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Infertility has become one of the most serious diseases worldwide, and 50% of this disease can be attributed to male-related factors. Spermatogenesis, by definition, is a complex process by which spermatogonial stem cells (SSCs) self-renew to maintain stem cell population within the testes and differentiate into mature spermatids. It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility. Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs. In this review, we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal, differentiation, and apoptosis of SSCs, and we illustrate the networks of genes and signaling pathways in SSC fate determinations. We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways. This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.

Abstract N 6 -methyladenosine (m6A) is a prevalent and dynamic RNA modification, critical in regulating gene expression. Recent research has shed light on its significance in the life cycle of viruses, especially animal viruses. Depending on the context, these modifications can either enhance or inhibit the replication of viruses. However, research on m6A modifications in animal virus genomes and the impact of viral infection on the host cell m6A landscape has been hindered due to the difficulty of detecting m6A sites at a single-nucleotide level. This article summarises the methods for detecting m6A in RNA. It then discusses the progress of research into m6A modification within animal viruses’ infections, such as influenza A virus, porcine epidemic diarrhoea virus, porcine reproductive, and respiratory syndrome virus. Finally, the review explores how m6A modification affects the following three aspects of the replication of animal RNA viruses: the regulation of viral genomic RNA function, the alteration of the m6A landscape in cells after viral infection, and the modulation of antiviral immunity through m6A modification. Research on m6A modifications in viral RNA sheds light on virus-host interactions at a molecular level. Understanding the impact of m6A on viral replication can help identify new targets for antiviral drug development and may uncover novel regulatory pathways that could potentially enhance antiviral immune responses.

Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

AIM: To evaluate the clinical effect of a new surgery technique (covering corneal stromal lenticule, CSL) for macular hole (MH) in pathological myopia. METHODS: This was a prospective non-randomized series case study. Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment (MHRD) were included in this study. All cases were treated with 25-gauge pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, covering CSL and C3F8 gas tamponade. These cases were followed for 6mo, and the best-corrected visual acuity (BCVA), healing status of MH, the reattached rate of retinal detachment (RD), and reoperation rate were analyzed. RESULTS: All cases were successfully performed the surgery and the postoperative follow-up was completed. After surgery, MHs were healed in all 14 eyes (100%, 14/14) after assessed by optical coherence tomography. The reattachment of retina was achieved in all 6 eyes (100%, 6/6) with MHRD. BCVA was improved in 12 eyes (85.71%, 12/14), and had no significant change in 2 eyes (14.29%, 2/14). The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR (F=10.46, P

Abstract Background This paper reviews the scope of research on kinesiophobia in patients after cardiac surgery. Further, it reviews the current situation, evaluation tools, risk factors, adverse effects, and intervention methods of kinesiophobia to provide a reference for promoting early rehabilitation of patients after cardiac surgery. Methods Guided by the scoping methodology, the Web of Science, PubMed, CINAHL, Cochrane Library, China Biomedical Literature Database, VIP Database, Wanfang Database, CNKI, and other databases were searched from database inception until July 31, 2024. The studies obtained were screened, summarised and systematically analysed by two researchers. Results Eighteen studies (16 cross-sectional studies, one qualitative study, and one randomised controlled trial) were included. The incidence of kinesiophobia in patients after cardiac surgery was 39.20–82.57%, and the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to evaluate this incidence. The influencing factors of kinesiophobia in patients after cardiac surgery included demographic characteristics, pain severity, frailty, exercise self-efficacy, disease-related factors, and psychosocial factors. Kinesiophobia led to adverse health outcomes such as reduced recovery, prolonged hospital stays, and decreased quality of life in patients after cardiac surgery, and there were few studies on intervention methods for postoperative kinesiophobia. Conclusion The kinesiophobia assessment tools suitable for patients after cardiac surgery should be improved, and intervention methods to promote the early recovery of patients after major clinical surgery and those with difficult and critical diseases should be actively researched.

ObjectiveThe present study aims to explore the initial dosage optimization of sertraline in pediatric major depressive disorder (MDD) patients based on model-informed precision dosing (MIPD).MethodsA total of 111 pediatric MDD patients treated with sertraline were included for analysis using MIPD. Sertraline concentration levels, physiological and biochemical indexes of pediatric MDD patients, combined drug information were included in the construction of model.ResultsWeight and zopiclone co-administration influenced sertraline clearance in pediatric MDD patients. With the same weight, the sertraline clearance rates were 0.453:1 in patients with, or without zopiclone, respectively. Furthermore, without zopiclone, for once-daily sertraline scheme, the dosages of 4.0, and 3.0 mg/kg/day were suggested for pediatric MDD patients with body weight of 30–38.5, and 38.5–80 kg, respectively; for twice-daily sertraline scheme, the dosage of 2.0 mg/kg/day was suggested for pediatric MDD patients with body weight of 30–80 kg. With zopiclone, for once-daily sertraline scheme, the dosage of 1.0 mg/kg/day was suggested for pediatric MDD patients with body weight of 30–80 kg; for twice-daily sertraline scheme, the dosage of 0.5 mg/kg/day was suggested for pediatric MDD patients with body weight of 30–80 kg.ConclusionThis study first explored the initial dosage optimization of sertraline in pediatric MDD patients based on MIPD, and recommended the optimal sertraline initial dosage in pediatric MDD patients based on zopiclone co-administration.

The present study aimed to characterize the chromosome features of cherry (Prunus pseudocerasus Lindl.) germplasm in Guizhou Province, China, in order to facilitate the selection and breeding programs of this economically and ornamentally valuable species. The stem tip chromosome preparation technique was employed for ploidy identification and karyotype analysis, and the results were further validated by flow cytometry. The findings revealed that the 28 cherry accessions from Guizhou province exhibited a chromosomal base of x = 8, comprising 19 tetraploid and nine hexaploid individuals. Karyotype analysis showed two chromosome types, “m” and “sm,” with the longest chromosome/shortest chromosome (Lc/Sc) ranging from 1.6 to 2.65, the mean arm ratio (MAR) varying from 1.15 to 1.56, and index of the karyotypic asymmetry (As.K) ranging from 53.74 to 61.6. Three karyotype types, “1A,” “1B,” and “2B,” were identified among the studied accessions. The most evolutionarily advanced accession was HZ152, while DCZC27 represented the most primitive karyotype. This study expands the ploidy database of Chinese cherry and provides valuable information for the conservation and utilization of cherry germplasm resources in Guizhou province.

Abstract BackgroundWith climate change, the number of natural disasters is increasing globally, and the resulting weather-related events lead to increased loss of life and property. Meanwhile, the significance of disaster education is becoming increasingly important. Despite natural disasters being hard to predict, people’s responses to such events can be improved by education and training. Gamification, an innovative teaching method, has demonstrated great potential across various fields, including disaster education. ObjectiveWe aimed to investigate the different application types of gamification in disaster education, focusing on nursing staff, medical professionals, university students, and disaster relief workers. Specifically, the goal was to identify the types of gamified teaching used in disaster education. MethodsThis scoping review was conducted according to the Joanna Briggs Institute methodology. The Participants, Concept, Context (PCC) model was used to frame the inclusion criteria. We performed a systematic search of the relevant literature across the Cochrane Library, PubMed, CINAHL, Embase, Web of Science, CNKI, Wanfang, VIPC, and SinoMed databases. Articles published in Chinese and English were selected for the review. The search was conducted to identify literature published from the establishment of the respective databases to April 21, 2024. Two researchers independently screened the literature according to the inclusion and exclusion criteria and extracted the data. ResultsWe included a total of 16 studies in this review, originating from 8 different countries. These studies involved 1744 participants: nursing students (n=451), medical students from other majors (n=420), college students (n=287), hospital decision makers (n=264), hospital medical staff (n=262), and disaster relief workers (n=60). The gamification approaches for teaching and learning encompassed the following 7 categories: tabletop games, serious games, scenario simulation games, virtual reality and mobile games, theme games, board games, and escape room games. The objectives of the studies were diverse. Three studies conducted randomized controlled trials, with only 1 performing a comparative analysis between different games. Two studies carried out long-term outcome evaluations. ConclusionsThis scoping review explored 7 types of games for disaster education and provided evidence for future education and training. Further research is needed to establish a long-term evaluation mechanism and a better game-based teaching program to provide more insights into the future of disaster education.

IntroductionTime banking, known as “Community/Neighborhood Pension,” instantiates a form of co-creation that can provide a new solution to fulfil the unmet social service needs of community members with idle resources, which is a feasible solution to alleviate pension pressure. The sustainable operation of time banks relies on the co-creation and active participation of community members. Therefore, in this study, we investigate the motivation of members to participate in web-based time banks from a service requirement narrative perspective.MethodsWe collected data of 21969 service requirement projects from publicly available information on the website of Nansha Timebank (nstimebank.com, a web-based time bank platform in China). Using the data, we built a model to assess how the intrinsic and extrinsic cues underlying service requirement narratives affect the time bank participation decisions of service providers drawing on grounded theory. Then we conducted a regression analysis to test our hypotheses.ResultsWe find that participants respond positively to time coins return and narratives highlighting social connection and value fulfilment but respond negatively to service hour costs and empathy-altruism cues.DiscussionOur findings suggest that people who receive services in web-based time banking platform should utilize different linguistic cues in service requirement descriptions to improve service exchange results.

ObjectiveBipolar affective disorder (BAD) is a mood disorder with high morbidity and mortality. Quetiapine can be used in the treatment of patients with BAD; however, the precise administration regimen of quetiapine in these patients is still unknown. In this study, a population pharmacokinetic (PPK) model of quetiapine in patients with BAD was constructed based on model-informed precision dosing (MIPD) and real-world clinical data and an optimal initial dose of quetiapine in these patients was recommended.MethodsA total of 99 patients with BAD treated with quetiapine were included. At the same time, the quetiapine concentrations, the physical and chemical indices of the patients, and the drug combination information were collected. A quetiapine PPK model for patients with BAD was then constructed and an initial dose based on Monte Carlo simulation was recommended.ResultsIn the final model of quetiapine for patients with BAD, the apparent oral clearance (CL/F) and the apparent volume of distribution (V/F) were 76.1 L/h and 530 L, respectively. For patients with BAD weighing 40–66 kg, the initial dose recommendation was 16 mg kg−1 day−1, the probability of reaching the therapeutic window was 78.8%–82.2%, and the probability of exceeding the upper limit of the therapeutic window was 5.2%–10.3%. For patients with BAD weighing 66–120 kg, the initial dose recommendation was 12 mg kg−1 day−1, the probability of reaching the therapeutic window was 81.5%–85.5%, and the probability of exceeding the upper limit of the therapeutic window was 3.6%–8.1%.ConclusionThe present study, for the first time, recommended an initial dose of quetiapine in patients with BAD based on MIPD and real-world data, providing an individualized reference for the administration of quetiapine in these patients.

Objectives The aim of this study was to determine the strength of the association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis.Design A systematic review and meta-analysis.Setting and participants Patients aged ≥18 years who were undergoing maintenance hemodialysis.Methods PubMed, Web of Science, Embase, the Cochrane Library, Scopus, the China Knowledge Resource Integrated Database, the Wanfang Database and the Weipu Database were searched from inception until 11 April 2024. The reviewers independently selected the studies, extracted the data and evaluated the quality of the studies. Stata 15.1 software was used to perform the meta-analysis.Results A total of 36 articles were included in this study, including 56,867 patients. The primary outcome events in this study were mortality, hospitalization, and vascular access events. The secondary outcomes were depression, cognitive impairment, falls, fracture, sleep disturbances, and quality of life. This study suggested that frailty was associated with mortality in patients undergoing maintenance hemodialysis [hazard ratio (HR), 1.97; 95% CI, 1.62–2.40]. Frailty increased the risk of mortality in patients [odds ratio (OR), 2.33; 95% CI, 1.47–3.68]. In addition, we found that frailty was significantly associated with hospitalization in patients undergoing maintenance hemodialysis (OR, 2.47; 95% CI, 1.52–4.03). Patients who were undergoing maintenance hemodialysis and who were frail had a greater risk of hospitalization [RR, 1.47; 95% CI, 1.05–2.08] and emergency visits (RR, 2.28; 95% CI, 1.78–2.92). The results of this study also suggested that frailty was associated with a greater risk of vascular access events (HR, 1.72; 95% CI, 1.50–1.97). Finally, frailty increased the risk of depression (OR, 4.31; 95% CI, 1.83–10.18), falls and fractures, and reduced quality of life.Conclusions The findings of this study suggested that frailty was an important predictor of adverse outcomes in patients undergoing maintenance hemodialysis. In the future, medical staff should regularly evaluate signs of weakness, formulate individual diagnosis and treatment plans, adjust dialysis plans according to the patient’s condition, and reduce the occurrence of adverse events.Registration The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023486239).

Objective To systematically review the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients.Methods A combination of subject words + free words was used to search the relevant literature published in CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Web of Science, Cochrane Library, Mediline and other databases. The search period was from the establishment of the databases to June 25, 2024. Revman 5.4 software and Stata15.0 software was used to meta-analyze the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients.Results A total of 23 studies were included in this meta-analysis, describing 15 variables, 3793 patients, and using 7197 filters. Meta-analysis results showed that risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients were as follows: Low mean arterial pressure [OR = 1.02, 95%CI (1.00, 1.03), p

Abstract Fibroblast growth factor 2 (FGF2) is a crucial factor in odontoblast differentiation and dentin matrix deposition, which facilitates pulpodentin repair and regeneration. Nevertheless, the specific biological function of FGF2 in odontoblastic differentiation remains unclear because it is controlled by complex signalling pathways. This study aimed to investigate the mechanism underlying the effect of FGF2 on osteo/odontogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were pretreated with conditioned media containing FGF2 for 1 week, followed by culturing in induced differentiation medium for another week. RNA sequencing (RNA-seq) combined with quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the pathways affected by FGF2 in SCAP. Osteo/odontogenic differentiation of SCAP was determined using Alizarin red S staining, alkaline phosphatase staining, RT-qPCR, and western blotting. Pretreatment with FGF2 for 1 week increased the osteo/odontogenic differentiation ability of SCAP. RNA-seq and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that phosphatidylinositol 3-kinase (PI3K)/AKT signalling is involved in the osteogenic function of FGF2. RT-qPCR results indicated that SCAP expressed FGF receptors, and western blotting showed that p-AKT was reduced in FGF2-pretreated SCAP. The activation of the PI3K/AKT pathway partially reversed the stimulatory effect of FGF2 on osteo/odontogenic differentiation of SCAP. Our findings suggest that pretreatment with FGF2 enhances the osteo/odontogenic differentiation ability of SCAP by inhibiting the PI3K/AKT pathway.

Abstract Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism. Graphical Abstract

Gastrochilus is an orchid genus containing 73 species of mainly epiphytic on trees or rocks in mountain forests of tropical and subtropical Asia. Previous phylogenetic analyses and morphological assessments have failed to produce a well-resolved phylogeny at the infrageneric level. In the present study, a new infrageneric classification of Gastrochilus is proposed based on thoroughly morphological and phylogenetic analyses based on 52 species. Our phylogenetic analysis divided the genus into six sections including three new sections, G. sect. Pseudodistichi, G. sect. Brachycaules and G. sect. Acinacifolii. We also reinstate G. suavis to the specific rank. Furthermore, two new species, G. armeniacus Jun Y. Zhang, B. Xu & Yue H. Cheng and G. minjiangensis Jun Y. Zhang, B. Xu & Yue H. Cheng, are described and illustrated. A key to six sections of the genus is presented.

Abstract Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

ObjectiveAlthough quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug–drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).MethodsNinety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs.ResultsIt was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40–50 and 50–120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40–120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range.ConclusionThe present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine.

Abstract In this letter, to improve the performance and reduce leakage currents of bulk low‐temperature multi‐layer SiGe/Si superlattice (SL) fin field‐effect transistors (FinFETs), a p‐type omega‐shaped channel (Ω‐channel) SL FinFET is realized by etching a Si/Si0.7Ge0.3 triple‐layer stacked structure in a replacement metal gate (RMG) module on a silicon‐on‐insulator (SOI) substrate. In addition, a self‐allied Ni0.9Pt0.1 silicide process and a low‐thermal‐budget (≤400°C) integration procedure were performed on the Ω‐channel SL FinFET. Test results demonstrate that the on‐state current (Ion) is increased by 5.5 times (from 78 to 429 µA/µm) and the off‐state current (Ioff) is reduced by 78.8% (from 5.2 × 10−3 to 1.1 × 10−3 µA/µm) when compared with the corresponding currents of traditional bulk SL FinFETs.

ABSTRACT Background Emerging evidence has indicated possible efficacy benefit of platinum‐based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple‐negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. Materials and Methods Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum‐based neoadjuvant treatment. We prospectively enrolled women with stage IIB‐IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline‐based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease‐free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled. Results The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3‐year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS. Conclusions Platinum‐based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline‐ and taxane‐based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.

Abstract This study illustrated the effectiveness of the knowledge, attitude, practice (KAP) intervention model for community hypertension in the elderly by the community physician‐led, describing the study design and baseline data. The aim of the study was to compare the changes in the elderly hypertensive population before and after the KAP intervention model by managing the elderly hypertensive patients for a period of 1 year. Basic information and risk factors affecting blood pressure control based on baseline data of recruited elderly hypertensive patients. The management approach consists of two parts: (1) the unified management of the community physician to whom the patient belongs; and (2) the management of the contracted patient by the community physician. The aim was to demonstrate the anti‐hypertensive effectiveness (control rate, blood pressure reduction, and pulse pressure), the distribution of blood pressure types, and the change of the KAP in elderly hypertensive patients before and after the intervention. The KAP intervention model was administered to 2660 elderly hypertensive patients in a 1‐year period. The blood pressure control rate improved by 54.03%. Mean values of overall systolic and diastolic blood pressure decreased by 16.00 and 5.31 mmHg, respectively. The proportion of isolated systolic hypertension (ISH) and systolic‐diastolic hypertension (SDH) decreased by 29.14% and 24.81%, respectively. The KAP compliance improved significantly. These results suggest that the community physician‐led KAP intervention model is effective in the management of hypertension in the elderly.

Abstract Objectives The endometrium of most unexplained infertility (UI) patients has been altered histologically. Shear wave elastography (SWE) is utilized to assess the signature of living tissue. This study aimed to explore the value of SWE in evaluating endometrial receptivity (ER) in UI patients. Methods In total, 59 UI patients (UI group) and 52 normal control women (NC group) who received fertility consultation in our hospital were included between January 2022 and June 2023. We divided them into the late-proliferative phase of UI group (LPUI; n = 59), mid-secretory phase of UI group (MPUI; n = 41), late-proliferative phase of NC group (LPNC; n = 52), and mid-secretory phase of NC group (MPNC; n = 45). Transvaginal ultrasonography and SWE were performed during the LP and MP. Endometrial thickness (EMT), uterine artery pulsatility index (UA-PI), endometrial mean elasticity (E-mean), and mean shear wave velocities (SWV-mean) were measured. Results There were significant differences in E-mean, SWV-mean, EMT, and UA-PI between the UI group and the NC group during both the LP and MP (p MPNC vs MPUI < 0.05, p LPNC vs LPUI < 0.05). E-mean and SWV-mean decreased with increasing EMT but increased with increasing UA-PI (p < 0.05). The most effective parameter for evaluating ER in UI patients is the E-mean (AUC = 0.89). Conclusions UI patients exhibited thinner endometrium, increased endometrial stiffness, and poor endometrial blood perfusion. E-mean was the most effective parameter to evaluate ER in UI patients. The study preliminarily proved that SWE is a promising non-invasive tool for evaluating the condition of endometrium. Critical relevance statement This study aimed to explore the significance of endometrial elasticity measured by SWE in evaluating patients with UI. The findings revealed a correlation between EMT, UA-PI, and E-mean. Endometrial elasticity can serve as an effective indicator for predicting ER. Key points 1. To explore the significance of endometrial elasticity in assessing patients with UI. 2. The endometrium of UI patient exhibited thinness, stiffness, and poor blood perfusion. 3. Endometrial elasticity serves as a valuable indicator for evaluating endometrial receptivity. Graphical Abstract

ObjectivesOlanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study.MethodsThirty-nine patients with BPD from the real-world study were collected to construct the MIPD model.ResultsWeight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60 mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05 mg/kg/day was suitable for 40- to 100-kg BPD patients.ConclusionThis study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients.

Objective Icotinib has been approved for adjuvant treatment of stage II–IIIA non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations in China, yet the long-term costs and outcomes of this strategy are unknown. Thus, we examined the cost effectiveness of adjuvant icotinib, compared with adjuvant chemotherapy, for the treatment of resected stage II–IIIA EGFR-mutated NSCLC.Design We performed a cost-effectiveness analysis from the perspective of the Chinese healthcare system, comparing 2-year adjuvant icotinib with four cycles of adjuvant chemotherapy. Costs and quality-adjusted life years (QALYs) were estimated using a Markov model. Model inputs were obtained from local data and literature. The influence of model parameters and assumptions was explored in sensitivity analyses. All costs are expressed in 2022 US dollars, and costs and QALYs were discounted at a rate of 5% per year. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product.Setting The Chinese healthcare system perspective.Participants A hypothetical Chinese cohort of patients with resected stage II–IIIA EGFR-mutated NSCLC.Interventions Icotinib versus chemotherapy.Primary outcome measure Costs, QALYs, incremental cost-effectiveness ratio.Results The incremental cost per QALY gained with the use of 2-year icotinib, from the Chinese healthcare system perspective, was $3440.66 compared with adjuvant chemotherapy. At a WTP threshold of $40 500, adjuvant icotinib was the optimal treatment in over 99% of replications. The interpretation of the results was insensitive to model and input assumptions.Conclusions Compared with adjuvant chemotherapy, adjuvant icotinib may be a cost-effective treatment for resected stage II–IIIA EGFR-mutated NSCLC as the WTP threshold is set at $40 500 per QALY.

Mesenchymal stem cells (MSCs) have been studied for decades as candidates for cellular therapy, and their secretome, including secreted extracellular vesicles (EVs), has been identified to contribute significantly to regenerative and reparative functions. Emerging evidence has suggested that MSC-EVs alone, could be used as therapeutics that emulate the biological function of MSCs. However, just as with MSCs, MSC-EVs have been shown to vary in composition, depending on the tissue source of the MSCs as well as the protocols employed in culturing the MSCs and obtaining the EVs. Therefore, the importance of careful choice of cell sources and culture environments is receiving increasing attention. Many factors contribute to the therapeutic potential of MSC-EVs, including the source tissue, isolation technique, and culturing conditions. This review illustrates the molecular landscape of EVs derived from different types of MSC cells along with culture strategies. A thorough analysis of publicly available omic datasets was performed to advance the precision understanding of MSC-EVs with unique tissue source-dependent molecular characteristics. The tissue-specific protein and miRNA-driven Reactome ontology analysis was used to reveal distinct patterns of top Reactome ontology pathways across adipose, bone marrow, and umbilical MSC-EVs. Moreover, a meta-analysis assisted by an AI technique was used to analyze the published literature, providing insights into the therapeutic translation of MSC-EVs based on their source tissues.

BackgroundThe present study aimed to investigate the drug–drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics.Research design and methodsA total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects.ResultsThe weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg−1 day−1 were recommended for patients with schizophrenia weighing 40–95 and 95–120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg−1 day−1 was recommended for those weighing 40–120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg−1 day−1 was recommended for patients with schizophrenia weighing 40–120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg−1 day−1 were recommended for those weighing 40–60 and 60–120 kg, respectively.ConclusionThis is the first investigation of the effects of fluoxetine on aripiprazole via drug–drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia.

IntroductionChronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more).MethodsThirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network.ResultsThe differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia.DiscussionIn our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Abstract Background The organizational climate that fosters and supports the implementation of evidence is a key factor influencing the effective implementation of evidence-based practice (EBP). Nurses, being the largest group of medical staff, play a crucial role in EBP implementation. The perception of the climate for EBP implementation among nurses in their organizations is unknown, especially among Chinese nurses. Aims To clarify the implementation climate of EBP among Chinese nurses and identify the factors associated with the implementation and development of evidence-based nursing practices. Methods This study employed a descriptive cross-sectional study design. From March 2023 to April 2023, a sample of nurses (n = 1260) from two Tertiary care hospitals in central China were selected and surveyed by self-designed social-demographic questionnaire and Implementation Climate Scale. Multiple linear stepwise regression analysis was conducted to determine the predictors of implementation climate. Results The nurses achieved a mean ICS score of 59.10 ± 11.22, with mean scores exceeding 3 points for each sub-dimension and item. In the results of multiple linear regression, income satisfaction, implementation of evidence-based nursing practice project(s) within the unit, experience of evidence-based nursing practice during working life, and specific training or courses in evidence-based nursing practice were predictors of ICS. Of these, income satisfaction was the most significant predictor. These factors could explain 17.5% of the total variance in implementation climate. Conclusion The climate for implementing EBP in Chinese nursing organizations was relatively strong. Nursing managers can enhance the climate for implementing EBP in their organizations by actively improving salary and enhancing EBP-related trainings and practices. Relevance to clinical practice Understanding nurses’ perceptions of the EBP implementation climate in their organizations can help to identify specific barriers and facilitators to the development of EBP and facilitate its successful implementation. Patient or public contribution Clinical nurses were involved in data collection and completed the questionnaires on EBP implementation climate.

Abstract Clostridioides difficile is the leading cause of antibiotic-associated infectious diarrhea. The development of C.difficile infection is tied to perturbations of the bacterial community in the gastrointestinal tract, called the gastrointestinal microbiota. Repairing the gastrointestinal microbiota by introducing lab-designed bacterial communities, or defined microbial communities, has recently shown promise as therapeutics against C.difficile infection, however, the mechanisms of action of defined microbial communities remain unclear. Using an antibiotic- C.difficile mouse model, we report the ability of an 18-member community and a refined 4-member community to protect mice from two ribotypes of C.difficile (CD027, CD078; p

Abstract Background The case mix index (CMI) may reflect the severity of disease and the difficulty of care objectively, and is expected to be an ideal indicator for assessing the nursing workload. The purpose of this study was to explore the quantitative relationship between daily nursing worktime (DNW) and CMI to provide a method for the rational allocation of nursing human resources. Methods Two hundred and seventy-one inpatients and 36 nurses of the department of hepatobiliary surgery were prospectively included consecutively from August to September 2022. The DNW of each patient were accurately measured, and the CMI data of each patient were extracted. Among 10 curve estimations, the optimal quantitative model was selected for constructing the nursing human resource allocation model. Finally, the applicability of the allocation model was preliminarily assessed by analyzing the relationship between the relative gap in nursing human resources and patient satisfaction, as well as the incidence of adverse events in 17 clinical departments. Results The median (P25, P75) CMI of the 271 inpatients was 2.62 (0.92, 4.07), which varied by disease type (F = 3028.456, P

Tendons enable movement through their highly aligned extracellular matrix (ECM), predominantly composed of collagen I. Tendinopathies disrupt the structural integrity of tendons by causing fragmentation of collagen fibers, disorganization of fiber bundles, and an increase in glycosaminoglycans and microvasculature, thereby driving the apparent biomechanical and regenerative capacity in patients. Moreover, the complex cellular communication within the tendon microenvironment ultimately dictates the fate between healthy and diseased tendon, wherein extracellular vesicles (EVs) may facilitate the tendon’s fate by transporting biomolecules within the tissue. In this study, we aimed to elucidate how the EV functionality is altered in the context of tendon microenvironments by using polycaprolactone (PCL) electrospun scaffolds mimicking healthy and pathological tendon matrices. Scaffolds were characterized for fiber alignment, mechanical properties, and cellular activity. EVs were isolated and analyzed for concentration, heterogeneity, and protein content. Our results show that our mimicked healthy tendon led to an increase in EV secretion and baseline metabolic activity over the mimicked diseased tendon, where reduced EV secretion and a significant increase in metabolic activity over 5 days were observed. These findings suggest that scaffold mechanics may influence EV functionality, offering insights into tendon homeostasis. Future research should further investigate how EV cargo affects the tendon’s microenvironment.

Marxist political economy provides a theoretical framework for sustainable supply chains, while the implementation of sustainable supply chains embodies and deepens the practical application of Marxist principles. This paper studies supply chain sustainability from the perspective of Marxist political economy, proposing a novel analytical framework to address sustainability challenges. The primary research focuses on (1) Identifying Influencing Factors: Influencing factors of Marxist political economy and supply chain sustainability are categorized into four main areas: society and government, environment, economy, and the supply chain itself. Through classification analysis, 16 key factors influencing sustainable supply chain implementation are identified. (2) DEMATEL Analysis (Decision-Making Trial and Evaluation Laboratory Method): Data are gathered through investigations and questionnaires to construct a direct influence matrix. Subsequently, a decision test method quantitatively analyzes the interactions among these factors, resulting in a comprehensive influence matrix and a cause–effect diagram. To enhance the overall benefits of supply chain sustainability and foster sustainable development.

Abstract Background To investigate the effects of a single injection technique with ultrasound-guided superficial cervical fascia block combined with brachial plexus block in clavicular surgery. Methods Forty patients, 25 males and 15 females, aged 18–85 years with ASA class I or II underwent unilateral clavicular fracture internal fixation. The patients were randomly divided into a superficial cervical plexus block group (group S, n = 20) and a superficial cervical fascia block group (group F, n = 20). First, the brachial plexus of the intermuscular sulcus of all patients was blocked with an ultrasound-guided injection of one injection with 15ml 0.33% ropivacaine 15ml in both groups. Second, the superficial cervical plexus was blocked by another injection of 5-8ml 0.33% ropivacaine in group S, and the superficial cervical fascia was blocked by an injection with 5-8ml 0.33% ropivacaine in Group F. We evaluated operation time, onset time of anaesthesia, effective time and the grades of nerve block effect in the two groups. Additionally, we evaluated the incidences of local anaesthetic poisoning, hoarseness, dyspnoea, and postoperative nausea and vomiting, and the number of patients requiring remedial analgesia within 24 h. Repeated measurements were analysed by repeated data analysis of variance, and count data were compared by the χ2 test. A P value

Abstract Background Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. Results Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. Conclusion This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.

Forest therapy has been proven to have a quantifiable positive impact on human physiological and psychological health. Given that graduating students at university are easy to stress due to changes in life, pressure from their studies, and independence in finance. The main purpose of this research was to explore the effects of guided forest therapy on graduating college students through a field experiment in Pacific Spirit Regional Park which held significant geographical value. This paper investigated the pressure of graduating college students and their needs for forest therapy, and explored the psychological and physiological changes after guided forest therapy. This study also analyzed gender-related psychological and physiological differences. Thirty-six healthy graduating college students were invited to participate in a 2-hour forest therapy program. Likert scales were used to assess students' pressure and the demand for forest therapy. Most of the students were facing the pressure of graduation and were willing to participate in forest therapy. Systolic and diastolic blood pressure, pulse rate, and heart rate variability (HRV) were used as physiological measurement indices. Our physiological results indicated that blood pressure significantly decreased, the high-frequency component of HRV (HF) was significantly larger, and the low-to-high-frequency component ratio (LF/HF) was smaller after the forest therapy program, and some beneficial changes in females were more significant than that in males. The participants' mean HR decreased throughout the forest therapy, but there were no significant differences. Mental status was assessed before and after forest therapy using the Profile of Mood States (POMS), employment stress scale and State-Trait Anxiety Inventory (STAI) for participants. Overall, the guided forest therapy program effectively reduced participants' employment stress and state anxiety. Our research showed that guided forest therapy had positive physiological and psychological benefits for graduating college students. In addition, females obtained more positive physiological benefits than males, and males obtained more positive psychological benefits than females throughout forest therapy.

Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF.

BackgroundAs one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism.PurposeThe objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism.MethodsHPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway.ResultsGallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins.ConclusionTSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

Quantitative structure-activity relationship (QSAR) is a cost-effective solution to directly and accurately estimating the environmental safety thresholds (ESTs) of pollutants in the ecological risk assessment due to the lack of toxicity data. In this study, QSAR models were developed for estimating the Predicted No-Effect Concentrations (PNECs) of petroleum hydrocarbons and their derivatives (PHDs) under dietary exposure, based on the quantified molecular descriptors and the obtained PNECs of 51 PHDs with given acute or chronic toxicity concentrations. Three high-reliable QSAR models were respectively developed for PHDs, aromatic hydrocarbons and their derivatives (AHDs), and alkanes, alkenes and their derivatives (ALKDs), with excellent fitting performance evidenced by high correlation coefficient (0.89–0.95) and low root mean square error (0.13–0.2 mg/kg), and high stability and predictive performance reflected by high internal and external verification coefficient (Q2LOO, 0.66–0.89; Q2F1, 0.62–0.78; Q2F2, 0.60–0.73). The investigated quantitative relationships between molecular structure and PNECs indicated that 18 autocorrelation descriptors, 3 information index descriptors, 4 barysz matrix descriptors, 6 burden modified eigenvalues descriptors, and 1 BCUT descriptor were important molecular descriptors affecting the PNECs of PHDs. The obtained results supported that PNECs of PHDs can be accurately estimated by the influencing molecular descriptors and the quantitative relationship from the developed QSAR models, that provided a new feasible solution for ESTs derivation in the ecological risk assessment.