system in diagnosing thyroid nodules and compare it with the performance levels of different radiologists. Method: This study involved 426 patients screened for thyroid nodules at the First Affiliated Hospital of Guangzhou Medical University between July 2017 and March 2019. All of the nodules were evaluated by radiologists with various levels of experience and an AI system. The diagnostic performances of two junior and two senior radiologists, an AI system, and an AI-assisted junior radiologist were compared, as were their diagnostic results with respect to nodules of different sizes. Result: The senior radiologists, the AI system, and the AI-assisted junior radiologist performed better than the junior radiologist (p < 0.05). The area under the curves of the AI system and the AI-assisted junior radiologist were similar to the curve of the senior radiologists (p > 0.05). The diagnostic results concerning the two nodule sizes showed that the diagnostic error rates of the AI system, junior radiologists, and senior radiologists for nodules with a maximum diameter of ≤1 cm (Dmax ≤ 1 cm) were higher than those for nodules with a maximum diameter of ＞1 cm (Dmax > 1 cm) (23.4% vs. 12.1%, p = 0.002; 26.6% vs. 7.3%, p < 0.001; and 38.3% vs. 14.6%, p < 0.001). Conclusion: The AI system is a decision-making tool that could potentially improve the diagnostic efficiency of junior radiologists. Micronodules with Dmax ≤ 1cm were significantly correlated with diagnostic accuracy; accordingly, more micronodules of this size, in particular, should be added to the AI system as training samples. Other: The system could be a potential decision-making tool for effectively improving the diagnostic efficiency of junior radiologists in the community.

Xin Zhang,1– 3 Xiangbo Bu,4 Wenyu Jia,1,2 Yu Ying,1,2 Shanrong Lv,1,2 Guan Jiang1,2 1Department of Dermatology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China; 2Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Department of Dermatology, Xuzhou Children’s Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 4Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, 221009, People’s Republic of ChinaCorrespondence: Guan Jiang, Email dr.guanjiang@xzhmu.edu.cnIntroduction: Nanophototherapy has emerged as a novel and promising therapeutic strategy for cancer treatment; however, its efficacy in dermatological tumors and precancerous lesions remains severely limited. This study aimed to use the gas-liquid injection technique to fully utilize the synergistic photodynamic therapy (PDT)/photothermal therapy (PTT) of nanomaterials to enhance the antitumor effect.Methods: A novel oxygen-generating nanocomposite (TSL-IR820-CAT) was synthesized by encapsulating the photosensitizer IR820 and catalase (CAT) using a matrix encapsulation method based on thermosensitive liposomes (TSL).–The liquid injection technology enhances the treatment of cutaneous squamous cell carcinoma (cSCC). The combined PDT/PTT therapeutic effect of TSL-IR820-CAT on cSCC was investigated using in vivo and in vitro experiments.Results: TSL-IR820-CAT, with good stability, efficient drug release, and photothermal conversion ability, was successfully developed. Nanoparticles injected through a needle-free syringe efficiently accumulate in the tumor tissue. As TSL-IR820-CAT was consumed by A431 cells, some of it localized to the mitochondria and produced oxygen to relieve hypoxia, thereby enhancing the efficacy of PDT. PDT/PTT combination therapy resulted in irreversible apoptosis and inhibited cSCC growth. TSL-IR820-CAT coupled with gas-liquid injection was free from apparent systemic side effects.Conclusion: This article discusses new strategies and ideas for treating skin tumors and has significant application value.Keywords: skin squamous cell carcinoma, nanoparticles, gas-liquid injection technology, photodynamic therapy, photothermal therapy

Background. Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and HE in cirrhotic patients. Methods. We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results. Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73-11.32, P = 0.002 ). The heterogeneity was moderate ( I 2 = 66 %), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions. Our meta-analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.

Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer.This prospective study enrolled 76 suspected and 5 progressed lung cancer patients. Transbronchial biopsy tissues, BWF supernatant (BWF_Sup) and BWF precipitant (BWF_Pre) were tested by a targeted panel of 1021 genes.BWF_Sup cell-free DNA (cfDNA) was superior to tissue biopsy and BWF_Pre in determining mutational allele frequency, tumour mutational burden, and chromosomal instability. Moreover, BWF_Sup and BWF_Pre achieved comparable efficacy to tissue samples in differentiating malignant and benign patients, but only BWF_Sup persisted differentiated performance after excluding 55 malignancies pathologically diagnosed by bronchoscopic biopsy. Among 67 malignant patients, 82.1% and 71.6% of tumour-derived mutations (TDMs) were detected in BWF_Sup and BWF_Pre, respectively, and the detectability of TDMs in BWF_Sup was independent of the cytological examination of BWF. BWF_Sup outperformed BWF_Pre in providing more subclonal information and thus might yield advantage in tracking drug-resistant markers.BWF_Sup cfDNA is a reliable medium for lung cancer diagnosis and genomic profiles and may provide important information for subsequent therapeutic regimens.

Reconstructing an esthetic interimplant papilla remains challenging with implant-supported restorations, especially for patients with a thin gingival biotype. This technique report describes a modified approach to rebuilding an interimplant papilla by joining 2 elevated connective tissue flaps at the second-stage surgery.

Patients presenting breast actinic damage or implant-related complications require an autologous approach to breast reconstruction. However, when they are not good candidates for microsurgical procedures, alternative solutions must be sought. Latissimus dorsi (LD) is a workhorse flap in breast reconstruction, but often the amount of skin and volume achievable are insufficient. Taking inspiration from the Kiss flap concept, the authors hereby describe the "Kiss" LD flap to achieve totally autologous breast reconstruction.A prospective service evaluation of all patients who underwent breast reconstruction with Kiss LD flap between 2018 and 2020 was performed. Patient demographics and operative variables were recorded, together with early and late complications. Patient satisfaction and quality of life were registered using the latest BREAST-Q reconstruction module, which includes specific LD scales. The questionnaire was administered to patients preoperatively and six months postoperatively.Thirty patients underwent total autologous breast reconstruction with Kiss LD flap. Breast cancer and breast sarcoma resection were followed by reconstruction. The timing of reconstruction was immediate in 3 cases and delayed in 27 cases. No major complications nor total flap loss were registered. BREAST-Q scores postoperatively were significantly higher than the preoperative ones in every domain (p0.0001) except for the physical well-being of back and shoulder, where the scores differed slightly and non-significantly (p=0.05).The Kiss LD flap allows to harvest a large amount of skin to restore the breast envelope and a considerable volume to reconstruct the breast mound in a completely autologous procedure.

Previous studies have reported the effects of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation (STN-DBS) of Parkinson's disease (PD) patients. However, available data involving these issues are not consistent. In particular, the effect of age and disease duration on the initial efficacy of STN-DBS has not been established.A total of 51 patients with PD treated with bilateral STN-DBS were involved in the present study. They received clinical symptom evaluation during the preoperative, initial, and chronic stages of surgery. The correlations between age when undergoing surgery/age at disease onset/disease duration and outcomes of STN-DBS were measured.The preoperative levodopa response was negatively associated with age. During the initial stage, the age when undergoing surgery and age at disease onset were negatively correlated with the effect on bradykinesia, with better symptom control of general symptoms in long-term disease patients. Similarly, patients with an early time of surgery and disease onset and long-term disease duration showed better control of bradykinesia and axial symptoms at the chronic stage. Furthermore, a long-term disease duration and early disease onset benefited from an increase of therapeutic efficacy in general, rigid, and axial symptoms with STN-DBS after a long period. Nevertheless, patients with late disease onset achieved a better relief of stigma.Age and disease durations played a unique role in controlling the symptoms of PD patients treated with STN-DBS. These results may contribute to patient selection and adjustments of expectations of surgery, based on the age, disease duration, and different symptoms.

Fu-zhen Yuan,1 Wei Shui,2 Yan-li Xing,2 Yuan-yuan Niu,2 Xin Zhang,2 Chang-ran Zhang2 1Department of General Practice Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of General Medicine, The Eastern Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Chang-ran Zhang, Department of General Medicine, The Eastern Hospital of the First Affiliated Hospital, Sun Yat-sen University, No. 183, Huangpu East Road, Huangpu District, Guangzhou, People’s Republic of China, Tel +86 13711409903, Email zhcr2303@sina.comPurpose: Previous studies have shown that the red cell index (RCI) can be considered as a simple and useful method to evaluate respiratory function. However, at present its association with adverse hospitalization outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not fully understood. Our study aimed to examine the relationship between adverse hospitalization outcomes and RCI among AECOPD patients.Patients and Methods: We performed a retrospective analysis of consecutive patients from January 2015 to October 2021. In this study, RCI was the independent variable, measured at baseline, and adverse hospitalization outcome was the dependent variable. According to the RCI median (RCI=2.221), we divided 377 patients into two roughly equal groups (188 and 189, respectively). Next, the association between RCI and adverse hospitalization outcomes was explored using multivariable logistic regression models. To identify any non-linear relationship, a generalized additive model (GAM) was employed.Results: With a total of 377 patients with AECOPD, we divided them into two roughly equal groups to compare the clinical factors and RCI levels. The patients in the higher RCI group showed poorer outcome incidence (18 [9.57%] vs 31 [16.40%]; p = 0.049). After accounting for potential confounders, the results showed that RCI was positively associated with adverse hospitalization outcomes (odds ratio [OR] = 1.15, 95% CI: 1.01– 1.32). In addition, a non-linear relationship was detected between RCI and adverse hospitalization outcomes, which had an inflection point of 3.2. There were odds ratios and confidence intervals of 0.8 (0.7– 1.0) and 1.3 (1.2– 1.4) on the left and right sides of the inflection point, respectively.Conclusion: The RCI and adverse hospitalization outcomes exhibited a non-linear relationship in the AECOPD patients. RCI is strongly positively correlated with adverse hospitalization outcomes when it was greater than 3.2.Keywords: AECOPD, RCI, worse hospitalization outcomes, non-linearity

The chances of people suffering from cognitive impairments increase gradually with age. Diet and lifestyle are closely related to the occurrence and development of cognitive function. Dietary flavonoid supplementation has been shown to be one of the protective factors against cognitive decline. Flavonoids belong to a class of polyphenols that have been proposed for the treatment of cognitive decline. Recent evidence has shown that intestinal flora in the human body can interact with flavonoids. Intestinal microbiota can modify the chemical structure of flavonoids, producing new metabolites, the pharmacological activities of which may be different from those of the parent; meanwhile, flavonoids and their metabolites can, in turn, regulate the composition and structure of intestinal flora. Notably, intestinal flora affect host nervous system activity through the gut-brain axis, ultimately causing changes in cognitive function. This review therefore summarizes the interaction of dietary flavonoids and intestinal flora, and their protective effect against cognitive decline through the gut-brain axis, indicating that dietary flavonoids may ameliorate cognitive impairment through their interaction with intestinal microbiota. © 2022 Society of Chemical Industry.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case-control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy-PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy-PAHs were statistically significantly higher in the ASD group, with the exception of 2-hydroxynaphthalene (2-OHNap) and 4-hydroxyphenanthrene (4-OHPhe). Moreover, urinary hydroxy-PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1-hydroxynaphthalene (1-OHNap, β = 3.32), hydroxyphenanthrenes (1/2/3 + 9-OHPhes, β = 3.41-5.12), 1-hydroxypyrene (1-OH-Pyr; β = 3.91), 2-hydroxybenzofuran (2-OHDBF; β = 3.93), and ∑OH-PAHs (β = 4.67) were positively associated with CARS scores after adjusting for covariates (all p lt; 0.05). When applying the ABC scale, 1-OHPyr levels were positively associated with ABC total scores (β = 18.54), with the strongest associations evidenced in regard to the social relatedness (β = 6.51) and language domains (β = 6.51) (all p lt; 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels in regard to CARS scores, and for 1-OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy-PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism. LAY SUMMARY: We conducted an epidemiologic study evaluating the associations of urinary hydroxy-PAH levels with autism spectrum disorder (ASD), autism symptomology, and autistic behaviors. We found that urinary hydroxy-PAHs were statistically significantly associated with ASD. We note strong statistically significant associations between 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels and increased severity of autism symptomology, as well as a strong statistically significant association between 1-OHPyr levels and behavioral characteristics within the social and linguistic domains. This work, if confirmed, will contribute to the future development of diagnostics for children with mild autism, as well as to environmental measures to promote the health and wellbeing of children with autism spectrum disorders.

Food additives are widespread in the human diet; however, their excessive intake can have an impact on the quality of health. This study evaluated food additives in bread and pasta products consumed by residents in various regions of Jilin Province, People's Republic of China, from 2019 to 2021. We collected samples of bread and six types of pasta products from farmers' markets and morning markets and used high-performance liquid chromatography, UV-visible spectrophotometry, and graphite furnace atomic absorption spectrometry to detect the content of the following food additives: sodium formaldehyde sulfoxylate, aluminum, and borate compounds. For 836 samples in total, we detected the presence of sodium formaldehyde sulfoxylate, aluminum, and borate compounds in excess rates reaching 3.5, 10, and 4.7%, respectively. Aluminum in fried breadsticks exceeded the standard by 40%. The results of this study can be used to assess the overall pass rate of bread and pasta products sold in Jilin Province and support the detection of possible food safety problems.

The highly proliferative nature of hepatocellular carcinoma (HCC) frequently results in a hypoxic intratumoural microenvironment, which creates a therapeutic challenge owing to a lack of mechanistic understanding of the phenomenon. We aimed to identify critical drivers of HCC development and progression in the hypoxic microenvironment.We performed integrative analysis of multiple transcriptomic and genomic profiles specific for HCC and hypoxia and identified the Ephrin-A3/Eph receptor A2 (EphA2) axis as a clinically relevant and hypoxia-inducible signalling axis in HCC. The functional significance and mechanistic consequences of the Ephrin-A3/EphA2 axis were examined in EFNA3- and EPHA2- knockdown/overexpressing HCC cells. The potential downstream pathways were investigated by transcriptome sequencing, quantitative reverse-transcription PCR, western blotting analysis and metabolomics.EFNA3 was frequently upregulated in HCC and its overexpression was associated with more aggressive tumour behaviours. HIF-1α directly and positively regulated EFNA3 expression under hypoxia. EFNA3 functionally contributed to self-renewal, proliferation and migration in HCC cells. EphA2 was identified as a key functional downstream mediator of EFNA3. Functional characterisation of the Ephrin-A3/EphA2 forward-signalling axis demonstrated a promotion of self-renewal ability and tumour initiation. Mechanistically, the Ephrin-A3/EphA2 axis promoted the maturation of SREBP1 and expression of its transcriptional target, ACLY, was significantly associated with the expression of EFNA3 and hypoxia markers in clinical cohorts. The metabolic signature of EPHA2 and ACLY stable knockdown HCC cells demonstrated significant overlap in fatty acid, cholesterol and tricarboxylic acid cycle metabolite profiles. ACLY was confirmed to mediate the self-renewal function of the Ephrin-A3/EphA2 axis.Our findings revealed the novel role of the Ephrin-A3/EphA2 axis as a hypoxia-sensitive modulator of HCC cell metabolism and a key contributor to HCC initiation and progression.Hepatocellular carcinoma (HCC) is a fast-growing tumour; hence, areas of the tumour often have insufficient vasculature and become hypoxic. The presence of hypoxia within tumours has been shown to negatively impact on the survival of patients with tumours, including HCC. Herein, we identified the Ephrin-A3/EphA2 axis as a key functional driver of tumour initiation and progression in response to hypoxia. Additionally, we showed that SREBP1-ACLY-mediated metabolic rewiring was an important downstream effector that induced cancer stemness in response to Ephrin-A3/EphA2 forward-signalling.

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.

Early warning of hypertensive disorder in pregnancy (HDP) can improve maternal and infant outcomes. However, few studies had evaluated the warning value of high-normal blood pressure (BP) before the onset of HDP. This was a prospective cohort study to investigate the relationship between high-normal BP in the first half of pregnancy and the risk of HDP. According to the maximum BP measured before 20

Pancreatic ductal adenocarcinoma (PDAC) represents the most common primary pancreatic malignancy. An understanding of the cytomorphologic features of conventional ductal adenocarcinoma and its variants is important to ensure accurate diagnoses.The clinicopathological and cytological data of serous fluids in PDAC patients were obtained from the electronic medical records and pathology database. All samples were analyzed and reclassified according to the "The International System for Reporting Serous Fluid Cytopathology" guidelines. Cytomorphologic features were examined with SurePath automatically prepared slides and stained using the Pap method in malignant (MAL) effusion specimens from 21 patients with PDAC. Immunocytochemical staining was conducted on 12 cell blocks from MAL PDAC effusion.A total of 137 serous fluids specimens of PDACs were included, among which 61 (44.5%), 9 (6.6%), 13 (9.5%), 52 (38.0%), and 2 (1.5%) patients were classified into malignancy, suspicious for malignancy, atypia of undetermined significance, negative for malignancy and nondiagnostic groups, respectively. The key cytologic features for the conventional type of PDAC included cohesive clusters of ductal cells in glandular crowding and disorganized "drunken honeycomb" pattern or intercalated duct-like structure with anisonucleosis, cytoplasmic vacuoles, and concomitant "Indian-file" configuration. Undifferentiated carcinoma was comprised of enlarged, undifferentiated, pleomorphic MAL cells. Adenosquamous carcinoma could show glandular and/or squamous differentiation. Colloid carcinoma was composed of three-dimensional cancer cell clusters floating in thick mucin.Crowding and disorganized "drunken honeycomb" pattern or intercalated duct-like structure with anisonucleosis, may represent an important clue for diagnosing PDAC in serous fluids. Immunocytochemical staining in combination with review of medical records and cytomorphological data can serve as useful adjuncts for distinguishing between PDAC and its variants.

This study was designed to evaluate the bioequivalence of the newly developed delayed-release oral suspension (test) 40 mg esomeprazole magnesium compared to its marketed counterpart (40 mg; reference) in healthy adult Chinese subjects. We conducted randomized, open-label, two-period, single-dose, two-way crossover trials over a 7-day washout period, comprising a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period. Then, in the next session, they received the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to assess the bioequivalence of esomeprazole peak plasma concentration (C

To identify the clinical significance of sparing submandibular glands (SMG) for the amelioration of acute xerostomia using diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT).The prospective study enrolled 42 participants treated with HT. All patients underwent five times of DKI scans before HT (pre-HT), in the middle of the HT course (mid-HT), immediately after HT (post-HT), and 1 months (1m-HT), 3 months post-HT(3m-HT). Mean diffusion (MD) and mean kurtosis (MK) of SMG, parotid glands (PG) and sublingual glands (SLG), saliva flow rate measures under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire scores (XQ) were recorded. Comparisons between the SMG-spared and -unspared groups were analyzed using two-factor repeated-measures ANOVA for the group as the inter-subject factor and the time as the intra-subject factor.When sparing SMG, the dose of spared-SMG and ipsilateral SLG was lower compared to that of unspared glands (p 0.001). MD of spared-SMG and ipsilateral SLG in SMG-spared group were lower than that of SMG-unspared group (the simple effect for the group, p-value at mid-HT, post-HT, 1m- and 3m-HT was 0.014, 0.011, 0.000 and 0.000, respectively), MK of spared-SMG was higher conversely (the main effect for the group, p 0.001), while uSFR and sSFR were significantly lower in SMG-unspared group (the main effect for the group, p = 0.002, and p = 0.045, respectively). No significant differences were detected in MK of SLG, MD/MK of PG, and XQ between the two groups (the main effect for the group, p values were 0.9, 0.37, 0.15, 0.86, respectively). There were significant differences in the effect of the time for all MD/MK of the salivary glands and for uSFR, sSFR, and XQ between the SMG-spared and -unspared groups (p values were all0.001).Sparing SMG is of great clinical significance in alleviating acute xerostomia for NPC patients treated by helical tomotherapy as evaluated by diffusion kurtosis imaging and saliva flow rate.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders. The etiology of autism remains unclear, but a growing body of evidence indicates that phthalates play a role in its pathogenesis. The aim of this study was to compare the urine levels of phthalates in children with ASD and healthy children. We also explored whether phthalates have an effect on ASD symptoms. The participants in this study included 101 children with ASD (79 boys and 22 girls) and 101 sex- and age-matched controls. The levels of phthalates were analyzed by gas chromatography-mass spectrometry (GC-MS). We detected significant differences in monoethyl phthalate (MEP) levels between the severe ASD and control groups (p0.05). Mono-n-butyl phthalate (MBP) concentration was positively correlated with language skill impairment in ASD (β: 0.387, p = 0.041). MEP levels were associated with the CARS "Imitation" score in all children (OR: 1.470). MBP levels were associated with the "Nonverbal Communication" score among boys (OR: 1.233), and MEP levels were associated with the "Nonverbal Communication" score among girls (OR: 2.648). MEP levels were related to the CARS total score after adjustment for sex (β: 1.524, p = 0.047). Compared with the reference mono(2-ethylhexyl) phthalate (MEHP) group, children with ASD in the medium-exposure group had an OR of 3.370 for aggravating ASD severity. These results suggested that increased exposure to phthalates contributes to more ASD symptoms and that there are potentially sex-specific associations. These findings warrant further confirmation.

Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib.We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR.In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib.Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.

The unprecedented COVID-19 outbreak impacted the world in many aspects. Air pollutants were largely reduced in cities worldwide in 2020. Using samples from two snow pits dug separately in 2019 and 2020 in Urumqi Glacier No. 1 (UG1) in the Xinjiang Uygur Autonomous Region (Xinjiang), China, we measured water-stable isotopes, soluble ions, and black and organic carbon (BC and OC). Both carbon types show no significant variations in the snow-pit profiles dated from 2018 through 2020. The deposition of anthropogenically induced soluble ions (K

The treatment of lung cancer patients, especially those with epidermal growth factor receptor (EGFR)-mutant T790M-negative adenocarcinoma, after first- or second-line tyrosine kinase inhibitor (TKI) treatment failure is challenging due to the poor prognosis and limited effectiveness of platinum two-drug chemotherapy or chemotherapy plus anti-angiogenesis therapy. It is well-known that pembrolizumab monotherapy exhibits low toxicity and long-term survival, but it is unknown in these patients.From September 2018 to March 2021, 460 patients in Jiangmen Central Hospital were included and 82 patients with disease progression in lung adenocarcinoma who remained T790M-negative on the second biopsy were screened. Two groups were divided according to treatment status, and simple random sampling was performed to obtain 32 cases respectively. The safety of the patients was subsequently evaluated by telephone follow-up.The objective response rate (ORR) and disease control rate (DCR) in the pembrolizumab group were 15.63% and 53.13%. In the chemotherapy group, the ORR was 8.33% and the DCR was 25% (P0.05). In the pembrolizumab group, the progression-free survival (PFS) [14.65 months, 95% confidence interval (CI): 13.03 to 16.28] was significantly higher than that of the control group (9.54 months, 95% CI: 8.43 to 10.65) (P0.05). In the univariate analysis, programmed cell death protein 1 ligand (PD-L1) expression, smoking status, gender, and whether first-line chemotherapy was associated with survival. In the multivariate analysis, gender [P=0.001; hazard ratio (HR) 10.98, 95% CI: 2.49-46.67], first-line chemotherapy (P=0.037; HR 4.5, 95% CI: 1.1-4.81), and PD-L1 expression (P=0.039; HR 0.16, 95% CI: 0.04-0.68) were correlated with patient survival. Grade 3 or grade 4 treatment-related adverse events were not found in the pembrolizumab group, while 2 cases of grade 3 or 4 treatment-related adverse events occurred in the control group.In advanced lung adenocarcinoma patients with EGFR-mutant T790M-negative after TKI treatment, pembrolizumab had a higher ORR and PFS. Pembrolizumab in women with first-line chemotherapy and PD-L1 ≥25% of those patients may have a good response and a low rate of adverse reactions. A multicenter, prospective, evidence-based study of pembrolizumab salvage therapy in those patients is warranted for posterior line treatment.

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of

This study aimed to determine the effect of miR-186-3p and KRT18 interaction on the biological behavior of colon cancer cells. A biotin-microRNA pull-down assay was performed to identify potential miRNAs. qRT-PCR was used to verify the KRT18 and miR-186-3p levels. In addition, Western blotting was used to detect the KRT18 protein levels. The functional connection between KRT18 and miR-186-3p was confirmed using a dual luciferase reporter assay. BrdU incorporation, MTT assay, and flow cytometry were performed to verify the biological function coupled with in vivo assays. A significant decrease in miR-186-3p expression was observed in colon carcinoma tissues and cells. Functionally, overexpression of miR-186-3p displayed an obvious suppressive action on cell proliferation and viability, and a stimulatory action on the apoptotic ability of SW620 and SW480 cells. Conversely, reduced miR-186-3p had a marked stimulatory effect on proliferation and viability, and a suppressive apoptotic effect. Inhibition of tumorigenesis was observed in mice treated with the miR-186-3p agomir. Furthermore, we identified that miR-186-3p regulated KRT18 levels in colon carcinoma, where silenced KRT18 suppressed proliferation and viability and promoted apoptosis. However, the addition of a miR-186-3p inhibitor weakened the effects of si-KRT18. Additionally, the activation of MAPK signaling pathway upon miR-186-3p silencing was antagonized by the combined transfection of si-KRT18 and miR-186-3p inhibitor. miR-186-3p suppresses proliferation and viability, but facilitates apoptosis in colon cancer cells by targeting KRT18 and negatively regulating the MAPK signaling pathway, indicating that the miR-186-3p/KRT18 axis may be a promising therapeutic target for colon carcinoma. Abbreviations: KRT18: keratin 18; NC: negative control; si‑: small interfering RNA; inhibitor: miR-186-3p inhibitor; OD: optical density; PI: propidium iodide; FITC: fluorescein isothiocyanate; 3’UTR: 3’untranslated region; WT: wild-type; MUT: mutant-type; miR: microRNA

Our review explains the role of surfactant protein D (SP-D) in different kinds of bacterial infection based on its presence in different ocular surface tissues. We discuss the potential role of SP-D against invasion by pathogens, with the aim of identifying new prospects for the possible mechanism of SP-D-mediated immune processes, and the diagnosis, prognosis, or treatment of ocular bacterial infection.We reviewed articles about the role of SP-D in various ocular bacterial infections or infection-related ocular diseases through PubMed, Google Scholar, and the Web of Science databases.SP-D acts as an important immune factor that can resemble molecules in different polymerization states and that defends against pathogen invasion. The increased SP-D production and secretion in tear fluid and the cornea after ocular bacterial infections such as Staphylococcus aureus, Pseudomonas aeruginosa keratitis, and infection-related ocular diseases, was shown to have potential anti-inflammatory effects. The mechanisms of SP-D's action against ocular bacterial infections include presenting, aggregating, opsonizing, and phagocytizing antigens, as well as regulating anti-bacterial immunity processes, including toll-like receptor-5 (TLR-5) pathway and IL-8 effect, TLR-4 and TLR-2 pathways and other possible ways remained to be elucidated in more detail. The findings demonstrate the potential of SP-D as an important clinical diagnostic biomarker prognosis predictor, and target for ocular immunotherapy.SP-D participates in invasion by different ocular bacteria and infection-related ocular diseases through multiple immune mechanisms. This finding provides new prospects for the diagnosis, prognosis and treatment of ocular bacterial infection.

The rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T-cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T-cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS-CoV-2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T-cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T-cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T-cell responses to the SARS-CoV-2 Omicron variant.

Breast cancer (BRCA) is one of the leading causes of death among women worldwide, and drug resistance often leads to a poor prognosis. Necroptosis is a type of programmed cell death (PCD) and exhibits regulatory effects on tumor progression, but few studies have focused on the relationships between necroptosis-associated lncRNAs and BRCA. In this study, we established a signature basis of 7 necroptosis-related lncRNAs associated with prognosis and divided BRCA patients into high- and low-risk groups. Kaplan-Meier curves all showed an adverse prognosis for patients in the high-risk group. Cox assays confirmed that risk score was an independent prognostic factor for BRCA patients. The receiver operating characteristic (ROC) curve proved the predictive accuracy of the signature and the area under the curve (AUC) values of the risk score reached 0.722. The nomogram relatively accurately predicted the prognosis of the patients. GSEA analysis suggested that the related signaling pathways and biological processes enriched in the high- and low-risk groups may influence the tumor microenvironment (TME) of BRCA. ssGSEA showed the difference in immune cell infiltration, immune pathway activation, and immune checkpoint expression between the two risk groups, with the low-risk group more suitable for immunotherapy. According to the significant difference in IC50 between risk groups, patients can be guided for an individualized treatment plan. Overall, the authors established a prognostic signature consisting of 7 necroptosis-associated lncRNAs that can independently predict the clinical outcome of BRCA patients. The difference in the tumor immune microenvironment between the low- and high-risk populations may be the reason for the resistance to immunotherapy in some patients.

Xiao-Qi Chen,&ast; Yun-Xia Zhao,&ast; Chuan-Lei Zhang, Xin-Ting Wang, Xin Zhang, Xi Chen, Chang-Wei Yuan, Qing Zhao, Xin-Ju Chen Department of Gastroenterology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin-Ju Chen, Department of Gastroenterology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, No. 19, Renmin Road, Jinshui District, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86-13700867158, Email chxj888@163.comPurpose: Anlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China.Patients and Methods: Between July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results: Of the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30– 17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31– 15.47) and 6.21 months (95% CI: 2.23– 15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66– 13.14] vs 11.86 months [95% CI: 4.27– 15.93]) and OS (4.90 [95% CI: 2.56– 13.60] vs 11.04 months [95% CI: 1.31– 17.18]) between the two groups (all p> 0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%).Conclusion: Anlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.Keywords: anlotinib, objective response rate, PD-1 blockades, primary hepatocellular carcinoma

Human health and environmental protection demand wood-based panel industry for innovative soy-based adhesives with high production efficiency, straightforward synthesis processes, non-toxicity, and high bonding performance. A simple and efficient microwave pretreatment process and low addition of bio-derived crosslinking agent was used in this study to prepare a non-toxic and high-bonding performance soybean protein-based adhesive. After 4 min of microwave pretreatment time, the complex quaternary structure of soybean protein molecule unfolds, the soybean protein disperses evenly and stably, and active groups of soybean protein molecules are exposed. After adding 3.85% crosslinking agent, the moisture absorption rate of the soybean protein-based adhesive decreases by 41.77%, the residual rate increases by 3.68%, and the wet shear strength of the resultant plywood increases to 1.12 MPa, which satisfies requirement of interior use plywood. Compared with previously reported soy-based adhesives, this adhesive is dependent on fewer chemical reagents, but has good bonding performance. The 204.41% of relative cell viability indicates the resultant adhesive was non-toxic. The proposed high-efficiency, high-performance, non-toxic biomass adhesive has great prospects for the industrial application.

With the wide application of magnetic resonance imaging in hospitals and permanent magnets in household items, people have increased exposure to various types of static magnetic fields (SMFs) with moderate and high intensities, which has caused a considerable amount of public concern. Studies have shown that some aspects of gametogenesis and early embryonic development can be significantly affected by SMFs, while others have shown no effects. This review summarizes the experimental results of moderate to high-intensity SMFs (1 mT-16.7 T) on the reproductive development of different model animals, and we find that the effects of SMFs are variable depending on experimental conditions. In general, the effects of inhomogeneous SMFs seem to be more significant compared to that of homogeneous SMFs, which is likely due to magnetic forces generated by the magnetic field gradient. Moreover, some electromagnetic fields may have induced bioeffects because of nonnegligible gradient and heat effect, which are much reduced in superconducting magnets. We hope this review can provide a starting point for more in-depth analysis of various SMFs on reproduction, which is indispensable for evaluating the safety and potential applications of SMFs on living organisms in the future. © 2022 Bioelectromagnetics Society.

Clear cell renal carcinoma (ccRCC) is one of the most common renal carcinomas worldwide, which has worse prognosis compared with other subtypes of tumors. We propose a potential RNA regulatory mechanism associated with ccRCC progression. Accordingly, we screened out clinical factors and the expression of RNAs and miRNAs of ccRCC from the TCGA database. 9 lncRNAs (FGF12-AS2, WT1-AS, TRIM36-IT1, AC009093.1, LINC00443, TCL6, COL18A1-AS1, AC110619.1, HOTTIP), 2 miRNAs (mir-155 and mir-21), and 3 mRNAs (COL4A4, ERMP1, PRELID2) were selected from differential expression RNAs and built predictive survival models. The survival models performed very well in predicting prognosis and were found to be highly correlated with tumor stage. In addition, the survival-related lncRNA-miRNA-mRNA (ceRNA) network was constructed by 18 RNAs including 12 mRNAs, 2 miRNAs, and 4 lncRNAs. It is found that the “ECM-receptor interaction,” “Pathways in cancer,” and “Chemokine signaling pathway” as the main pathways in KEGG pathway analysis. Overall, we established predictive survival model and ceRNA network based on multivariate Cox regression analysis. It may open a new approach and potential biomarkers for clinical prognosis and treatment of ccRCC patients.

To delineate the mutations of the TGFBI gene in Eastern China by whole-exome sequencing (WES) in eight Chinese families with lattice corneal dystrophy (LCD).This retrospective study included eight families with LCD from Eastern China. Clinical features were examined using slit-lamp examination, anterior segment optical coherence tomography, and in vivo confocal microscopy. Peripheral blood samples of probands were collected for WES, and saliva samples from family members were collected for TGFBI screening using Sanger sequencing. The physicochemical effects of mutations were investigated using bioinformatics tools.Family 1 presented a classic LCD I with a p.R124C mutation of the TGFBI gene, while the other seven families were diagnosed with LCD IIIA. Six of the seven LCD IIIA families had heterozygous single-gene mutations (p.A546D, p.L565 H, p.T621P), and one had a compound heterozygous (cis) mutation (p.P501T and p.N622 H). The mutation of p.L565 H was the first time of integrated family report in contrast to the cases reported in 2019, and the p.T621P mutation was first reported in a Chinese population. Notably, the family with the compound mutation was associated with an obvious early-onset (in the 2nd decade of life) compared to the LCD IIIA patients with each single mutation (p.P501T or p.N622 H) showing late-onset (in the 7th decade of life).WES is efficient for the genomic testing of LCD and genetic relationship identification in different families with the same mutated gene. We identified a compound heterozygous mutation (p.P501T and p.N622 H) and two mutations (p.T621P and p.L565 H) uncommon in China.

Evidence is needed on the presence of SARS-CoV-2 in various types of environmental samples and on the estimated transmission risks in non-healthcare settings on campus.The objective of this research was to collect data on SARS-CoV-2 viral load and to examine potential infection risks of people exposed to the virus in publicly accessible non-healthcare environments on a university campus.Air and surface samples were collected using wetted wall cyclone bioaerosol samplers and swab kits, respectively, in a longitudinal environmental surveillance program from August 2020 until April 2021 on the University of Michigan Ann Arbor campus. Quantitative rRT-PCR with primers and probes targeting gene N1 were used for SARS-CoV-2 RNA quantification. The RNA concentrations were used to estimate the probability of infection by quantitative microbial risk assessment modeling and Monte-Carlo simulation.In total, 256 air samples and 517 surface samples were collected during the study period, among which positive rates were 1.6% and 1.4%, respectively. Point-biserial correlation showed that the total case number on campus was significantly higher in weeks with positive environmental samples than in non-positive weeks (p = 0.001). The estimated probability of infection was about 1 per 100 exposures to SARS-CoV-2-laden aerosols through inhalation and as high as 1 per 100,000 exposures from contacting contaminated surfaces in simulated scenarios.Viral shedding was demonstrated by the detection of viral RNA in multiple air and surface samples on a university campus. The low overall positivity rate indicated that the risk of exposure to SARS-CoV-2 at monitored locations was low. Risk modeling results suggest that inhalation is the predominant route of exposure compared to surface contact, which emphasizes the importance of protecting individuals from airborne transmission of SARS-CoV-2 and potentially other respiratory infectious diseases.Given the reoccurring epidemics caused by highly infectious respiratory viruses in recent years, our manuscript reinforces the importance of monitoring environmental transmission by the simultaneous sampling and integration of multiple environmental surveillance matrices for modeling and risk assessment.

To determine the prevalence of anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ-Ab) and to explore its associations with clinical features in patients with dermatomyositis.Sixteen kinds of myositis-specific/associated antibodies were examined in 141 dermatomyositis patients by western blotting. Clinical features and laboratory data were collected. The frequency of anti-TIF1-γ-Ab positivity and its correlations with clinical phenotypes were analyzed using SPSS 23.0 software.Dermatomyositis patients with anti-TIF1-γ-Ab were prone to malignancy (P 0.001); were more likely to present with heliotrope rash (P = 0.007), shawl sign (P 0.001), and V sign (P 0.001); and had relatively longer disease duration (P = 0.031), but were less likely to present with interstitial lung disease (P 0.001) and mechanic's hand (P = 0.003) than the anti-TIF1-γ-Ab-negative subgroup. Anti-TIF1-γ-Ab status was independently associated with the presence of malignancy during multivariate logistic regression analysis. Among the anti-TIF1-γ-Ab-positive dermatomyositis patients, the subgroup with malignancy was prone to present with all types of rashes (87.5% vs. 13.3%, P = 0.001) and has higher incidence of male than the without-malignancy subgroup (50% vs. 6.7%, P = 0.033).Anti-TIF1-γ-Ab positivity was identified as a specific serological indicator of dermatomyositis with malignancy. Men with anti-TIF1-γ-Ab positivity were more likely to have malignancy than women. Increasing types of rashes were associated with greater likelihood of developing malignancy. Key Points • The clinical features of anti-TIF1-γ-Ab in patients with dermatomyositis.

Studies have indicated that RIG-I may act as a tumor suppressor and participate in the tumorigenesis of some malignant diseases. However, RIG-I induces distinct cellular responses via different downstream signaling pathways depending on the cell type. To investigate the biological function and underlying molecular mechanism of RIG-I in the tumorigenesis of melanoma, we constructed RIG-I knockout, RIG-I-overexpressing B16-F10 and RIG-I knockdown A375 melanoma cell lines, and analyzed the RIG-I-mediated change in the biological behavior of tumor cells in spontaneous and poly (I:C)-induced RIG-I activation. Cell proliferation, cell cycling, apoptosis and migration were detected by CCK-8 assay, BrdU incorporation assay, Annexin V–PI staining assay and Transwell assay, respectively. In vivo tumorigenicity was evaluated by tumor xenograft growth in nude mice and subsequently by Ki67 staining and TUNEL assays. Furthermore, Western blotting was utilized to explore the underlying mechanism of RIG-I in melanoma cells. Our data showed that RIG-I promotes apoptosis and inhibits proliferation by G1 phase cell cycle arrest in the melanoma cell lines. Mechanistically, RIG-I induced the phosphorylation of p38 MAPK and MAPK kinases MKK3 and MKK4. In conclusion, the current study demonstrated that RIG-I suppressed the development of melanoma by regulating the activity of the MKK/p38 MAPK signaling pathway, which is relevant to research on novel therapeutic targets for this malignant disease.

To explore the impact of pre-hospital ACEI and ARB exposure on the prognosis of ARF patients.A single-center retrospective cohort study.Medical Information Mart for Intensive Care-III (MIMIC-III) database.The patients meeting ICD-9 code of acute respiratory failure were enrolled.The primary exposure was the pre-hospital exposure of ACEI and ARB.The primary outcome was in-hospital mortality. Multiple logistic regression analysis was conducted to determine the independent effect of ACEI/ARB exposure on mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. 5335 adult ARF patients were enrolled. Mortality was significantly decreased in patients with ACEI/ARB exposure before and after PSM, and the adjusted odds ratio (OR) of ACEI/ARB exposure was 0.56 (95% CI 0.43-0.72). In the subgroup analysis, ACEI/ARB lost its protective effect in young subgroup, but no significant interaction was found between ACEI/ARB exposure and age (p = 0.082). The point estimation and lower 95% limit of E-value was 2.97 and 2.12. In sensitivity analysis, ACEI/ARB exposure showed similar effect in ARDS cohort, but no significantly difference was found in the MIMIC-IV database, which may be explained by small sample size of the ACEI/ARB group.Among patients with acute respiratory failure, pre-hospital ACEI/ARB exposure was associated with better outcomes and acted as an independent factor. The relationship between ACEI/ARB and prognosis of ARF is worth investigating further.

The dysregulation of U2 Small Nuclear RNA Auxiliary Factor 2 (U2AF2) is associated with malignant behaviors of multiple types of tumors. In this study, we explored the association between

This study was conducted to investigate the roles of lncRNA PLAC2 and XiaP in hepatocellular carcinoma (HCC). HCC and paired non-tumor tissues were collected from 62 HCC patients who received cisplatin-based treatment. At 0, 2, and 4 months of post-cisplatin-based therapy, blood samples (5 ml) were collected from all patients and prepared plasma samples. LncRNA PLAC2 expression in tissue and plasma samples was determined by RT-qPCR. The interactions between lncRNA PLAC2 and XiaP in HCC cell lines were assessed by overexpression experiments. Cell viability and apoptosis under cisplatin treatment were analyzed by MTT assay and cell apoptosis assay, respectively. The direct interaction between lncRNA PLAC2 and miR-96, which can target XiaP, was analyzed by performing RNA-RNA pulldown assay. It was observed that lncRNA PLAC2 was upregulated in HCC tissues than in non-tumor tissues. LncRNA PLAC2 expression in HCC tissues was not affected by HBV and HCV but upregulated after cisplatin-based treatment. Similarly, cisplatin treatment of HCC cells increased PLAC2 expression. LncRNA PLAC2 and XiaP overexpression increased viability and decreased apoptosis of cisplatin-treated HCC cells, while lncRNA PLAC2 knockdown decreased viability and increased apoptosis of cisplatin-treated HCC cells. Western blot analysis showed that lncRNA PLAC2 increased XiaP protein accumulation, while lncRNA PLAC2 siRNA silencing decreased XiaP expression in HCC cells. LncRNA PLAC2 and miR-96 directly interacted with each other, while they failed to regulate the expression of each other. In conclusion, lncRNA PLAC2 negatively regulates the chemosensitivity of HCC cells to cisplatin, possibly by sponging miR-96 to upregulate miR-96.

Rice is a major food crop around the world, and its various quality and safety problems are closely related to human health. As an important area of food safety research, the rice supply chain has attracted increasing attention. Based on blockchain technology, this study investigated problems of data privacy and circulation efficiency caused by complex rice supply networks, long circulation cycles, and various risk factors in each link. First, we deconstructed the quality and safety of each link of the rice supply chain at the information level and established a key information classification table for each link. On that basis, we built a rice supply chain information supervision model based on blockchain. Various encryption algorithms are used to secure the sensitive data of enterprises in the supply chain to meet regulators’ needs for efficient supervision. Moreover, we propose a practical Byzantine fault-tolerant consensus algorithm that scores the credit of enterprise nodes, optimizes the selection strategy of master nodes, and ensures high efficiency and low cost. Then, we built a prototype system based on the open-source framework of hyperledger fabric, analyzed the model’s viability, and implemented the system using cases. The results indicated that the proposed system can optimize the information supervision process of rice supply chain regulators and provide a feasible solution for the quality and safety supervision of grain and oil.

Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (Hsub2/sub) can selectively reduce intratumoral overexpressed hydroxyl radicals (•OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (Osub2/sub) deficiency in the tumor microenvironment (TME) and the electron-hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnOsub2/sub/Ce6@HA (PHMCH) yolk-shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnOsub2/sub) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnOsub2/suband Ce6 can efficiently facilitate electron-hole separation for increasing singlet oxygen (sup1/supOsub2/sub). Moreover, MnOsub2/subnanoshells generate Osub2/subin TME for ameliorating hypoxia and further improving Osub2/sub-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the Hsub2/sub-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.

To develop a scale that measured the perioperative anxiety symptoms of uterine fibroids (PASM-UF) treated with focused ultrasound ablation surgery (FUAS).A panel of gynecologists, nurses, and patient-reported outcome (PRO) experts created a draft of the PASM-UF scale. Women who underwent FUAS for uterine fibroids were recruited for its psychometric validation. Assessments were conducted during admission, before surgery, and at discharge. The Symptom Checklist-90 (SCL-90) was administered to assess criterion validity. We assessed the relationship between the developed PASM-UF and the SCL-90We included five items, pain, lack of appetite, fatigue (tiredness), disturbed sleep, and anxiety, in the final version of the PASM-UF. Data were collected from 228 patients. Cronbach's alpha was 0.745, whereas the correlation coefficient between SCL-90 and PASM-UF was 0.345 (The PASM-UF is a valid, reliable, and sensitive scale for assessing perioperative anxiety levels among women with uterine fibroids. Statistical analysis suggests that it is also an effective instrument for scientific research.Key MessageWe developed a brief scale to assess anxiety in perioperative patients with uterine fibroids. In addition, the scale monitored the anxiety levels at multiple frequencies and did not increase burden on the patients. The scale has been proven to be effective, reliable, and highly sensitive.

Background The outbreak of COVID-19 has been a big challenge for senior high school students in China who are facing tremendous pressure of the highly competitive College Entrance Examination. Methods To evaluate the psychological impact of the event in the population, we conducted an anonymous online survey among senior high school students in China between 26 Feb and 4 March, 2020. Information collected included demographic characteristics, attitude toward medical study, infection of COVID-19 in acquaintances, anxiety symptoms evaluated using the GAD-7, and health literacy level measured using the IDSHL. Results Of 21,085 participants, 3,575 (17.0%), 943 (4.5%) and 448 (2.1%) reported with mild, moderate, and severe anxiety. Female, higher academic year, worse self-evaluated academic performance, negative attitude toward medical study, living in Hubei province and having acquaintance infected with COVID-19 were significantly associated with anxiety level, while higher education level of mother and higher IDSHL score were associated with a lower risk. The score of IDSHL, particularly of the domain “infectious disease prevention”, was associated with the GAD-7 score in a linear pattern (β=-0.0371, p

Subthalamic nuclei deep brain stimulation (STN-DBS) is a well-established treatment for Parkinson’s disease (PD). Some studies have confirmed the long-term efficacy is associated with brain connectivity; however, whether the initial outcome is associated with brain connectivity and efficacy of prediction based on these factors has not been well investigated. In the present study, a total of 98 patients were divided into a training set (n = 78) and a test set (n = 20). The stimulation and medication responses were calculated based on the motor performance. The functional and structural connectomes were established based on a public database and used to measure the association between stimulation response and brain connectivity. The prediction of initial outcome was achieved via a machine learning algorithm-support vector machine based on the model established with the training set. It was found that the initial outcome of STN-DBS was associated with functional/structural connectivities between the volume of tissue activated and multiple brain regions, including the supplementary motor area, precentral and frontal areas, cingulum, temporal cortex, and striatum. These factors could be used to predict the initial outcome, with an r value of 0.4978 (P = 0.0255). Our study demonstrates a correlation between a specific connectivity pattern and initial outcome of STN-DBS, which could be used to predict the initial outcome of DBS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01208-9.

Background Current studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them. Methods The baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI 2), normal weight (18.5–23.9 kg/m2), overweight (24.0–27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG. Results During an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08–1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27–1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39–3.54). Conclusions In China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage.

Near-infrared (NIR) synaptic devices integrate NIR optical sensitivity and synaptic plasticity, emulating the basic biomimetic function of the human visual system and showing great potential in NIR artificial vision systems. However, the lack of semiconductor materials with appropriate band gaps for NIR photodetection and effective strategies for fabricating devices with synaptic behaviors limit the further development of NIR synaptic devices. Here, a two-terminal NIR synaptic device consisting of the In