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Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated β-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis., Graphical abstract, Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. We found that circGNAQ, a circular RNA enriched in vascular endothelium, inhibited endothelial cell senescence and atherosclerosis progression, implying that circGNAQ-based gene therapy could serve as a novel therapeutic strategy to protect against atherosclerosis development.

Background The Forgotten Joint Score is a patient-reported outcome measure validated in assessing patients post knee arthroplasty, anterior cruciate ligament (ACL) reconstruction surgery and patellar dislocation. A previous study had established the normative scores of a population in the USA but included knees with pathology. The aim of our study is to obtain normative Forgotten Joint Scores in young Asian adults without any pre-existing knee pathologies to increase the interpretability of the Forgotten Joint Score-12 (FJS-12) score. Methods We conducted a cross-sectional study across young healthy Asian adults via electronic platforms. Participants who had sought either Western medical consultation, physiotherapy or traditional medical therapies were excluded. Demographic data, occupation, type of sport played, and FJS-12 scores were collected. Scores were stratified into subgroups and analysed. Results There were 172 participants who met our inclusion criteria for this study. The average age of participants in our study was 28.1 ± 10.5 years (range 14–70 years), with 83 (47.7%) participants falling into the ages 21–25 years. Average body mass index (BMI) was 21.9 ± 3.3 kg/m2 (range 14.7–36.3 kg/m2). The average FJS-12 score was 62.8 ± 25.6. The median FJS-12 was 63.5 with a range of 4.2–100. Nine participants (5.2%) scored the maximum score possible, and 56 (32.6%) participants scored below the midpoint score of 50. The percentiles for each subgroup of participants were tabulated and reported. Notably, males aged 46–70 years old scored the highest average FJS-12 score of 73.4 ± 5.5, and females aged 31–45 years old scored the lowest FJS-12 score of 57.1 ± 25.1. Females scored lower than males, although the difference was not statistically significant (p = 0.157). There were no significant correlations between BMI, age, or type of sport played with FJS-12; however, interestingly, we observed that women reported similar FJS-12 scores across all age groups, while men reported better scores with increasing age.Interestingly, we observed that women reported similar FJS-12 scores across all age groups, while men reported better scores with increasing age. Conclusion Having normative values provides opportunities for benchmarking and comparing individuals against age- and gender-matched peers in the general population. Knowledge of normative values for FJS-12 scores would aid evaluating and tracking progress in patients recovering from injuries or undergoing post-surgery rehabilitation. This would help clinicians determine if they return to ‘normal’ post intervention.

Introduction: In China, patients with chronic cholecystitis account for approximately 10% of the total population, in which over 90% of cholecystitis is caused by cholelithiasis. This study aimed to discuss the possible mechanism of electroacupuncture on the Yanglingquan acupoint promoting gallbladder contractibility of patients with chronic cholecystitis. Methods: 60 patients were randomly divided into a trial group and a control group. Doppler ultrasound and color Doppler blood flow imaging was applied. The trial group adopted the BT701-1B electroanesthesia apparatus to perform electroacupuncture on the bilateral acupoints of Yanglingquan, while electroacupuncture was made on sham acupoints in the control group. Results: Before the electroacupuncture, gallbladder volume was 49.6 ± 5.66 ml, after 15 min and 30 min of electroacupuncture, the gallbladder volume was then 32.9 ± 5.66 ml and 23.0 ± 2.83 ml respectively. The comparison before and after electroacupuncture was obviously and statistically different (P < 0.01). The comparison between after 15 min and 30 min is obviously statistically different (P < 0.01). Before the electroacupuncture, the gallbladder artery Vmax, Vmin, and RI were 18.4 ± 2.69 cm/s, 9.7 ± 0.07 cm/s, and 0.47 ± 0.06, respectively; the cystic artery Vmax, Vmin, and RI after 30 min were 8.1 ± 0.92 cm/s, 3.1 ± 0.57 cm/s, and 0.61 ± 0.02. The comparison in gallbladder artery Vmax and Vmin and the drag index (RI) before and after electroacupuncture was obviously and statistically different (P < 0.01). Conclusions: Electroacupuncture on the acupoints of Yanglingquan has the potential to promote the emptying of the gallbladder. The mechanism may be related to that the smooth muscle of the gallbladder contracts after electroacupuncture and the gallbladder empties.

Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.

Four new phenolic compounds, 2-{[3-(3,4-dihydroxyphenyl)propanoyl]oxy} propanoic acid (1), 2-{[3-(3,4-dihydroxyphenyl)propanoyl]oxy} propanoic acid methyl (2), (±)3-{2-[1-(3′,4′-dihydroxy-phenyl)ethyl]-4,5-dihydroxyphenyl} propanoic acid methyl (3), and (±)3-{2-[1-(3′,4′-dihydroxy-phenyl)ethyl]-4,5-dihydroxyphenyl} propanoic acid (4), together with five known compounds, methyl 3-(3,4-dihydroxyphenyl)-propanoate (5), 3,4-dihydroxybenzenepropionic acid (6), caffeic acid (7), protocatechuic acid (8), and 1,3-trans-5,6-dihydroxy-3-(3′,4′-dihydroxyphenyl) indan-1-methyl (9) were isolated from the tender leaves of Eucommia ulmoides Oliv. Compound 9 was isolated from Eucommiaceae for the first time. The structures of the new compounds were elucidated from the spectra of 1D NMR and 2D NMR, and MS data. Compounds 1-9 were tested to determine their inhibitory effect on LPS-induced NO production in macrophage RAW264.7 cells. Modest inhibitory activities were observed for compounds 2–5 and 9, with IC50 values ranging from 8.3 to 31.0 μM. This research enriches the current chemical information regarding the leaves of Eucommia ulmoides Oliv. and provides a reference for further research on its anti-inflammatory effects.

The accurate determination of the interface shear strength is essential in the design of geosynthetic-reinforced soil structures. The particle geometries of three types of soil materials and a spherical granular medium are imaged and quantified using binary image-based methods and described in terms of regularity. Cyclic direct shear tests are conducted to investigate the effects of particle regularity on the interface shear strength, stress–displacement relationship, shear stiffness, and damping ratio. The results reveal that the interface shear strength and deformation strongly depend on particle regularity. The vertical displacement ratio is found to increase with particle regularity under the same cycle number. The interface stiffness is observed to increase with the cycle number for particle regularities of 0.453, 0.565, and 0.672 but decreases with the cycle number for a particle regularity of 0.971. For a given regularity, the trend of damping ratio with the increasing cycle number is contrary to the that of shear stiffness. Finally, it is observed that the cyclic friction angle decreases with increasing particle regularity, the relationship of which is determined using linear regression. Thus, the systematic quantification of particle shape characteristics can lead to a better understanding of soil–geogrid interface behaviour.

Objective: Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer. Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia; validate an index of the hyperthermia chemotherapy sensitization enhancement ratio (HCSER) to identify the chemotherapeutics most enhanced by hyperthermia; and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment. Methods: Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines. Cells from both sources were encapsulated in 3D Matrigel droplets, which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres. The microspheres were seeded in 96-well plates, with each well containing a single microsphere that developed into an organoid after 7 days. The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37 °C as a control and 43 °C for 90 min to examine hyperthermia synergism. Cell viability was counted with 10% CCK8. Results: We successfully established a library of colorectal cancer organoids from 22 patient parental tumors. We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs. In 11 of the 22 patient organoids, raltitrexed had significant hyperthermia synergism, which was indexed as the highest HCSER score within each patient group. Conclusions: Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics. We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.

The cpxR gene, encoding a new cytoplasmic response regulator, which effects virulence, biofilm formation, chemotaxis, resistance to antimicrobials, and controls soft rot, was amplified by the polymerase chain reaction, cloned into the prokaryotic expression vector pET-15b, and expressed through the induction of isopropyl-β-d-thiogalactoside in Escherichia coli BL21 (DE3). Then, highly purified and stable CpxR protein was produced by nickel affinity chromatography and fast protein liquid chromatography, digested by thrombin and identified by Western blotting. Furthermore, the structure of the CpxR protein was estimated by circular dichroism spectroscopy and SWISS-MODEL. The CpxR protein was a functional part in signal transduction and bacterial resistance for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The resear ch of the protein stability indicated the CpxR protein had excellent thermal stability and was suitable for crystallization. Then the small crystals of CpxR protein were found in the crystallizing tank. The latest 34 cpxR sequences from the public database were selected and analyzed by molecular clustering and multisequence alignment. These cpxR sequences were roughly divided into four categories. These results laid an important foundation for the further structural study of the CpxR protein.

Antibody recruiting molecules (ARMs) represent an important class of "proximity-inducing" chemical tools with therapeutic potential. ARMs function by simultaneously binding to a hapten-specific serum antibody (Ab) (e.g., anti-dinitrophenyl (DNP)) and a cancer cell surface protein, enforcing their proximity. ARM anticancer efficacy depends on the formation of ARM:Ab complexes on the cancer cell surface, which activate immune cell recognition and elimination of the cancer cell. Problematically, ARM function in human patients may be limited by conditions that drive the dissociation of ARM:Ab complexes, namely, intrinsically low binding affinity and/or low concentrations of anti-hapten antibodies in human serum. To address this potential limitation, we previously developed a covalent ARM (cARM) chemical tool that eliminates the ARM:antibody equilibrium through a covalent linkage. In the current study, we set out to determine to what extent maximizing the stability of ARM:antibody complexes via cARMs enhances target immune recognition. We observe cARMs significantly increase target immune recognition relative to ARMs across a range of therapeutically relevant antibody concentrations. These results demonstrate that ARM therapeutic function can be dramatically enhanced by increasing the kinetic stability of ARM:antibody complexes localized on cancer cells. Our findings suggest that a) high titres/concentrations of target antibody in human serum are not neccessary and b) saturative antibody recruitment to cancer cells not sufficient, to achieve maximal ARM therapeutic function.

BackgroundBronchoscopy treatments of central airway obstruction (CAO) under general anesthesia are high-risky procedures, and posing a giant challenge to the anesthesiologists. We summarized and analyzed our clinical experience in patients with CAO undergoing flexible or rigid bronchoscopy, to estimate the safety of skeletal muscle relaxants application and the traditional Low-frequency ventilation.MethodsClinical data of 375 patients with CAO who underwent urgent endoscopic treatments in general anesthesia from January 2016 to October 2019 were retrospectively reviewed. The use ratio of skeletal muscle relaxants, dose of skeletal muscle relaxants used, the incidence of perioperative adverse events, adequacy of ventilation and gas exchange, post-operative recovery between rigid bronchoscopy and flexible bronchoscopy therapy, and risk factors for postoperative ICU admission were evaluated.ResultsOf the 375 patients with CAO, 204 patients were treated with flexible bronchoscopy and 171 patients were treated with rigid bronchoscopy. Muscle relaxants were used in 362 of 375 patients (including 313 cisatracurium, 45 rocuronium, 4 atracurium, and 13 unrecorded). The usage rate of muscle relaxants (96.5% in total) was very high in patients with CAO who underwent either flexible bronchoscopy (96.6%) or rigid bronchoscopy (96.5%) therapy. The dosage of skeletal muscle relaxants (Cisatracium) used was higher in rigid bronchoscopy compared with flexible bronchoscopy therapy (10.8 ± 3.8 VS 11.6 ± 3.6 mg, respectively,p p > 0.05). Three patients (1 in flexible and 2 in rigid) died, during the post-operative recovery, and the higher grade of American Society of Anesthesiologists (ASA) and obvious dyspnea or orthopnea were the independent risk factors for postoperative ICU admission.ConclusionThe muscle relaxants and low-frequency traditional ventilation can be safely used both in flexible and rigid bronchoscopy treatments in patients with CAO. These results may provide strong clinical evidence for optimizing the anesthesia management of bronchoscopy for these patients.

By examining outpatient consultations recorded in a hospital-based specialist clinic in China, the study reports a strikingly frequent occurrence of resistance in the diagnosis phase. Drawing on conversation analysis, we found that besides resistance patterns and resources previously studied, second-position repetition and the absence of uptake, both involving no substantive content of resistance, are also recurrently exploited by Chinese patients in diagnosis disalignment. As to resources of substantive resistance, temporarily absent symptoms, medical test results and self-proposed treatment recommendation are found in Chinese patients' reservoir, in addition to other common resources. Patients' disregard for epistemic vise is shown through their exploitation of expertise-demanding knowledge like interpreting medical test results to contest diagnostic decisions. The frequency, patterns and resources of diagnosis resistance in our data all point to the great recession of medical authority along with a significant rise of patients’ agency in Chinese medical encounters today.

In order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential “combination biomarker” for predicting prognosis of glioma patients.

To compare outcomes of early and late tracheostomy change in neonatal patients. Early tracheostomy change (ETC) occurred 3 to 4 days after surgery, and late tracheostomy change (LTC) occurred 5 to 7 days after surgery.Retrospective cohort.Tertiary neonatal/pediatric intensive care unit.A retrospective review of patients who underwent tracheostomy from 2015 to 2019 was performed for infants1 year old. Data were recorded regarding age at tracheostomy, days until tracheostomy tube change, postoperative complications, and total number of days on sedative or paralytic drugs.Forty-six patients were included: 18 (39%) were male, with a mean age of 140 days (SD, 78). Of these, 28 (61%) received ETC. There were no accidental decannulation events in either group. Wound breakdown developed in 4 (14%) patients with ETC versus 5 (28%) with LTC (ETC appears to be feasible in children less than a year of age. There does not appear to be an increased risk of accidental decannulation events or false passage tracts. Further investigations are warranted to investigate safety and possible impact on wound breakdown.

Parathyroid cysts (PCs) are rare, benign, cystic lesions, and PCs that occur in the mediastinum (mediastinal parathyroid cysts [MPCs]) are even more rare. Surgical resection is recommended as the first choice of treatment for MPCs. Sternotomy, thoracotomy, and thoracoscopic approaches are the most common methods for resection of MPCs. Herein, we report a case of robotic right portal minimally invasive resection of a giant nonfunctional MPC in the right anterosuperior mediastinum., Parathyroid cysts (PCs) are rare, benign, cystic lesions, and PCs that occur in the mediastinum (mediastinal parathyroid cysts [MPCs]) are even more rare. Herein, we report a case of robotic right portal minimally invasive resection of a giant nonfunctional MPC in the right anterosuperior mediastinum.

As a potential renewable and nitrogen-rich resource, millions of tons of feather waste are generated from poultry farming and this has been steadily increasing. Bioconversion is the most promising low-cost and environmentally benign recycling method, while the efficiency of the isolated natural feather degrading bacteria (FDB) cannot satisfy the requirements of industrial utilization. The process of bacterial degradation of feathers not only requires proteases but also involves complex reduction mechanisms that have not yet been revealed. Previous heterologous expression of keratinase genes in non-FDB hosts achieved only very limited success. In this study, the mechanism of sulfite production via cysteine dioxygenase (CDO1) oxidation was first identified in Streptomyces sp. SCUT-3, which is important for feather disulfide bond reduction. The knockdown of cdo1 significantly decreased the sulfite production (from 38.5 to 22.5 mg L−1) and feather degradation rate (from 45.7% to 39.5%) of SCUT-3 in 5% chicken feather medium (CFM) culture. The overexpression of cdo1 increased bacterial single-cell sulfite production and feather protein conversion efficiency by 3.8 and 2.5 fold, respectively, on day 2 in 5% CFM. On this basis, a new strategy is proposed for increasing feather degradation efficiency by enhancing the reducing power and keratinase activity of FDB according to their own feather degradation mechanism. Thus, the co-overexpression of CDO1 and protease Sep39 successfully increased SCUT-3's feather protein conversion efficiency (42.5% higher than the wild-type) on day 2 in 5% CFM culture. With the co-overexpression strain SCUT-Ocdo1-sep39, 57.5% of proteins in feathers were converted to soluble peptides and free amino acids (0.20 g and 0.29 g g−1 feather, respectively) by solid-state fermentation in 6 d, which was 28.6% higher than that obtained for wild-type SCUT-3. The method developed herein exhibits a much higher economic benefit and a lower ecological footprint than previously reported feather-processing methods and is powerful for industrial recycling of feather waste. This study also elucidates FDB's disulfide bond mechanism and provides a reference for further genetic modification of FDB.

l-Arabinose is a kind of plant-specific five-carbon aldose with benefits in type 2 diabetes mellitus. It has been shown to have good properties in improving glucose homeostasis, but the underlying molecular mechanisms are still not clear. Hepatic gluconeogenesis is critical for regulating glucose homeostasis. Here, this study aimed to investigate whether l-arabinose could improve glucose metabolism via suppressing hepatic gluconeogenesis. High-fat-high-sucrose diet (HFHSD) or high-sucrose diet (HSD)-fed mice were supplemented with or without l-arabinose for 12 weeks. Fasting blood glucose levels were measured and glucose tolerance test and the histological analysis were performed after l-arabinose administration. AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator activated receptor-γ coactivator-1α (PGC1α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression levels were determined by RT-PCR and western blotting. As expected, l-arabinose apparently decreased body weight and attenuated hyperglycemia and glucose intolerance caused by HFHSD or HSD. l-Arabinose also had beneficial effects on glycogen synthesis by inactivating GSK3β. The expression levels of gluconeogenic genes were all decreased by l-arabinose administration in vivo and in vitro. In addition, our work revealed that AMPK is required for the inhibitory effects of l-arabinose on hepatic gluconeogenesis. l-Arabinose significantly up-regulated the phosphorylated levels of AMPK and its downstream protein ACC. Furthermore, blocking AMPK signaling through an inhibitor (compound C) or siAMPK significantly attenuated the inhibition of hepatic gluconeogenesis and the promotion of glycogen synthesis with l-arabinose, indicating that the inhibitory effect of l-arabinose on hepatic gluconeogenesis was AMPK dependent. Our work revealed that l-arabinose is a promising natural product for the regulation of hyperglycemia through inhibition of hepatic gluconeogenesis by activating AMPK.

PURPOSE The coronavirus disease 2019 (COVID-19) pandemic has had a global impact, and Singapore has seen 33,000 confirmed cases. Patients with cancer, their caregivers, and health care workers (HCWs) need to balance the challenges associated with COVID-19 while ensuring that cancer care is not compromised. This study aimed to evaluate the psychological effect of COVID-19 on these groups and the prevalence of burnout among HCWs. METHODS A cross-sectional survey of patients, caregivers, and HCWs at the National Cancer Centre Singapore was performed over 17 days during the lockdown. The Generalized Anxiety Disorder-7 and Maslach Burnout Inventory were used to assess for anxiety and burnout, respectively. Self-reported fears related to COVID-19 were collected. RESULTS A total of 624 patients, 408 caregivers, and 421 HCWs participated in the study, with a response rate of 84%, 88%, and 92% respectively. Sixty-six percent of patients, 72.8% of caregivers, and 41.6% of HCWs reported a high level of fear from COVID-19. The top concern of patients was the wide community spread of COVID-19. Caregivers were primarily worried about patients dying alone. HCWs were most worried about the relatively mild symptoms of COVID-19. The prevalence of anxiety was 19.1%, 22.5%, and 14.0% for patients, caregivers, and HCWs, respectively. Patients who were nongraduates and married, and caregivers who were married were more anxious. The prevalence of burnout in HCWs was 43.5%, with more anxious and fearful HCWs reporting higher burnout rates. CONCLUSION Fears and anxiety related to COVID-19 are high. Burnout among HCWs is similar to rates reported prepandemic. An individualized approach to target the specific fears of each group will be crucial to maintain the well-being of these vulnerable groups and prevent burnout of HCWs.

Many articles have reported that Rab1A was overexpressed in a variety of human cancers and involved in tumor progression and metastasis. However, the biological function and molecular mechanism of Rab1A in nasopharyngeal carcinoma (NPC) remained unknown until now. Here we found that Rab1A overexpression is a common event and was positively associated with distant metastasis and poor prognosis of NPC patients. Functionally, Rab1A depletion inhibited the migration and EMT phenotype of NPC cells, whereas Rab1A overexpression led to the opposite effect. Furthermore, we reveal an important role for Rab1A protein in the induction of radioresistance via regulating homologous recombination (HR) signaling pathway. Mechanistically, Rab1A activated Wnt/β-catenin signaling by inhibiting the activity of GSK-3β via phosphorylation at Ser9. Then Wnt/β-catenin signaling induced NPC cells radioresistance and metastasis through nuclear translocation of β-catenin and transcription upregulation of HR pathway-related and EMT-related genes expression. In general, this study shows that Rab1A may serve as a potential biomarker for predicting prognosis in NPC patients. Targeting Rab1A and Wnt/β-catenin signaling may hold promise to overcome NPC radioresistance.

Purpose The Forgotten Joint Score (FJS-12) is a scoring system initially created to assess post arthroplasty outcomes. It has since been used to evaluate Anterior Cruciate Ligament surgery outcomes. Our study aims to evaluate the applicability and validity of the FJS-12 in post Anterior Cruciate Ligament reconstructed patients, and to assess correlation with established Patient Reported Outcome Measure Scores in the same population. Design Case series, level 3 evidence. Methods We conducted a cross sectional study across patients who had undergone Anterior Cruciate Ligament reconstruction and carried out the FJS-12 questionnaire by phone interview. Patients who had undergone primary Anterior Cruciate Ligament reconstruction were considered for the study. Results The average Forgotten Joint Score-12 for all 82 patients was 71.4 (±22.9), which corresponded to a normal distribution. The average Lysholm and Tegner score at the 2-year post-operative visit was 93.5 ± 9.5 and 5.8 ± 1.8 respectively and the distribution was non-normal. We noticed a large ceiling effect of 42.7% in the Lysholm scores, but only 8.4% in FJS-12. There was a weak correlation with Lysholm and a positive correlation with Tegner. Conclusions Forgotten Joint Score-12 seems to be a promising patient reported outcome measure that can be used in evaluating post Anterior Cruciate Ligament reconstruction outcomes. It is more discerning than traditional scores and is easy to administer thus it can used in the clinical follow-up of patients. With the scores being normally distributed, it makes for a meaningful PROMS and would allow more accurate application of parametric statistical tests.

To investigate the electrochemical reduction mechanism of Ta(V) in ethylene carbonate and aluminum chloride (EC−AlCl3) solvate ionic liquid, cyclic voltammetry experiments were conducted on a tungsten working electrode. Four reduction peaks were observed in the cyclic voltammogram of the EC−AlCl3−TaCl5 ionic liquid. The reduction peaks at −0.55, −0.72, and −1.12 V (vs Al) were related to the reduction of Ta(V) to tantalum metal by three stages including the formation of Ta(IV) and Ta(III) complex ions. The reduction of Ta(III) to tantalum metal was an irreversible diffusion-controlled reaction with a diffusion coefficient of 3.7×10−7 cm2/s at 323 K, and the diffusion activation energy was 77 kJ/mol. Moreover, the cathode products at 323 K were characterized by scanning electron microscopy, energy-dispersive spectroscopy, and X-ray photoelectron spectroscopy. The results showed that tantalum metal and tantalum oxides were obtained by potentiostatic electrodeposition at −0.8 V for 2 h.

Background Nonallergic rhinitis (NAR) is currently a diagnosis of exclusion with an unclear pathophysiologic mechanism and limited treatment options. In patients diagnosed with NAR based on symptoms, negative skin testing and positive optical rhinometry (ORM), the study's objective was to evaluate the therapeutic action of intranasal capsaicin in the management of rhinitic symptoms and the effect on ORM readings. Methods Patients with a history of NAR underwent screening by a diagnostic intranasal capsaicin challenge with ORM and skin-prick testing. Twenty-two NAR patients were enrolled and randomized to either treatment with 0.1mM capsaicin (n = 11) or placebo (n = 11). Treatment consisted of 5 consecutive intranasal applications separated by 1 hour with follow-up at 4 and 12 weeks. At each visit, subjects underwent intranasal capsaicin challenge with ORM reading and a visual analog scale scoring of rhinitis symptoms. Results Treatment with intranasal capsaicin resulted in a median change with improvement in total symptom score (TSS) of -5 from baseline vs an increase of 2 with placebo at 4 weeks, which remained significantly different between the groups at 12 weeks (p = 0.03). At 12 weeks posttreatment, 60% of the intervention group vs 80% of placebo-treated patients still met objective criteria for NAR by ORM. Conclusion Using ORM in the objective diagnosis of NAR, this trial showed that intranasal 0.1mM capsaicin not only improved rhinitic symptoms but also objectively reduced nasal reactivity and nasal congestion with a 40% responder rate at 12 weeks as noted by ORM.

Background Posterior edge separation of the vertebral body is an uncommon but non-rare orthopedic disease, the traditional treatment is posterior open surgery. Recently, a lot of attempts in minimally invasive treatment of lumbar posterior edge fracture have been made. We set to discover the value of minimally invasive surgery in the treatment of posterior edge separation, we designed this retrospective study. Methods Eighteen patients (10 males and 8 females) with posterior edge separation were included between September 2015 and May 2019. The mean age of the patients were 49.9 years. Patients that we included were divided into two groups: people in team A were treated with percutaneous endoscopic lumbar discectomy (PELD), while the other group (team B) were carried the minimally invasive spinal surgery-transforaminal lumbar interbody fusion (MISS-TLIF). The intraoperative/postoperative complications and index were recorded respectively. Visual analogue scale (VAS) and Oswestry disability index (ODI) were applied as evaluation parameters to evaluate the effect of the procedure. Results The mean operation time and notch length in PELD group were 71 min and 6.8 mm, while these date in the other group were 105 min and 31.2 mm. In PELD group, the blood loss during the operation were 5 mL and the time lying in bed after the surgery 24 h, the data in corresponding group were 101 mL and 96 h. People included in our trial (excluding 1 defaulters) had a mean follow-up of 9 months (range, 3-12 months). The VAS and ODI score before and after the surgery had insignificant difference between the two groups (P>0.05). Compared with the data before the operation, the VAS and ODI score had significantly improved after the surgery in two groups (P Conclusions The MISS-TLIF and PELD were all effective methods in the treatment of posterior edge separation.

Aim To classify polypoidal choroidal vasculopathy (PCV) into 2 subtypes based on the subfoveal choroidal thickness (SFCT) and to further evaluate their multimodal image features. Methods A retrospective observational case series study. Sixty-four eyes of 64 patients with PCV were enrolled and classified into 2 groups based on SFCT (thick-choroid group/thin-choroid group). Then further analyze the spectrum domain optical coherence tomography (SD-OCT) and indocyanine green angiography (ICGA) differences of the two subtypes. Imaging analysis included measurement of SFCT, maximum vascular diameter ratio (MVDR), choroidal vascularity index (CVI), central macular thickness (CMT), and the presence of pigment epithelial detachment (PED) on SD-OCT. Polypoidal lesions (polyps) number, branching vascular network (BVN) area, greatest linear dimension (GLD), and the choroidal vascular hyperpermeability (CVH) were analyzed by ICGA. Results The distribution of SFCT was bimodal with two peaks at 195 and 285 µm, and a trough at 225 µm. The 225 µm was taken as the cutoff point for the following classification of thick/thin choroid groups. The PCV eyes in the thick-choroid group presented with greater MVDR, CVI within 3 and 6 mm of the fovea, but lower CMT, less PED, small PED diameters on SD-OCT scans, and fewer polyps, smaller BVN and GLD, but more frequency of CVH on ICGA. Conclusion The SFCT at 225 µm can be used as a readily available indicator for the classification of PCV subtypes. The thick-choroid group presents much apparent enlargement of the choroidal layer and vasculature expansion, which indicates different pathogenesis of the two subtypes.

The original Gillquist maneuver is done by passing the arthroscope through a portal in the patella tendon between the medial femoral condyle and posterior cruciate ligament to enter the posterior compartment. This is done blind and has been documented to result in broken cameras and damaged equipment. It is also necessary to do a notchplasty to aid the advancement of the camera in patients. In our paper, we have made modifications to allow the Gillquist maneuver to be done safely under direct visualization, with just the aid of a simple switching stick. Our technique starts with the arthroscope in the anteromedial portal. We insert a long, cannulated switching stick through the anterolateral portal and pass it between the medial femoral condyle and the posterior cruciate ligament. The switching stick, being tapered and narrow, is able to traverse the transcondylar notch with minimal trauma. Once the switching stick enters the posterior compartment, the camera and trocar are removed and the trocar sleeve is guided over the switching stick past the intercondylar notch gently. The switching stick is then replaced by the arthroscope, which is advanced through the trocar sleeve and into the posterior compartment.

Purpose Motion artifacts induced by breathing variations are common in 4D-MRI images. This study aims to reduce the motion artifacts by developing a novel, robust 4D-MRI sorting method based on anatomic feature matching and applicable in both cine and sequential acquisition. Method The proposed method uses the diaphragm as the anatomic feature to guide the sorting of 4D-MRI images. Initially, both abdominal 2D sagittal cine MRI images and axial MRI images were acquired. The sagittal cine MRI images were divided into 10 phases as ground truth. Next, the phase of each axial MRI image is determined by matching its diaphragm position in the intersection plane to the ground truth cine MRI. Then, those matched phases axial images were sorted into 10-phase bins which were identical to the ground truth cine images. Finally, 10-phase 4D-MRI were reconstructed from these sorted axial images. The accuracy of reconstructed 4D-MRI data was evaluated by comparing with the ground truth using the 4D eXtended Cardiac Torso (XCAT) digital phantom. The effects of breathing signal, including both regular (cosine function) and irregular (patient data) in both axial cine and sequential scanning modes, on reconstruction accuracy were investigated by calculating total relative error (TRE) of the 4D volumes, Volume-Percent-Difference (VPD) and Center-of-Mass-Shift (COMS) of the estimated tumor volume, compared with the ground truth XCAT images. Results In both scanning modes, reconstructed 4D-MRI images matched well with ground truth with minimal motion artifacts. The averaged TRE of the 4D volume, VPD and COMS of the EOE phase in both scanning modes are 0.32%/1.20%/±0.05 ​mm for regular breathing, and 1.13%/4.26%/±0.21 ​mm for patient irregular breathing. Conclusion The preliminary evaluation results illustrated the feasibility of the robust 4D-MRI sorting method based on anatomic feature matching. This method provides improved image quality with reduced motion artifacts for both cine and sequential scanning modes.

Data on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD.This was a large population-based multicenter study in which the representative children aged 0-5 years were recruited from 13 Children's Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson's correlation and further tested using partial correlation in the additive model.A total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r=0.711, P0.001; r=0.727, P0.001; r=-0.318, P0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2kg, but started to gain slowlyand even decreased when the weight was over 21.2kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (β=-47.45, 95%CI=-85.07, -9.83, P=0.013).Adiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.

BackgroundThis study evaluated the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. MethodsSodium iodoacetate (3 mg/50 μL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50 μL of SVF (5 × 106 cells), ADSCs (1 × 106 cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. ResultsA macroscopic view of the articular cartilage revealed a damaged, concave, and inflamed appearance in the NS group. Histological sections revealed that the cartilage in the NS group was uneven and thin and had hyperchromatic cell infiltration. Notably, the conditions of articular cartilages improved on day 7 after the SVF and ADSC treatments. Furthermore, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups, and a thick cartilage layer was observed on histology. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1β levels on days 7 and 14 were reduced in the SVF and ADSC groups. Conclusion These results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.

Background: The LIM protein AJUBA is reported to play crucial roles in a variety of cellular processes and participate in the progression of human cancers. Uncovering proteins and pathways required for glioma growth is necessary for the development of novel targeted therapies.However, the expression and prognostic values of AJUBA related with Hippo signaling pathway remain poorly explored in glioma. Methods:In our study,Bioinformatics analysis revealed AJUBA and YAP1 mRNA and proteins as crucial in the Hippo signaling pathway in glioma.A total of 217 formalin-fixed paraffinembedded (FFPE) glioma tissue samples were used to verify the expressions of AJUBA and YAP1 via immunohistochemistry.Spearman correlation was performed to analyze the relationship of these proteins, and survival analysis was conducted to investigate their effects on prognosis.Results:The results showed that the mRNA levels of AJUBA and YAP1 were significantly up-regulated in glioma compared with normal tissues.The protein expressions of AJUBA and YAP1 in glioblastoma(HGG) were higher than that in low grade glioma(LGG). Survival analysis revealed glioma patients with high mRNA expression of AJUBA and YAP1 showed worse PFS. Additionally, Immunohistochemistry analysis indicated that AJUBA and YAP1 proteins were highly and positively expressed in glioma. AJUBA expression was related to WHO grade (p = 0.000), recurrence (p = 0.018) ,Tumor resection(p = 0.012) ,p53 expression (p = 0.000). Low expression of AJUBA was associated with 1p19q codeletion in LGG (r = -0.22,p = 0.009) . AJUBA was positively correlated with YAP1 (p < 0.001;r = 0.219) .In survival analysis, age, frontal location,recurrence,total tumor resection,WHO grade, ki-67 expression,AJUBA and YAP1 expressions independently predicted a short OS in total cohort (p < 0.05). Conclusions:AJUBA is a hub protein associated with Hippo signaling pathway in glioma, and its expression indicates poor prognosis in glioma. Therefore, AJUBA and YAP1 may be the promising potential prognostic biomarkers and therapeutic targets in glioma.

Background The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects. Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections. Results We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells’ renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance. Conclusion PC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, the alternation of either miR-146 or TUSC7 expression could lead to the circling loop to sustain the new homeostasis. Further in clinics, the combined delivery of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer.

BackgroundOccurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).MethodsPatients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.ResultsThis study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (PConclusionPreoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.

Background: Reliable use of surgical navigation depends upon the registration process. The gold standard is paired-point registration with bone-anchored fiducials, but contour-map registration is more practical. Surgeons may employ variable contour maps and less experienced team members often perform this critical step. The impact of these practices on target registration error (TRE) is not well-studied. Methods: A dry lab set-up consisting of a navigation system (Fusion ENT, Medtronic, Jacksonville, FL) and a sinus phantom with 2 mm radiopaque spheres in the sphenoid and ethmoid regions was developed. A CT (0.625 mm slice thickness) was obtained. Registration was performed with a contour-based protocol. Accuracy was determined using the software’s distance measurement tool. Registration was performed with narrow-field (NF; forehead points medial to the mid-pupillary line) and wide field (WF; entire forehead) contour maps. An experienced rhinologist and a resident surgeon performed each registration in triplicate and TRE at the sphenoid and ethmoid markers was measured in triplicate. Results: WF mapping had a lower TRE than NF (1.09 mm [95% Confidence Interval (CI) 0.96-1.22] vs 1.68 mm [95% CI 1.50-1.86]). The experienced surgeon had a lower TRE compared to the resident (1.21 mm [95% CI 1.08-1.34] vs 1.54 mm [95% CI 1.35-1.74]). Conclusions: In this navigation model, wide field mapping offers better accuracy than narrow-field mapping, and an experienced surgeon seemed to achieve better accuracy than a resident surgeon. These observations have potential implications for the use of this technology in the operating room.

Background: Brucellosis is an important zoonotic disease caused by Brucella spp. Brucellosis is widely distributed in more than 160 or 170 countries around the world, where it poses a huge threat to animal husbandry and human health. About 150 million head of water buffalo, distributed across more than 40 countries worldwide, are kept for the purposes of service, milk, and meat. High incidence of Brucella spp. in buffalo has negatively affected dairy products and meat products.Results: We searched all research related to seroprevalence of brucellosis in water buffalo anywhere in the world in PubMed, Science Direct, SpringerLink, China National Knowledge Infrastructure, Wanfang Database, and VIP Chinese Journal Databases. A total of 26 articles published from 1985 to 2020 met the final selection criteria. The overall seroprevalence of buffalo brucellosis worldwide was 9.7%. The seroprevalence before 2010 (20.8%) (95% CI: 5.6–42.2) was much higher than the seroprevalence rate from 2010 to 2020 (4.2%) (95% CI: 1.8–7.5). Subgroup analysis by feeding mode found that the point estimate of seroprevalence in stock buffalo (11.5%) (95% CI: 3.6–23.0) was higher than that in captive buffalo (10.6%) (95% CI: 4.9–18.1). Subgroup analysis by farming mode found that the seroprevalence was higher in captive-bred buffalo (10.7%) (95% CI: 6.6–15.7) than in intensively farmed buffalo (8.5) (95% CI: 0.9–22.2). The seroprevalence in buffalo living in dry lands (6.4%) (95% CI: 2.0–12.9) is greater than that in buffalo living in wetlands (5.1%) (95% CI: 1.8–10.4) (P < 0.05). The seroprevalence in female buffalo (10.1%) (95% CI: 3.4–19.7) was higher than that in male buffalo (4.4%) (95% CI: 2.0–7.4). The seroprevalence in lactating buffalo was higher than that in buffalo of other ages (26.9%) (95% CI: 1.8–66.5). Subgroup analysis by detection method found that the seroprevalence detected by the complement fixation test (27.3%) (95% CI: 0.7–70.8) was much higher than that detected by other methods.Conclusion: The results of this meta-analysis showed that buffalo brucellosis infection is very common in buffalo herds around the world. Although the seroprevalence of brucellosis in buffalo and humans is relatively low, serious effects upon animal husbandry and public health make it necessary to take effective control and preventive measures to control the spread of this disease.

A new phenolic glycoside 1, together with its enantiomer (2), was isolated from the ethanolic extract of Viburnum melanocarpum P. S. Hsu fruits by repeated column chromatography. Its structure was identified as (7R,8S)-guaiacylglycerol 4-O-β-D-(6-O-vanilloyl)glucopyranoside (1) by spectroscopic data (1H NMR, 13C NMR, HSQC, HMBC, and ORD) and chemical methods. In the intestinal α-glucosidase inhibitory activity test, compound 1 exhibited potent inhibitory activity with IC50 value of 10.04 μM in comparison with the positive control acarbose (IC50 16.37 μM).

Chronic rhinosinusitis (CRS) has been associated with comorbid depression, yet the prevalence of depression among all patients with CRS is not well described. The Patient Health Questionnaire-9 (PHQ-9), a validated instrument for diagnosing depression, has been used to assess depression in a variety of clinical settings. PHQ-9 scores ≥10 are the threshold for a depression diagnosis. The purpose of this study was to assess the prevalence of depression in a rhinology practice and compare the PHQ-9 with the 22-item Sinonasal Outcome Test (SNOT-22).Retrospective chart review.Tertiary rhinology practice.During the 2-month period ending April 30, 2018, all rhinology patients were asked to complete the PHQ-9 and SNOT-22.Among 216 patients, 46 (21.3%) had a self-reported history of depression, and 39 (18.1%) had a PHQ-9 score ≥10. Of the 39 patients screening positive for depression, 18 (41.9%) had no history of depression. Comparison of PHQ-9 with overall SNOT-22 score had a Pearson's coefficient of 0.632 (Depression rates (estimated by PHQ-9 responses) among rhinology patients are similar to chronic disease populations; depression may be underdiagnosed in rhinology patients. Higher SNOT-22 scores were associated with higher PHQ-9 scores. Further studies are warranted to understand the impact of comorbid conditions of depression and CRS in patient quality of life.

Purpose: Neoadjuvant chemoradiotherapy (neoCRT) is a standard treatment for locally advanced rectal cancer (LARC); however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to identify factors involved in the radioresistance of colorectal cancer and to clarify the underlying mechanisms. Experimental Design: A genome-wide RNAi screen was used to search for candidate radioresistance genes. After RFC4 knockdown or overexpression, colorectal cancer cells exposed to X-rays both in vitro and in a mouse model were assayed for DNA damage, cytotoxicity, and apoptosis. Moreover, the regulatory effects and mechanisms of RFC4 in DNA repair were investigated in vitro. Finally, the relationships between RFC4 expression and clinical parameters and outcomes were investigated in 145 patients with LARC receiving neoCRT. Results: RFC4, NCAPH, SYNE3, LDLRAD2, NHP2, and FICD were identified as potential candidate radioresistance genes. RFC4 protected colorectal cancer cells from X-ray–induced DNA damage and apoptosis in vitro and in vivo. Mechanistically, RFC4 promoted nonhomologous end joining (NHEJ)-mediated DNA repair by interacting with Ku70/Ku80 but did not affect homologous recombination–mediated repair. Higher RFC4 expression in cancer tissue was associated with weaker tumor regression and poorer prognosis in patients with LARC treated with neoCRT, which likely resulted from the effect of RFC4 on radioresistance, not chemoresistance. Conclusions: RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in colorectal cancer cells. In addition, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in patients with LARC.

Rationale & Objective Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN. Study Design Double-blind, randomized, placebo-controlled, phase 2 clinical trial. Setting & Participants Participants had IgAN (proteinuria with protein excretion of 0.75-3.5g/d and estimated glomerular filtration rate>30mL/min/1.73m2) and were receiving optimized RAAS inhibitor therapy. Interventions Patients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months. Outcomes The primary outcome was percentage change in proteinuria between baseline and 6 months. Results 60 participants (mean estimated glomerular filtration rate, 53.8mL/min/1.73m2; median urine protein excretion, 1.7g/d) were recruited and randomly assigned to receive HCQ (n=30) or placebo (n=30). Percentage change in proteinuria at 6 months was significantly different between the HCQ group and the placebo group (−48.4% [IQR, −64.2%, −30.5%] vs 10.0% [IQR, −38.7%, 30.6%]; P Limitations The short treatment period and lack of postwithdrawal observations limit conclusions about long-term renoprotective efficacy and safety. Conclusions HCQ in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events. These findings require confirmation in larger treatment trials. Funding This study was supported by grants from a government entity, the Capital of Clinical Characteristics, and the Applied Research Fund. Trial Registration Registered at ClinicalTrials.gov with study number NCT02942381.

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI50 values 60% bioavailability and rapid absorption; doses of 1–10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside.

Objectives: This study aimed to develop a procedure to explore the adverse drug reaction signals of drug-induced neutropenia (DIN) or drug-induced agranulocytosis (DIA) in children using an electro...

CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5-CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed 77 differentially expressed genes unique to CXCR5+CD8+ T cells. Among these, a signature comprised of 33 upregulated genes correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-β, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T cell subset with ability to suppress TFH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.