MICAL1 promotes the proliferation in acute myeloid leukemia and is associated with clinical prognosis and immune infiltration.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Research on carbon black and cerium co-doped Ti4O7-CB-Ce electrocatalytic oxidation of tetracycline-based antibiotics.

Elemental doping is a promising way for enhancing the electrocatalytic activity of metal oxides. Herein, we fabricate Ti/ Ti4O7-CB-Ce anode materials by the modification means of carbon black and cerium co-doped Ti4O7, and this shift effectively improves the interfacial charge transfer rate of Ti4O7 and •OH yield in the electrocatalytic process. Remarkably, the Ti4O7-CB-Ce anode exhibits excellent efficiency of minocycline (MNC) wastewater treatment (100% removal within 20 min), and the removal rate reduces from 100 to 98.5% after five cycles, which is comparable to BDD electrode. •OH and 1O2 are identified as the active species in the reaction. Meanwhile, it is discovered that Ti/ Ti4O7-CB-Ce anodes can effectively improve the biochemical properties of the non-biodegradable pharmaceutical wastewater (B/C values from 0.25 to 0.44) and significantly reduce the toxicity of the wastewater (luminescent bacteria inhibition rate from 100 to 26.6%). This work paves an effective strategy for designing superior metal oxides electrocatalysts.

Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel­resistant esophageal squamous cell carcinoma.

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem­like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti­tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)­resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit­8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT­related proteins and stem cell markers after sphere formation. Parental cells and drug­resistant cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX­resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug­resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX­resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX­resistant ESCC and could be a promising agent for the treatment of PTX­resistant ESCC cancers.

Prenylated Acetophenone Derivatives from the Leaves of Acronychia pedunculata and Their Anti-proliferative Activities.

Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.

Deciphering three predominant biopsy-proven phenotypes of IgG4-associated kidney disease: a retrospective study.

Background: IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods: We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results: The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions: This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.

CK2-HTATSF1-TOPBP1 signaling axis modulates tumor chemotherapy response.

Homologous recombination (HR) plays a key role in maintaining genomic stability, and the efficiency of the HR system is closely associated with tumor response to chemotherapy. Our previous work reported that CK2 kinase phosphorylates HIV Tat-specific factor 1 (HTATSF1) Ser748 to facilitate HTATSF1 interaction with TOPBP1, which in turn, promotes RAD51 recruitment and HR repair. However, the clinical implication of the CK2-HTATSF1-TOPBP1 pathway in tumorigenesis and chemotherapeutic response remains to be elucidated. Here, we report that the CK2-HTATSF1-TOPBP1 axis is generally hyperactivated in multiple malignancies and renders breast tumors less responsive to chemotherapy. In contrast, deletion mutations of each gene in this axis, which also occur in breast and lung tumor samples, predict higher HR deficiency scores, and tumor cells bearing a loss-of-function mutation of HTATSF1 are vulnerable to poly(ADP-ribose) polymerase inhibitors or platinum drugs. Taken together, our study suggests that the integrity of the CK2-HTATSF1-TOPBP1 axis is closely linked to tumorigenesis and serves as an indicator of tumor HR status and modulates chemotherapy response.

Hierarchical self-recognition and response in CSC and non-CSC micro-niches for cancer therapy.

Cancer stem cells (CSCs) characterized by self-renewal, invasiveness, tumorigenicity and resistance to treatment are regarded as the thorniest issues in refractory tumors. We develop a targeted and hierarchical controlled release nano-therapeutic platform (SEED-NPs) that self-identifies and responds to CSC and non-CSC micro-niches of tumors. In non-CSC micro-niche, reactive oxygen species (ROS) trigger the burst release of the chemotherapeutic drug and photosensitizer to kill tumor cells and reduce tumor volume by combining chemotherapy and photodynamic therapy (PDT). In CSC micro-niche, the preferentially released differentiation drug induces CSC differentiation and transforms CSCs into chemotherapy-sensitive cells. SEED-NPs exhibit an extraordinary capacity for downregulating the stemness of CD44+/CD24- SP (side population) cell population both in vitro and in vivo, and reveal a 4-fold increase of tumor-targeted accumulation. Also, PDT-generated ROS promote the formation of tunneling nanotubes and facilitate the divergent network transport of drugs in deep tumors. Moreover, ROS in turn promotes CSC differentiation and drug release. This positive-feedback-loop strategy enhances the elimination of refractory CSCs. As a result, SEED-NPs achieve excellent therapeutic effects in both 4T1 SP tumor-bearing mice and regular 4T1 tumor-bearing mice without obvious toxicities and eradicate half of mice tumors. SEED-NPs integrate differentiation, chemotherapy and PDT, which proved feasible and valuable, indicating that active targeting and hierarchical release are necessary to enhance antitumor efficacy. These findings provide promising prospects for overcoming barriers in the treatment of CSCs.

Association Between Physical Activity and the Prevalence of Kidney Stones in American Adults: Results From a Multiyear National Survey.

OBJECTIVE: To investigate the association between physical activity (PA) and the prevalence of kidney stones. METHODS: A cross-section study was conducted using data from National Health and Nutrition Examination Survey 2007-2018. PA was evaluated based on the Global Physical Activity Questionnaire. Multivariable logistic regression was performed to elucidate the association between PA (patterns, intensity, duration, and frequency of moderate and vigorous PA) and the prevalence of kidney stones after adjusting for potential confounders. Stratified and interaction analyses were conducted to detect potential effect modifiers. In addition, PA was assessed using metabolic equivalent and physical volume, and followed the regression above. Water intake was obtained from the day 2 dietary recall and was included in the sensitivity analysis. RESULTS: A total of 34,390 participants were included in the analysis. The multivariable logistic regression revealed that individuals who engaged in moderate PA for 30-60 minutes per day had a significant inverse association with the prevalence of kidney stones in the fully adjusted model (odds ratio=0.804, 95% confidence interval 0.700 to 0.923), while no more significant finding was observed for other PA parameters. Interaction and stratified analyses indicated no covariate modifying the association. The results above were robust in the sensitivity analysis. CONCLUSION: The duration of moderate PA (30-60 min/d) is inversely associated with the prevalence of kidney stones, while no more significant association was observed between other PA parameters (including patterns, intensity, duration, and frequency of vigorous PA, frequency of moderate PA) and kidney stones.

Sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction: a case report and literature review.

Immune checkpoint inhibitors could restore immune surveillance to attack tumor through targeting CTLA-4, PD-1 or PD-L1, and have achieved huge success. However, immune-related adverse events (irAEs) have been attracting attention as their application is expanding. Gastritis is relatively rare as a subtype of irAEs, particularly severe gastritis. Guidelines on its clinical management still remain undefined due to limited data. Sintilimab is a PD-1 inhibitor approved in China. Here we offer a case of sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction. Conventional proton pump inhibitors and mucosal protective agents did not take effect, so glucocorticoid was chosen. This severe gastritis was successfully cured finally. Our report describing its clinical performances, endoscopic characteristics and treatments, could assist clinicians to better know this rare irAE.

Immune checkpoint inhibitors are a type of drug which fight cancer through enhancing the body's immunity. They have significant anti-tumor effects. The side effects of these medications, called immune-related adverse events (irAEs), are becoming more obvious as more and more patients undergo immunotherapy. Sintilimab is an immune checkpoint inhibitor approved in China. This case report discusses an irAE in a patient treated with sintilimab. The patient suffered from gastritis, with severely erosive bloody inflammation and a narrow outflow tract of the stomach. Inhibiting stomach acid and protecting mucosa are classical methods to treat gastritis, but neither worked in this case. However, the patient was successfully treated with glucocorticoids, a type of steroid used to treat inflammation. Gastritis is an uncommon irAE for patients treated with immune checkpoint inhibitors and we are short of credible instructions to timely recognize and manage it. This case report might be valuable for other clinicians looking to treat patients with similar symptoms.

Reinforced Immunogenic Endoplasmic Reticulum Stress and Oxidative Stress via an Orchestrated Nanophotoinducer to Boost Cancer Photoimmunotherapy.

Cancer progression and treatment-associated cellular stress impairs therapeutic outcome by inducing resistance. Endoplasmic reticulum (ER) stress is responsible for core events. Aberrant activation of stress sensors and their downstream components to disrupt homeostasis have emerged as vital regulators of tumor progression as well as response to cancer therapy. Here, an orchestrated nanophotoinducer (ERsNP) results in specific tumor ER-homing, induces hyperthermia and mounting oxidative stress associated reactive oxygen species (ROS), and provokes intense and lethal ER stress upon near-infrared laser irradiation. The strengthened "dying" of ER stress and ROS subsequently induce apoptosis for both primary and abscopal B16F10 and GL261 tumors, and promote damage-associated molecular patterns to evoke stress-dependent immunogenic cell death effects and release "self-antigens". Thus, there is a cascade to activate maturation of dendritic cells, reprogram myeloid-derived suppressor cells to manipulate immunosuppression, and recruit cytotoxic T lymphocytes and effective antitumor response. The long-term protection against tumor recurrence is realized through cascaded combinatorial preoperative and postoperative photoimmunotherapy including the chemokine (C-C motif) receptor 2 antagonist, ERsNP upon laser irradiation, and an immune checkpoint inhibitor. The results highlight great promise of the orchestrated nanophotoinducer to exert potent immunogenic cell stress and death by reinforcing ER stress and oxidative stress to boost cancer photoimmunotherapy.

Discovery of Pyroptosis-inducing Drugs and Antineoplastic Activity Based on the ROS/ER Stress/Pyroptosis Axis.

BACKGROUND: Pyroptosis, a cell death process triggered by chemotherapy drugs, has emerged as a highly promising mechanism for combating tumors in recent years. As the lead of new drugs, natural products play an important role in the discovery of anticancer drugs. Compared to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior safety profile. Among a series of MFHNP molecular skeletons, this study found that only benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity of 1 remains to be improved. AIMS: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by modifying the chalcone structure. METHODS: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis, several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer activity was tested by MTT assay, and morphological indications of pyroptosis were observed in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore, to improve the activity of the chalcone skeleton, the anticancer group 3,4,5- trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed, synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally, a quantitative structure-activity relationship (QSAR) model was established using the eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore. Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular mechanisms of pyroptosis induced by the active compound. RESULTS: α, ß-unsaturated ketone was the functional group of the chalcone skeleton and played a pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients (R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft tumors. CONCLUSION: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis axis and is a kind of promising pyroptosis inducer.

The timing phase affected the inconsistency of APHE subtypes of liver observations in patients at risk for HCC on the multi-hepatic arterial phase imaging.

OBJECTIVE: To investigate whether liver observations in patients at risk for hepatocellular carcinoma (HCC) display inconsistent arterial phase hyperenhancement (APHE) subtypes on the multi-hepatic arterial phase imaging (mHAP) and to further investigate factors affecting inconsistent APHE subtype of observations on mHAP imaging. METHODS: From April 2018 to June 2021, a total of 141 patients at high risk of HCC with 238 liver observations who underwent mHAP MRI acquisitions were consecutively included in this retrospective study. Two experienced radiologists reviewed individual arterial phase imaging independently and assessed the enhancement pattern of each liver observation according to LI-RADS. Another two experienced radiologists identified and recorded the genuine timing phase of each phase independently. When a disagreement appeared between the two radiologists, another expert participated in the discussion to get a final decision. A separate descriptive analysis was used for all observations scored APHE by the radiologists. The Kappa coefficient was used to determine the agreement between the two radiologists. Univariate analysis was performed to investigate the factors affecting inconsistent APHE subtype of liver observations on mHAP imaging. RESULTS: The interobserver agreement was substantial to almost perfect agreement on the assessment of timing phase (κ = 0.712-0.887) and evaluation of APHE subtype (κ = 0.795-0.901). A total of 87.8% (209/238) of the observations showed consistent nonrim APHE and 10.2% (24/238) of the observations showed consistent rim APHE on mHAP imaging. A total of 2.1% (5/238) of the liver observations were considered inconsistent APHE subtypes, and all progressed nonrim to rim on mHAP imaging. 87.9% (124/141) of the mHAP acquisitions were all arterial phases and 12.1% (17/141) of the mHAP acquisitions obtained both the arterial phase and portal venous phase. Univariate analysis was performed and found that the timing phase of mHAP imaging affected the consistency of APHE subtype of liver observations. When considering the timing phase and excluding the portal venous phase acquired by mHAP imaging, none of the liver observations showed inconsistent APHE subtypes on mHAP imaging. CONCLUSION: The timing phase which mHAP acquisition contained portal venous phase affected the inconsistency of APHE subtype of liver observations on mHAP imaging. When evaluating the APHE subtype of liver observations, it's necessary to assess the timing of each phase acquired by the mHAP technique at first.

Urethrocutaneous fistula and glans dehiscence formation of hypospadias surgery in patients receiving caudal block vs. non-caudal block: A meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the difference in postoperative complications as urethrocutaneous fistula or glans dehiscence, in children undergoing primary hypospadias repair with caudal block (CB) versus non-caudal block (NCB). METHODS: Data were obtained from MEDLINE, Embase, Web of Science, and the Cochrane Library. Comparative studies of CB versus NCB were identified, with reports of complications published or presented until October 2022. Subgroup analyses were performed based on study type, meatal location (distal only), type of NCB, surgeon and technique, and concentration and dose of anesthetics. RESULTS: Compared to the reference group of NCB, CB was not significantly associated with the development of complications following primary hypospadias repair (OR 1.40, 95 % CI 0.88-2.23). After adjusting for confounding factors, such as type of study(OR 1.51, 95%CI: 0.29-7.91), type of NCB[PB (OR 1.82, 95 % CI: 0.87-3.84), GA (OR 1.26, 95 % CI: 0.39-4.04)], meatal location (distal only) (OR 1.22, 95 % CI: 0.61-2.43), surgeon and technique (OR 1.37, 95 % CI: 0.59-3.14) and concentration and dose of anesthetics(OR 2.74, 95 % CI: 0.82-9.20), subgroup analyses revealed no significant association between CB and NCB (P > 0.05). DISCUSSION: Previous studies have found a correlation between CB and increased incidence of postoperative complications (urethrocutaneous fistula or glans dehiscence) of hypospadias, but different literature have suggested that surgical technique, surgical duration and the severity of hypospadias, rather than CB, are closely related to the occurrence of complications. In order to reduce confounding factors, subgroup analyses were conducted. The results showed that no correlation could be found in postoperative complications and CB. CONCLUSIONS: This meta-analysis compared the incidence of urethrocutaneous fistula or glans dehiscence in the CB and NCB groups for primary hypospadias repair in children, indicating that no clear correlation could be found in postoperative complications and CB. Subgroup analyses on study type, type of NCB, meatal location (distal only), surgeon and technique, and regional anesthetic concentration and dose supported this conclusion.

Failure in Double-J stent inserting in laparoscopic pyeloplasty of ureteropelvic junction obstruction: the clinical features and outcomes.

BACKGROUND: Double-J (DJ) stent placement is an important procedure during laparoscopic pyeloplasty (LP). Failing to insert the DJ stent may indicate the patient was also complicated with uretero-vesical junction obstruction (UVJO), and surgeons have to change to another alternative drainage method. In the present study, we analyzed the risk factors of failure of DJ stent placement during the LP and reviewed the clinical outcomes of these challenging pyeloplasties. METHODS: We retrospectively analyzed the clinical data of patients with ureteropelvic junction obstruction (UPJO) who underwent LP in our department from January 2016 to September 2020. For patients who developed a difficult process of inserting the DJ stent, the externalized uretero-pyelostomy (EUP) stent was indwelled. Patients were finally divided into two groups: DJ group and EUP group. The primary outcomes were recurrent UPJO, postoperative uretero-vesical junction obstruction (UVJO) and complications. RESULTS: A total of 535 patients were included in the study, of which 37 patients (6.9%) failed to insert the DJ stent. Age was younger, and weight was lower (P < 0.05) in the EUP group. Within follow-up, recurrent UPJO occurred in ten (1.87%) patients, nine in the DJ group and one in the EUP group (P > 0.05). The incidence of postoperative UVJO in the EUP group was significantly higher than in the DJ group (10.8% vs. 0.2%, P < 0.01). 74 patients (13.8%) developed complications after surgery, 12 patients (32.4%) in the EUP group, significantly higher than that in the DJ group (32.4% vs. 12.4%, P < 0.01). Compared with the DJ group, the larger APD were observed in the EUP group at three months postoperatively (3.50 [3.02;4.58] vs. 2.20 [1.50;2.88], P < 0.05), but the difference vanished in further follow-up. CONCLUSION: The failure of DJ stent placement tends to occur in patients with younger age, lower weight, and larger preoperative APD. Failure may not increase the recurrent UPJO rate, but may indicate a higher probability of postoperative UVJO and may develop more postoperative complications and slower recovery.

Nickel-Doped Graphite and Fusible Alloy Bilayer Back Electrode for Vacuum-Free Perovskite Solar Cells.

With the rapid development of perovskite solar cells (PSCs), lowering fabrication costs for PSCs has become a prominent challenge for commercialization. At present, gold is commonly used as the back metal electrode in state-of-the-art n-i-p structured PSCs due to its compatible work function, chemical inertness, and high conductivity. However, the high cost of gold and the expensive and time-consuming vacuum-based thin-film coating facilities may impede large-scale industrialization of PSCs. Here, we report a bilayer back electrode configuration consisting of an Ni-doped natural graphite layer with a fusible Bi-In alloy. This back electrode can be deposited in a vacuum-free approach and enables PSCs with a power conversion efficiency of 21.0%. These inexpensive materials and facile ambient fabrication techniques provide an appealing disruptive solution to low-cost PSC industrialization.

A comparative study on the application of different endoscopic diagnostic methods in the differential diagnosis of benign and malignant bile duct strictures.

Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures. Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events. Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis. Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage.

COX7B Is a New Prognostic Biomarker and Correlates with Tumor Immunity in Esophageal Carcinoma.

Esophageal carcinoma (ESCA) refers to the most common type of malignant tumor, which reveals that it occurs often all over the world. ESCA is also correlated with an advanced stage and low survival rates. Thus, the development of new prognostic biomarkers is an absolute necessity. In this study, the aim was to investigate the potential of COX7B as a brand-new predictive biomarker for ESCA patients. COX7B expression in pancancer was examined using TIMER2. The statistical significance of the predictive value of COX7B expression was explored. The relationship between COX7B expression and tumor-infiltrating immune cells in ESCA was analyzed by using ssGSEA. In this study, the result indicated that several types of cancers had an abnormally high amount of COX7B. COX7B expression in samples from patients with ESCA was considerably higher than in nontumor tissues. A more advanced clinical stage may be anticipated from higher COX7B expression. According to the findings of Kaplan-Meier survival curves, patients with low COX7B levels had a more favorable prognosis than those with high COX7B levels. The result of multivariate analysis suggested that COX7B expression was a standalone prognostic factor for the overall survival of ESCA patients. A prognostic nomogram including gender, clinical stage, and COX7B expression was constructed, and TCGA-based calibration plots indicated its excellent predictive performance. An analysis of immune infiltration revealed that COX7B expression has a negative correlation with TFH, Tcm, NK cells, and mast cells. COX7B may serve as an immunotherapy target and as a biomarker for ESCA diagnosis and prognosis.

Design and Application of Hybrid Polymer-Protein Systems in Cancer Therapy.

Polymer-protein systems have excellent characteristics, such as non-toxic, non-irritating, good water solubility and biocompatibility, which makes them very appealing as cancer therapeutics agents. Inspiringly, they can achieve sustained release and targeted delivery of drugs, greatly improving the effect of cancer therapy and reducing side effects. However, many challenges, such as reducing the toxicity of materials, protecting the activities of proteins and controlling the release of proteins, still need to be overcome. In this review, the design of hybrid polymer-protein systems, including the selection of polymers and the bonding forms of polymer-protein systems, is presented. Meanwhile, vital considerations, including reaction conditions and the release of proteins in the design process, are addressed. Then, hybrid polymer-protein systems developed in the past decades for cancer therapy, including targeted therapy, gene therapy, phototherapy, immunotherapy and vaccine therapy, are summarized. Furthermore, challenges for the hybrid polymer-protein systems in cancer therapy are exemplified, and the perspectives of the field are covered.