High-intensity interval training and medium-intensity continuous training may affect cognitive function through regulation of intestinal microbial composition and its metabolite LPS by the gut-brain axis.

AIMS: The gut-brain axis is the communication mechanism between the gut and the central nervous system, and the intestinal flora and lipopolysaccharide (LPS) play a crucial role in this mechanism. Exercise regulates the gut microbiota composition and metabolite production (i.e., LPS). We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cognitive function in C57BL/6 J mice through gut-brain axis regulation of gut microbiota composition and LPS displacement. MAIN METHODS: C57BL/6 J male mice were randomly divided into sedentary, HIIT, and MICT groups. After 12 weeks of exercise intervention, the cognitive function of the brain and mRNA levels of related inflammatory factors were measured. RNA sequencing, Golgi staining, intestinal microbial 16 s rDNA sequencing, and ELISA were performed. KEY FINDINGS: HIIT and MICT affect brain cognitive function by regulating the gut microbiota composition and its metabolite, LPS, through the gut microbiota-gut-brain axis. HIIT is suspected to have a risk: it can induce "intestinal leakage" by regulating intestinal permeability-related microbiota, resulting in excessive LPS in the blood and brain and activating M1 microglia in the brain, leading to reduced dendritic spine density and affecting cognitive function. SIGNIFICANCE: This study revealed a potential link between changes in the gut microbiota and cognitive function. It highlighted the possible risk of HIIT in reducing dendritic spine density and affecting cognitive function.

Case report: Long-term intracranial effect of zimberelimab monotherapy following surgical resection of high PD-L1-expressing brain metastases from NSCLC.

Non-small cell lung cancer (NSCLC) accounted for the majority of lung cancer cases worldwide. Brain metastases (BM) frequently complicate NSCLC and portend a dismal prognosis. To control neurological symptoms, surgical resection is commonly followed by brain radiotherapy (RT). However, RT is often complicated by neurotoxicity. For patients with tumors that harbor positive driver genes, tyrosine kinase inhibitors are considered the standard of care. Nevertheless, treatment options for those without driver gene mutations are still debated. Programmed death receptor 1 (PD-1)/ligand 1 (PD-L1) inhibition has emerged as a novel therapeutic strategy for NSCLC patients with PD-L1-positive tumors, as well as for those with asymptomatic BM. However, the effect of anti-PD-1 antibodies on active BM within such specific populations is undetermined. Herein we present a case of a 65-year-old patient with NSCLC and high PD-L1-expressing BM. The patient underwent surgical resection of BM followed by first-line monotherapy with 31 cycles of zimberelimab, a novel anti-PD-1 antibody, and has already achieved 24 months of progression-free survival and intracranial recurrence-free survival. To our knowledge, this is the first report regarding the intracranial effect of zimberelimab on BM from primary lung cancer. This case report might facilitate an understanding of the intracranial effects of different anti-PD-1 antibodies for such populations.

The complete chloroplast genome assembly of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China.

Species in the Amorphophallus genus are important cash crops in many tropical and subtropical Asian countries. Although several molecular markers have been employed to determine relationships and assess genetic variation in the Amorphophallus genus, some conflicts remain in infrageneric classification and evolution. To aid in the phylogenetic research of the Amorphophallus genus, we collected one sample of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China. We assembled the first chloroplast genome of this species using high-throughput sequencing. The assembled genome was 169,341 bp long with a typical quadripartite structure (GenBank accession number: PP234804). The lengths of the large single-copy region, small single-copy region, and two inverted repeats were 90,705 bp, 15,640 bp, 31,498 bp, and 31,498 bp, respectively. We annotated 129 genes across the chloroplast genome of A. tonkinensis. The phylogenetic trees suggested that the Amorphophallus species distributed in continental Asia split into two main clades. The chloroplast genome reported in our study provided valuable genomic resources for the future phylogenetic research of the Amorphophallus genus.

Risk assessment of extra-uterine involvement and prognosis in young type I endometrial carcinoma with high or moderate differentiation and less than 1/2 myometrial invasion.

PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis. METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher's exact test. RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05). CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.

Whether surgical procedure can improve the prognosis of endometrial cancer arising in adenomyosis (EC-AIA)? A systematic review and meta-analysis.

PURPOSE: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, the authors summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. METHODS: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. RESULTS: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival. Univariable ( P =0.025, HR=0.25, 95% CI=0.08-0.84) and multivariable ( P =0.042, HR=0.13, 95% CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. CONCLUSION: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer.

PURPOSE: The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). METHODS: A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. RESULTS: Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558-7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327-5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919-8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344-6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1-1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056-16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933-12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003-17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. CONCLUSIONS: Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

Lactate/Hydroxycarboxylic Acid Receptor 1 in Alzheimer's Disease: Mechanisms and Therapeutic Implications-Exercise Perspective.

Lactate has a novel function different from previously known functions despite its traditional association with hypoxia in skeletal muscle. It plays various direct and indirect physiological functions. It is a vital energy source within the central nervous system (CNS) and a signal transmitter regulating crucial processes, such as angiogenesis and inflammation. Activating lactate and its associated receptors elicits effects like synaptic plasticity and angiogenesis alterations. These effects can significantly influence the astrocyte-neuron lactate shuttle, potentially impacting cognitive performance. Decreased cognitive function relates to different neurodegenerative conditions, including Alzheimer's disease (AD), ischemic brain injury, and frontotemporal dementia. Therefore, lactic acid has significant potential for treating neurodegenerative disorders. Exercise is a method that induces the production of lactic acid, which is similar to the effect of lactate injections. It is a harmless and natural way to achieve comparable results. Animal experiments demonstrate that high-intensity intermittent exercise can increase vascular endothelial growth factor (VEGF) levels, thus promoting angiogenesis. In vivo, lactate receptor-hydroxycarboxylic acid receptor 1 (HCAR1) activation can occur by various stimuli, including variations in ion concentrations, cyclic adenosine monophosphate (cAMP) level elevations, and fluctuations in the availability of energy substrates. While several articles have been published on the benefits of physical activity on developing Alzheimer's disease in the CNS, could lactic acid act as a bridge? Understanding how HCAR1 responds to these signals and initiates associated pathways remains incomplete. This review comprehensively analyzes lactate-induced signaling pathways, investigating their influence on neuroinflammation, neurodegeneration, and cognitive decline. Consequently, this study describes the unique role of lactate in the progression of Alzheimer's disease.

Treadmill exercise can regulate the redox balance in the livers of APP/PS1 mice and reduce LPS accumulation in their brains through the gut-liver-kupffer cell axis.

A growing body of clinical data has shown that patients with Alzheimer's disease (AD) have symptoms such as liver dysfunction and microbial-gut-brain axis dysfunction in addition to brain pathology, presenting a systemic multisystemic pathogenesis. Considering the systemic benefits of exercise, here, we first observed the effects of long-term treadmill exercise on liver injuries in APP/PS1 transgenic AD mice and explored the potential mechanisms of the gut-liver-brain axis's role in mediating exercise's ability to reduce bacterial lipopolysaccharide (LPS) pathology in the brain. The results showed that the livers of the AD mice were in states of oxidative stress, while the mice after long-term treadmill exercise showed alleviation of their oxidative stress, their intestinal barriers were protected, and the ability of their Kupffer cells to hydrolyze LPS was improved, in addition to the accumulation of LPS in their brains being reduced. Notably, the livers of the AD mice were in immunosuppressed states, with lower pro-oxidative and antioxidative levels than the livers of the wild-type mice, while exercise increased both their oxidative and antioxidative levels. These results suggest that long-term exercise modulates hepatic redox homeostasis in AD mice, attenuates oxidative damage, and reduces the accumulation of LPS in the brain through the combined action of the intestine-liver-Kupffer cells.

Genomic insights into differentiation and adaptation of Amorphophallus yunnanensis in the mountainous region of Southwest China.

The role of geographical isolation and environmental adaptation in driving the differentiation and radiation of species has been a hotspot in evolutionary biology. The extremely complicated and fragmented geography of the mountainous region of Southwest China provides an excellent system for investigating the process of species divergence in heterogeneous habitats. Amorphophallus yunnanensis is a species of extreme habitat preference that resides mainly in the mountainous region of Southwest China. Here, we used restriction site-associated DNA sequencing (RAD-seq) to characterize the geographic pattern of genetic variation among 19 populations of A. yunnanensis as well as the genomic basis of environmental adaptation. A pattern of low population genetic diversity and high level of genetic differentiation was observed. The genomic data revealed a clear east-west genetic differentiation, with two distinct genetic lineages corresponding to the Guizhou plateau and Yunnan plateau, respectively. However, we discovered demographic expansion of the Guizhou Plateau lineage and recent hybridization in populations at the contact region. Significant levels of isolation by distance along with isolation by environment were detected. Outlier tests and genome-environment association analyses identified 89 putatively adaptive loci that might play a role in environmental adaptation. Our results suggest that the genetic divergence of A. yunnanensis is attributed to geographical isolation together with divergent selection in the mountainous region of Southwest China.

A cost-effectiveness analysis of lung cancer screening with low-dose computed tomography and a polygenic risk score.

INTRODUCTION: Several studies have proved that Polygenic Risk Score (PRS) is a potential candidate for realizing precision screening. The effectiveness of low-dose computed tomography (LDCT) screening for lung cancer has been proved to reduce lung cancer specific and overall mortality, but the cost-effectiveness of diverse screening strategies remained unclear. METHODS: The comparative cost-effectiveness analysis used a Markov state-transition model to assess the potential effect and costs of the screening strategies incorporating PRS or not. A hypothetical cohort of 300,000 heavy smokers entered the study at age 50-74 years and were followed up until death or age 79 years. The model was run with a cycle length of 1 year. All the transition probabilities were validated and the performance value of PRS was extracted from published literature. A societal perspective was adopted and cost parameters were derived from databases of local medical insurance bureau. Sensitivity analyses and scenario analyses were conducted. RESULTS: The strategy incorporating PRS was estimated to obtain an ICER of CNY 156,691.93 to CNY 221,741.84 per QALY gained compared with non-screening with the initial start age range across 50-74 years. The strategy that screened using LDCT alone from 70-74 years annually could obtain an ICER of CNY 80,880.85 per QALY gained, which was the most cost-effective strategy. The introduction of PRS as an extra eligible criteria was associated with making strategies cost-saving but also lose the capability of gaining more LYs compared with LDCT screening alone. CONCLUSION: The PRS-based conjunctive screening strategy for lung cancer screening in China was not cost-effective using the willingness-to-pay threshold of 1 time Gross Domestic Product (GDP) per capita, and the optimal screening strategy for lung cancer still remains to be LDCT screening for now. Further optimization of the screening modality can be useful to consider adoption of PRS and prospective evaluation remains a research priority.

Willingness to pay for cancer prevention versus treatment in China: implications for cost-effectiveness threshold.

BACKGROUND: Empirical support for the appropriate cost-effectiveness threshold (CET) in China remains sparse. OBJECTIVE: This study aimed to estimate the willingness to pay (WTP) for cancer prevention and treatment from the perspective of healthcare policy-makers (i.e. supply side) and to investigate whether there is a difference between the estimated WTP in two scenarios. METHODS: We conducted a web-based survey from May to July 2022 among experts who offering consultation to the government. We surveyed 79 experts from a national think-tank (84.81% response rate) using contingent valuation method, a method for estimating the monetary value that individuals place on a non-market service. RESULTS: The mean WTP for two scenarios were estimated at 1.29 times of per capita Gross Domestic Product (GDP) of China and 1.90 times of per capita GDP, respectively. There was a difference between the WTP in the two scenarios and the WTP for treatment was significantly higher than prevention. CONCLUSION: The findings suggest that though there is a smaller gap between the two scenarios in China as compared to other countries, the WTP may vary under different scenarios. So there's a need to further refine the development of CET by adding parameters like prevention instead of defining one universal threshold.

CUDC-907 exhibits potent antitumor effects against ovarian cancer through multiple in vivo and in vitro mechanisms.

PURPOSE: CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo. METHODS: Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo. RESULTS: Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest. CONCLUSION: Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.

Screen exposure among children aged 6-12 years in Hainan Province / 预防医学

Objective@#To investigate the screen exposure status and influencing factors among 6-12 year-old children in Hainan Province, so as to provide insights into screen exposure intervention for children.@*Methods@#Children aged 6-12 years from 18 counties (cities) in Hainan Province were selected using multi-stage stratified cluster sampling method from December 2020 to July 2021. Demographic information, parents' educational level, family type and screen time was collected using questionnaire surveys. The screen exposure rate of children was analyzed, and factors affecting screen exposure were identified using a multivariable logistic regression model.@*Results@#A total of 27 501 children were surveyed, including 13 901 boys (50.55%) and 13 600 girls (49.45%). The mean age was (9.22±1.86) years. Among them, 3 925 children had screen exposure, with a screen exposure rate of 14.27%. Multivariable logistic regression analysis showed that gender (female, OR=0.859, 95%CI: 0.796-0.926), age (OR=1.078, 95%CI: 1.049-1.108), ethnicity (ethnic minorities, OR=1.147, 95%CI: 1.041-1.254), place of residence (rural area, OR=0.869, 95%CI: 0.801-0.944), father's educational level (high school or technical secondary school, OR=0.879, 95%CI: 0.788-0.981; college degree or above, OR=0.686, 95%CI: 0.589-0.818), mother's educational level (college degree or above, OR=0.706, 95%CI: 0.588-0.846), family type (others, OR=1.250, 95%CI: 1.105-1.414), and annual family income (>100 000 Yuan, OR=0.741, 95%CI: 0.619-0.885) were the influencing factors for screen exposure among children aged 6-12 years.@*Conclusion@#The screen exposure among children aged 6-12 years in Hainan Province was affected by gender, age, ethnicity, place of residence, parental education level, family type and annual family income.

Comparison of clinical characteristics and prognosis in endometrial carcinoma with different pathological types: a retrospective population-based study.

BACKGROUND: Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. METHODS: Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. RESULTS: In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231-39.599, P < 0.001; USC: HR = 5.958, 95%CI = 2.404-14.765, P < 0.001; UMC: HR = 1.777, 95%CI = 0.209-15.114, P = 0.599) and PFS (UCCC: HR = 8.696, 95%CI = 1.972-38.354, P = 0.004; USC: HR = 4.131, 95%CI = 1.243-13.729, P = 0.021; UMC: HR = 5.356, 95%CI = 0.935-30.692, P = 0.060). Compared with UEC patients, the OS of UCCC patients in stage I-II and USC patients in stage III-IV were significantly worse, while UMC patients in stage I-II favored poorer PFS. The OS of UCCC patients receiving no postoperative adjuvant therapy or chemotherapy alone were significantly worse. CONCLUSIONS: The baseline characteristics of UEC and other rare EC types varied greatly, and the prognostic significance of different pathological types on EC patients depended on clinical tumor stages and therapeutic options.

Investigating the role of mitochondrial DNA D-loop variants, haplotypes, and copy number in polycystic ovary syndrome: implications for clinical phenotypes in the Chinese population.

Background: The presence of genetic variations in mitochondrial DNA (mtDNA) has been associated with a diverse array of diseases. The objective of this study was to examine the correlations between mtDNA D-loop, its haplotypes, and polycystic ovary syndrome (PCOS) in the Chinese population, and the associations between mtDNA D-loop and symptoms of PCOS. The study also sought to determine whether the mtDNA copy number in Chinese patients with PCOS differed from that of individuals in the control group. Methods: Infertile individuals who only had tubal or male factor treatment were the focus of research by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). mtDNA haplotypes were categorized using polymorphic D-loop sites. mtDNA D-loop, PCOS features, and mtDNA haplotypes were analyzed using R software to determine the strength of the association between the three. There are certain DNA haplotypes linked to PCOS. Microdroplet digital polymerase chain reaction (PCR) was used to determine the mtDNA copy number in a convenience sample of 168 PCOS patients and 83 controls. Results: Among the research group, the majority of D-loop mutations were infrequent (frequency< 1%), with only 45 variants displaying a minimum allele frequency (MAF) of 5% or higher. No association was found between polymorphism loci in PCOS patients and body mass index (BMI). Noteworthy, C194T, 1A200G, 523delAC, and C16234T showed positive correlations with elevated LH/FSH levels. Additionally, specific polymorphic loci G207A, 16036GGins, and 16049Gins within the D-loop region of mtDNA potentially exerted a protective role in PCOS development. Conversely, no statistical significance was observed in the expression levels of C16291T and T489C. Chinese women with mtDNA haplotype A15 exhibited a decreased risk of developing PCOS. Moreover, a significant difference in mtDNA copy number was detected, with controls averaging 25.87 (21.84, 34.81), while PCOS patients had a mean of 129.91 (99.38, 168.63). Conclusion: Certain mtDNA D-loop mutations and haplotypes appear to confer protection against PCOS in Chinese women. In addition, elevated mtDNA copy number may serve as an indicator during early stages of PCOS.

Complete assembly of the chloroplast genome of Amorphophallus coaetaneus S. Y. Liu & S. J. Wei 1986 (Araceae) from southwestern China.

Amorphophallus coaetaneus S. Y. Liu & S. J. Wei 1986 is a perennial herb belonging to the Araceae family in southwestern China (Guangxi and Yunnan provinces). Although this species have not been list in the red list of International Union for Conservation of Nature (IUCN), the populations are declining due to human over exploitation. To help to genetic diversity studies, we sequenced and assembled the complete chloroplast (cp) genome of A. coaetaneus (GenBank accession number of national center for biotechnology information (NCBI): OQ404947). The assembled genome revealed 175,465 bp in length with a GC content of 34.90%, including a large single-copy (LSC) region (98,561 bp), a small single-copy (SSC) region (16,504 bp) and two inverted repeat regions (IRs) (30,200 bp each). A total of 133 genes were annotated, of which 85 are protein-coding genes, 40 are tRNA genes and 8 are rRNA genes. As an output of this study, a maximum likelihood (ML) phylogenetic inference of 16 Araceae species clustered all four Amorphophallus species in one clade, and showed a relatively close relationship between the tribes Pythonieae and Colocasieae. The cp genome will serve as a basis in a more extensive molecular works covering all possible extant population of Amorphophallus, as well as conservation, breeding, and other ethnobotanical utilization of this species.

Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice.

Impaired cholesterol synthesizing ability is considered a risk factor for the development of Alzheimer's disease (AD), as evidenced by reduced levels of key proteases in the brain that mediate cholesterol synthesis; however, cholesterol deposition has been found in neurons in tangles in the brains of AD patients. Although it has been shown that statins, which inhibit cholesterol synthesis, reduce the incidence of AD, this seems paradoxical for AD patients whose cholesterol synthesizing capacity is already impaired. In this study, we aimed to investigate the effects of aerobic exercise on cholesterol metabolism in the brains of APP/PS1 mice and to reveal the mechanisms by which aerobic exercise improves cognitive function in APP/PS1 mice. Our study demonstrates that the reduction of SEC24D protein, a component of coat protein complex II (COPII), is a key factor in the reduction of cholesterol synthesis in the brain of APP/PS1 mice. 12 weeks of aerobic exercise was able to promote the recovery of SEC24D protein levels in the brain through activation of protein kinase B (AKT), which in turn promoted the expression of mem-brane-bound sterol regulatory element-binding protein 2 (SREBP2) nuclear translocation and the expression of key proteases mediating cholesterol synthesis. Simultaneous aerobic exercise restored cholesterol transport capacity in the brain of APP/PS1 mice with the ability to efflux excess cholesterol from neurons and reduced neuronal lipid rafts, thereby reducing cleavage of the APP amyloid pathway. Our study emphasizes the potential of restoring intracerebral cholesterol homeostasis as a therapeutic strategy to alleviate cognitive impairment in AD patients.

Effect of Exercise and Oral Niacinamide Mononucleotide on Improving Mitochondrial Autophagy in Alzheimer's Disease.

Oral niacinamide mononucleotide (NMN) and aerobic exercise have been shown to enhance niacinamide adenine dinucleotide (NAD+) in the body. NAD+ plays a critical role in the body and can directly and indirectly affect many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cell aging, and immune cell function. It is noteworthy that the level of NAD+ decreases gradually with increasing age. Decreased levels of NAD+ have been causally associated with a number of diseases associated with aging, including cognitive decline, cancer, metabolic diseases, sarcopenia, and frailty. Many diseases related to aging can be slowed down or even reversed by restoring NAD+ levels. For example, oral NMN or exercise to increase NAD+ levels in APP/PS1 mice have been proven to improve mitochondrial autophagy, but currently, there is no regimen combining oral NMN with exercise. This review summarizes recent studies on the effect of oral NMN on the enhancement of NAD+ in vivo and the improvements in mitochondrial autophagy abnormalities in AD through aerobic exercise, focusing on (1) how oral NMN improves the internal NAD+ level; (2) how exercise regulates the content of NAD+ in the body; (3) the relationship between exercise activation of NAD+ and AMPK; (4) how SIRT1 is regulated by NAD+ and AMPK and activates PGC-1α to mediate mitochondrial autophagy through changes in mitochondrial dynamics. By summarizing the results of the above four aspects, and combined with the synthesis of NAD+ in vivo, we can infer how exercise elevates the level of NAD+ in vivo to mediate mitochondrial autophagy, so as to propose a new hypothesis that exercise interferes with Alzheimer's disease (AD).

Global research trends on immunotherapy in cancer: A bibliometric analysis.

Cancer immunotherapy has been gradually introduced and has undergone noteworthy developments in recent years. The number of scientific publications has been expanding, and the progression in this field has been rapidly evolving with time. This study aimed to use bibliometric analysis to examine the past 20 years of research on cancer immunotherapy and identify future hotspots. A literature search for medical publications on immunotherapy in cancer from 2000 to 2021 was conducted in the Web of Science Core Collection on March 1, 2022. Visualization analysis was performed using VOSviewer software (version 1.6.16). From 2000 to 2021, a total of 18,778 publications were retrieved. Annual publication output grew rapidly from 366 in 2000 to 3,194 in 2021. The USA issued the largest number of publications (n = 6,739, 35.89%), with the University of Texas System making the largest contribution (n = 802, 4.27%). A total of 976 meaningful topics were identified and further classified into 4 different clusters (immune mechanism, cancer biology, immunotherapy and clinical trials). The most common research topics included 'expression', 'chemotherapy', 'dendritic cells', 'pembrolizumab' and 'open-label'. Highly identified cancer types included hepatocellular, bladder, breast and lung cancer. A shift in popularity from mechanism research to clinical trials was observed, indicating that clinical application would be the center of attention in the future. Attention has been given to the field of cancer immunotherapy, and this trend will continue in the future. This study provides an unbiased visualization analysis on this topic in a scale-efficient manner for further research.

Value for Money of CAR-T Cell Therapy for Patients with Diffuse Large B-cell Lymphoma in China: Evidence from a Cost-Effectiveness Analysis.

OBJECTIVE: This research assesses the cost effectiveness of Axicabtagene ciloleucel (Axi-cel), Tisagenlecleucel (Tis-cel), Relmacabtagene autoleucel (Rel-cel) and Lisocabtagene maraleucel (Lis-cel) against standard of care (SOC) for patients with diffuse large B-cell lymphoma (DLBCL) in the first-line setting (1L), second-line setting (2L) and third-line or later setting (3L+). METHODS: Markov modelling based on a flexible survival model was adopted to evaluate four chimeric antigen receptor T-cell (CAR-T) therapies compared with SOC for patients with diffuse large B-cell lymphoma (DLBCL). The clinical inputs and utility values of the model were derived from the most recent clinical trials and the health care costs from a Chinese provincial clinical center. Costs and quality-adjusted life years (QALYs) were used to derive incremental cost-effectiveness ratios (ICERs) from the Chinese health care system perspective. RESULTS: The ICER of Axi-cel (1L) versus SOC was approximately Chinese Yuan (CNY) 2,125,311 per QALY. The ICER for Axi-cel (2L), Tis-cel (2L) and Liso-cel (2L)) versus SOC in transplant-eligible patients were approximately CNY363,977, CNY32,066,781 and CNY347,746 per quality-adjusted life year (QALY), respectively. The ICER for Liso-cel (2L) versus SOC in transplant-ineligible patients was approximately CNY1,233,972 per QALY. The ICERs for Axi-cel (3L+), Tis-cel (3L+), Rel-cel (3L+) and Liso-cel (3L+) versus SOC were approximately CNY346,009, CNY654,344, CNY280,964 and CNY436,858 per QALY, respectively. In the scenario analysis using mixture cure models, the long-term survival benefit for CAR-T and SOC groups was found higher, and only Rel-cel (3L+) was found to be cost effective. CONCLUSION: Our results demonstrated that CAR-T treatments are not cost effective in any-line settings for DLBCL patients at the WHO-recommended willingness-to-pay threshold (CNY257,241 per QALY) in the base-case analysis. Price reduction of CAR-T therapies is the main approach for lowering ICERs and ensuring that the drug costs are proportional to patient health benefits.