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Abstract Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations. Aggressive GISTs harbor remarkably more genomic aberrations than low-/intermediate-risk GISTs. Complex genomic alterations, chromothripsis and kataegis, occur selectively in aggressive GISTs. Despite the paucity of mutations, recurrent inactivating YLPM1 mutations are identified (10.3%, 7 of 68 patients), enriched in high-risk/metastatic GIST and functional study further demonstrates YLPM1 inactivation promotes GIST proliferation, growth and oxidative phosphorylation. Spatially and temporally separated GISTs from individual patients demonstrate complex tumor heterogeneity in metastatic GISTs. Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment.

AbstractContext Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs.Objective This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC.Methods The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data.Results Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96–3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia.Conclusions Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Endometrial cancer (EC) is one of the most common gynecologic malignancies, which lacking effective drugs for intractable conditions or patients unsuitable for surgeries. Recently, the patient-derived organoids (PDOs) are found feasible for cancer research and drug discoveries. Here, we have successfully established a panel of PDOs from EC and conducted drug repurposing screening and mechanism analysis for cancer treatment. We confirmed that the regulatory β subunit of methionine adenosyltransferase (MAT2B) is highly correlated with malignant progression in endometrial cancer. Through drug screening on PDOs, we identify JX24120, chlorpromazine derivative, as a specific inhibitor for MAT2B, which directly binds to MAT2B (Kd = 4.724 μM) and inhibits the viability of EC PDOs and canonical cell lines. Correspondingly, gene editing assessment demonstrates that JX24120 suppresses tumor growth depending on the presence of MAT2B in vivo and in vitro. Mechanistically, JX24120 induces inhibition of S-adenosylmethionine (SAMe) synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism and protein synthesis, and eventually apoptosis. Taken together, our study offers a novel approach for drug discovery and efficacy assessment by using the PDOs models. These findings suggest that JX24120 may be a potent MAT2B inhibitor and will hopefully serve as a prospective compound for endometrial cancer therapy.

Abstract Tourism product design and development is anxious with intricate decision-making processes that need to strike a balance between many criteria, goals, and limitations. In today's diversified and ever-changing tourist business, there are substantial sprints in developing and implementing products that appeal to middle-aged and older travellers. In this research, the utilization of fuzzy decision support system (FDSS) is investigated to personalize travel experiences for the elderly based on their unique interests and requirements. The main objective of this study is to reduce the complex tourism business patterns. This study presents a systematic framework for middle-aged and senior tourism products based on the literature on tourism trends, FDSS, and product creation in the tourism industry. This study proposes a middle-aged and elderly tourism product based on fuzzy decision support system (METP–FDSS) that employs fuzzy logic. This approach takes into account cultural sensitivities, accessibility concerns, travel preferences, and demographic data to create tourism experiences that are welcoming and immersive for older tourists. Through the application of fuzzy logic concepts, FDSS provides a flexible and robust decision-making platform that can aid in the development of personalized, inclusive, and immersive tourist experiences for the elderly. Customer happiness, accessibility, and the decision support system's ability to steer product development are all highlighted in the proposed METP–FDSS framework. Research on tourism among the middle-aged and the elderly also benefits from understanding user experience, cost effectiveness, competitive advantage, and social and environmental impact. While navigating the complexity of today's tourism sector, this study recommends using fuzzy logic as a decision support system to provide one-of-a-kind experiences for older and middle-aged tourists.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of

The application of green prevention and control techniques (GCTs) is a vital measure for improving the quality of agricultural products and enhancing the safety of the ecological environment and agricultural production. However, realistically, limited by the small-scale, part-time and decentralized business model, the adoption of GCTs by family farms in China faces practical problems such as insufficient internal transformation force and ability, as well as low external supervision efficiency. To reveal the directions of promoting family farms' GCTs adoption behavior, we establish a comprehensive theoretical model through the application of a novel integrated approach combining two dominant psychological theories of behavior change: the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM). We apply this framework to targeted research of vegetable growers in Henan Province in China using survey data (sample n = 653) analyzed through structural equation modeling (SEM). The integrated TPB-NAM model provides insight into both internal motivation and external environmental conditions for farmers' predicted adoption of GCTs. First, internal motivation, value cognition and personal norms are all driving factors affecting the GCTs behavioral intention of vegetable family farms. When GCTs are driven by the dual motivations of “self-interest” (personal norms) and “others-interest” (value cognition), personal norms can be activated by two factors: awareness of consequences and responsibility attribution. Furthermore, social norms, capital endowment and government regulation are the pressure and obstacle factors affecting the GCTs application of vegetable family farms. Social norms can indirectly affect the application of GCTs by forming personal norms. In addition, there are differences between the influencing factors and mechanism of GCTs adoption behavior intention of family farms of different sizes. Based on this, we propose some specific policy suggestions from three aspects: enhance value cognition, improve environmental awareness and responsibility perception, fill in the shortcomings of capital endowment, and implement differentiated incentive and restraint policies.

Abstract Institutional distance is well-recognised as having a significant influence on MNE subsidiary performance in host countries. However, there is less clarity as to how the institutional distance is managed by top management teams of MNEs. Specifically, it is not known whether the previous work experiences of the top management team (TMT) can moderate how institutional distance impacts subsidiary performance. The purpose of our research is to address the research question, how do different work experiences among the TMT moderate the relationship between institutional distance and subsidiary performance? To empirically answer this question, we use a sample of 6119 Chinese MNE subsidiaries with 34,870 TMT managers. We apply ordinary least square (OLS) regression and bias-corrected and accelerated bootstrap (BCa) to the data. The results indicate that the strength of the negative relationship between institutional distance and MNE subsidiary performance is conditional on the different work experiences of the TMT. We show that the negative relationship between institutional distance and MNE subsidiary performance is strengthened with an increase in expatriates in the TMT who have home country work experience (β = −0.346, p

Abstract Objective The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. Methods This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. Results Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs’ perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. Conclusion This study found that from the HPPs’ perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.

ObjectiveThere is a notable research gap on the mental health challenges faced by hospital pharmacists in the post-pandemic era. Therefore, the present study aims to explore mental health status, influencing factors, coping strategies, and the mediating effect of resilience of home quarantine hospital pharmacists (HQHPs).MethodsAn embedded mixed-method study was conducted in Zhengzhou, a megalopolis in central China, from 20 October to 3 November 2022. For the qualitative study, semi-structured interviews and focus group discussions were conducted among HQHPs to understand their mental health state，the factors that affect their mental health, and the alleviating strategies they used. For the quantitative study, the Generalized Anxiety Disorder Scale (GAD-7) and the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC-25) were used to explore the mental health level of HQHPs. Meanwhile, the mediating effect of resilience was explored and verified with the bootstrap method or the structural equation model.Results20 HQHPs participated in the qualitative study. Two themes were identified in terms of the factors that influenced the HQHPs’ mental health levels. The positive factors include optimism, family company, and connection with friends, while the negative factors include inadequate supplies, inadequate information, and other emergencies. 210 HQHPs participated in the quantitative study, with a median resilience score of 66 [55.75, 74] in the lowest score range and an anxiety score of 5 [2, 7] in the mild anxiety range. The correlation analysis showed that nine of the 10 influencing factors identified in qualitative research were positively correlated with CD-RISC-25 scores and negatively correlated with the GAD-7 score. The mediating effect of resilience on anxiety was significant (95% bootstrap CI [−1.818, −0.384], p

Background Cancer immunotherapies can induce durable tumor regression, but most patients do not respond. SETD2 mutation has been linked to the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy. The functional importance of the SETD2 inactivation and how to modulate immunotherapy response remains unclear.Methods To explore the function of SETD2 in immunotherapy, knockout and subsequent functional experiments were conducted. Bulk RNA-seq, ATAC-seq, Chip-seq and single-cell RNA-seq were performed to dissect the mechanism and explore the immune microenvironment of mouse tumor. Flow cytometry was used to assess cell surface antigen and intratumoral T cell levels.Results We comprehensively determine the effect of SETD2 inactivation in ICIs therapy and elucidate the mechanistic impact on tumor immunity. Murine syngeneic tumors harboring Setd2 inactivation are sensitive to ICIs. By bulk and single-cell RNA-seq, we further reveal that SETD2 inactivation reprograms intratumoral immune cells and inflames the tumor microenvironment, which is characterized by high infiltration of T cells and enhanced antigen presentation to activate CD8+ T cell-mediated killing. Mechanistically, via an integrated multiomics analysis using ATAC-seq, ChIP-seq and RNA-seq, we demonstrate that SETD2 inactivation reduces NR2F1 transcription by impairing H3K36me3 deposition and chromatin accessibility, which activates the STAT1 signaling pathway to promote chemokines and programmed cell death protein-1 (PD-1) expression and enhance antigen presentation. All these regulatory mechanisms synergistically promote the effects of anti-programmed cell death ligand 1 immunotherapy in Setd2-knockout syngeneic mouse models. The SETD2-NR2F1-STAT1 regulatory axis is conserved in human and murine cancers. Finally, cancer patients harboring SETD2 mutations who received ICIs show increased durable clinical benefits and survival.Conclusions These findings provide novel insights into the biology of SETD2 inactivation regulation and reveal a new potential therapeutic biomarker for ICIs immunotherapy in various refractory cancers.

High relative humidity (RH) and high temperature are expected more frequently due to climate change, and can severely affect the growth of chrysanthemums. In order to analyze the interactive effects of RH and high temperature on the photosynthetic performance of chrysanthemum, a completely randomized block experiment was conducted with three factors, namely temperature (Day/night temperature, 35°C/18°C, 38°C/18°C, 41°C/18°C), RH (Whole day RH, 50%, 70%, 90%), and treatment duration (3d, 6d, 9d). The control (CK) temperature was 28°C/18°C and RH was 50%. The results showed that with the increase of temperature, the apparent quantum efficiency (AQE), maximum net photosynthetic rate (Pn-max), net photosynthetic rate (Pn), transpiration rate (Tr), water use efficiency (WUE), maximal recorded fluorescence intensity (Fm), PSII maximal photochemical efficiency (Fv/Fm), absorption flux per cross section (ABS/CSm), trapped energy flux per cross section (TRo/CSm), electron transport flux per cross section (ETo/CSm) and photosynthetic pigment content of leaves significantly decreased, the minimal recorded fluorescence intensity (Fo), fluorescence intensity at point J of the OJIP curve (Fj) and non-photochemical quenching per cross section (DIo/CSm) significantly increased, the fluorescence difference kinetics of the OJ phase of chrysanthemum leaves showed K-bands. Pn, AQE, Fm, Fv, Fv/Fm, ABS/CSm, TRo/CSm, ETo/CSm and photosynthetic pigment content were higher at 70% RH than the other two RH conditions. The dominant factor causing the decrease of Pn in leaves was stomatal limitation at 35°C,38°C, three RH conditions, 3d and 6d, but non-stomatal limitation at 41°C and 9d. There was an interaction between temperature and RH, with a significant impact on Pn. The temperature had the greatest impact on Pn, followed by RH. This study confirms that heat stress severely affects the photosynthesis of chrysanthemum leaves, and when the temperature reaches or exceeds 35°C, adjusting the RH to 70% can effectively reduce the impact of heat stress on chrysanthemum photosynthesis.

Objectives Intensive care unit (ICU) dying patients are the most important source of organ donation. This study explores the reasons affecting organ donation in the Chinese sociocultural context from the perspectives of coordinators and physicians, and further seeks countermeasures to alleviate the shortage of organs.Design and setting Semistructured interviews conducted in a large tertiary hospital in China.Participants and method 15 respondents (including 8 organ coordinators and 7 ICU physicians) were interviewed. Participants were invited to describe the factors that influence organ donation and the underlying reasons behind it. Bronfenbrenner’s socioecological system model was used as theoretical support to construct a theoretical model of the factors influencing organ donation. Respondents participated in semistructured qualitative interviews that were audio-recorded and transcribed. The relevant data were analysed using thematic analysis.Results Four themes that influenced organ donation were identified including the influence of the deceased person’s attributes, immediate family members, surrounding people and the environment, and the social-level factors. In addition, we obtained four strategies from the interviews to improve the organ shortage to ameliorate the current supply–demand imbalance in organ donation. These include multilevel publicity, relevant policy support, increasing other forms of supply and reducing organ demand.Conclusions Factors affecting organ donation after the death of a Chinese citizen include the personal characteristics of the donor, the decisions of family members such as immediate family members and the indirect influence of surrounding people such as collateral family members, in addition to factors related to the humanistic environment, religious beliefs and social opinion.

BackgroundFolate was involved in oxidative stress, hepatic lipid metabolism and chronic hepatic inflammation. However, evidence about the association between serum folate level and non-alcoholic fatty liver disease (NAFLD) in general population is scarce. This study aimed to explore the relationship between serum folate level and NAFLD among adults.Methods7,146 adult participants aged 20 years and over who have complete data of serum folate level and liver function biomarkers in NHANES 2011–2018 were included. Serum folate level was measured by isotope-dilution high-performance liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). And suspected NAFLD was defined according to the United States fatty liver index (USFLI). Logistic regression and the restricted cubic spline models were performed.ResultsSerum folate level was inversely associated with the presence of NAFLD. When comparing the second, third and fourth quartiles of serum folate level to the lowest quartile, the adjusted ORs of the presence of NAFLD were 0.62 (0.49–0.78), 0.65 (0.51–0.84), and 0.43 (0.32–0.56) respectively (p for trend

Encouraging farmers to adopt green prevention and control techniques (GCTs) is conducive to ensuring the quality and safety of agricultural products, the ecological environment and agricultural production in China. To explore the factors influencing vegetable farmers’ adoption of GCTs, this study utilized the “information-motivation-behavior” intervention (IMB) model and ordered logistic model to empirically study the adoption behavior of 653 vegetable farmers in Henan Province, China. Estimation results indicated that the IMB model significantly predicted farmers’ adoption of GCTs: 1) From the perspective of adoption decisions, 88.82% of the farmers have adopted GCTs, but the degree of adoption is low. 2) the farmers’ adoption of GCTs IMB model specifies that higher levels of GCTs information, motivation, and behavioral skills should result in a greater likelihood of engaging in GCTs adoption behavior. 3) Motivation and behavioral skills are activated through information. 4) Finally, motivation can indirectly affect farmers’ GCTs adoption behavior through behavioral skills. The results of this study support the need for the government to promote the use of GCTs for vegetable pest control, as well as advance integrated prevention and control in the agricultural industry.

Objective: Traditional chemical synthesis methods are cumbersome and inefficient. In this study, a novel antitumor molecule, 4-(4-(3-((6,7-bis(2-methoxyethoxy)quinazolin-4-yl)amino)phenyl)-1H-1,2,3-triazol-1-yl)phenyl sulfurofluoridate (P19G1), was identified by screening a library of Erlotinib derivatives synthesized by modular click chemistry, and the antitumor activity and underlying mechanism of P19G1 were further revealed. Methods: A series of Erlotinib derivatives (840 compounds) were synthesized using a modular click-chemistry method, and then the thiazolyl blue (MTT) method was used to screen and evaluate the inhibitory effect of these compounds on the growth and metastasis of A549 lung adenocarcinoma cells. Among them, the compound P19G1 showed the best inhibitory activity. Furthermore, the antitumor activity and mechanism of P19G1 were investigated with in vitro cell biology and in vivo assays in an animal model. Results: In vitro pharmacological studies showed that P19G1 had inhibitory effects on a variety of tumor cell lines with IC 50 values in the range of 1 to 5 μM. Moreover, P19G1 significantly inhibited the proliferation and migration of the human lung adenocarcinoma cell line A549 and human colorectal cancer cell line RKO and promoted cell apoptosis. In vivo tumor-bearing mouse model experiments revealed that 50 mg/kg P19G1 effectively inhibited the growth and metastasis of A549 tumors without obvious toxicity to the host. Conclusions: The rapid structural modification of lead compounds using novel modular click-chemistry reactions holds great potential for use in obtaining diverse derivatives for tumor drug screening and development. P19G1 was discovered because of the application of click chemistry in this study, and it is an antitumor candidate molecule worthy of development.

Virtual reality (VR) has developed rapidly, drawing more businesses to such development. Based on the diffusion of innovations theory (DIT), the study combines the flow theory and the satisfaction perspective to explore purchase intention influencing customers’ adoption of the VR shopping platform system. This study found that satisfaction and flow experience enhance their purchase intention. In technological characteristics, relative advantage, service compatibility, spatial presence, and complexity are important in satisfaction. Among them, both relative advantage and spatial presence impact flow experience. Additionally, a cluster analysis based on gender was conducted, and the study found a significant difference between relative advantages, service compatibility, and complexity in women and men users. The flow experience is an important factor affecting women users’ shopping intention, while insignificant for male users. The implications of these findings are discussed.

It is believed in many studies that the servitization of manufactures is driven by internal economy, but the situation in China may be somewhat different. In this study, we consider the influence of external institutional environment on manufacturers’ servitization and the final performance, and discuss the moderating effect of organizational identity orientation on firms’ response to external institutional pressures. We conduct a survey where we collect responses from 312 manufacturers in China. Regression analyses are performed to test whether institutional pressures (normative pressure, mimetic pressure, and coercive pressure) coming from the external institutional environment have a positive effect on the level of manufacturing servitization or not. Moreover, we study if this positive effect is moderated by the individualistic identity orientation and the relational identity orientation. We also examine the impact of servitization strategy on manufacture’s market performance and financial performances. Furthermore, we separate out the influences comes from institutional pressures by using a new estimated method and try to explain the cause of “servitization paradox.” Our study is innovative in that it bridges the servitization and institutional theory, and provides practical guidance for the adoption of manufacturing servitization strategy.

With the development of an ecological civilization gaining increasing attention in our country, an analysis of the environmental and economic impacts of all aspects of life has been developed gradually. However, because the study on the environmental and economic benefits of the tailwater diversion project is a weak link, the discussion on the environmental and economic benefits of the tailwater diversion project is novel. The variable fuzzy evaluation model is used to evaluate the comprehensive environmental and economic benefits of tailwater diversion engineering, in order to facilitate the exploration and application of tailwater diversion engineering. Simultaneously, by evaluating the method using the analytic hierarchy process and fuzzy optimum seeking method, linear comprehensive fuzzy optimization, average comprehensive fuzzy optimization, and variable fuzzy pattern recognition model of optimizing method, the results demonstrate that the method not only can be used to plan optimization but can also provide a good evaluation for each program, the result is reasonable and reliable, and applicable to the comprehensive benefits of water resource management.

Despite the fact that companies increasingly value online star endorsements as Internet celebrity economy booms, scientific knowledge on the effect of online star endorsements on consumers’ purchase intention is limited. Based on the theories of self and construal level theory, this study investigates the impact of online star vs. celebrity endorsements on purchase intention and explores the underlying mechanism as well as boundary conditions. The results of four studies reveal the following: (1) Compared with no endorsement, both celebrity endorsements and online star endorsements lead to increases in consumers’ purchase intention, with no significant difference between the two. (2) Self-concept mediates these relationships; specifically, celebrity and online star endorsements activate the ideal and actual self respectively, and enhance consumers’ willingness to purchase. (3) The effect of endorsements on consumers’ purchase intention is moderated by advertising appeals. That is, celebrity endorsements enhance purchase intention when consumers are exposed to symbolic appeals in advertisements, and online star endorsements enhance purchase intention when it is matched with functional advertising appeals.

Background: Peptide receptor radionuclide therapy (PRRT) is an emerging therapeutic option for the treatment of neuroendocrine tumors (NETs), and the number of publications in this field has been increasing in recent years. The aim of the present study was to present the research status and summarize the key topics through bibliometric analysis of published PRRT literature.Methods: A literature search for PRRT research from 2000 to 2019 was conducted using the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE) on August 4, 2020. The VOSviewer, R-bibliometrix, and CiteSpace software were used to conduct the bibliometric analysis.Results: From 2000 to 2019, a total of 681 publications (523 articles and 158 reviews) were retrieved. Annual publication outputs grew from three to 111 records. Germany had the largest number of publications, making the largest contribution to the field (n = 151, 22.17%). Active cooperation between countries/regions was observed. Kwekkeboom from the Erasmus Medical Center is perhaps a key researcher in the field of PRRT. The European Journal of Nuclear Medicine and Molecular Imaging and Journal of Nuclear Medicine ranked first for productive (n = 84, 12.33%) and co-cited (n = 3,438) journals, respectively. Important topics mainly included matters related to the efficacy of PRRT (e.g., 90Y-dotatoc and 177Lu-dotatate), the long-term adverse effects of PRRT (e.g., hematologic and renal toxicities), standardization of NETs and PRRT in practice, the development of medical imaging techniques, and the individual dose optimization of PRRT.Conclusion: Using bibliometric analysis, we gained deep insight into the global status and trends of studies investigating PRRT for the first time. The PRRT field is undergoing a period of rapid development, and our study provides a valuable reference for clinical researchers and practitioners.

Pharmacist-led interventions have demonstrated significant benefits for older adults, with a plethora of studies dedicated to this subject. A bibliometric study was conducted to assess the current state of research and summarize key themes in the domain of pharmacist-led interventions for older adults. The analysis encompassed publications available in the Web of Science Core Collection from its inception until September 8, 2022. To perform the bibliometric analysis, VOSviewer and CiteSpace software were employed. The initial query yielded a substantial 6 084 relevant documents spanning the period from 1995 to September 8, 2022. Of these, 5496 (constituting 90.34%) were categorized as "Article". Notably, the yearly output of publications displayed an upward trajectory. This body of work emanated from 120 countries and regions, with the United States being the foremost contributor, accounting for the majority of publications (n = 2637). The University of Sydney in Australia emerged as the institution with the highest number of publications (n = 155). Timothy F Chen, affiliated with the University of Sydney, was the most prolific author, boasting 35 publications. Joseph T Hanlon, a scholar affiliated with the University of the Sciences in Philadelphia, emerged as the most frequently co-cited author. When considering journal productivity, The Journal of Managed Care & Specialty Pharmacy stood out as the most prolific journal (n = 251). Conversely, the Journal of the American Geriatrics Society garnered the highest number of co-citations (n = 5293). The predominant research themes encompassed the development of new criteria, updates to existing criteria, the utilization of criteria for identifying potentially inappropriate medications in older populations, concerns surrounding inappropriate polypharmacy in this demographic, and the evaluation of the positive impact of pharmacist -led interventions for older adults. In conclusion, this comprehensive bibliometric analysis offers a panoramic view of pharmacist-led interventions for older adults, providing valuable insights into the field's evolution over the past three decades. [ABSTRACT FROM AUTHOR]

Abstract RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N 6-methyladenosine (m6A) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and m6A recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level. Loss of YTHDF2 in T cells exacerbates tumor progression and confers unresponsiveness to PD-1 blockade in mice and in humans. In addition to initiating RNA decay that is necessary for mitochondrial fitness, YTHDF2 orchestrates chromatin changes that promote T cell polyfunctionality. YTHDF2 interacts with IKZF1/3, which is important for sustained transcription of their target genes. Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of IKZF1/3 inhibitor lenalidomide in a mouse model. Thus, YTHDF2 coordinates epi-transcriptional and transcriptional networks to potentiate T cell immunity, which could inform therapeutic intervention.

Abstract Background Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium. Case presentation This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy. Conclusion We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.