Targeting the PI3K/AKT/mTOR pathway offer a promising therapeutic strategy for cholangiocarcinoma patients with high doublecortin-like kinase 1 expression.

BACKGROUND: Cholangiocarcinoma (CCA), characterized by high heterogeneity and extreme malignancy, has a poor prognosis. Doublecortin-like kinase 1 (DCLK1) promotes a variety of malignant cancers in their progression. Targeting DCLK1 or its associated regulatory pathways can prevent the generation and deterioration of several malignancies. However, the role of DCLK1 in CCA progression and its molecular mechanisms remain unknown. Therefore, we aimed to investigate whether and how DCLK1 contributes to CCA progression. METHODS: The expression of DCLK1 in CCA patients was detected using Immunohistochemistry (IHC). We established DCLK1 knockout and DCLK1 overexpression cell lines for Colony Formation Assay and Transwell experiments to explore the tumor-promoting role of DCLK1. RT-PCR, Western blot and multiple fluorescent staining were used to assess the association between DCLK1 and epithelial-mesenchymal transition (EMT) markers. RNA sequencing and bioinformatics analysis were performed to identify the underlying mechanisms by which DCLK1 regulates CCA progression and the EMT program. RESULTS: DCLK1 was overexpressed in CCA tissues and was associated with poor prognosis. DCLK1 overexpression facilitated CCA cell invasion, migration, and proliferation, whereas DCLK1 knockdown reversed the malignant tendencies of CCA cells, which had been confirmed both in vivo and in vitro. Furthermore, we demonstrated that DCLK1 was substantially linked to the advancement of the EMT program, which included the overexpression of mesenchymal markers and the downregulation of epithelial markers. For the underlying mechanism, we proposed that the PI3K/AKT/mTOR pathway is the key process for the role of DCLK1 in tumor progression and the occurrence of the EMT program. When administered with LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, the tumor's ability to proliferate, migrate, and invade was greatly suppressed, and the EMT process was generally reversed. CONCLUSIONS: DCLK1 facilitates the malignant biological behavior of CCA cells through the PI3K/AKT/mTOR pathway. In individuals with cholangiocarcinoma who express DCLK1 at high levels, inhibitors of the PI3K/AKT/mTOR signaling pathway may be an effective therapeutic approach.

Application of the "Plan-Do-Check-Action" plan in improving the pass rate of the "National Medical Licensing Examination".

BACKGROUND: The National Medical Licensing Examination (NMLE) is the only objective, standardized metric to evaluate whether a medical student possessing the professional knowledge and skills necessary to work as a physician. However, the overall pass rate of NMLE in our hospital in 2021 was much lower than that of Peking Union Medical College Hospital, which was required to be further improved. METHODS: To find the reasons for the unsatisfactory performance in 2021, the quality improvement team (QIT) organized regular face-to-face meetings for in-depth discussion and questionnaire, and analyzed the data by "Plato analysis" and "Brainstorming method". After finding out the reasons, the "Plan-Do-Check-Action" (PDCA) cycle was continued to identify and solve problems, which included the formulation and implementation of specific training plans by creating the "Gantt charts", the check of effects, and continuous improvements from 2021 to 2022. Detailed information about the performance of students in 2021 and 2022, and the attendance, assessment, evaluation and suggestions from our hospital were provided by the relevant departments, and the pass rate-associated data was collected online. RESULTS: After the PDCA plan, the pass rate of NMLE in our hospital increased by 10.89% from 80.15% in 2021 to 91.04% in 2022 (P = 0.0109), with the pass rate of skill examination from 95.59% in 2021 to 99.25% in 2022 (P = 0.0581) and theoretical examination from 84.5% in 2021 to 93.13% in 2022 (P = 0.027). Additionally, the mean scores of all examinees increased with the theoretical examination score increasing from 377.0 ± 98.76 in 2021 to 407.6 ± 71.94 in 2022 (P = 0.004). CONCLUSIONS: Our results showed a success application of the PDCA plan in our hospital which improved the pass rate of the NMLE in 2022, and the PDCA plan may provide a practical framework for future medical education and further improve the pass rate of NMLE in the next year.

In vivo and in vitro studies on the role of regulating Smac expression in the occurrence and development of colon cancer.

We aimed to explore the role of regulating Smac expression levels in the occurrence and development of colon cancer through in vitro and in vivo experiments. Colon cancer cells HT-29 were cultured and transfected into different groups. qRT-PCR was used to detect the expression level of Smac in cells; Flow cytometry was used to detect the apoptotic ability of each group of cells; Western blot was used to detect the protein expression of Smac and apoptosis-related factors Survivin and Caspase-3; The nude mouse tumorigenesis experiment was conducted to detect the regulatory effect of regulating Smac expression levels on the growth of colon cancer transplanted tumors in vivo. In comparison to the FHC group, the HT-29 group exhibited a decrease in Smac expression. The si-Smac group, when compared with the si-NC group, showed significant reductions in Smac mRNA and protein levels, weaker cell apoptosis, increased Survivin, and decreased Caspase-3 expression. Contrarily, the oe-Smac group, against the oe-NC group, displayed increased Smac mRNA and protein levels, enhanced apoptosis, reduced Survivin, and elevated Caspase-3 expression. In nude mice tumor transplantation experiments, the LV-sh-Smac group, as opposed to the LV-sh-NC group, had tumors with greater volume and weight, reduced Smac and Caspase-3, and increased Survivin expression. In contrast, the LV-oe-Smac group, compared with the LV-oe-NC group, showed tumors with decreased volume and mass, increased expressions of Smac and Caspase-3, and decreased Survivin. Smac is lowly expressed in colon cancer. Upregulation of Smac expression can inhibit the occurrence and development of colon cancer, possibly by inhibiting Survivin expression and promoting Caspase-3 expression, thereby enhancing the pro-apoptotic function.

Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

AIMS: About 20-40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. METHODS: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. RESULTS: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg's and Egger's tests. CONCLUSIONS: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. INTERNATIONAL PROSPECTIVE REGISTER FOR SYSTEMATIC REVIEW (PROSPERO) NUMBER: CRD.42020144642.

Intravitreal injection of new adeno-associated viral vector: Enhancing retinoschisin 1 gene transduction in a mouse model of X-linked retinoschisis.

Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection still needs to be improved. In this study, we investigated the transduction efficiency of AAV-DJ (K137R)-GFP in different retinal cells of normal mice, as well as the therapy effection of AAV-DJ (K137R)-Rs1 on retinal function and structure in Rs1-KO mice. The intravitreal injection of AAV-DJ (K137R)-GFP demonstrated that this vector transduced cells in all layers of the retina, including the inner nuclear layer and photoreceptor layer. The intravitreal injection of AAV-DJ (K137R)-Rs1 found that 3 months post-injection of this vector improved retinal function and structure in Rs1-KO mice. Our conclusion is that AAV-DJ (K137R) vector can efficiently and safely penetrate the inner limiting membrane and transduce different layers of retinal cells in the long term, as well as being able to continuously and efficiently express target therapeutic proteins, making it a candidate therapeutic vector for X-linked retinoschisis (XLRS).

Enhanced Oxidation of Cr(III)-Fe(III) Hydroxides by Oxygen in Dark and Alkaline Environments: Roles of Fe/Cr Ratio and Siderophore.

The current understanding of Cr(III)-Fe(III) hydroxide (Cr1-xFex(OH)3) oxidation in the dark is primarily focused on strong oxidants, yet the role of oxygen has generally been overlooked. Meanwhile, the effects of organic ligands on the Cr(III) oxidation are poorly known. Herein, we determined the kinetics of Cr1-xFex(OH)3 oxidation by oxygen in the dark as a function of pH and Fe/Cr ratio with/without the presence of a representative organic ligand-siderophore. Results showed that the Cr(III) oxidation rate increased linearly with increasing pH and Fe/Cr ratio. Thermodynamic calculations suggested that the enhanced Cr1-xFex(OH)3 oxidation with increasing pH was primarily due to the decreased ΔG value (i.e., the Gibbs free energy change) at higher pH. The decreased redox potentials (Eh) of Cr1-xFex(OH)3 suspensions with increasing Fe/Cr ratio accounted for the enhanced Cr(III) oxidation of iron-rich Cr1-xFex(OH)3. The siderophore greatly accelerated the Cr1-xFex(OH)3 oxidation at alkaline pH by promoting the formation of soluble organically complexed Cr(III), which can be oxidized readily by oxygen via mineral-surface catalyzed oxidation. Overall, this study highlights the specific role of oxygen and its synergistic role with the siderophore in the oxidation of solid Cr1-xFex(OH)3, which should be taken into consideration in assessing the long-term stability of Cr(III)-Fe(III) hydroxides.

Condensate cooperativity underlies transgenerational gene silencing.

Biomolecular condensates have been shown to interact in vivo, yet it is unclear whether these interactions are functionally meaningful. Here, we demonstrate that cooperativity between two distinct condensates-germ granules and P bodies-is required for transgenerational gene silencing in C. elegans. We find that P bodies form a coating around perinuclear germ granules and that P body components CGH-1/DDX6 and CAR-1/LSM14 are required for germ granules to organize into sub-compartments and concentrate small RNA silencing factors. Functionally, while the P body mutant cgh-1 is competent to initially trigger gene silencing, it is unable to propagate the silencing to subsequent generations. Mechanistically, we trace this loss of transgenerational silencing to defects in amplifying secondary small RNAs and the stability of WAGO-4 Argonaute, both known carriers of gene silencing memories. Together, these data reveal that cooperation between condensates results in an emergent capability of germ cells to establish heritable memory.

Clinical features and current treatment status of essential thrombocythemia in older adults: a multicenter real-world study in China.

Approximately half of patients diagnosed with essential thrombocythemia (ET) are older adults (aged ≥ 60 years), but to date, little is known about the clinical and molecular characteristics of older patients diagnosed according to the 2016 World Health Organization criteria. We retrospectively collected clinical and molecular data from 282 older (≥ 60 years) and 621 younger ET patients (18-59 years) in China from March 1, 2012 to November 1, 2021 and summarized the clinical characteristics and treatment of these older ET patients. Compared to younger patients, older patients had a higher incidence of the JAK2V617F mutation (P = 0.001), a lower incidence of CALR mutations (P = 0.033) and a higher rate of epigenetic mutations (P < 0.001), TP53 mutations (P = 0.005), and RNA splicing mutations (P < 0.001). Older patients had not only a higher incidence of thrombosis but also a higher incidence of bleeding events. Furthermore, older patients had a significantly higher mortality rate after disease progression (P = 0.050) or after thrombotic events (P = 0.013). Risk factors for thrombosis or prognosis were significantly different between older patients and the entire ET cohort. In older patients, non-driver mutations contributed significantly to thrombotic complications and a poor prognosis, while the JAK2V617F mutation was a risk factor for overall survival but not for thrombotic events. The application of interferon in older ET patients was not inferior to that of hydroxyurea in terms of efficacy and safety. Older patients presented unique characteristics different from those of younger patients, which could provide new information for formulating more appropriate treatment and follow-up strategies.

Anti-Leukemia Activity of Polysaccharide from Sargassum fusiforme via the PI3K/AKT/BAD Pathway In Vivo and In Vitro.

Studies have shown that Sargassum fusiforme and its extracts are effective herbal treatments for leukemia. We previously found that a polysaccharide from Sargassum fusiforme, SFP 2205, stimulated apoptosis in human erythroleukemia (HEL) cells. However, the structural characterization and antitumoral mechanisms of SFP 2205 remain uncertain. Here, we studied the structural characteristics and anticancer mechanisms of SFP 2205 in HEL cells and a xenograft mouse model. The results demonstrated that SFP 2205, with a molecular weight of 41.85 kDa, consists of mannose, rhamnose, galactose, xylose, glucose, and fucose with monosaccharides composition of 14.2%, 9.4%, 11.8%, 13.7%, 11.0%, and 38.3%, respectively. On animal assays, SFP 2205 significantly inhibited growth of HEL tumor xenografts with no discernible toxicity to normal tissues. Western blotting showed that SFP 2205 therapy improved Bad, Caspase-9, and Caspase-3 protein expression, and ultimately induced HEL tumor apoptosis, indicating mitochondrial pathway involvement. Furthermore, SFP 2205 blocked the PI3K/AKT signaling pathway and 740 Y-P, an activator of the PI3K/AKT pathway, rescued the effects of SFP 2205 on HEL cell proliferation and apoptosis. Overall, SFP 2205 may be a potential functional food additive or adjuvant for preventing or treating leukemia.

Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing.

Metazoans guard their germlines against transposons and other foreign transcripts with PIWI-interacting RNAs (piRNAs). Due to the robust heritability of the silencing initiated by piRNAs in Caenorhabditis elegans (C. elegans), previous screens using C. elegans were strongly biased to uncover members of this pathway in the maintenance process but not in the initiation process. To identify novel piRNA pathway members, we have utilized a sensitized reporter strain which detects defects in initiation, amplification, or regulation of piRNA silencing. Using our reporter, we have identified Integrator complex subunits, nuclear pore components, protein import components, and pre-mRNA splicing factors as essential for piRNA-mediated gene silencing. We found the small nuclear processing cellular machine termed the Integrator complex is required for both type I and type II piRNA production. Notably, we identified a role for nuclear pore and nucleolar components NPP-1/Nup54, NPP-6/Nup160, NPP-7/Nup153, and FIB-1 in promoting the perinuclear localization of anti-silencing CSR-1 Argonaute, as well as a role for Importin factor IMA-3 in nuclear localization of silencing Argonaute HRDE-1. Together, we have shown that piRNA silencing in C. elegans is dependent on evolutionarily ancient RNA processing machinery that has been co-opted to function in the piRNA-mediated genome surveillance pathway.

Transcriptome-wide analyses of piRNA binding sites suggest distinct mechanisms regulate piRNA binding and silencing in C. elegans.

PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposon mRNAs and some endogenous mRNAs in various animals. However, C. elegans piRNAs only trigger gene silencing at select predicted targeting sites, suggesting additional cellular mechanisms regulate piRNA silencing. To gain insight into possible mechanisms, we compared the transcriptome-wide predicted piRNA targeting sites to the in vivo piRNA binding sites. Surprisingly, while sequence-based predicted piRNA targeting sites are enriched in 3' UTRs, we found that C. elegans piRNAs preferentially bind to coding regions (CDS) of target mRNAs, leading to preferential production of secondary silencing small RNAs in the CDS. However, our analyses suggest that this CDS binding preference cannot be explained by the action of antisilencing Argonaute CSR-1. Instead, our analyses imply that CSR-1 protects mRNAs from piRNA silencing through two distinct mechanisms-by inhibiting piRNA binding across the entire CSR-1 targeted transcript, and by inhibiting secondary silencing small RNA production locally at CSR-1 bound sites. Together, our work identifies the CDS as the critical region that is uniquely competent for piRNA binding in C. elegans. We speculate the CDS binding preference may have evolved to allow the piRNA pathway to maintain robust recognition of RNA targets in spite of genetic drift. Together, our analyses revealed that distinct mechanisms are responsible for restricting piRNA binding and silencing to achieve proper transcriptome surveillance.

Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing.

Metazoans guard their germlines against transposons and other foreign transcripts with PIWI-interacting RNAs (piRNAs). Due to the robust heritability of the silencing initiated by piRNAs in C.elegans , previous screens using Caenorhabditis elegans were strongly biased to uncover members of this pathway in the maintenance process but not in the initiation process. To identify novel piRNA pathway members, we have utilized a sensitized reporter strain which detects defects in initiation, amplification, or regulation of piRNA silencing. Using our reporter, we have identified Integrator complex subunits, nuclear pore components, protein import components, and pre-mRNA splicing factors as essential for piRNA-mediated gene silencing. We found the snRNA processing cellular machine termed the Integrator complex is required for both type I and type II piRNA production. Notably, we identified a role for nuclear pore and nucleolar components in promoting the perinuclear localization of anti-silencing CSR-1 Argonaute, as well as a role for Importin factor IMA-3 in nuclear localization of silencing Argonaute HRDE-1. Together, we have shown that piRNA silencing is dependent on evolutionarily ancient RNA processing machinery that has been co-opted to function in the piRNA mediated genome surveillance pathway.

Women and girls with haemophilia: A retrospective cohort study in China.

INTRODUCTION: Women and girls with haemophilia (WGH) may have spontaneous/traumatic bleeding similar to that in males with haemophilia, and in addition excessive bleeding during menstruation and delivery. AIM: To characterize WGH in China and provide guidance for better management. METHODS: We retrospectively analysed the characteristics of WGH registered in the Haemophilia Treatment Center Collaborative Network of China (HTCCNC) Registry, including demographics, diagnosis and treatment, bleeding characteristics, obstetrical and gynaecological experiences, and surgical history. RESULTS: A total of 61 females had confirmed haemophilia. Diagnosis and treatment were typically delayed, longer in mild haemophilia than in severe and moderate. The most frequently reported bleeding manifestations were haemarthrosis in severe and moderate patients, and cutaneous bleeding in mild patients. Among 45 postmenarcheal WGH, 21 (46.7%) had history of heavy menstrual bleeding, but only three received treatments. Prenatal diagnosis and management of perinatal haemorrhage were inadequate. Of 34 deliveries in 30 women, nine deliveries were complicated by postpartum haemorrhage, and 22 offspring carried mutations causing haemophilia. Forty-four surgical procedures were performed in 29 patients. Those procedures receiving preoperative coagulation factors coverage were significantly less likely to have excessive bleeding than those who did not (P = .003). CONCLUSION: This is the first and largest study describing WGH in China. There are currently deficiencies in the identification, diagnosis, and management of these patients. Improving health insurance policies, establishing haemophilia centres, and multidisciplinary teams for bleeding and perinatal or perioperative management will help reduce morbidity and mortality.

Factor IX inhibitors in haemophilia B: A report of National Haemophilia Registry in China.

INTRODUCTION: The development of inhibitors against factor FIX (FIX) is the most serious complication of FIX replacement therapy in haemophilia B (HB) patients. Currently, only few cohorts of HB inhibitor patients have been reported worldwide. AIM: This Chinese nationwide study of HB inhibitor patients explored their risk factors for FIX inhibitor development and experience on their management. METHODS: We retrospectively analysed patient characteristics, F9 genotypes, treatment strategies and outcomes of HB inhibitor patients registered to the Chinese National Registry and Patient Organization Registry. RESULTS: Forty-four unique HB inhibitor patients were identified in 4485 unique HB patients registered by year 2021 to the two Registries. Inhibitor diagnosis were usually delayed and the low prevalence (.98%) may suggest some inhibitor patients were not identified. Their median age at inhibitor diagnosis was 7.5 (IQR, 3.0-14.8) years. Most patients (95.5%) had high-titre inhibitors. Allergic/Anaphylactic reactions occurred in 59.1% patients. Large deletions and nonsense mutations were the most common F9 mutation types in our FIX inhibitor patients. Patients with large F9 gene deletions were more likely to develop inhibitors (p = .0002), while those with missense mutations had a low risk (p < .0001). Thirteen (29.5%) patients received immune tolerance induction (ITI) therapy using low-dose prothrombin complex concentrate regimens. Twelve completed ITI with three (25.0%) achieving success. Nephrotic syndrome developed in two (16.7%) patients during ITI. CONCLUSION: This study reports the largest Chinese cohort of HB inhibitor patients. Large deletions were most significantly associated with inhibitor development. Low-dose ITI might be feasible for FIX inhibitor eradication.

GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance.

piRNAs function as guardians of the genome by silencing non-self nucleic acids and transposable elements in animals. Many piRNA factors are enriched in perinuclear germ granules, but whether their localization is required for piRNA biogenesis or function is not known. Here we show that GLH/VASA helicase mutants exhibit defects in forming perinuclear condensates containing PIWI and other small RNA cofactors. These mutant animals produce largely normal levels of piRNA but are defective in triggering piRNA silencing. Strikingly, while many piRNA targets are activated in GLH mutants, we observe that hundreds of endogenous genes are aberrantly silenced by piRNAs. This defect in self versus non-self recognition is also observed in other mutants where perinuclear germ granules are disrupted. Together, our results argue that perinuclear germ granules function critically to promote the fidelity of piRNA-based transcriptome surveillance in C. elegans and preserve self versus non-self distinction.

The difference of auxiliary examination parameters between margin recurrence and granuloma on enhanced computed tomography after sublobar resection.

Background: Imaging examinations following sublobar resection of lung cancer often find thickened neoplasms around the resection margin. Identifying whether the neoplasms are postoperative recurrence or margin granulomas is vitally important. However, the identification mainly depends on the empirical judgment of the imaging department or clinicians in each clinical center at present, and there are few relevant studies, so it is hard to formulate a relatively unified standard. Therefore, we collected data from patients with thickened neoplasms around the resection margin after sublobar resection and sought to discover how to differentiate granulomas from tumor recurrence. Methods: We examined the clinical records of 15 patients with neoplasms around the margins which identified as malignant in auxiliary examination reports, and received second surgery after first sublobar resection. We collected their postoperative pathology and auxiliary examination parameters. The univariate predictors helpful in distinguishing between recurrence and granuloma were analyzed as a diagnostic test. Results: Of the 15 patients with neoplasms around the resection margin, six were diagnosed with benign granulomas, and nine were diagnosed with primary lung cancer recurrence. The results revealed that age, gender, specific surgical method, maximum standardized fluorodeoxyglucose uptake value (SUVmax), and follow-up time were not significantly different, but there were significant differences in enhanced computed tomography (CT) values in several analyses, which calculated by the hospital imaging system. The maximum CT values of the tumor recurrence and granuloma were 104.9±8.051 and 130.3±7.017 (P=0.045), the minimum CT values (15.67±5.113 vs. -17.17±4.826, P=0.0007) and in the floating range CT values (148.00±5.471 vs. 88.11±7.671, P<0.0001), respectively. Conclusions: Differentiating between tumor recurrence and granulomas after sublobar resection remains difficult. However, examining the differences in enhanced CT allows the clinician to make an informed diagnosis that aids further investigation and treatment.

Cr(VI) Reduction by Siderophore Alone and in Combination with Reduced Clay Minerals.

Siderophores and iron-containing clays are known to influence the transformation of chromium in the environment. The role of clays in hexavalent chromium [Cr(VI)] reduction has been reported extensively. However, the mechanisms of Cr(VI) reduction by siderophores and their combination with iron-bearing clays are poorly known. Herein, we report the kinetics and products of Cr(VI) reduction by a siderophore alone or in combination with reduced clays. Results showed that Cr(VI) reduction by a tri-hydroxamate siderophore─desferrioxamine B (DFOB)─at a pH of 6 was achieved by one-electron transfer via the formation of Cr(V) intermediate. The formed Cr(V) was further reduced to organically complexed Cr(III). The Cr(VI) reduction rate and extent in the presence of both DFOB and reduced clays unexpectedly decreased relative to that with reduced clays alone, despite both serving as Cr(VI) reductants. The interaction between DFOB and clays (e.g., adsorption/intercalation, dissolution, and/or oxidation) was primarily responsible for Cr(VI) reduction inhibition. The extent of inhibition increased at higher DFOB concentrations in the presence of iron-rich nontronite but decreased in the presence of iron-poor montmorillonite, which may be related to their different Cr(VI) reduction mechanisms. This study highlights the importance of siderophores in chromium transformation and its impact on the reactivity of iron-bearing clays toward heavy metal reduction in the environment.

Protective Effects of the Bilobalide on Retinal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats.

Diabetic retinopathy (DR) is a diabetes mellitus (DM) complication that causes visual acuity impairment and loss of sight in the working population, mainly in developed countries. According to the WHO, DR accounts for 5% of the world's 37 million blind people. The prevalence of diabetic retinopathy was highest in Africa, followed by North America and the Caribbean and South and Central America. Hyperglycemia can generate excessive ROS that activates multiple pathways, which can damage the cells. Oxidative stress and inflammatory process are intricate in the DR pathological mechanism. Bilobalide is the main bioactive compound isolated from the Ginkgo biloba, a plant utilized in folklore medicine. Bilobalide, a sesquiterpene trilactone, exhibits excellent antioxidant activity. But the molecular mechanisms associated with such effects, especially the antioxidant-related mechanism, have not been documented. Hence, this investigation explored whether bilobalide may attenuate DR in streptozotocin (STZ)-prompted diabetic rats. The effects of bilobalide on parameters of antioxidant content, oxidative stress, and inflammatory factors in the retinal tissues were evaluated by ELISA, RT-PCR, and immunohistochemistry methods. Bilobalide improved caloric management by reducing food consumption and increasing body weight. Furthermore, the administration of bilobalide decreases the blood glucose level and glycosylated (HbA1c) hemoglobin. The anti-retinopathy activity of bilobalide was established by the increase in the total retina thickness (TRT), inner nuclear layer (INL), and outer nuclear layer (ONL) in diabetic rats. Additionally, the serum level of MDA was decreased. In contrast, the antioxidant enzyme (SOD and CAT) levels were increased with TAC plus lower Keap1 and higher Nrf2 expression in the retina when associated with the DM rats. Moreover, bilobalide increased the nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) expression level and inflammatory mediators (NF-κß p65, TNF-α, IL-1ß, and VEGF), thus inhibiting oxidative stress. Bilobalide can be effective against DR, and the possible mechanism may be relatively elucidated by decreasing oxidative stress and anti-inflammatory activities. But the further investigation should be directed to expose the precise mechanism.

Digital single-operator cholangioscopy for biliary stricture after cadaveric liver transplantation.

BACKGROUND: Biliary strictures after liver transplantation (LT) remain clinically arduous and challenging situations, and endoscopic retrograde cholangiopancreatography (ERCP) has been considered as the gold standard for the management of biliary strictures after LT. Nevertheless, in the treatment of biliary strictures after LT with ERCP, many studies show that there is a large variation in diagnostic accuracy and therapeutic success rate. Digital single-operator peroral cholangioscopy (DSOC) is considered a valuable diagnostic modality for indeterminate biliary strictures. AIM: To evaluate DSOC in addition to ERCP for management of biliary strictures after LT. METHODS: Nineteen patients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between March 2019 and March 2020 at Beijing Chaoyang Hospital, Capital Medical University, were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis. Biliary strictures after LT were classified according to the manifestations of choledochoscopic strictures and the manifestations of transplanted hepatobiliary ducts. RESULTS: Twenty-one biliary strictures were found in a total of 19 patients, among which anastomotic strictures were evident in 18 (94.7%) patients, while non-anastomotic strictures in 2 (10.5%), and space-occupying lesions in 1 (5.3%). Stones were found in 11 (57.9%) and loose sutures in 8 (42.1%). A benefit of cholangioscopy was seen in 15 (78.9%) patients. Cholangioscopy was crucial for selective guidewire placement prior to planned intervention in 4 patients. It was instrumental in identifying biliary stone and/or loose sutures in 9 patients in whom ERCP failed. It also provided a direct vision for laser lithotripsy. A space-occupying lesion in the bile duct was diagnosed by cholangioscopy in one patient. Patients with biliary stricture after LT displayed four types: (A) mild inflammatory change (n = 9); (B) acute inflammatory change edema, ulceration, and sloughing (n = 3); (C) chronic inflammatory change; and (D) acute suppurative change. Complications were seen in three patients with post-interventional cholangitis and another three with hyperamylasemia. CONCLUSION: DSOC can provide important diagnostic information, helping plan and perform interventional procedures in LT-related biliary strictures.

ASXL2 mutated myelodysplastic syndrome in a novel germline G6b variant.

The 2016 revised World Health Organization classification identified myeloid neoplasms with germline predisposition as a new diagnostic category. Germline loss-of-function mutations in G6b (G6b-B, C6orf25 or MPIG6B) are associated with congenital macro-thrombocytopenia with focal myelofibrosis, a rare autosomal recessive disease. It is unclear whether germline G6b variants increase the risk of developing a myeloid neoplasm. Here we describe an adult with Myelodysplastic syndromes and a homozygous germline G6b mutation who achieved hematopoietic reconstitution by hematopoietic stem cell transplantation. As far as we know, this is the first report of adult Myelodysplastic syndromes with germline G6b homozygous variant in the literatures.