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Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

Abstract Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) μg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

ABSTRACTSolid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%–64.5% N = 18) and 90.2% (95% CI 80.9%–96.6% N = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%–90.7% N = 50) and 98.9% (95% CI 97.6%-99.7% N = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%–95.9% N = 21) and 99.8% (95% CI 98.1%-100.0% N = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3′-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Background: Our aim was to summarize our experience with the diagnosis and surgical treatment of solid pseudopapillary neoplasm (SPN) of the pancreas to provide a reference for the management of this rare condition. Methods: We collected and analyzed retrospective data on the clinical presentation, laboratory investigations, radiologic imaging, pathology and operative details of patients with SPN of the pancreas diagnosed between February 2001 and December 2009. Results: In all, 23 of 24 patients were women, and the mean age of all patients was 31 years. The most common clinical presentation was vague abdominal pain. Abdominal imaging showed solid or solid cystic masses in the pancreas, mostly in the tail or head of the gland. All patients were treated surgically. There were no postoperative deaths. After follow-up ranging from 4 to 109 months (median 68 mo), 20 of 22 patients who underwent curative resection were alive with no evidence of disease recurrence. Of the 2 patients with R1 resections, 1 died 42 months after surgery, whereas the other underwent a second operation and was alive after 36 months' follow-up. Conclusion: Solid pseudopapillary neoplasm of the pancreas is a relatively indolent tumour. The initial diagnosis of SPN of the pancreas is suggested by radiologic imaging findings but should be considered in the context of clinical and histopathologic characteristics. We advocate for complete surgical resection once SPN is diagnosed. Contexte : Nous voulions resumer notre experience du diagnostic et du traitement chirurgical du neoplasme pseudo-papillaire solide (NPS) du pancreas afin d'etablir un point de reference pour la prise en charge de ce probleme rare. Methodes : Nous avons reuni et analyse des donnees retrospectives sur la manifestation clinique, les examens de laboratoire, l'imagerie radiologique, la pathologie et les details operatoires de patients atteints de NPS du pancreas diagnostique entre fevrier 2001 et decembre 2009. Resultats : Au total, 23 des 24 patients etaient des femmes et l'age moyen de tous les patients s'etablissait a 31 ans. La manifestation clinique la plus courante etait une vague douleur abdominale. L'imagerie abdominale a revele la presence de masses solides ou kystiques solides au pancreas, surtout a la queue ou a la tete de la glande. Tous les patients ont ete traites par chirurgie. Il n'y a pas eu de deces apres l'intervention. Apres un suivi echelonne sur 4 a 109 mois (mediane de 68 mois), 20 des 22 patients qui ont subi une resection curative etaient vivants et ne presentaient aucun signe de reapparition de la maladie. Des 2 patients qui ont subi une resection R1, 1 est decede 42 mois apres l'intervention tandis que l'autre a subi une deuxieme intervention et etait vivant apres un suivi de 36 mois. Conclusion : Le neoplasme pseudo-papillaire solide du pancreas est une tumeur relativement indolente. Le diagnostic initial de NPS du pancreas est indique par les resultats d'imagerie radiologique, mais il faudrait l'envisager en presence de caracteristiques cliniques et histopathologiques. Nous preconisons la resection chirurgicale complete apres le diagnostic., A solid pseudopapillary neoplasm (SPN) of the pancreas is a rare pancreatic tumour. It was first described by Dr. Frantz in 1959,1 and was defined by the World Health Organization [...]

Education with advanced technologies improves the learning of students. Experiential learning prepares students to thrive in today’s digital world. Experiential learning and advanced technologies in education offer a lot of room to be explored. Thus, the objective of this study is to explore the student’s experience in using a business simulation and gamification platform on the student's knowledge of business competency and soft skills. This study also aimed to discover the experiential learning experience using the MonsoonSIM platform as a case study. This study used content analysis and narrative analysis to analyse the results. The focus group interview was carried out with the Universiti Malaysia Pahang Al-Sultan Abdullah (UMPSA) from Gambang and Pekan students who have played MonsoonSIM more than 10 times. The results indicated that business simulation and gamification can improve the students’ knowledge and soft skills by using MonsoonSIM. This study also provided significant implications for experiential learning, business simulation and gamification in the future for Malaysian education.

Abstract Geriatric assessment can aid in optimizing treatment strategies and supportive interventions for older patients with diffuse large B‐cell lymphoma (DLBCL). Fondazione Italiana Linformi has recently introduced novel geriatric assessment tools, simplified Geriatric Assessment (sGA) and Elderly Prognostic Index (EPI), aimed at tailoring the treatment and predicting the outcomes for older patients with DLBCL. The objectives of this study are the validation and possible modification of the sGA and EPI in China. In the study, both sGA and EPI demonstrated the predictive capabilities for overall survival (OS) and early mortality (both p

Abstract Background We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second‐line versus later‐line. Here, we present an updated pooled analysis with a longer follow‐up of 35.2 months. Methods Data were pooled from two studies—BGB‐3111‐AU‐003 (NCT02343120) and BGB‐3111‐206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second‐line and the later‐line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression‐free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. Results Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second‐line and 71 (63.4%) patients as later‐line therapy. After weighting, OS was significantly improved in the second‐line versus later‐line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second‐line versus later‐line group (27.8 vs. 22.1 months). ORR was numerically higher in the second‐line versus later‐line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. Conclusion Zanubrutinib in second‐line treatment was associated with significantly improved OS compared with later‐line treatment of R/R MCL.

Abstract Objective To identify DNA methylation and clinical features, and to construct machine learning classifiers to assign the patients with major depressive disorder (MDD) into responders and non-responders after a 2-week treatment into responders and non-responders. Method Han Chinese patients (291 in total) with MDD comprised the study population. Datasets contained demographic information, environment stress factors, and the methylation levels of 38 methylated sites of tryptophan hydroxylase 2 (TPH2) genes in peripheral blood samples. Recursive Feature Elimination (RFE) was employed to select features. Five classification algorithms (logistic regression, classification and regression trees, support vector machine, logitboost and random forests) were used to establish the models. Performance metrics (AUC, F-Measure, G-Mean, accuracy, sensitivity, specificity, positive predictive value and negative predictive value) were computed with 5-fold-cross-validation. Variable importance was evaluated by random forest algorithm. Result RF with RFE outperformed the other models in our samples based on the demographic information and clinical features (AUC = 61.2%, 95%CI: 60.1-62.4%) / TPH2 CpGs features (AUC = 66.6%, 95%CI: 65.4-67.8%) / both clinical and TPH2 CpGs features (AUC = 72.9%, 95%CI: 71.8-74.0%). Conclusion The effects of TPH2 on the early-stage antidepressant response were explored by machine learning algorithms. On the basis of the baseline depression severity and TPH2 CpG sites, machine learning approaches can enhance our ability to predict the early-stage antidepressant response. Some potentially important predictors (e.g., TPH2-10-60 (rs2129575), TPH2-2-163 (rs11178998), age of first onset, age) in early-stage treatment response could be utilized in future fundamental research, drug development and clinical practice.

Objective This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.Design Retrospective cohort study between 2018 and 2021.Setting The largest haematological centre in southern China.Results A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p

Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m 2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65−90) years. The median follow-up time was 22.2 (range, 4.6−38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.

Abstract Objective To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. Methods The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non‐PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. Results Three patients in the non‐PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non‐PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non‐PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. Conclusions The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.

The discovery of hydrocarbon in the Pagoda Formation in South China has received attention from the petroleum industry. This research paper identifies the discontinuity surface underlying the Pagoda Formation. The Upper Ordovician strata were correlated in different regions using the conodont biostratigraphy, and δ13C and δ18O isotope stratigraphy. The biostratigraphic result illustrates that three conodont zones can be established in each study section, and one to three conodont zones are missing in the lower Pagoda Formation and the strata underlying the Pagoda Formation of the Upper Yangtze Platform. Moreover, the chemostratigraphic result highlighted that the development of the lower δ13C isotope positive excursion events in the Xiaogangwan and Liangcun areas was less complete than that in the Jiaodingshan area. Combined with the cyclostratigraphic results, the development of the δ13C isotope positive excursion is not complete. The development of the δ13C excursion event is more complete in the south and east than in the center and north. This demonstrates that the Pagoda Formation began its deposition at different times and the transgression process may have advanced from the southeast to the north and that the contact between the Pagoda Formation and the underlying formation is not conformable. It is proposed that the Late Ordovician in the South China Plate was affected by the tectonic movement and the cooling paleoclimate at that time, which resulted in the discontinuity between the Pagoda Formation and the underlying strata. The unconformity could be the channel for hydrocarbon migration or for the high-quality oil and gas reservoirs being developed and preserved under the unconformity surface.

Objective The distal tibiofibular syndesmosis (DTS) is a fretting joint and it is still a hot issue how to satisfy strong internal fixation while allowing fretting. This study described and evaluated a new method for elastic fixation of DTS injury with Nice Knot. Methods The study was designed as a retrospective study. Between June 2020 and June 2021, 31 patients who were diagnosed with ankle fracture and DTS injury without additional orthopedic injuries were enrolled in this case series. The study included 22 males and nine females, with an average age of 34.71 ± 14.66 years. All patients were treated with Nice Knot binding for DTS. Surgical time, length of stay, time of DTS fixation, total weight‐bearing time, complications, imaging parameters, and functional scores at follow‐up were recorded. Paired sample t‐tests or single factor analyses of variance were used at intra‐group comparison. Results All patients completed surgery with normal syndesmotic parameters. The recovery of DTS injury was verified by Hook and lateral malleolus rotation tests. The average follow‐up time was 15.97 ± 3.30 months. Only one case showed superficial infection after surgery, and the wound healed after symptomatic treatment. In terms of imaging, there were no significant differences in tibiofibular clear space (TFCS), tibiofibular overlap distance (TFOS), medial clear space (MCS), and superior clear space (SCS) immediately and at different follow‐up points after surgery. All obtained excellent and good outcomes according to the AOFAS score at least follow‐up after surgery. Conclusions Nice Knot elastic fixation of DTS injury is firm and stable while maintaining the physiological micromotion of the ankle joint.

Abstract Background The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p

Summary: Sequence variation resulting from the evolution of IGH clones and immunophenotypic drift makes it difficult to track abnormal B cells in children with precursor B cell acute lymphoblastic leukemia (pre-B-ALL) by flow cytometry, qPCR, or next-generation sequencing (NGS). The V-(D)-J regions of immunoglobulin and T cell receptor of 47 pre-B-ALL samples were sequenced using the Illumina NovaSeq platform. The IGH rod-like tracer consensus sequence was extracted based on its rod-like alpha-helices structural similarity predicted by AlphaFold2. Additional data from published 203 pre-B-ALL samples were applied for validation. NGS-IGH (+) patients with pre-B-ALL had a poor prognosis. Consistent CDR3-coded protein structures in NGS-IGH (+) samples could be extracted as a potential follow-up marker for pre-B-ALL children during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a class of biomarker with significant predictive values for the dynamic monitoring of MRD in pre-B-ALL children.

Abstract Background Ibrutinib has revolutionized the treatment of mantle cell lymphoma (MCL). Both ibrutinib monotherapy and ibrutinib‐based combination therapy are important salvage options for patients with relapsed/refractory (R/R) MCL. The real‐world efficacy and safety profile of the two strategies in Chinese patients with R/R MCL remain unclarified. Methods In the present study, data of 121 R/R MCL patients who received either ibrutinib monotherapy (N = 68) or ibrutinib combination therapy (N = 53) in 13 medical centers in China were retrospectively reviewed. Results With a median follow‐up of 20.5 months, the overall response rate was 60.3% versus 84.9% (p = 0.003), complete remission rate was 16.2% versus 43.4% (p

Abstract Background Several methods can assist in detecting early esophageal cancer (EEC) and staging esophageal cancer (EC) invasion depth. Objective To evaluate the accuracy of magnifying endoscopy with narrow-band imaging (ME-NBI) plus endoscopic ultrasonography (EUS) for diagnosing EC. Methods We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for relevant studies. The Quality Assessment of Diagnostic Accuracy Studies 2 (QADAS2) was used to assess the studies’ methodological quality. The sensitivity, specificity, positive likelihood (LR+), negative likelihood (LR−), and diagnostic odds ratio (DOR) were calculated, and the summary receiver operating characteristic (SROC) curves were drawn to evaluate the diagnostic performance. Results Seven studies were included. The meta-analysis suggested that the pooled sensitivity, specificity, LR+, LR−, and DOR of ME-NBI plus EUS for diagnosing EC were 0.947 (95% confidence interval [CI], 0.901–0.975), 0.894 (95% CI, 0.847–0.931), 7.989 (95% CI, 4.264–14.970), 0.066 (95% CI, 0.035–0.124), and 137.96 (95% CI, 60.369–315.27), respectively. Those values for staging the invasive depth were 0.791 (95% CI, 0.674–0.881), 0.943 (95% CI, 0.906–0.968), 13.087 (95% CI, 7.559–22.657), 0.226 (95% CI, 0.142–0.360), and 61.332 (95% CI, 27.343–137.57). The areas under the curves (AUCs) for diagnosis and staging were 0.97 and 0.95, respectively. Conclusions ME-NBI plus EUS might be an adequate diagnostic and staging modality for EC. Due to the study limitations, more large-scale, high-quality studies are needed to confirm the diagnostic accuracy of ME-NBI plus EUS.

Background & AimsThe pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association between the gut microbiome and hypertension. Given that the microbiota is in part determined by host genetics, we used the two-sample Mendelian randomization (MR) analysis to address the bidirectional causal link between gut microbiota and hypertension.MethodsWe selected genetic variants (P

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0–3.4; OS, 54.9 months vs. NR, p

An asymmetric aza-BODIPY analogue bearing quinoxaline moiety was synthesized via a titanium tetrachloride-mediated Schiff-base-forming reaction of 6,7-dimethyl-1,4-dihydroquinoxaline-2,3-dione and benzo[d]thiazol-2-amine. This novel aza-BODIPY analogue forms a complementary hydrogen-bonded dimer due to the quinoxaline moiety in the crystal structure. It also shows intense absorption and fluorescence, with fluorescence quantum yields close to unity. The electrochemical measurements and the DFT calculations revealed the presence of the low-lying HOMO, which benefits their potential applications as an electron-transporting material.

Objective: Acute myeloid leukemia (AML) is primarily a malignant disorder affecting the elderly. We aimed to compare the outcomes of different treatment patterns in elderly AML patients and to propose a prognostic scoring system that could predict survival and aid therapeutic decisions. Methods: Patients aged ≥ 60 years who had been diagnosed with AML at 7 hospitals in China were enrolled (n = 228). Treatment patterns included standard chemotherapy, low intensity therapy, and best supportive care (BSC). Results: The early mortality rates were 31%, 6.8%, and 6.3% for the BSC, low intensity therapy, and standard chemotherapy groups, respectively. The complete remission rate of the standard chemotherapy group was higher than that of the low intensity therapy group. The median overall survival (OS) was 561 days and 222 days for the standard chemotherapy and low intensity therapy groups, respectively, and were both longer than that of the BSC group (86 days). Based on multivariate analyses, we defined a prognostic scoring system that enabled classification of patients into 3 risk groups, in an attempt to predict the OS of patients receiving chemotherapies and low intensity therapies. Low and intermediate risk patients benefited more from standard chemotherapies than from low intensity therapies. However, the median OS was comparable between standard chemotherapies and low intensity therapies in high risk patients. Conclusions: Our prognostic scoring system could predict survival and help select appropriate therapies for elderly AML patients. Standard chemotherapy is important for elderly AML patients, particularly for those categorized into low and intermediate risk groups.

Abstract Background Abnormal epiphyseal growth plate development of the proximal tibia in hemophilia patients leads to notable morphological changes in the mature knee joint. This study aimed to compare the morphological characteristics of tibial component placement cut surface in patients with hemophilic arthritis (HA) and osteoarthritis (OA) and to determine the tibial component rotational alignment axis’ best position for HA patients. Methods Preoperative computed tomography scans of 40 OA and 40 HA patients who underwent total knee arthroplasty were evaluated using a three-dimensional (3D) software. The tibial component’s placement morphological parameters were measured. The tibial component’s rotational mismatch angles were evaluated, and the most appropriate 0°AP axis position for HA patients was investigated. Results In the two groups, the morphology was significantly different in some of the parameters (p

Environmental pollution by organic pollutants poses a great threat to the ecosystem and human development. Solar-powered catalytic oxidation technology can solve the existing energy and pollution crisis. Hence, in this work, cubic nano-In2O3 modified g-C3N4 composite was synthesized by in situ calcination, then it was coupled with hydrogen peroxide for the degradation of antibiotic under visible light. The results of SEM and XPS showed that In2O3 and g-C3N4 were closely combined. The catalytic oxidation efficiency of the antibiotic doxycycline was greatly improved when the as-prepared compound was coupled with hydrogen peroxide, and 88.2% of doxycycline was degraded within 80 min. By designing the active species inhibition test, it was found that a large number of hydroxyl radicals were generated in the system after adding hydrogen peroxide, which accelerated the degradation of the target. Hydrogen peroxide not only acts as a source of hydroxyl radical, but also as an active electron acceptor, which promotes the separation of photogenerated electron-hole pairs in the composite photocatalyst. Therefore, the double oxidation system formed by In2O3/g-C3N4 coupled with hydrogen peroxide can degrade the target at a higher rate. This work provided a research basis for the synthesis of In2O3 with regular morphology and simplified synthesis of In2O3/g-C3N4, and explored the practicability of the coupling method of double advanced oxidation for pollutant degradation.

Schizophrenia (SCZ) and obsessive–compulsive disorder (OCD) are complex polygenic disorders with brain morphology abnormalities. The etiologies and relationship of both disorders remain elusive, and should be further investigated. Thus, induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) from an OCD patient, his mother with SCZ and his healthy father with reprograming method. All iPSCs were characterized to have normal karyotype and expression of pluripotency makers. These iPSCs will be a valuable model to elucidate the pathophysiological mechanisms and association of both diseases.