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Background: Papillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto's thyroiditis, presenting significant challenges in clinical diagnosis and treatment. Case demonstration: A 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis. Conclusions: The concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto's thyroiditis. The patient's favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases. [ABSTRACT FROM AUTHOR]

Catalpa bungei is a precious timber species distributed in North China where drought often occurs. To clarify adaptive responses of C. bungei to partial- and full- root-zone drought under the influence of nitrogen forms, a two-factor experiment was conducted in which well-watered (WW), partial root-zone drought in horizontal direction (H-PRD) and in vertical direction (V-PRD), and full root-zone drought (FRD) were combined with nitrate-nitrogen (NN) and ammonium-nitrogen (AN) treatments. C. bungei responded to FRD by sharply closing stomata, decreasing gas exchange rate and increasing leaf instantaneous water use efficiency (WUEi). Under FRD condition, the growth of seedlings was severely inhibited and the effect of N forms was covered up by the drastic drought effect. In comparison, stomata conductance and gas exchanges were moderately inhibited by PRDs. WUEi in V-PRD treatment was superior to H-PRD due to the active stomata regulation resulting from a higher ABA level and active transcription of genes in abscisic acid (ABA) signaling pathway under V-PRD. Under both PRDs and FRD, nitrate benefited antioxidant defense, stomata regulation and leaf WUEi. Under V-PRD, WUEi in nitrate treatment was superior to that in ammonium treatment due to active stomata regulation by signaling network of nitric oxide (NO), Ca2+ and ABA. Under FRD, WUEi was higher in nitrate treatment due to the favoring photosynthetic efficiency resulting from active NO signal and antioxidant defense. The interactive effect of water and N forms was significant on wood xylem development. Superoxide dismutase (SOD) and catalase (CAT) largely contributes to stress tolerance and xylem development. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature. Case presentation: A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured. Conclusion: M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial. [ABSTRACT FROM AUTHOR]

Objective: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. Methods: This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan–Meier. Results: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. Conclusion: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether the high metabolic region of fluorine-18-fluorode-oxyglucose (18F-FDG) in the primary lesion is the crux for recurrence in patients with nasopharyngeal carcinoma (NPC), to assess the feasibility and rationale for use of biological target volume (BTV) based on 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT). Methods: The retrospective study included 33 patients with NPC who underwent 18F-FDG-PET/CT at the time of initial diagnosis as well as the time of diagnosis of local recurrence. Paired 18F-FDG-PET/CT images for primary and recurrent lesion were matched by deformation coregistration method to determine the cross-failure rate between two lesions. Results: The median volume of the Vpri (primary tumor volume using the SUV thresholds of 2.5), the Vhigh (the volume of high FDG uptake using the SUV50%max isocontour), and the Vrecur (the recurrent tumor volume using the SUV thresholds of 2.5) were 22.85, 5.57, and 9.98 cm3, respectively. The cross-failure rate of Vrecur∩high showed that 82.82% (27/33) of local recurrent lesions had < 50% overlap volume with the region of high FDG uptake. The cross-failure rate of Vrecur∩pri showed that 96.97% (32/33) of local recurrent lesions had > 20% overlap volume with the primary tumor lesions and the median cross rate was up to 71.74%. Conclusion: 18F-FDG-PET/CT may be a powerful tool for automatic target volume delineation, but it may not be the optimal imaging modality for dose escalation radiotherapy based on applicable isocontour. The combination of other functional imaging could delineate the BTV more accurately. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma of the head and neck (SCCHN) is globally the sixth most common cancer. TGF-β1 is a key regulator of cell proliferation and differentiation, and it induces the epithelial-mesenchymal transition (EMT) by activating Smad2 signaling in SCCHN cells. Previous studies have revealed that oleuropein (OL) can inhibit the EMT alterations and migration of cancer cells. The aim of this study was to examine the involvement of TGF-β1 signaling pathway in SCCHN and the effect of OL on it.Methods: Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines.Results: We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays.Conclusion: This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival. [ABSTRACT FROM AUTHOR]

Introduction: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas.Materials and Methods: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed.Results: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group.Conclusions: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis. [ABSTRACT FROM AUTHOR]

Background: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. Method: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. Result: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-βR1) and the abundance of miR-27b-3p was negatively regulated by TGF-βR1/Smad. Conclusion: miR-27b-3p targeting the TGF-βR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-βR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the effectiveness and cost-effectiveness of nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Methods: LA-NPC patients treated between October 2013 and December 2016 were retrospectively reviewed. A well-balanced cohort of patients who received nimotuzumab in addition to standard treatment (n = 50) and patients who did not receive nimotuzumab (n = 100) was selected using propensity score-matching method (1:2 ratio) for the cost-effectiveness analysis.Results: Compared with concurrent chemoradiotherapy (CCRT) alone, addition of nimotuzumab to CCRT significantly improved the 3-year overall survival (OS) (98.00% vs. 91.00%, P = 0.032). On multivariate analysis, nimotuzumab (hazard ratio = 0.124, 95% confidence interval: 0.017-0.902, P = 0.039) showed prognostic significance for OS. No serious treatment-related adverse events were observed in the nimotuzumab group (P > 0.05). Cost-effectiveness analysis revealed that addition of nimotuzumab increased the average treatment costs by $14,364.63. The additional cost for every one percent increase in OS rate was $ 2,052.09.Conclusion: Addition of nimotuzumab to CCRT for LA-NPC confers significant survival benefits; however, it is not cost-effective. [ABSTRACT FROM AUTHOR]

Objective: To identify the main risk factors for metachronous metastatic nasopharyngeal carcinoma (NPC) in different periods after radiotherapy and estimate the weight of various factors in the early or late metachronous metastasis (EMM/LMM) groups. Methods: This retrospective registry consists of 4434 patients with newly diagnosed NPC. Cox regression analysis was used to assess the independent significance of various risk factors. The Interactive Risk Attributable Program (IRAP) was used to calculate the attributable risks (ARs) for metastatic patients during different periods. Results: Among 514 metastatic patients, 346 (67.32%) patients diagnosed with metastasis within 2 years after treatment were classified into the EMM group, while other 168 patients were classified into the LMM group. The ARs of T-stage, N-stage, pre-Epstein-Barr virus (EBV) DNA, post-EBV DNA, age, sex, pre-neutrophil-to-lymphocyte ratio, pre-platelet-to-lymphocyte ratio, pre-hemoglobin (HB), and post-HB were 20.19, 67.25, 2.81, 14.28, 18.50, - 11.17%, 14.54, 9.60, 3.74% and - 9.79%, respectively, in the EMM group. In the LMM group, the corresponding ARs were 3.68, 49.11, - 18.04%, 2.19, 6.11, 0.36, 4.62, 19.77, 9.57 and 7.76%, respectively. After multivariable adjustment, the total AR for tumor-related factors was 78.19%, and that for patient-related factors was 26.07% in the EMM group. In the LMM group, the total AR of tumor-related factors was 43.85%, while the weights of patient-related factors was 39.97%. In addition, except for these identified tumor- and patient-related factors, other unevaluated factors played a more important role in patients with late metastasis, with the weight increasing by 15.77%, from 17.76% in the EMM group to 33.53% in the LMM group. Conclusion: Most metachronous metastatic NPC cases occurred in the first 2 years after treatment. Early metastasis was mainly affected by tumor-related factors, which accounted for a declining percentage in the LMM group. [ABSTRACT FROM AUTHOR]

Background: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET).Methods: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan-Meier and Cox regression analyses were used to assess survival.Results: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039-3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021-2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214-5.325, P = 0.013).Conclusion: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential. [ABSTRACT FROM AUTHOR]

Background: The Pi2/9 locus contains multiple nucleotide binding site-leucine-rich repeat (NBS-LRR) genes in the rice genome. Although three functional R-genes have been cloned from this locus, little is known about the origin and evolutionary history of these genes. Herein, an extensive genome-wide survey of Pi2/9 homologs in rice, sorghum, Brachypodium and Arabidopsis, was conducted to explore this theme. Results: In our study, 1, 1, 5 and 156 Pi2/9 homologs were detected in Arabidopsis, Brachypodium, sorghum and rice genomes, respectively. Two distinct evolutionary patterns of Pi2/9 homologs, Type I and Type II, were observed in rice lines. Type I Pi2/9 homologs showed evidence of rapid gene diversification, including substantial copy number variations, obscured orthologous relationships, high levels of nucleotide diversity or/and divergence, frequent sequence exchanges and strong positive selection, whereas Type II Pi2/9 homologs exhibited a fairly slow evolutionary rate. Interestingly, the three cloned R-genes from the Pi2/9 locus all belonged to the Type I genes. Conclusions: Our data show that the Pi2/9 locus had an ancient origin predating the common ancestor of gramineous species. The existence of two types of Pi2/9 homologs suggest that diversifying evolution should be an important strategy of rice to cope with different types of pathogens. The relationship of cloned Pi2/9 genes and Type I genes also suggests that rapid gene diversification might facilitate rice to adapt quickly to the changing spectrum of the fungal pathogen M. grisea. Based on these criteria, other potential candidate genes that might confer novel resistance specificities to rice blast could be predicted. [ABSTRACT FROM AUTHOR]

Background: Objectively measured differences in physical activity (PA) and sleep have been documented among people with osteoarthritis (OA) and rheumatoid arthritis (RA) compared to non-arthritic controls. However, it is not clear whether OA and RA subgroups also differ on these indexes or the extent to which distinct arthritis subgroups versus controls can be accurately identified on the basis of objective PA and sleep indexes compared to self-report responses on questionnaires. This study addressed these gaps.Methods: This case-control study comprised Chinese adults with OA (N = 40) or RA (N = 40) diagnoses based on physician assessments as well as a control group of adults without chronic pain (N = 40). All participants wore a Sensewear Armband (SWA) for consecutive 7 days and completed the International Physical Activity Questionnaire Short Form-Chinese as well as Pittsburgh Sleep Diary to obtain objective and subjective PA and sleep data, respectively.Results: There were no differences between the three groups on any self-report indexes of PA or sleep. Conversely, OA and RA subgroups displayed significantly lower PA levels and more sleep problems than controls did on a majority of SWA indexes, though arthritis subgroups were not differentiated from one another on these measures. Logistic regression analyses indicated four non-multicollinear SWA indexes (i.e., steps, active energy expenditure, vigorous activity, time awake after sleep onset) correctly identified the subgroup membership of 75.0-82.5% of participants with RA or OA while classification accuracy results were attenuated for controls.Conclusions: Where possible, objective measures should be used to assess PA and sleep of adults with OA and RA while particular self-report PA questionnaires should be used sparingly. [ABSTRACT FROM AUTHOR]

Background: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET). Methods: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan–Meier and Cox regression analyses were used to assess survival. Results: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039–3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021–2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214–5.325, P = 0.013). Conclusion: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential. [ABSTRACT FROM AUTHOR]

Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables' pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p < 0.001; depression: t = 2.220, p = 0.030), and higher bulimia (t = 3.400, p = 0.001) than the healthy control group. Positive correlations were found in every pairwise combination of BMI, childhood emotional abuse, anxiety, and bulimia. Multiple mediation analyses indicate that childhood emotional abuse is positively linked to BMI (β = 1.312, 95% CI = 0.482–2.141). The model using anxiety and bulimia as the multiple mediating variables is attested to play roles in the relationship between childhood emotional abuse and obesity (indirect effect = 0.739, 95% CI = 0.261–1.608, 56.33% of the total effect). These findings confirm that childhood emotional abuse contributes to adulthood obesity through the multiple mediating effects of anxiety and bulimia. The present study adds another potential model to facilitate our understanding of the eating psychopathology of obesity. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are involved in the regulation of progression and drug resistance in ovarian cancer (OC). In the present study, we aimed to explore the role of circRAD23B, a newly identified circRNA, in the regulation of carboplatin-resistant OC. Methods: CircRAD23B expression levels were measured using qRT-PCR. The biological roles of circRAD23B were analysed using CCK-8, colony formation, EDU, flow cytometry, and cell viability assays. RNA pull-down and luciferase assays were used to investigate the interactions of circRAD23B with mRNAs and miRNAs. Results: CircRAD23B was significantly increased in carboplatin-resistant OC tissues. CircRAD23B promoted proliferation and reduced sensitivity to carboplatin in cell lines and patient-derived organoids (PDOs), consistent with in vivo findings. Mechanistically, circRAD23B acted as a molecular sponge, abrogating its inhibitory effect on Y-box binding protein 1 (YBX1) by adsorbing miR-1287-5p. Rescue experiments confirmed that the pro-proliferation and carboplatin resistance mediated by circRAD23B was partially reversed by the upregulation of miR-1287-5p. Conclusions: Our results demonstrated, for the first time, the role of the circRAD23B/miR-1287-5p/YBX1 axis in OC progression and carboplatin resistance in cell lines, PDOs, and animal models, providing a basis for the development of targeted therapies for patients with OC. [ABSTRACT FROM AUTHOR]

Background: We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here, we propose that MT2 within the spinal dorsal horns participates in the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN).Methods: The rat model of CIPN was established by 5 consecutive injections of oxaliplatin (0.4 mg/100 g/day). Genetic restoration of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment, and also, genetic inhibition by metallothionein-2 siRNA was performed. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism.Results: We found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. Overall locomotor activity was not impaired after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and inactive transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons.Conclusions: Metallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism. [ABSTRACT FROM AUTHOR]

Background: As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort. Methods: In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro. Results: Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML. Conclusions: In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation. [ABSTRACT FROM AUTHOR]

Background: High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives. Results: We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod. Conclusions: Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies. [ABSTRACT FROM AUTHOR]

Background: With breast cancer becoming the most diagnosed cancer in the world, the number of breast cancer-afflicted mothers with adolescent daughters is also rising. Further, adolescent daughters' mothers serve as role models for in identity formation processes, especially concerning gender and sexuality. Nevertheless, breast cancer threats mother's health, including such a key symbol of her womanhood-the breast-which may adversely affect the development of an adolescent daughter's own sense of personal identity and womanhood. However, few researchers and practitioners have paid attention to mother-daughter interactions in the context of breast cancer. Therefore, this study aimed to uncover the nuances of the interactive challenges with adolescent daughters from breast cancer-afflicted mothers' perspective.Methods: We conducted a qualitative study following the sample saturation principle, collecting data through semi-structured interviews with 21 breast cancer patients who met the inclusion criteria. We utilized thematic analysis and partially integrated the Foucauldian discourse approach to analyze the data.Results: Three major themes emerged from the data: (1) mothers are lost in chaos (inability to handle the shock of cancer, feelings of powerlessness about the uncertainty of their life span, and confusion about how to respond to daughter's curiosity); (2) mothers struggle to maintain balance (torn between protecting daughters and letting them be independent, and making a tough choice between being a mother or a patient); and (3) mothers are immersed in guilt (increasing daughters' risk of cancer, influencing daughters' development, and imposing burdens on daughters).Conclusions: Our research explored the interactive experience of breast cancer-afflicted mothers and adolescent daughters. The insights uncovered by this study will help mothers enhance interaction with their daughters and assist health practitioners in devising interventions. [ABSTRACT FROM AUTHOR]

Background: The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown.Methods: Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior.Results: The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats.Conclusions: These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. Methods: We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. Results: A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87–0.98), 0.93(95% CI 0.87–0.96), 13.65(95% CI 6.89–27.08), and 0.06(95% CI 0.02–0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52–941.11) and 0.98 (95% CI 0.96–0.99), respectively. Conclusion: Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study. [ABSTRACT FROM AUTHOR]

Background: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge.Methods: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated.Results: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores.Conclusion: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously. Methods: This open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival. Results: One hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0–52.8), and the disease control rate was 66.0% (95% CI 56.0–75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5–97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7–82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1–2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events. Conclusions: This is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer. Trial registration ClinicalTrials.gov, NCT03667170. Registered 10 September 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03667170. [ABSTRACT FROM AUTHOR]

Background: To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly.Methods: We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model.Results: Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656-1.722), rural population cases (OR 3.411, 95% CI 3.320-3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193-1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3, P < 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005-2010 APC = -7.2%, P < 0.05; 2010-2014 APC = -22.6%, P < 0.05; 2014-2017 APC = -9.0%, P = 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48-38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4, P<0.05).Conclusions: Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets. [ABSTRACT FROM AUTHOR]

Background: Magnetic nanoparticles such as magnetosomes modified with antibodies allow a high probability of their interaction with targets of interest. Magnetosomes biomineralized by magnetotactic bacteria are in homogeneous nanoscale size and have crystallographic structure, and high thermal and colloidal stability. Camelidae derived nanobodies (Nbs) are small in size, thermal stable, highly water soluble, easy to produce, and fusible with magnetosomes. We aimed to functionalize Nb-magnetosomes for the analysis of the insecticide fipronil. Results: Three recombinant magnetotactic bacteria (CF, CF+ , and CFFF) biomineralizing magnetosomes with different abundance of Nbs displayed on the surface were constructed. Compared to magnetosomes from the wild type Magnetospirillum gryphiswaldense MSR-1, all of the Nb-magnetosomes biosynthesized by strains CF, CF+ , and CFFF showed a detectable level of binding capability to fipronil-horseradish peroxidase (H2-HRP), but none of them recognized free fipronil. The Nb-magnetosomes from CFFF were oxidized with H2O2 or a glutathione mixture consisting of reduced glutathione and oxidized glutathione in vitro and their binding affinity to H2-HRP was decreased, whereas that to free fipronil was enhanced. The magnetosomes treated with the glutathione mixture were employed to develop an enzyme-linked immunosorbent assay for the detection of fipronil in water samples, with average recoveries in a range of 78–101%. Conclusions: The economical and environmental-friendly Nb-magnetosomes biomineralized by the bacterial strain MSR-1 can be potentially applied to nanobody-based immunoassays for the detection of fipronil or nanobody-based assays in general. [ABSTRACT FROM AUTHOR]

Background: Human noroviruses (HuNoVs) are a major cause of nonbacterial gastroenteritis in all age groups worldwide. HuNoVs can be detected in vitro using molecular assays such as RT-PCR and RT-qPCR. However, these molecular-based techniques require special equipment, unique reagents, experienced personnel, and extended time to obtain results. Besides, the diversity of viral genotypes is high. Therefore, methods that are rapid, broad-range and effective in the detection of HuNoVs are desiderated for screening the feces or vomit of infected people during outbreaks. Results: In this study, a colloidal-gold-based immunochromatographic assay (ICA) was developed for effective detection of HuNoVs in clinical samples. Monoclonal antibodies (MAbs) against the shell (S) domain in the major capsid protein of HuNoVs were used in the ICA. The limitations of detection for HuNoVs in clinical samples were 1.2 × 106 genomic copies per gram of stool sample (gc/g) and 4.4 × 105 gc/g for genogroup I and II (GI and GII) HuNoVs, respectively. A total of 122 clinical samples were tested for HuNoVs by ICA and compared against RT-qPCR. The relative sensitivity, specificity and agreement of ICA was 84.2% (95% CI: 83.6–84.8%), 100.0% (95% CI: 98.5–100.0%) and 87.7% (95% CI: 85.6–89.8%), respectively. No cross-reaction with other common enteric viruses or bacteria was observed. The ICA detected a broad range of genotypes, including GI.1, GI.3, GI.4, GI.6, GI.14, GII.2, GII.3, GII.4, GII.6, GII.13, and GII.17 HuNoVs. Conclusions: This study demonstrates that ICA targeting the S domain of VP1 is a promising candidate for effectively identifying the different genotypes of HuNoVs in clinical samples with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence.Methods: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention.Results: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017.Conclusion: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care. [ABSTRACT FROM AUTHOR]

Background: Sevoflurane preconditioning improves brain function in MCAO rats, and there are several methods for determining appropriate concentration and time windows for preconditioning. This study investigated the brain protective effects with a single sevoflurane preconditioning at different concentrations and different time windows on MCAO rats. Methods: Adult Sprague-dawley rats were randomly assigned to 14 groups. The rats in the sevoflurane preconditioning group inhaled 0.5 MAC, 1.0 MAC, and 1.3 MAC sevoflurane, respectively for 3 h, and then MCAO models were established at 6 h, 12 h, 24 h, and 48 h. MCAO and sham groups underwent no preconditioning with sevoflurane. The neurological severity score, cerebral infarct volume and brain water content of the rats were measured 24 h after reperfusion. Results: After inhalation of 1.3 MAC sevoflurane for 3 h of preconditioning, the MCAO model was established after 24 h. This preconditioning improved the neurological severity score, reduce cerebral infarct volume and brain water content in MCAO rats. After inhalation of 1.0 MAC sevoflurane for 3 h of preconditioning, MCAO model established after 24 h reduced the cerebral infarct volume and brain water content of MCAO rats, but the neurological severity score showed no significant improvement, and no significant brain protective effects were observed at other concentrations and time windows. Conclusions: These results suggested that after inhalation of 1.3 MAC sevoflurane for 3 h of preconditioning, MCAO model established after 24 h demonstrated significant brain protective effects in MCAO rats. [ABSTRACT FROM AUTHOR]

Background and Purpose: We evaluated the relationship between patient-, tumor-, and treatment-related features and radiation-induced lymphopenia (RIL) and evaluated the correlation between RIL and survival outcome in NPC patients to help improve the treatment strategy.Methods: This retrospective study included 374 patients with stage II-IVa NPC who had been treated with definitive RT and were enrolled from 2004 to 2015; The associations between the G3-4 RIL (absolute lymphocyte count, ALC <  0.5 × 109 cells/L) during RT and patient-, tumor-, and treatment-related factors were assessed using Cox regression analyses. The correlation between ALC nadir and survival was examined using a Kaplan-Meier analysis, compared with the log-rank test, and confirmed by a Cox proportional hazards analysis.Results: In the multivariate analysis, lower baseline ALC and intensity modulated radiation therapy (IMRT) (vs. 2 dimensional-conformal radiation therapy,2D-CRT) were identified as 2 independent factors that were associated with G3-4 RIL. In the multivariate survival analysis, patients with G3-4 ALC nadir had longer local recurrence-free survival durations (LRFS) (vs. G0-2 nadir, HR = 0.548, P = 0.005) and longer progression-free survival durations (PFS) (vs. G0-2 nadir, HR = 0.676, P = 0.022), while patients with G4 ALC nadir had a shorter distant-metastasis-free survival duration (DMFS) (vs. G0-2 nadir, hazard ratio [HR] = 2.567, P = 0.037).Conclusions: In the study, lymphopenia during RT were affected by baseline ALC and RT modality independently. Moreover, G3-4 ALC nadir was independently linked with longer PFS and LRFS durations, while G4 ALC nadir was independently linked with a shorter DMFS duration. [ABSTRACT FROM AUTHOR]

Background: Hypertension is one of primary clinical presentations of pre-eclampsia. The occurrence and progress of hypertension are closely related to vascular dysfunction. However, information is limited regarding the pathological changes of vascular functions in pre-eclamptic fetuses. Human umbilical cord vein was used to investigate the influence of pre-eclampsia on fetal blood vessels in this study. Results: The present study found that the vasoconstriction responses to arginine vasopressin (AVP) and oxytocin (OXT) were attenuated in the pre-eclamptic umbilical vein as compared to in normal pregnancy, which was related to the downregulated AVP receptor 1a (AVPR1a), OXT receptor (OXTR), and protein kinase C isoform β (PKCβ), owing to the deactivated gene transcription, respectively. The deactivated AVPR1a, OXTR, and PKCB gene transcription were respectively linked with an increased DNA methylation within the gene promoter. Conclusions: To the best of our knowledge, this study first revealed that a hyper-methylation in gene promoter, leading to relatively reduced patterns of AVPR1a, OXTR, and PKCB expressions, which was responsible for the decreased sensitivity to AVP and OXT in the umbilical vein under conditions of pre-eclampsia. The data offered new and important information for further understanding the pathological features caused by pre-eclampsia in the fetal vascular system, as well as roles of epigenetic-mediated gene expression in umbilical vascular dysfunction. [ABSTRACT FROM AUTHOR]

Background: The yak (Bos grunniens) is a long-haired bovine that lives at high altitudes and is an important source of milk, meat, fiber and fuel. The recent sequencing, assembly and annotation of its genome are expected to further our understanding of the means by which it has adapted to life at high altitudes and its ecologically important traits. Description: The Yak Genome Database (YGD) is an internet-based resource that provides access to genomic sequence data and predicted functional information concerning the genes and proteins of Bos grunniens. The curated data stored in the YGD includes genome sequences, predicted genes and associated annotations, non-coding RNA sequences, transposable elements, single nucleotide variants, and three-way whole-genome alignments between human, cattle and yak. YGD offers useful searching and data mining tools, including the ability to search for genes by name or using function keywords as well as GBrowse genome browsers and/or BLAST servers, which can be used to visualize genome regions and identify similar sequences. Sequence data from the YGD can also be downloaded to perform local searches. Conclusions: A new yak genome database (YGD) has been developed to facilitate studies on high-altitude adaption and bovine genomics. The database will be continuously updated to incorporate new information such as transcriptome data and population resequencing data. The YGD can be accessed at http://me.lzu.edu.cn/yak. [ABSTRACT FROM AUTHOR]

Background: Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC).Methods: To examine this significance, we ran a 2 year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n = 32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~ 2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2).Results: We found CAMLs in 88% (n = 28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n = 22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs < 50 μm by the completion of CRT over patients with CAMLs ≥ 50 μm; PFS (HR = 12.0, 95% CI = 2.7-54.1, p = 0.004) and OS (HR = 9.0, 95%CI = 1.9-43.5, p = 0.019).Conclusions: Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and further studies are warranted to determine if presence of these cells prior to treatment suggest diagnostic value for at-risk populations. [ABSTRACT FROM AUTHOR]

Background: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018.Methods: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out.Results: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model.Conclusion: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups. [ABSTRACT FROM AUTHOR]

Background: Magnetosomes (also called bacterial magnetic nanoparticles; BMPs) are biomembrane-coated nanoparticles synthesized by magnetotactic bacteria (MTB). Engineered BMPs fused to protein A (termed ∆F-BMP-FA) bind antibodies (Abs) automatically, and thus provide a series of potential advantages. However, no report so far has systematically evaluated functional applicability of genetically engineered BMPs. Results: We evaluated properties of ∆F-BMP-FA, and developed/optimized culture methods for host strain Magnetospirillum gryphiswaldense ΔF-FA, ∆F-BMP-FA extraction conditions, conditions for Ab conjugation to ∆F-BMP-FA surface, and procedures for antigen detection using ∆F-BMP-FA/Ab complexes (termed BMP-A-Ab). Fed-batch culture for 36 h in a 42-L fermentor resulted in yields (dry weight) of 2.26 g/L for strain ΔF-FA and 62 mg/L for ∆F-BMP-FA. Optimal wash cycle number for ∆F-BMP-FA purification was seven, with magnetic separation following each ultrasonication step. Fusion of protein A to BMPs resulted in ordered arrangement of Abs on BMP surface. Linkage rate 962 μg Ab per mg ∆F-BMP-FA was achieved. BMP-A-Ab were tested for detection of pathogen (Vibrio parahaemolyticus; Vp) surface antigen and hapten (gentamicin sulfate). Maximal Vp capture rate for BMP-A-Ab was 90% (higher than rate for commercial immunomagnetic beads), and detection sensitivity was 5 CFU/mL. ∆F-BMP-FA also bound Abs from crude mouse ascites to form complex. Lowest gentamicin sulfate detection line for BMP-A-Ab was 0.01 ng/mL, 400-fold lower than that for double Ab sandwich ELISA, and gentamicin sulfate recovery rate for BMP-A-Ab was 93.2%. Conclusion: Our findings indicate that engineered BMPs such as ∆F-BMP-FA are inexpensive, eco-friendly alternatives to commercial immunomagnetic beads for detection or diagnostic immunoassays, and have high Ab-conjugation and antigen-adsorption capacity. [ABSTRACT FROM AUTHOR]

Background: Diabetes is often accompanied by dyslipidemia. Lipid control is very important in the management of diabetes. There are limited real world data on the lipid control in diabetic inpatients in southwest China. Methods: An observational study was conducted to assess the characteristics of lipid profiles and lipid control. Diabetic patients from February 2009 to December 2013 at West China Hospital of Sichuan University were identified. Results: A total of 56,784 inpatients were included and 85.9% of them had at least one lipid panel. The proportions of inpatients with optimal low-density lipoprotein cholesterol (LDL-C) level (< 2.59 mmol/L), optimal triglyceride (TG) level (< 1.70 mmol/L), optimal high-density lipoprotein cholesterol (HDL-C) level (men ≥1.04 mmol/L; women ≥1.30 mmol/L) and optimal non-high-density lipoprotein cholesterol (non-HDL-C) level (< 3.37 mmol/L) were 61.1, 64.6, 49.9 and 64.5%, respectively. Only 23.1% of inpatients obtained optimal levels for all the above four lipid parameters. Of diabetic inpatients with ischemic heart disease, the proportions of inpatients with optimal LDL-C level (< 1.81 mmol/L), optimal TG level (< 1.70 mmol/L), optimal HDL-C level (men ≥1.04 mmol/L; women ≥1.30 mmol/L) and optimal non-HDL-C level (< 2.59 mmol/L) were 38.0, 66.3, 48.1 and 48.7%, respectively. Of diabetic inpatients with cerebrovascular disease, the proportions were 28.3, 64.8, 49.9 and 38.1%, respectively. Older people and men were more likely to obtain optimal lipid levels. However, inpatients between 46 and 64 years were least likely to obtain optimal LDL-C levels. Conclusions: The lipid control of diabetic inpatients in southwest China is worrisome. Individualized strategies of lipid management should be taken to bridge the gap between the recommendations of clinical guidelines and the real situation of clinical practice. [ABSTRACT FROM AUTHOR]

Background: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. Methods: Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. Results: We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. Conclusions: These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury. [ABSTRACT FROM AUTHOR]