Reversal and resumption of anticoagulants in patients with anticoagulant-associated intracerebral hemorrhage.

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Efficient Production of Self-Assembled Bioconjugate Nanovaccines against Klebsiella pneumoniae O2 Serotype in Engineered Escherichia coli.

Nanoparticles (NPs) have been surfacing as a pivotal platform for vaccine development. In our previous work, we developed a cholera toxin B subunit (CTB)-based self-assembled nanoparticle (CNP) and produced highly promising bioconjugate nanovaccines by loading bacterial polysaccharide (OPS) in vivo. In particular, the Klebsiella pneumoniae O2 serotype vaccine showcased a potent immune response and protection against infection. However, extremely low yields limited its further application. In this study, we prepared an efficient Klebsiella pneumoniae bioconjugate nanovaccine in Escherichia coli with a very high yield. By modifying the 33rd glycine (G) in the CNP to aspartate (D), we were able to observe a dramatically increased expression of glycoprotein. Subsequently, through a series of mutations, we determined that G33D was essential to increasing production. In addition, this increase only occurred in engineered E. coli but not in the natural host K. pneumoniae strain 355 (Kp355) expressing OPSKpO2. Next, T-cell epitopes were fused at the end of the CNP(G33D), and animal experiments showed that fusion of the M51 peptide induced high antibody titers, consistent with the levels of the original nanovaccine, CNP-OPSKpO2. Hence, we provide an effective approach for the high-yield production of K. pneumoniae bioconjugate nanovaccines and guidance for uncovering glycosylation mechanisms and refining glycosylation systems.

Cross-cultural experiences and self-development: a psychobiographical study of Bruce Lee.

A common challenge people face in today's cross-cultural world is how to solve a series of adaptation problems caused by cultural conflict. Exploring Bruce Lee's successful cross-cultural experiences through psychobiography offers some inspiration and thoughts. How did Bruce Lee successfully integrate martial arts, symbolising the Eastern culture, with films representing the Western culture, finally propelling kung fu films onto the international stage? Numerous publicly available materials about Bruce Lee were collected for this study, and the research data were evaluated using thematic analysis. Bruce Lee's success benefitted from reconstructing cultural environment information and exercising his initiative to shape a new cultural environment. His life experiences reflect individual cognition behaviour and social and cultural environments as two aspects of a dynamic circulation system and show that the two have reached internal and spiralling harmony through mutual integration. In the context of the Oriental collectivism culture's family narrative, Chinese adults' personality development features the unique theme of 'inheritance and innovation'. Dealing with the relationship between self-actualisation and familism is another important and challenging task in developing the Chinese personality.

Evolving Therapeutic Landscape of Intracerebral Hemorrhage: Emerging Cutting-Edge Advancements in Surgical Robots, Regenerative Medicine, and Neurorehabilitation Techniques.

Intracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal reprogramming, and brain-computer interfaces. Despite the limited expansion of the drug armamentarium for ICH over the past few decades, the judicious selection of more efficacious therapeutic modalities and the exploration of multimodal combination therapies represent opportunities to improve patient prognoses after ICH.

Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis.

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.

Detoxification of tetracycline and synthetic dyes by a newly characterized Lentinula edodes laccase, and safety assessment using proteomic analysis.

Fungal laccase has strong ability in detoxification of many environmental contaminants. A putative laccase gene, LeLac12, from Lentinula edodes was screened by secretome approach. LeLac12 was heterogeneously expressed and purified to characterize its enzymatic properties to evaluate its potential use in bioremediation. This study showed that the extracellular fungal laccase from L. edodes could effectively degrade tetracycline (TET) and the synthetic dye Acid Green 25 (AG). The growth inhibition of Escherichia coli and Bacillus subtilis by TET revealed that the antimicrobial activity was significantly reduced after treatment with the laccase-HBT system. 16 transformation products of TET were identified by UPLC-MS-TOF during the laccase-HBT oxidation process. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that LeLac12 could completely mineralize ring-cleavage products. LeLac12 completely catalyzed 50 mg/L TET within 4 h by adding AG (200 mg/L), while the degradation of AG was above 96% even in the co-contamination system. Proteomic analysis revealed that central carbon metabolism, energy metabolism, and DNA replication/repair were affected by TET treatment and the latter system could contribute to the formation of multidrug-resistant strains. The results demonstrate that LeLac12 is an efficient and environmentally method for the removal of antibiotics and dyes in the complex polluted wastewater.

Functionality and Usability of mHealth Apps in Patients with Peritoneal Dialysis: A Systematic Review.

mHealth has been utilized in the care of patients with chronic kidney disease, allowing the collection of patient health-related data, offering disease-related information, enabling the tracking and recording of biochemical parameters, and enabling communication with healthcare providers in real time through applications. mHealth may improve the health outcomes in patients with peritoneal dialysis. This systematic review aimed to summarize evidence regarding the functionality and usability of mHealth apps in patients with peritoneal dialysis. We conducted a comprehensive literature review, searching in five databases, including CINAHL, Cochrane, PsycINFO, PubMed, and Web of Science, to retrieve titles and abstracts related to peritoneal dialysis and mHealth applications for PRISMA recommendations from January 2013 to December 2023. Overall, 11 studies met all the inclusion criteria. The functionality of mHealth apps included inform, instruct, record, display, guide, remind/alert, and communicate. Most of the apps have multifunctionality. The usability was categorized into three aspects: efficiency (self-efficacy and usability), satisfaction, and effectiveness (underwent kidney transplantation and switched to hemodialysis, rehospitalization, peritonitis rate, infection rates at exit sites, mortality, fluid overload, inadequate solute clearance, biochemical values, quality of life, consumer quality index, and technology readiness). Generally, outcomes in the intervention group had better effects compared to those in the control group. Multifunctional mHealth apps show a good potential in improving the efficiency, satisfaction, and effectiveness for patients compared to traditional care. Future research should include more studies and participants to explore and verify the long-term effectiveness of mHealth apps.

Inhibition of DCUN1D1 attenuates periodontitis by suppressing NF-κB signaling.

Nuclear factor kappa-B (NF-κB) signaling-mediated inflammation contributes greatly to the pathogenesis of periodontitis. Neddylation, a ubiquitin-like posttranslational modification, is known to regulate NF-κB signaling. DCUN1D1 (defective in cullin neddylation 1 domain containing 1) is a critical factor in neddylation and has been shown to regulate NF-κB activation. However, the previse roles of DCUN1D1 in periodontitis are not fully elucidated. To explore the roles of DCUN1D1 in periodontitis, the expression of DCUN1D1 was measured in gingival tissues of patients with periodontitis. We inhibited DCUN1D1 by siRNA knocking down or using inhibitor in gingival fibroblasts and the lipopolysaccharides (LPS)-induced expression of IL-6 and TNF-α, and activation of NF-κB were measured. The expression of DCUN1D1 was increased in gingival tissues of patients with periodontitis. Knocking down or inhibiting DCUN1D1 suppressed LPS-induced production of IL-6 and TNF-α, decreased NF-κB activity, and inhibited LPS-induced activation of NF-κB. Inhibiting DCUN1D1 ameliorates periodontitis by suppressing NF-κB signaling.

A Streptomyces species from the ginseng rhizosphere exhibits biocontrol potential.

Plants and their associated microbes live in complicated, changeable, and unpredictable environments. They usually interact with each other in many ways through multidimensional, multiscale, and multilevel coupling manners, leading to challenges in the coexistence of randomness and determinism or continuity and discreteness. Gaining a deeper understanding of these diverse interaction mechanisms can facilitate the development of data-mining theories and methods for complex systems, coupled modeling for systems with different spatiotemporal scales and functional properties, or even a universal theory of information and information interactions. In this study, we use a "closed-loop" model to present a plant-microbe interaction system and describe the probable functions of microbial natural products. Specifically, we report a rhizosphere species, Streptomyces ginsengnesis G7, which produces polyketide lydicamycins and other active metabolites. Interestingly, these distinct molecules have the potential to function both as antibiotics and as herbicides for crop protection. Detailed laboratory experiments conducted in Arabidopsis (Arabidopsis thaliana), combined with a comprehensive bioinformatics analysis, allow us to rationalize a model for this specific plant-microbe interaction process. Our work reveals the benefits of exploring otherwise neglected resources for the identification of potential functional molecules and provides a reference to better understand the system biology of complex ecosystems.

ITGB4 upregulation is associated with progression of lower grade glioma.

Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients.

Emergence of Novel Norovirus GII.4 Variant.

We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.

A robust method for simultaneous determination of eight B vitamins in human serum by liquid chromatography tandem mass spectrometry.

The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra-high-performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin. Limit of quantification, precision, trueness, and matrix effect were validated according to the European Medicines Agency and United States Food and Drug guidelines and Clinical and Laboratory Standards Institute guidelines on bioanalytical method. The limit of quantification for thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin was 0.4, 0.4, 0.8, 2.0, 0.4, 0.1, 0.4, and 0.04 ng/mL separately, respectively. Intra- and interday precisions were 1.1%-12.4% and 2.0%-13.5%, respectively. The relative errors were between 0.3% and 13.3%, and the matrix effects were between 2.6% and 10.4%.

Risk factors of local control in adrenal metastases treated by stereotactic body radiation therapy - a systematic review and meta-analysis.

Purpose: This study is aimed to explore risk factors affect the therapy outcomes of adrenal metastases (AM) for stereotactic body radiation therapy (SBRT) and guide clinical dose selection. Methods and materials: PubMed, Embase and Web of Science were searched in September 22, 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Subgroup analysis and meta-regression were used to search for sources of heterogeneity and identify risky outcomes factors. Publication bias test and sensitivity analysis were also conducted. Results: Thirty-three studies with full text from 2009 to 2022 about AM with SBRT on 1483 patients were included. Pooled 1- and 2-year local control (LC) and overall survival(OS) were 81.7% (95% confidence interval [CI], 75.6%-86.5%), 62.8% (95% CI, 53.8%-71.8%), 67.4% (95%CI, 61.8%-73.1%) and 46.5% (95%CI, 40.4%-52.6%), respectively. Biological effective dose (BED, α/ß=10Gy) and dose per fraction affected 1-year LC (Qm=23.89, 15.10; P<0.0001, 0.0001). In the range of 60-80Gy (BED10), the group of dose per fraction ≥ 9Gy achieved the excellent 1-year LC (< 9Gy: ≥ 9Gy =78%, 91%; χ2 = 10.16, P = 0.001). Tracking technology significantly affected 1- and 2-year OS (Qm = 5.73, 8.75; P = 0.017, 0.003) and high tracking adoption group showed excellent 1- and 2- year OS (78.7% [95%CI, 68.6%- 88.9%]; and 62.9% [95%CI, 53.1%-72.7%]). Conclusion: Increasing the dose per fraction appropriately may help control locally AM lesious. Tracking technology might contribute to improve survival of advanced patients with AM. But these results need prospective studies to verify them.

Design and test of rack-integrated cavity combiner for China initiative accelerator driven system project.

The next-generation 650 MHz solid state power amplifier designed by the Institute of Modern Physics will utilize 24 modules with an output power of 60 kW. The outputs of each of the 12 modules will be combined using a 12-in-1 rectangular cavity combiner integrated into the rack. This cavity combiner, requiring only a single stage to combine power, is characterized by a minimal power loss and a high combining efficiency. The input couplers of the combiner are adjustable to change the number of combination channels. In the event of one amplifier module failure, the corresponding port can be adjusted to decouple, transforming the combiner to an (N-1)-channel combiner with a combining efficiency decay of 0.2%. The prototype of the combiner has been fabricated and tested with a small signal. The combining efficiency is 98.5%. In this paper, we will validate the feasibility of the combiner from the design, simulation, and experiment.

The Role of ICP Monitoring in Minimally Invasive Surgery for the Management of Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the second major stroke type, with high incidence, high disability rate, and high mortality. At present, there is no effective and reliable treatment for ICH. As a result, most patients have a poor prognosis. Minimally invasive surgery (MIS) is the fastest treatment method to remove hematoma, which is characterized by less trauma and easy operation. Some studies have confirmed the safety of MIS, but there are still no reports showing that it can significantly improve the functional outcome of ICH patients. Intracranial pressure (ICP) monitoring is considered to be an important part of successful treatment in traumatic brain diseases. By monitoring ICP in real time, keeping stable ICP could help patients with craniocerebral injury get a good prognosis. In the course of MIS treatment of ICH patients, keeping ICP stable may also promote patient recovery. In this review, we will take ICP monitoring as the starting point for an in-depth discussion.

Enhanced efficacy of a novel aspirator in uniportal video-assisted thoracoscopic mediastinal lymph node dissection: a non-randomized prospective clinical trial.

Background: Video-assisted thoracoscopic surgery (VATS) is the standard approach in early-stage non-small cell lung cancer (NSCLC) and surgical aspirators play a crucial role. Traditional aspirators lack the ability to pull and lift tissue and cannot achieve optimal exposure. Therefore, we designed a new surgical aspirator that combined the function of thoracoscopic forceps. In this study, we aimed to validate the efficacy and safety of this new surgical aspirator. Methods: We performed a prospective non-randomized intervention trial and enrolled 504 consecutive patients scheduled for uniportal VATS in early NSCLC requiring mediastinal lymph node dissection. A novel aspirator we developed with a clamping function via a front pliers-like structure was implemented in intervention group, whereas traditional aspirator was used in control group. Time spent for nodal dissection in No. 2/4R and No. 7R/L (No. 7 lymph nodes resected through right or left side) lymph nodes and perioperative adverse events related to lymph node dissection were recorded. Mann-Whitey U test was applied to analyze sex and pathological type, an independent-samples t-test was applied to analyze surgery time and age. Results: In total, 250 of enrolled patients were allocated into traditional aspirator group and 254 of them were allocated into new aspirator group. Surgeons spent 544.71±120.80 (range, 332-917, median 541) seconds dissecting No. 2/4R lymph nodes with traditional aspirators and 507.54±100.00 (range, 348-702, median 520) seconds dissecting with new aspirators (P=0.008). The traditional aspirator group had an average surgery time of 507.11±104.61 (range, 310-785, median 510) seconds for No. 7R lymph nodes and 608.47±128.50 (range, 397-919, median 606) seconds for No. 7L lymph nodes, while that in the new aspirator group was 465.09±94.94 (range, 271-744, median 476) seconds (P=0.001) and 549.39±102.11 (range, 368-782, median 538) seconds (P<0.001). The new aspirator showed an efficacy advantage in mediastinal lymph node dissection in VATS, without additional risk. Conclusions: This is the first report about a new suction device combining the functions of both traditional surgical aspirators and forceps, which can effectively shorten the time of mediastinal lymph node dissection and improve the efficiency of thoracoscopic surgery without increasing lymph node dissection-related adverse events.

One-step preparation of a self-assembled bioconjugate nanovaccine against Brucella.

Brucellosis, caused by Brucella, is a severe zoonosis, and the current Brucella live attenuated vaccine cannot be used in humans due to major safety risks. Although polysaccharide antigens can be used to prepare the Brucella vaccine, their lower immunogenicity limits them from producing efficient and broad protection. In this study, we produced a high-performance bioconjugate nanovaccine against different species of Brucella by introducing a self-assembly nanoparticle platform and an O-linked glycosylation system into Yersinia enterocolitica serotype O:9, which has an O-polysaccharide composed of the same unit as Brucella. After successfully preparing the vaccine and confirming its stability, we subsequently demonstrated the safety of the vaccine in mice by high-dose immunization. Then, by a series of mouse experiments, we found that the nanovaccine greatly promoted antibody responses. In particular, the increase of IgG2a was more obvious than that of IgG1. Most importantly, this nanovaccine could provide cross-protection against B. abortus, B. melitensis, and B. suis strains by lethal dose challenged models, and could improve the clearance of B. melitensis, the most common pathogenic species in human brucellosis, by non-lethal dose infection. Overall, for the first time, we biocoupled polysaccharide antigens with nano carriers to prepare a Brucella vaccine, which showed pronounced and extensive protective effects in mice. Thus, we provided a potential candidate vaccine and a new direction for Brucella vaccine design.

Safety, tolerability, and pharmacokinetics of ibrexafungerp in healthy Chinese subjects: a randomized, double-blind, placebo-controlled phase 1 trial.

Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against Candida spp., Aspergillus spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, n = 42), and multiple ascending dose (MAD, n = 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including Cmax, AUC, and t1/2. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, Cmax, and AUC increased in an approximately dose-proportional manner in the dose range of 300-1,500 mg. The mean t1/2 was within 18.29-21.30 hours. In the MAD stage, an accumulation of exposure (Cmax and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Patient-derived organoids as personalized avatars and a potential immunotherapy model in cervical cancer.

Cervical cancer remains a significant health issue in developing countries. However, finding a preclinical model that accurately reproduces tumor characteristics is challenging. Therefore, we established a patient-derived organoids (PDOs) biobank containing 67 cases of heterogeneous cervical cancer that mimic the histopathological and genomic characteristics of parental tumors. The in vitro response of the organoids indicated their ability to capture the radiological heterogeneity of the patients. To model individual responses to adoptive T cell therapy (ACT), we expanded tumor-infiltrating lymphocytes (TILs) ex vivo and co-cultured them with paired organoids. The PDOs-TILs co-culture system demonstrates clear responses that correspond to established immunotherapy efficiency markers like the proportion of CTLs. This study supports the potential of the PDOs platform to guide treatment in prospective interventional trials in cervical cancer.