[Medium to long-term efficacy of tension-free vaginal tape procedure in the treatment of female recurrent stress urinary incontinence].

OBJECTIVE: To investigate the effectiveness and clinical efficacy of tension-free vaginal tape (TVT) surgery in treating female recurrent stress urinary incontinence (rSUI). METHODS: A retrospective analysis was conducted on 24 patients who experienced recurrence of mid-urethral sling failure and were treated with TVT surgery at Beijing Chao-Yang Hospital from January 2016 to June 2020. Basic patient information was collected. The International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) was used to record urinary incontinence symptom scores preoperatively, 1-year postoperatively, and more than three years postoperatively. The changes in various ICI-Q-SF scores and total scores were compared. Additionally, clinical symptom severity of urinary incontinence was recorded and compared preoperatively and more than three years postoperatively. RESULTS: Among the 24 patients included in the follow-up, one patient was lost to follow-up due to death from a cerebrovascular accident one year postoperatively, leaving 23 patients with a follow-up period ranging from 3.9 to 7.3 years, with an ave-rage follow-up time of (5.2±1.1) years. Preoperatively, the median ICI-Q-SF total score was 20.0 (16.0, 21.0); at the 1-year follow-up, the median ICI-Q-SF total score was 5.0 (1.5, 7.8) (P < 0.001); at an average follow-up of five years, the median ICI-Q-SF total score was 6.0 (3.0, 9.0), still showing a statistically significant difference compared with preoperative scores (P < 0.001). The individual ICI-Q-SF scores were significantly lower at the 1-year and average five-year follow-ups compared with preoperative scores (P < 0.001). Regarding the severity of urinary incontinence, all the patients had moderate to severe urinary incontinence preoperatively; Five years postoperatively, 87.0% (20/23) of the patients had no or only mild urinary incontinence, and 13.0% (3/23) had recurrent moderate to severe urinary incontinence (P < 0.001). CONCLUSION: TVT surgery is effective in treating female recurrent stress urinary incontinence, with an average 5-year cure and improvement rate of 87.0%.

The impact of gender differences on the clinical characteristics of critically ill patients with venous thromboembolism: A retrospective, observational study.

The aim of this study is to describe the general information, disease and treatment of venous thromboembolism (VTE) in critically ill patients, to explore the characteristics of severe patients with deep venous VTE and provide clinical reference data for the prevention and treatment of VTE in critically ill patients. This study carried out a retrospective study on the medical records of patients who were treated in the intensive care unit of Affiliated Hospital of Jining Medical College from 2020 to 2022. The general data, general conditions, drug use, past history, VTE prevention measures, post-VTE conditions, and Padua risk score of 297 patients with VTE during the period of hospitalization in intensive care unit (ICU) were classified and statistically analyzed. A total of 297 including 171 male and 126 male patient medical records were included in the analysis, we compared multiple clinical indicators between male and female patients. Compared to women, male patients have a higher acute physiology and chronic health evaluation II score(APACHE-II score) (P = .027), a higher state of consciousness (P = .003), a higher rate of smoking and drinking history (P < .001), a lower rate of heart failure (P = .003) and chronic depression (P = .013), and a higher rate of recommended operations for male patients after VTE (P = .031). The prothrombin time (PT) (P = .041) and activated partial thromboplastin time (APTT) (P = .040) of male patients were significantly higher than those of female patients, while triglyceride (P = .009) and total cholesterol (TC) (P = .001) were significantly lower than those of female patients. The difference in D-dimer (P = .739) was not significant. This study shows that male and female patients with VTE in the ICU have significant differences in general characteristics, general clinical conditions, history of past illness, thrombosis character, and examination items, this may be the reason for the different rates of VTE between male and female patients in the ICU.

A novel inhalable nanobody targeting IL-4Rα for the treatment of asthma.

BACKGROUND: Inhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several mAbs targeting IL-4 receptor α chain (IL-4Rα) have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges. OBJECTIVE: Capitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma. METHODS: Three IL-4Rα immunized Nb libraries were used to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising 2 HuNb103 units, was constructed with a high affinity and specificity for human IL-4Rα. The efficacy, pharmacokinetics, and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4RA humanized mice. RESULTS: LQ036 inhibited secreted embryonic alkaline phosphatase reporter activity, inhibited TF-1 cell proliferation, and suppressed phosphorylated signal transducer and activator of transduction 6 in T cells from patients with asthma. Crystal structure analysis revealed a binding region similar to dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited ovalbumin-specific IgE levels in serum, CCL17 levels in bronchoalveolar lavage fluid, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4RA humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety, and tissue distribution, with higher concentrations observed in the lungs and bronchi. CONCLUSIONS: These findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.

Efficacy of Mid-Urethral Sling and Urethral Dilation for Stress Urinary Incontinence Combined with Urethral Stricture in Women.

OBJECTIVE: To investigate the potential clinical benefits of mid-urethral sling (MUS) and urethral dilatation (UD) operations for the treatment of stress urinary incontinence (SUI) combined with urethral stricture. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China, from January 2017 to 2022. METHODOLOGY: Patients with Qmax <15ml/s or PVR >50ml, and video urodynamic study (VUDS) capable of confirming the presence and position of urethral stricture were included. The clinical efficacy was evaluated by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire, maximum flow rate (Qmax), and postvoid residual (PVR) urine. ICIQ-SF, Qmax, and PVR were measured presurgery, on postoperative 2-week, and 1-month postsurgery. RESULTS: There were total 19 patients with an average age of 61.37 ± 11.28 years (range 39-84) with SUI and urethral stricture. ICIQ-SF scores were decreased significantly at one month postoperatively compared with the preoperative [5.0 (0.0, 7.0) vs. 14.0 (13.0, 15.0), p <0.001]. Qmax was increased dramatically compared with the preoperative [21.3 (14.0, 28.4) vs. 13.0 (8.7,18.0), p <0.001], and PVR was decreased remarkably than the preoperative [0.0 (0.0,0.0) vs. 0.0 (0.0,60.0), p = 0.018]. Of 19 patients primarily managed with MUS and UD, two patients experienced recurrence requiring repetitive dilation till sling excision surgery was conducted, and improvement was evident in one patient after repeating UD. CONCLUSION: The overall incidence of SUI combined with urethral stricture in women is low. With a success rate of 89.5%, MUS and UD were effective therapies for the co-existence of SUI with urethral stricture, and repeated UD can be performed safely if necessary in long-term follow-up. KEY WORDS: Stress urinary incontinence, Urethral stricture, Mid-urethral sling, Urethral dilatation.

MR defecography in assessing stress urinary incontinence with or without symptomatic pelvic organ prolapse.

PURPOSE: Utilize magnetic resonance defecography (MRD) to analyze the primary pelvic floor dysfunctions in patients with stress urinary incontinence (SUI) associated with pelvic organ prolapse (POP), and in SUI patients with asymptomatic POP. METHOD: We performed MRD in both SUI and POP subjects. As a primary analysis, the functional MR parameters were compared between the isolated POP and POP combined SUI groups. As a secondary analysis, the functional MR data were compared between the POP combined SUI and the SUI with asymptomatic POP (isolated SUI) groups. RESULTS: MRD noted the main characteristics of SUI combined moderate or severe POP, including the shorter closed urethra length (1.87 cm vs. 2.50 cm, p < 0.001), more prevalent urethral hypermobility (112.31° vs. 85.67°, p = 0.003), bladder neck funneling (48.28% vs. 20.51%, p = 0.020), lower position of vesicourethral junction (2.11 cm vs. 1.67 cm, p = 0.030), and more severe prolapse of the posterior bladder wall (6.26 cm vs. 4.35 cm, p = 0.008). The isolated SUI patients showed the shortest length of the closed urethra (1.56 cm vs. 1.87 cm, p = 0.029), a larger vesicourethral angle (153.80° vs. 107.58°, p < 0.001), the more positive bladder funneling (84.85% vs. 48.28%, p = 0.002) and a special urethral opening sign (45.45% vs. 3.45%, p < 0.001). CONCLUSIONS: Patients with SUI accompanying POP primarily exhibit excessive urethral mobility and a shortened urethral closure. SUI patients with asymptomatic POP mainly show dysfunction of the urethra and bladder neck, characterized by the opening of the urethra and bladder neck and a shortened urethral closure.

Posterior circulation ischemic stroke: radiomics-based machine learning approach to identify onset time from magnetic resonance imaging.

PURPOSE: Posterior circulation ischemic stroke (PCIS) possesses unique features. However, previous studies have primarily or exclusively relied on anterior circulation stroke cases to build machine learning (ML) models for predicting onset time. To date, there is no research reporting the effectiveness and stability of ML in identifying PCIS onset time. We aimed to build diffusion-weighted imaging-based ML models to identify the onset time of PCIS patients. METHODS: Consecutive PCIS patients within 24 h of definite symptom onset were included (112 in the training set and 49 in the independent test set). Images were processed as follows: volume of interest segmentation, image feature extraction, and feature selection. Five ML models, naïve Bayes, logistic regression, tree ensemble, k-nearest neighbor, and random forest, were built based on the training set to estimate the stroke onset time (binary classification: ≤ 4.5 h or > 4.5 h). Relative standard deviations (RSD), receiver operating characteristic (ROC) curves, and the calibration plot was performed to evaluate the stability and performance of the five models. RESULTS: The random forest model had the best performance in the test set, with the highest area under the curve (AUC, 0.840; 95% CI: 0.706, 0.974). This model also achieved the highest accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (83.7%, 64.3%, 91.4%, 75.0%, and 86.5%, respectively). Furthermore, the model had high stability (RSD = 0.0094). CONCLUSION: The PCIS case-based ML model was effective for estimating the symptom onset time and achieved considerably high specificity and stability.

The application value of 3D ASL in evaluating the effectiveness of stent implantation for vertebrobasilar artery stenosis.

OBJECTIVE: To evaluate the effect of stent implantation for vertebrobasilar artery stenosis，by using 3D arterial spin labeling (3D ASL) technique. METHODS: A retrospective analysis was conducted on the clinical and 3D ASL data of 48 patients who underwent vertebral-basilar artery stenting. Post-labeling delay times (PLD) of 1.5 s and 2.5 s were chosen, and the average regional cerebral blood flow (rCBF) values were measured in nine brain regions of the posterior circulation: bilateral thalamus, bilateral occipital lobes, bilateral cerebellar hemispheres, midbrain, pons, and medulla. The 48 patients were divided into two groups based on the presence or absence of acute ischemic stroke in the posterior cerebral circulation region detected by diffusion-weighted imaging (DWI). The preoperative and postoperative rCBF results were statistically analyzed. RESULTS: In the infarct group, there were significant increases in rCBF values of all nine brain regions at both PLD = 1.5 s and 2.5 s postoperatively compared to preoperatively. At PLD = 1.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were found in the right thalamus, left cerebellum, midbrain, and pons regions (P < 0.05). At PLD = 2.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were observed in the left occipital lobe, right cerebellum, midbrain, and pons regions (P < 0.05). When analyzing the rCBF values of the brain regions with recent infarcts in the infarct group, there was a significant increase in postoperative rCBF values compared to preoperative values (P < 0.05). After excluding the data from brain regions with recent infarcts, the CBF values in the remaining brain regions were also increased postoperatively, and some brain regions showed statistically significant differences in rCBF values between the preoperative and postoperative periods (P < 0.05). In the non-infarct group, there were no statistically significant differences in the preoperative and postoperative rCBF values in all brain regions at both PLD = 1.5 s and 2.5 s (P > 0.05). CONCLUSION: The application of 3D ASL technology shows significant value in assessing the surgical efficacy of vertebral-basilar artery stenting, especially in patients with acute posterior circulation infarction.

The Effects of Exogenous 2,4-Epibrassinolide on the Germination of Cucumber Seeds under NaHCO3 Stress.

This investigation focused on the suppressive impact of varying NaHCO3 concentrations on cucumber seed germination and the ameliorative effects of 2,4-Epibrassinolide (EBR). The findings revealed a negative correlation between NaHCO3 concentration and cucumber seed germination, with increased NaHCO3 concentrations leading to a notable decline in germination. Crucially, the application of exogenous EBR significantly counteracted this inhibition, effectively enhancing germination rates and seed vigor. Exogenous EBR was observed to substantially elevate the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), thereby mitigating oxidative damage triggered under NaHCO3 stress conditions. Additionally, EBR improved enzyme activity under alkaline stress conditions and reduced starch content in the seeds. Pertinently, EBR upregulated genes that were associated with gibberellin (GA) synthesis (GA20ox and GA3ox), and downregulated genes that were linked to abscisic acid (ABA) synthesis (NCED1 and NCED2). This led to an elevation in GA3 concentration and a reduction in ABA concentration within the cucumber seeds. Therefore, this study elucidates that alleviating oxidative stress, promoting starch catabolism, and regulating the GA and ABA balance are key mechanisms through which exogenous EBR mitigates the suppression of cucumber seed germination resulting from alkaline stress.

High performance production process development and scale-up of an anti-TSLP nanobody.

Nanobodies (Nbs) represent a class of single-domain antibodies with great potential application value across diverse biotechnology fields, including therapy and diagnostics. Thymic Stromal Lymphopoietin (TSLP) is an epithelial cell-derived cytokine, playing a crucial role in the regulation of type 2 immune responses at barrier surfaces such as skin and the respiratory/gastrointestinal tract. In this study, a method for the expression and purification of anti-TSLP nanobody (Nb3341) was established at 7 L scale and subsequently scaled up to 100 L scale. Key parameters, including induction temperature, methanol feed and induction pH were identified as key factors by Plackett-Burman design (PBD) and were optimized in 7 L bioreactor, yielding optimal values of 24 °C, 8.5 mL/L/h and 6.5, respectively. Furthermore, Diamond Mix-A and Diamond MMC were demonstrated to be the optimal capture and polishing resins. The expression and purification process of Nb3341 at 100L scale resulted in 22.97 g/L titer, 98.7% SEC-HPLC purity, 95.7% AEX-HPLC purity, 4 ppm of HCP content and 1 pg/mg of HCD residue. The parameters of the scaling-up process were consistent with the results of the optimized process, further demonstrating the feasibility and stability of this method. This study provides a highly promising and competitive approach for transitioning from laboratory-scale to commercial production-scale of nanobodies.

Discovery of Natural Potent HMG-CoA Reductase Degraders for Lowering Cholesterol.

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.

TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited treatment options and a poor prognosis. Trophoblast cell surface antigen 2 (TROP2), a cell surface antigen overexpressed in the tumors of more than half of pancreatic cancer patients, has been identified as a potential target for antibody-drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are of the IgG type and have been poorly studied in pancreatic cancer. Here, we aimed to develop a novel nanobody-drug conjugate (NDC) targeting TROP2 for the treatment of pancreatic cancer. RESULTS: In this study, we developed a novel TROP2-targeted NDC, HuNbTROP2-HSA-MMAE, for the treatment of TROP2-positive pancreatic cancer. HuNbTROP2-HSA-MMAE is characterized by the use of nanobodies against TROP2 and human serum albumin (HSA) and has a drug-antibody ratio of 1. HuNbTROP2-HSA-MMAE exhibited specific binding to TROP2 and was internalized into tumor cells with high endocytosis efficiency within 5 h, followed by intracellular translocation to lysosomes and release of MMAE to induce cell apoptosis in TROP2-positive pancreatic cancer cells through the caspase-3/9 pathway. In a xenograft model of pancreatic cancer, doses of 0.2 mg/kg and 1 mg/kg HuNbTROP2-HSA-MMAE demonstrated significant antitumor effects, and a dose of 5 mg/kg even eradicated the tumor. CONCLUSION: HuNbTROP2-HSA-MMAE has desirable affinity, internalization efficiency and antitumor activity. It holds significant promise as a potential therapeutic option for the treatment of TROP2-positive pancreatic cancer.

Case Report: Analysis of four cases of metastatic bladder masses after radical prostatectomy.

Objective: The aim of this study is to investigate the clinical characteristics and diagnostic and therapeutic methods of bladder metastasis after radical prostatectomy and to improve its diagnosis and treatment. Methods: The clinical data of four patients with bladder metastasis after radical prostatectomy were retrospectively analyzed from January 2011 to December 2021. Three cases suffered from intermittent gross hematuria, and only one case was found to have an elevated prostate-specific antigen (PSA) value. Transurethral resection of bladder tumor was performed in four cases, in which one case also underwent resection of urethral mass. Three cases received endocrine therapy, one of which added intravesical instillation and radiation therapy. Another case received chemotherapy based on comprehensive treatment. Results: According to the pathological and immunohistochemical results, three cases were acinar adenocarcinoma of the prostate with Gleason score of 9, and all cases were PSA positive and negative for cytokeratin 7 (CK7) and GATA binding protein 3 (GATA-3). One case was small cell neuroendocrine carcinoma of the prostate and was positive for chromogranin A (CGA), synaptophysin (SYN), and cluster of differentiation 56 (CD56). During the follow-up period of 4 to 13 months, one case was lost to follow-up and three cases were alive. Conclusion: Bladder metastasis after radical prostatectomy is rare, and pathology combined with immunohistochemistry is the gold standard for its diagnosis. Pathological type determines its treatment. Systemic treatment is essential, and local treatment is the most palliative means. Early diagnosis and treatment is significant for better prognosis.

Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.

Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

The Clinical Study on Short-Term Efficacy of Pelvic Magnetic Stimulation Combined with Pelvic Muscle Biofeedback on Female Idiopathic Overactive Bladder.

Objective: To evaluate the short-term efficacy of pelvic magnetic stimulation combined with pelvic muscle biofeedback on female Idiopathic Overactive Bladder (IOAB). Methods: 96 cases of IOAB females were randomly divided into control group (magnetic stimulation treatment n=48) and observation group (magnetic stimulation with biofeedback n=48). All the patients were dealt with the sacralneuromagnetic stimulation (once, qod), with 5 times in total. Then the patients in observation group were processed with biofeedback (10 times). Overactive Bladder Symptom Score (OABSS), Patients Perception Bladder Condition (PPBC) and Incontinence Quality of Life Scale (I-QOL) were evaluated as the indexes. Results: The effective rate of control group and observation group respectively were 89.58% and 93.75%. There were significant differences (P=0.67). The OABSS and PPBC of two groups were decreased, I-QOL were increased after treatment (P<0.05). Difference was statistically significant in OABSS three months after treatment between the two groups (P=0.00).The recurrence rate of three months after treatment of the two groups were 18.75% and 6.38% (P=0.04). Conclusions: Both magnetic stimulation alone and magnetic stimulation with biofeedback were effective and safe in female patients with IOAB. Magnetic stimulation with biofeedback may reduce the recurrence rate and continue to improve the symptoms in a certain extent.

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study.

BACKGROUND Delayed graft function (DGF) caused by ischemia-reperfusion injury is a common pathophysiological process that should be monitored by specific biomarkers in addition to serum creatinine. Thus, this single-center retrospective study aimed to investigate the association between levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18) in DGF associated with acute kidney injury in kidney transplant recipients (KTRs) and estimated glomerular filtration rate (eGFR) at 3 years post-transplant. MATERIAL AND METHODS A total of 102 KTRs [14(13.7%) of DGF and 88(86.3%) of NON-DGF] were enrolled. DGF was defined as "dialysis is needed within 1 week after kidney transplantation". NGAL, KIM-1, L-FABP, and IL-18 were obtained from perfusate samples of donation-after-cardiac-death (DCD) kidneys, and measured by ELISA. RESULTS Compared to the NON-DGF group, KTRs in the DGF group had a statistically significant increase in levels of NGAL (P<0.001) and KIM-1 (P<0.001). Multiple logistic regression analyses showed that NGAL (OR=1.204, 95% CI 1.057-1.372, P=0.005) and KIM-1 (OR=1.248, CI=1.065-1.463, P=0.006) could be regarded as independent risk factors. The accuracy of NGAL and KIM-1 was 83.3% and 82.1%, respectively, calculated using the area under the receiver operating characteristic curve. Furthermore, the eGFR at 3 years post-transplant had a moderate negative correlation with NGAL (r=-0.208, P=0.036) and KIM-1 (r=-0.260, P=0.008). CONCLUSIONS Our results support those from previous studies showing that perfusate levels of NGAL and KIM-1 are associated with DGF in KTRs and also with reduced eGFR at 3 years post-transplant.

Scintillation Properties of Lanthanide Doped Pb4Lu3F17 Nanoparticles.

Inorganic scintillators are of great significance in the fields of medical CT, high-energy physics and industrial nondestructive testing. In this work, we confirm that the Pb4Lu3F17: Re (Re = Tb, Eu, Sm, Dy, Ho) crystals are promising candidates for a new kind of scintillator. Detailed crystal structure information is obtained by the Rietveld refinement analysis. Upon X-ray irradiation, all these scintillators exhibited characteristic 4f-4f transitions. The Ce and Gd ions were verified to be useful for enhancing the scintillation intensity via introducing energy transfer processes. The integrated scintillation intensity of the Pb4Lu3F17: Tb/Ce is about 16.8% of the commercial CsI (Tl) single crystal. Our results manifested that Pb4Lu3F17: Re has potential application in X-ray detection and imaging.

Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy.

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

Changes in sensory-related brain networks of patients with moyamoya disease with limb paresthesia: A resting-state fMRI-based functional connectivity analysis.

This study's aim was to investigate functional brain connectivity changes among patients with moyamoya disease (MMD) with limb paresthesia, using functional connectivity analysis based on resting-state functional magnetic resonance imaging (rs-fMRI). A total of 181 patients with MMD were enrolled, including 57 with left limb paresthesia (MLP group), 61 with right limb paresthesia (MRP group), and 63 without paresthesia (MWP group). Encephaloduroarteriosynangiosis (EDAS) was performed in 20 of the 57 patients with left limb paresthesia and 15 of the 61 patients with right limb paresthesia. Twenty-nine age- and sex-matched healthy controls (HC group) were recruited during the same period. All participants underwent rs-fMRI examination, and the patients treated with EDAS were re-examined 3-4 months after the surgery. After data preprocessing, we selected Brodmann area 3 on each side of the brain as the seed region to construct a functional connectivity network of the whole brain, and then we analyzed the differences in functional connectivity between the HC group, MWP group, MLP group, and MRP group. The functional connectivity of Brodmann area 3 (on either side) with the ipsilateral frontal (superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus) and parietal (supramarginal gyrus, angular gyrus, and superior parietal lobule) cortices was increased among patients with MMD. The functional connectivity enhancement in these brain regions was broader and greater in patients with contralateral limb paresthesia than in patients without paresthesia, and the regions with functional connectivity changes were roughly distributed symmetrically among the MLP group and the MRP group. There were no changes 3-4 months after EDAS in the increased functional connectivity between the frontal and parietal cortices and Brodmann area 3. Limb paresthesia in patients with MMD may be driven by abnormal functional connectivity in the frontal and parietal cortices. Functional changes in associated brain regions may be a target for evaluating the severity of MMD and its response to treatment.

Factors Associated with Housing Damage Caused by an EF4 Tornado in Rural Areas of Funing, China.

Rural areas are vulnerable to natural disasters and tend to suffer severe losses. An EF4 tornado occurred in Funing on 23 June 2016, killing 99 people, injuring at least 846 people, and destroying more than 2000 houses. Using a multinomial logistic regression model, this study explored the influencing factors between housing damage and variables of building conditions, tornado intensity, and village environmental factors. The results show that 2-story houses and masonry houses were more likely to be slightly damaged or be in a dangerous state. Furthermore, the building area was positively related to houses in two categories: slight damage (SD) and dangerous and requiring immediate repair (DR), indicating that the larger or taller the house, the more severe the damage. In terms of tornado intensity, houses classified as SD were more likely to be hit by EF4 tornados than by EF3 tornados, and houses were damaged more by EF1 or EF2 tornados. This finding demonstrates that the level of housing damage was not strongly correlated with the tornado intensity. Slightly damaged houses exhibited the highest correlation with environmental factors. The proportion of slightly damaged houses was positively correlated with the water area in the village, unlike the proportion of houses in the DR and unable to be repaired (UR) categories. Moreover, the larger the water area of a village, the less housing damage it suffered. These findings provide new insights into minimizing housing damage in wind disasters to improve disaster prevention planning in rural areas.