The prediction of pCR and chemosensitivity for breast cancer patients using DLG3, RADL and Pathomics signatures based on machine learning and deep learning.

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

Comparison of the S8 navigation system and the TINAVI orthopaedic robot in the treatment of upper cervical instability.

The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery.

Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma.

BACKGROUND: Surgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment. METHODS: A dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic_Sig), Radiomics Signature (Rad_Sig) and the Deep Transformer Learning Signature (DTL_Sig). Additionally, we fused the Rad_Sig with the DTL_Sig to create the Deep Learning Radiomic Signature (DLR_Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA). RESULTS: The DLR_Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97-0.99) for the training cohort and 0.79(95% CI: 0.67-0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR_Sig was significantly better than that of the Clinic_Sig(P < 0.05 both the training and test cohorts). The calibration plot of DLR_Sig indicated excellent consistency between the actual and predicted probabilities, while the DCA curve demonstrating greater clinical utility for predicting the pathological features for adjuvant radiotherapy. CONCLUSION: DLR_Sig based on intratumoral and peritumoral MRI images has the potential to preoperatively predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma (ESCSCC).

Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil.

OBJECTIVE: This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. METHODS: Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. RESULTS: A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. CONCLUSION: There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.

Barriers and Facilitators of Medication Adherence in Hypertension Patients: A Meta-Integration of Qualitative Research.

The aim of this qualitative systematic review is to analyze the barriers and facilitators to the uptake of antihypertensive medication in hypertensive patients. The databases of PubMed, Embase, Web of Science, CINAHL, Cochrane Library, MEDLINE, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical were searched from inception to June 2023. The studies were screened, extracted, and assessed independently by two researchers. Previously, the researchers used the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research to assess the quality of the included studies. A total of 27 studies were considered, resulting in two combined findings: a good level of knowledge, belief, and behavior and adequate social support were facilitators of medication adherence in hypertensive patients. In contrast, lack of medication literacy, difficulty adapting to roles, reduced sense of benefit from treatment, limited access to healthcare resources, and unintentional nonadherence were barriers. Medication adherence in hypertensive patients remains a challenge to be addressed. Future research should explore how complex interventions using a combination of evidence-based strategies and targeting multiple adherence behaviors (eg, long-term adherence to medication) are effective in improving medication adherence.

From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration.

The incidence of lumbar disc herniation has gradually increased in recent years, and most patients have symptoms of low back pain and nerve compression, which brings a heavy burden to patients and society alike. Although the causes of disc herniation are complex, intervertebral disc degeneration (IDD) is considered to be the most common factor. The intervertebral disc (IVD) is composed of the upper and lower cartilage endplates, nucleus pulposus, and annulus fibrosus. Aging, abnormal mechanical stress load, and metabolic disorders can exacerbate the progression of IDD. Among them, high glucose and high-fat diets (HFD) can lead to fat accumulation, abnormal glucose metabolism, and inflammation, which are considered important factors affecting the homeostasis of IDD. Diabetes and advanced glycation end products (AGEs) accumulation- can lead to various adverse effects on the IVD, including cell senescence, apoptosis, pyroptosis, proliferation, and Extracellular matrix (ECM) degradation. While current research provides a fundamental basis for the treatment of high glucose-induced IDD patients. further exploration into the mechanisms of abnormal glucose metabolism affecting IDD and in the development of targeted drugs will provide the foundation for the effective treatment of these patients. We aimed to systematically review studies regarding the effects of hyperglycemia on the progress of IDD.

Association between inflammatory bowel disease and frailty: a two-sample Mendelian randomization study.

BACKGROUND: An association has been identified between inflammatory bowel disease (IBD) and frailty; however, the causal nature of this connection remains uncertain. We consequently conducted a two-sample Mendelian randomization (MR) analysis to explore this particular association. METHODS: We acquired distinct datasets for inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and frailty from the published genome-wide association studies (GWAS) database, meticulously selecting instrumental variables (IVs). Subsequently, we employed a bidirection MR to examine the causal relationship between IBD (including CD and UC) and frailty. We utilized statistical methods, with a primary emphasis on inverse-variance weighted (IVW), accompanied by a series of sensitivity analyses to confirm heterogeneity and pleiotropy influenced the outcomes of the MR. RESULTS: We found positive causal effects of genetically increased frailty risk on IBD (OR: 1.015, 95% CI 1.005-1.025, P = 0.004). Furthermore, when scrutinizing specific IBD subtypes, both Crohn's disease (CD) and ulcerative colitis (UC) demonstrated an increased predisposition to frailty (OR: 1.018, 95% CI 1.01-1.027, P < 0.05) and (OR = 1.016, 95% CI 1.005-1.027, P < 0.05). Nevertheless, despite the consistent trends observed in the weighted median and MR-Egger regression analyses for both conditions, statistical significance remained elusive. Notably, the results of the inverse MR analysis did not establish an association between frailty and an elevated risk of IBD development. CONCLUSIONS: Our research indicates that IBD, encompassing both CD and UC, may augment the propensity for frailty. Clinical practitioners must prioritize early frailty assessment in individuals afflicted with inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, facilitating proactive measures and timely interventions. However, our findings do not provide evidence supporting a causal effect of frailty on IBD (including CD and UC). Consequently, further studies are essential to explore the intricate mechanisms that clarify the effect of frailty on IBD.

Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study aimed to investigate the interactions among three core elements of respiratory infection-pathogen, lung microbiome, and host response-and their avocation with the severity and outcomes of Mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: We prospectively collected bronchoalveolar lavage fluid from a cohort of 41 children with MPP, including general MPP (GMPP) and complicated MPP (CMPP), followed by microbiome and transcriptomic analyses to characterize the association among pathogen, lung microbiome, and host response and correlate it with the clinical features and outcomes. RESULTS: The lung microbiome of patients with CMPP had an increased relative abundance of Mycoplasma pneumoniae (MP) and reduced alpha diversity, with 76 differentially expressed species. Host gene analysis revealed a key module associated with neutrophil function and several inflammatory response pathways. Patients with a high relative abundance of MP, manifested by a specific lung microbiome and host response type, were more prone to CMPP and had a long imaging recovery time. CONCLUSION: Patients with CMPP have a more disrupted lung microbiome than those with GMPP. MP, lung microbiome, and host response interacts with each other and are closely related to disease severity and outcomes in children with MPP.

ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis.

Mono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4). In this study, we systematically examined the homology, expression, and localization pattern of the hARTC family, with a particular focus on hARTC1. Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1. We also identified vesicle-associated membrane protein-associated protein B (VAPB) as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site. Furthermore, we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis, highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis. In summary, our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.

Exploration of novel clusters and prognostic value of immune­related signatures and identify HAMP as hub gene in colorectal cancer.

Immune checkpoint inhibitors currently serve an important role in prolonging patients' overall survival. However, the prognostic signatures of immune checkpoint inhibitors in colorectal cancer (CRC) remain uncertain and more knowledge on the genetic characteristics of colorectal cancer is needed. Patients with CRC from The Cancer Genome Atlas were classified into high-immunity group and low-immunity group based on median scores from single-sample gene set enrichment analysis using the GSVA package. We explored immune status by immune scores, stromal scores and tumor purity scores in ESTIMATE package and surveyed the difference of immune cells distribution with CIBERSORT package. Eighteen genes were selected using the LASSO Cox regression method and a prognostic risk model was constructed. Compared with patients in the low-risk group, those in the high-risk group had a significantly shorter survival time. For assessment of the prognostic validity of the risk model, receiver operating characteristic curves with areas under the curve of 0.769, 0.774 and 0.771 for 1, 3 and 5 years respectively. Differences in molecular mechanisms between high- and low-risk groups were analyzed using the clusterProfiler package. Tumor Immune Dysfunction and Exclusion data were downloaded and analyzed. The top 5 enriched pathways in the high-risk group involved 'calcium signaling', 'dilated cardiomyopathy', 'extracellular matrix receptor interaction', 'hypertrophic cardiomyopathy' and 'neuroactive ligand receptor interaction'. HAMP was identified as a hub gene, which was highly expressed in tumor samples. The results of the present study indicate that the prognostic model based on both immune-related genes and HAMP has the potential to support personalized treatment.

Nicotinamide mononucleotide supplementation mitigates osteopenia induced by modeled microgravity in rats.

Exposure to weightlessness causes severe osteopenia, resulting in raised fracture risk. The current study aimed to investigate whether nicotinamide mononucleotide (NMN) supplementation protected against the osteopenia in hindlimb unloading (HLU) rats in vivo and modeled microgravity-induced osteoblastic dysfunction in vitro. The 3-mo-old rats were exposed to HLU and intragastrically administered NMN every 3 days (500 mg/kg body weight) for 4 weeks. NMN supplementation mitigated HLU-induced bone loss, evidenced by greater bone mass and biomechanical properties and better trabecular bone structure. NMN supplementation mitigated HLU-induced oxidative stress, evidenced by greater levels of nicotinamide adenine dinucleotide and activities of superoxide dismutase 2 and lesser malondialdehyde levels. Modeled microgravity stimulation using rotary wall vessel bioreactor in MC3T3-E1 cells inhibited osteoblast differentiation, which was reversed by NMN treatment. Furthermore, NMN treatment mitigated microgravity-induced mitochondrial impairments, evidenced by lesser reactive oxygen species generation and greater adenosine triphosphate production, mtDNA copy number, and activities of superoxide dismutase 2 and Complex I and II. Additionally, NMN promoted activation of AMP-activated protein kinase (AMPK), evidenced by greater AMPKα phosphorylation. Our research suggested that NMN supplementation attenuated osteoblastic mitochondrial impairment and mitigated osteopenia induced by modeled microgravity.

A nomogram for predicting severe adenovirus pneumonia in children.

Adenoviral pneumonia in children was an epidemic that greatly impacted children's health in China in 2019. Currently, no simple or systematic scale has been introduced for the early identification and diagnosis of adenoviral pneumonia. The early recognition scale of pediatric severe adenovirus pneumonia was established based on an analysis of the children's community-acquired pneumonia clinical cohort. This study analyzed the clinical data of 132 children with adenoviral pneumonia who were admitted to the Children's Hospital of Nanjing Medical University. The clinical parameters and imaging features were analyzed using univariate and multivariate logistic regression analyses. A nomogram was constructed to predict the risk of developing severe adenovirus pneumonia in children. There were statistically significant differences in age, respiratory rate, fever duration before admission, percentage of neutrophils and lymphocytes, CRP, ALT, and LDH between the two groups. Logistic regression analysis was conducted using the R language, and respiratory rate, percentage of neutrophils, percentage of lymphocytes, and LDH were used as scale indicators. Using the ROC curve, the sensitivity and specificity of the scale were 93.3% and 92.1%. This scale has good sensitivity and specificity through internal verification, which proves that screening for early recognition of severe adenovirus pneumonia can be realized by scales. This predictive scale helps determine whether a child will develop severe adenovirus pneumonia early in the disease course.

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8+ T cells (P = 0.033), CD20+ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1+ cells (P = 0.042), and PD-L1+CD68+ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20+ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8+ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20+ and CD163+ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4+ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8+ cells pre-NACT (P = 0.042) were independently associated with improved OS.

The Impacts of Fiscal Subsidies on the Carbon Emissions of Mining Enterprises: Evidence from China.

Lowering carbon output and reducing emissions have been worldwide concerns as global warming and environmental pollution worsen. Governments play a key role in driving corporate action related to carbon and emission reduction. In this paper, mining companies listed in China's A-share market were taken as samples to analyze the impacts of fiscal subsidies on the carbon emissions of mining enterprises through empirical tests. These findings demonstrated that fiscal subsidies could substantially lower corporate carbon emissions by incentivizing and enhancing their green-technology innovation. Financing constraints provided no prominent mediator effects between fiscal subsidies and carbon emissions, and these subsidies failed to considerably relieve their financing constraints in order to restrain carbon emissions. These results indicate that government policies on fiscal subsidies could represent significant guidance for corporate low-carbon and environmental-protection efforts, thereby providing empirical evidence for governmental environmental-protection policies.

Chemodivergent Synthesis of Aza-Heterocycles with a Quarternary Carbon Center via [4 + 1] Annulation between Azoalkenes and α-Bromo Carbonyl Compounds.

An efficient [4 + 1] annulation reaction between in situ generated azoalkene intermediates and α-bromocarbonyls has been established. A series of skeletally diverse aza-heterocycles with a functionalized quaternary center were obtained in up to 89% yield under mild conditions.

Degarelix vs. leuprorelin for the treatment of prostate cancer in China: A cost-utility analysis.

Objective: To explore the cost-effectiveness of degarelix acetate for injection (degarelix) compared to leuprorelin in prostate cancer (Pca) castration treatment from Chinese healthcare system perspective. Methods: A Markov model, adapted from the one established in Finland was conducted for the cost-effectiveness analysis of degarelix and leuprorelin for Pca treatment. The main data were derived from global phase III clinical trials of degarelix (CS21), published study and expert surveys. Outcomes, utility and costs of prostate cancer patients were calculated on a 30-year time horizon. The CS21 study based population of intention-to-treat (ITT) population and three scenarios were modeled. Taking three times of the Gross domestic product (GDP) per capita (242,928 yuan, 2021) as the acceptable threshold for cost-effectiveness. One-way and probabilistic sensitivity analyses were performed on key parameters, including transition probabilities, costs, utility, and discount rate to test the robustness of the model. Results: Base case analysis for ITT population revealed that total costs of degarelix and leuprorelin were 566,226 yuan and 489,693 yuan, while the total quality-adjusted life years (QALYs) were 5.19 and 4.51 during the 30-year time horizon, resulting an incremental cost effectiveness ratio (ICER) of 112,674 yuan/QALY which was 1.39 times the GDP per capita, lower than willingness-to-pay level of three times the GDP per capita. The results for scenario analyses revealed that compared to leuprorelin, degarelix for Pca treatment in China was cost-effective. One-way sensitivity analysis showed that the model was most sensitive to price of 80 mg degarelix, utility of 1st-line therapy, hazard ratio of PSA recurrence, price of 3.75 mg leuprorelin, response rate of docetaxel per cycle, and discount rate of cost. In probabilistic sensitivity analysis, compared to leuprorelin, the probability of degarelix to be cost-effective was 53 and 81% for willingness-to-pay threshold of one and three times the GDP per capita. Conclusion: Compared to leuprorelin, degarelix for prostate cancer treatment is cost-effective. Moreover, scenario, one-way, and probabilistic sensitivity analyses revealed that the model was robust.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of "essential medicine" and "national medicine policy" were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.

Genome-wide scan for selection signatures and genes related to heat tolerance in domestic chickens in the tropical and temperate regions in Asia.

Heat stress is one of the major environmental stressors challenging the global poultry industry. Identifying the genes responsible for heat tolerance is fundamentally important for direct breeding programs. To uncover the genetic basis underlying the ambient temperature adaptation of chickens, we analyzed a total of 59 whole genomes from indigenous chickens that inhabit South Asian tropical regions and temperate regions from Northern China. We applied FST and π-ratio to scan selective sweeps and identified 34 genes with a signature of positive selection in chickens from tropical regions. Several of these genes are functionally implicated in metabolism (FABP2, RAMP3, SUGCT, and TSHR) and vascular smooth muscle contractility (CAMK2), and they may be associated with adaptation to tropical regions. In particular, we found a missense mutation in thyroid-stimulating hormone receptor (41020238:G>A) that shows significant differences in allele frequency between the chicken populations of the two regions. To evaluate whether the missense mutation in TSHR could enhance the heat tolerance of chickens, we constructed segregated chicken populations and conducted heat stress experiments using homozygous mutations (AA) and wild-type (GG) chickens. We found that GG chickens exhibited significantly higher concentrations of alanine aminotransferase, lactate dehydrogenase, and creatine kinase than AA chickens under heat stress (35 ± 1°C) conditions (P < 0.05). These results suggest that TSHR (41020238:G>A) can facilitate heat tolerance and adaptation to higher ambient temperature conditions in tropical climates. Overall, our results provide potential candidate genes for molecular breeding of heat-tolerant chickens.

Vimentin Protein In Situ Expression Predicts Less Tumor Metastasis and Overall Better Survival of Endometrial Carcinoma.

Background: Vimentin, a cytoplasmic intermediate filament protein, has been recently identified to be a prognostic biomarker in some cancers. However, the function of vimentin in endometrial carcinoma (EC) remains unclear. Our study aimed at evaluating vimentin expression in EC and preliminarily exploring the role of vimentin in EC progression. Methods: In total, 341 EC patients who underwent surgical follow-up were enrolled in the retrospective study. Vimentin expression levels in EC tissues were analyzed using immunohistochemistry. Furthermore, the vimentin (VIM) gene expression levels in 547 samples in The Cancer Genome Atlas (TCGA) were analyzed. To examine the prognostic value of vimentin in EC, Kaplan-Meier survival analysis was performed, and a Cox model was established. Gene set enrichment analysis (GSEA) was also conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to explore the role of vimentin in EC progression. Results: Negative vimentin expression in EC correlated significantly with lymph node metastasis, deep myometrium invasion (MI), lymph vascular space invasion (LVSI), advanced Federation International of Gynecology and Obstetrics Association (FIGO) stages (III and IV), and high tumor grade. Vimentin negativity was more common in type 2 EC than that in type 1 EC, and vimentin-negative patients had poorer overall survival compared with vimentin-positive patients. The results of GSEA suggested that vimentin may interact with classical pathways in EC. Conclusions: Negative vimentin expression correlates with tumor metastasis and worse overall survival in EC, suggesting that it may be an excellent prognostic biomarker for this disease. The mechanism by which vimentin contributes to EC progression needs to be explored in the future.

Chemokine CCL17 Affects Local Immune Infiltration Characteristics and Early Prognosis Value of Lung Adenocarcinoma.

CCL17 is an important chemokine that plays a vital immunomodulatory role in the tumor microenvironment (TME). Analysis of lung adenocarcinoma (LUAD) data in Kaplan-Meier plotter databases found that the overall survival of patients in the CCL17 high-expression group was higher than that of the low-expression group, especially for patients with early (stages I and II) LUAD, which has a more positive prognostic value. Expression of CCL17 in LUAD was positively correlated with the proportion of tumor-infiltrating lymphocytes, immunostimulators, and major histocompatibility complexes using the TISIDB databases. Based on the RNA-seq and clinical data of 491 LUAD patients obtained from the TCGA database, 1,455 differential genes were found between the CCL17 high- and low-expression groups. Using WGCNA analysis confirmed that the expression of differential genes in the blue module is negatively correlated with poor survival and clinical stages of LUAD patients, and CCL17 and CCR4 genes belong to the hub genes in the blue module. Further analysis by the ESTIMATE and CIBERSORT algorithm found that the naive B cells and CD8+ T cells in the CCL17 high-expression group have a higher distribution ratio in the early LUAD patients, and the high immune score has a positive relationship with the overall survival rate. Using somatic mutation data of TCGA-LUAD, we found that 1) the tumor mutation burden values of the CCL17 high-expression group were significantly lower than those of the CCL17 low-expression group and 2) the expression levels of CCL17 and the tumor mutation burden values were negatively correlated. Transwell chemotaxis and cytotoxicity assays confirmed that CCL17 contributes to the migration of CCR4-positive lymphocytes into the H1993 LUAD TME and enhances the specific lysis of LUAD cells. In summary, high expression of CCL17 in the LUAD TME promotes local immune cell infiltration and antitumor immune response, which may contribute to the better survival and prognosis of patients with early LUAD.