Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Rare-Earth Metal-Organic Framework with Nonplanar Porphyrin Groups for High-Efficiency Photocatalysis.

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

Biomechanical evaluation of a modified intramedullary nail for the treatment of unstable femoral trochanteric fractures.

Background: The Proximal Femoral Nail Antirotation (PFNA) device is the most commonly used implant to fix unstable femoral trochanteric fractures (UFTFs), but it has a relatively high incidence of complications. Due to this factor, the modified intramedullary nail (MIN) was created to treat patients with UFTFs. The aim was to exhibit the MIN and make a comparison with PFNA and InterTAN using biomechanical methods. Methods: An adult UFTF model was developed using Mimics software. The PFNA, InterTAN nail, and MIN models were drawn referring to the corresponding parameters and installed in the fracture models. Vertical, anteroposterior (AP) bending, and torsion loads of the femoral head were set in advance and loaded onto the fracture models. The value of maximal displacement and von Mises stress was evaluated via finite element analysis (FEA). Results: The MIN model had smaller values for maximal displacement than that of the PFNA model, and the increase in displacement was less pronounced for the MIN compared to PFNA under increasing vertical loads. For the indicator of von Mises stress, the MIN model showed lower stress compared with the PFNA model in vertical loads ranging from 300 N to 2100 N. Except for the maximal stress at implants under AP bending loads, the MIN demonstrated the most superior biomechanical properties under AP bending and torsional loads. Conclusion: The MIN offered obvious advantages in terms of mechanical stability and stress distribution among the three studied implants, providing a promising implant option for patients with UFTFs.

Changes in wound symptoms and quality of life of patients with newly diagnosed malignant fungating wounds.

OBJECTIVE: This study examined changes in wound symptoms and the health-related quality of life (HRQoL) of patients with newly diagnosed malignant fungating wounds, and explored the factors that impacted the changes in HRQoL. METHOD: This prospective longitudinal study included patients from three hospitals in China who had been diagnosed with malignant fungating wounds. Questionnaires were used to assess patients' HRQoL and their wound symptoms at the time of diagnosis (T0), as well as at one, three and six (T1, T2 and T3, respectively) months following the treatment period. Factors related to changes in HRQoL were analysed using generalised estimating equation models. RESULTS: A total of 162 patients were included in the study. The patients reported low overall HRQoL. In three health-related dimensions (functional status, social relations and mental health), patients reported lower functional status at the time of wound diagnosis (T0), which then increased slowly with treatment over time. A lower QoL was associated with odour, exudate, bleeding, pruritus, a low performance status and the need for the dressing of wounds. CONCLUSION: The HRQoL of patients with malignant fungating wounds exhibited significant changes across different periods. It is thus of great importance to formulate pragmatic, patient and family-centred palliative wound care management strategies.

Controlled solvothermal synthesis of self-assembled SrTiO3 microstructures for expeditious solar-driven photocatalysis dye effluents degradation.

In this work, the self-assembled SrTiO3 (STO) microstructures were synthesized via a facile one-step solvothermal method. As the solvothermal temperature increased from 140 °C to 200 °C, the STO changed from a flower-like architecture to finally an irregularly aggregated flake-like morphology. The photocatalytic performance of as-synthesized samples was assessed through the degradation of rhodamine B (RhB) and malachite green (MG) under simulated solar irradiation. The results indicated that the photocatalytic performance of STO samples depended on their morphology, in which the hierarchical flower-like STO synthesized at 160 °C demonstrated the highest photoactivities. The photocatalytic enhancement of STO-160 was benefited from its large surface area and mesoporous configuration, hence facilitating the presence of more reactive species and accelerating the charge separation. Moreover, the real-world practicality of STO-160 photocatalysis was examined via the real printed ink wastewater-containing RhB and MG treatment. The phytotoxicity analyses demonstrated that the photocatalytically treated wastewater increased the germination of mung bean seeds, and the good reusability of synthesized STO-160 in photodegradation reaction also promoted its application in practical scenarios. This work highlights the promising potential of tailored STO microstructures for effective environmental remediation applications.

Carbide lime as substrates to boost energy recuperation and dyestuff removal in constructed wetland-microbial fuel cell integrated with copper oxide/carbon cloth cathode.

Methylene blue (MB) was regarded as a highly toxic and hazardous substance owing to its irreparable hazard and deplorable damage on the ecosystem and the human body. The treatment of this colorant wastewater appeared to be one of the towering challenges in wastewater treatment. In this study, a microbial fuel cell coupled with constructed wetland (CW-MFC) with effective MB elimination and its energy recuperation concurrently based on the incorporation of carbide lime as a substrate in a new copper oxide-loaded on carbon cloth (CuO/CC) cathode system was studied. The crucial influencing parameters were also delved, and the MB degradation and chemical oxygen demand (COD) removal efficiencies were correspondingly incremented by 97.3% and 89.1% with maximum power output up to 74.1 mW m-2 at optimal conditions (0.2 g L-1 carbide lime loading and 500 Ω external resistance). The carbide lime with high calcium ion content was greatly conducive for the enrichment of critical microorganism and metabolic activities. The relative abundances of functional bacteria including Proteobacteria and Actinobacteriota were vividly increased. Moreover, the impressive results obtained in printed ink wastewater treatment with a COD removal efficiency of 81.3% and a maximum power density of 58.2 mW m-2, which showcased the potential application of CW-MFC.

Characteristics of reproductive tract infections caused by common pathogens among the outpatients of reproductive medicine center in Putian: retrospective study.

BACKGROUND: This study aims to explore the infection and age distribution of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Herpes simplex virus type II (HSV II) among the outpatients of Reproductive Medicine Center in Putian, Fujian Province to provide a clinical basis for the early diagnosis and treatment of various reproductive tract diseases and infertility in this region. METHODS: A total of 1736 samples of secretions and exfoliated cervical cells were collected from the outpatients of the Reproductive Medicine Center of the Affiliated Hospital of Putian University from December 2021 to April 2023. The infections of UU, CT, NG and HSVII were detected by real-time fluorescence polymerase chain reaction (PCR), and the infection statuses of the patients with different genders, ages and diagnoses were analysed. RESULTS: Among the 1736 patients, 611 were male and 1125 were female. The male patients had higher UU infection rate but lower HSV II infection rate than the female patients. No significant difference in CT and NG infection rates was observed between the genders. The CT infection rate gradually decreased with the increase in the age. The difference in UU, NG and HSV II infection rates among the different age groups was not statistically significant. For UU infection, the male infertile patients had the highest rate of 37.72% (172/456). Meanwhile, the differences in CT, NG and HSV II infection rates among the different diagnosis groups were not statistically significant. Among the male and female infertile patients, the CT infection rate was the highest in the 21-25 years of age group at 11.11% (2/18) and 9.47% (9/95), respectively. No statistically significant difference in UU, CT, NG and HSV II infection rates was observed among the different age groups of patients diagnosed in relation to the family planning guidance and between the male and female patients with other diagnoses results. CONCLUSIONS: This study showed that UU was the most frequently identified pathogen in infertile men in Putian, Fujian Province. The CT infection rate was the highest in people under 20 years old, and the infection showed a tendency toward young individuals. Therefore, the publicity of sexual health knowledge must be strengthened, and the prevention and treatment of venereal diseases among young and middle-aged people must be improved. Moreover, the pathogen infection is related to infertility to a certain extent, which is conducive to clinical diagnosis and treatment.

Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer's disease.

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.

Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report.

BACKGROUND: Gastric stromal tumors, originating from mesenchymal tissues, are one of the most common tumors of the digestive tract. For stromal tumors originating from the muscularis propria, compared with conventional endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR) can remove deep lesions and digestive tract wall tumors completely. However, this technique has major limitations such as perforation, postoperative bleeding, and post-polypectomy syndrome. Herein, we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR. Feasible treatment options to address this complication are described. CASE SUMMARY: A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography, located at the upper gastric curvature adjacent to the stomach fundus, with a smooth surface mucosa and poor mobility. The lesion was 19.3 mm × 16.1 mm in size and originated from the fourth ultrasound layer. Computed tomography (CT) revealed no significant evidence of lymph node enlargement or distant metastasis. Using conventional ESD technology for mucosal pre-resection, exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis. Based on its morphology and immunohistochemical expression of CD117 and DOG-1, the lesion was proven to be consistent with a gastric stromal tumor. Six days after exposed EFTR, CT showed a large amount of encapsulated fluid and gas accumulation around the stomach. In addition, gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding. Based on these findings, the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor. The patient received combined treatments, such as hemostasis under gastroscopy, gastrointestinal decompression, and abdominal drainage. All examinations were normal within six months of follow-up. CONCLUSION: This patient developed serous surface bleeding in the gastric cavity following exposed EFTR. Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice. The combined treatment may replace certain surgical techniques.

Diabetes treatment by conversion of gut epithelial cells to insulin-producing cells.

Insulin-deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi-closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high-risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin-producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin-deficient diabetes, these inhibitors have resulted in robust glucose-lowering responses and generation of insulin-producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

Native Amino Group Directed Meta-Selective C-H Arylation of Primary Amines Via Pd/Norbornene Catalysis.

The selective functionalization of remote C-H bonds in free primary amines holds significant promise for the late-stage diversification of pharmaceuticals. However, to date, the direct functionalization of the meta position of amine substrates lacking additional directing groups remains underexplored. In this Letter, we present a successful meta-C-H arylation of free primary amine derivatives using aryl iodides, resulting in synthetically valuable yields. This meta-selective C-H functionalization is achieved through a sequence involving native amino-directed Pd-catalyzed seven-membered cyclometalation, followed by the utilization of a norbornene-type transient mediator.

[Association Between Dietary Diversity and Caregiver Self-Efficacy for Complementary Feeding Among Infants and Young Children Aged 6-23 Months in Rural Nanchong City,Sichuan Province].

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy. Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for complementary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diversity and caregiver self-efficacy for complementary feeding of infants and young children. Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56%(474/770) for all the infants and young children and 45.00%(108/240),69.16%(287/415),and 68.70%(79/115) for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respectively.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing factor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR=1.42,95%CI=1.17-1.73,P<0.001). Conclusion The dietary diversity for infants and young children in rural Nanchong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.

Causal relationship between affect disorders and endometrial cancer: a Mendelian randomisation study.

BACKGROUND: The aim was to assess the causal relationship between depression and anxiety disorders and endometrial cancer. METHOD: We performed two-sample Mendelian randomisation analysis using summary statistics from genome-wide association studies to assess associations of major depressive disorder, anxiety and stress-related disorders with endometrial cancer. The genome-wide association studies(GWASs) data were derived from participants of predominantly European ancestry included in the Genome-wide Association Research Collaboration. Inverse variance-weighted, MR-Egger and weighted median MR analyses were performed, together with a range of sensitivity analyses. RESULTS: Mendelian randomisation analysis showed no statistically significant genetic responsibility effect of anxiety and stress-related disorders on any pathological type of endometrial cancer. Only the effect of major depressive disorder under the inverse variance weighting method increasing the risk of endometrial endometrial cancer (effect 0.004 p = 0.047) and the effect of major depressive disorder under the MR-Egger method decreasing endometrial cancer of all pathology types (effect -0.691 p = 0.015) were statistically significant. Other Mendelian randomisation analyses did not show a statistically significant effect. CONCLUSION: Major depressive disorder(MDD), anxiety and stress-related disorders(ASRD) are not genetically responsible for endometrial cancer. We consider that emotional disorders may affect endometrial cancer indirectly by affecting body mass index. This study provides us with new insights to better understand the aetiology of endometrial cancer and inform prevention strategies.

This study used public genomic data to analyse association between affective disorders, including depression and anxiety, and endometrial cancer. Genes treated as instrumental variables help us understand the causal link between affective disorders and endometrial cancer through bioinformatics. In addition to this, we added type 2 diabetes, body mass index, polycystic ovary syndrome, and age at menopause for multivariate Mendelian randomisation analyses with the aim of reducing confounding bias. Because we consider these factors may potentially influence the relationship between affective disorders and endometrial cancer. Ultimately we believe that the association between depression and endometrial cancer is not as strong as that of obesity, due to the genetic correlation between depression and obesity.

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Interior and Exterior Surface Modification of Zr-Based Metal-Organic Frameworks for Trace Benzene Removal.

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

Mapping multi-omics characteristics related to short-term PM2.5 trajectory and their impact on type 2 diabetes in middle-aged and elderly adults in Southern China.

The relationship between PM2.5 and metabolic diseases, including type 2 diabetes (T2D), has become increasingly prominent, but the molecular mechanism needs to be further clarified. To help understand the mechanistic association between PM2.5 exposure and human health, we investigated short-term PM2.5 exposure trajectory-related multi-omics characteristics from stool metagenome and metabolome and serum proteome and metabolome in a cohort of 3267 participants (age: 64.4 ± 5.8 years) living in Southern China. And then integrate these features to examine their relationship with T2D. We observed significant differences in overall structure in each omics and 193 individual biomarkers between the high- and low-PM2.5 groups. PM2.5-related features included the disturbance of microbes (carbohydrate metabolism-associated Bacteroides thetaiotaomicron), gut metabolites of amino acids and carbohydrates, serum biomarkers related to lipid metabolism and reducing n-3 fatty acids. The patterns of overall network relationships among the biomarkers differed between T2D and normal participants. The subnetwork membership centered on the hub nodes (fecal rhamnose and glycylproline, serum hippuric acid, and protein TB182) related to high-PM2.5, which well predicted higher T2D prevalence and incidence and a higher level of fasting blood glucose, HbA1C, insulin, and HOMA-IR. Our findings underline crucial PM2.5-related multi-omics biomarkers linking PM2.5 exposure and T2D in humans.

Differences in the perceptions of patients with primary biliary cholangitis and physicians from various hospital departments: An online survey.

OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.

Analyzing the nitrogen removal performance and cold adaptation mechanism of immobilized cold-acclimation ANAMMOX granules at low temperatures.

To improve the treatment performance of anaerobic ammonium oxidation (ANAMMOX) processes at low temperatures, the immobilized cold-acclimation ANAMMOX granules (R3) were prepared and their low-temperature nitrogen removal ability as well as the cold adaptation mechanism were analyzed. The results indicated that the total inorganic nitrogen (TIN) removal efficiency of R3 was significantly higher than that of R2 (cold-acclimation granules without immobilization) and R1 (common granules), especially at 11 ± 2 and 7 ± 2°C (68% and 54%). These were attributed to the remarkable biomass retention capacity of R3, high up to 4.3-4.9 mg/gVSS even at 5-18°C. Besides, higher protein (PN) content of tightly bound extracellular polymeric substances (TB-EPS) also facilitated microbial aggregation in R3. Meanwhile, R3 granules retained higher ANAMMOX activity and heme c content at 5-25°C. The original dominant ANAMMOX genus (Candidatus Kuenenia) in R3 kept higher abundance (49%-57%) at 23 ± 2 and 16 ± 2°C, whereas Candidatus Brocadia became the dominant ANAMMOX genus (25%-32%) in R3 at 11 ± 2 and 7 ± 2°C. Notably, different ANAMMOX genera in R3 may adapt to cold environment by regulating the expression of cold-stress proteins (CspA, CspB, PpiD, and UspA). PRACTITIONER POINTS: Immobilized cold-acclimation ANAMMOX granules showed higher nitrogen removal efficiency at 23°C → 5°C. Immobilization method effectively retained biomass (Candidatus Kuenenia and Candidatus Brocadia). Immobilization facilitated TB-EPS release and biological aggregation in cold-acclimation granules. Expression of cold-stress proteins in immobilized cold-acclimation granules was more active.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

[Development of a Catalytic Hairpin Assembly-Based Fluorescent Assay for the Rapid Detection of SARS-CoV-2 Target RNA]. / åŸºäºŽå‚¬åŒ–å‘å¤¹è‡ªç»„è£ æŠ€æœ¯çš„æ–°åž‹å† çŠ¶ç— æ¯’é¶RNAå¿«é€Ÿè§å ‰æ£€æµ‹æ³•çš„å»ºç«‹.

Objective: To develop a catalytic hairpin assembly (CHA)-based fluorescent assay for the detection of the target RNA of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), so as to realize the rapid nucleic acid testing of SARS-CoV-2. Methods: A 24-nt segment of the SARS-CoV-2 nucleocapsid protein gene (N gene, NC_045512.2) was chosen as the target RNA and the hairpin motif 1 (H1) and hairpin motif 2 (H2) were designed based on the principle of CHA reaction. The H1 motif was labelled with a fluorophore group as well as a quencher group. When the target RNA was added to the hairpin motifs, CHA reaction was triggered at room temperature (25 ℃), which led to the amplification of fluorescence signal, thereby enabling the rapid detection of the target RNA. After the optimization of the hairpin motifs and the experimental conditions, the sensitivity and the specificity of the testing method were measured to evaluate its performance. Results: We successfully constructed a CHA-based fluorescent assay specifically for the target RNA of SARS-CoV-2. With this method, testing could be completed at room temperature within 30 min. This testing method exhibited excellent specificity and could be used to accurately distinguish the perfectly-matched target RNA from the target RNA with single-base mutations. In addition, the testing method demonstrated good sensitivity, with a detection limit of 50 pmol/L. Conclusion: The proposed assay enables the simple and rapid detection of the SARS-CoV-2 target RNA with excellent sensitivity and specificity, showing great promise for further optimization and subsequent clinical application for the rapid detection of SARS-CoV-2 nucleic acid.