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Abstract Purpose To build an Mult-Task Learning (MTL) based Artificial Intelligence(AI) model that can simultaneously predict clinical stage, histology, grade and LNM for cervical cancer before surgery. Methods This retrospective and prospective cohort study was conducted from January 2001 to March 2014 for the training set and from January 2018 to November 2021 for the validation set at Beijing Chaoyang Hospital, Capital Medical University. Preoperative clinical information of cervical cancer patients was used. An Artificial Neural Network (ANN) algorithm was used to build the MTL-based AI model. Accuracy and weighted F1 scores were calculated as evaluation indicators. The performance of the MTL model was compared with Single-Task Learning (STL) models. Additionally, a Turing test was performed by 20 gynecologists and compared with this AI model. Results A total of 223 cervical cancer cases were retrospectively enrolled into the training set, and 58 cases were prospectively collected as independent validation set. The accuracy of this cervical cancer AI model constructed with ANN algorithm in predicting stage, histology, grade and LNM were 75%, 95%, 86% and 76%, respectively. And the corresponding weighted F1 score were 70%, 94%, 86%, and 76%, respectively. The average time consumption of AI simultaneously predicting stage, histology, grade and LNM for cervical cancer was 0.01s (95%CI: 0.01–0.01) per 20 patients. The mean time consumption doctor and doctor with AI were 581.1s (95%CI: 300.0-900.0) per 20 patients and 534.8s (95%CI: 255.0-720.0) per 20 patients, respectively. Except for LNM, both the accuracy and F-score of the AI model were significantly better than STL AI, doctors and AI-assisted doctors in predicting stage, grade and histology. (P

Abstract 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). 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.

Abstract 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.

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.

Abstract 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. Graphical Abstract

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.

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.

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.

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.

Most of the malignant melanomas are already in the middle and advanced stages when they are diagnosed, which is often accompanied by the metastasis and spread of other organs. Besides, the prognosis of patients is bleak. The characteristics of the local immune microenvironment in metastatic melanoma have important implications for both tumor progression and tumor treatment. In this study, data on patients with metastatic melanoma from the TCGA and GEO datasets were selected for immune, stromal, and estimate scores, and overlapping differentially expressed genes were screened. A nine-IRGs prognostic model (ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) was established by univariate COX regression, LASSO and multivariate COX regression. Receiver operating characteristic curves were used to test the predictive accuracy of the model. Immune infiltration was analyzed by using CIBERSORT and Xcell in high-risk and low-risk groups. The immune infiltration of the high-risk group was significantly lower than that of the low-risk group. Immune checkpoint analysis revealed that the expression of PDCD1, CTLA4, TIGIT, CD274, HAVR2 and LAG3 demonstrated the visible difference in groups with different levels of risk scores. WGCNA analysis found that the yellow-green module contained seven genes from the nine-IRG prognostic model, and the yellow-green module had the highest correlation with risk scores. The results of GO and KEGG suggested that the genes in the yellow-green module were mainly enriched in immune-related biological processes. Finally, the expression characteristics of ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22 were analyzed between metastatic melanoma and normal samples. Overall, a prognostic model for metastatic melanoma based on the tumor immune microenvironment characteristics was established, which left plenty of space for further studies. It could function well in helping people to understand characteristics of the immune microenvironment in metastatic melanoma.

The meandering channel deposit of the upper member of Neogene Guantao Formation in Shengli Chengdao extra-shallow sea oilfield is characterized by rapid change in sedimentary facies. In addition, affected by surface tides and sea water reverberation, the double sensor seismic data processed by conventional methods has low signal-to-noise ratio and low resolution, and thus cannot meet the needs of seismic description and oil-bearing fluid identification of thin reservoirs less than 10 meters thick in this area. The two-step high resolution frequency bandwidth expanding processing technology was used to improve the signal-to-noise ratio and resolution of the seismic data, as a result, the dominant frequency of the seismic data was enhanced from 30 Hz to 50 Hz, and the sand body thickness resolution was enhanced from 10 m to 6 m. On the basis of fine layer control by seismic data, three types of seismic facies models, floodplain, natural levee and point bar, were defined, and the intelligent horizon-facies controlled recognition technology was worked out, which had a prediction error of reservoir thickness of less than 1.5 m. Clearly, the description accuracy of meandering channel sand bodies has been improved. The probability semi-quantitative oiliness identification method of fluid by prestack multi-parameters has been worked out by integrating Poisson's ratio, fluid factor, product of Lame parameter and density, and other prestack elastic parameters, and the method has a coincidence rate of fluid identification of more than 90%, providing solid technical support for the exploration and development of thin reservoirs in Shengli Chengdao extra-shallow sea oilfield, which is expected to provide reference for the exploration and development of similar oilfields in China.

Abstract Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the “eraser” O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.

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.

ObjectiveTo explore the cost-effectiveness of degarelix acetate for injection (degarelix) compared to leuprorelin in prostate cancer (Pca) castration treatment from Chinese healthcare system perspective.MethodsA 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.ResultsBase 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.ConclusionCompared to leuprorelin, degarelix for prostate cancer treatment is cost-effective. Moreover, scenario, one-way, and probabilistic sensitivity analyses revealed that the model was robust.

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.

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC. Keywords: DHX15, lncRNA, lung cancer, metastasis, stabilization

To assess the efficacy and safety of wet cupping in adults with hypertension, we conducted a systematic review and meta-analysis using 13 databases. Wet cupping alone or in combination with antihypertensive medication or acupuncture was used. Seven randomized trials were included, most not of high methodological quality. A few small studies suggested that wet cupping alone versus antihypertensive medication significantly reduced blood pressure and Traditional Chinese Medicine syndrome (hypertension-related symptoms). However based on current evidence, no firm conclusions can be drawn and no clinical recommendations made. Research projects included need validation. Studies indicate that wet cupping is a safe therapy.

Terrestrial ecosystem health (TEH) is the basis of regional sustainability development. The state of TEH is an important research direction in the land science field. The purpose of this paper was to explore the development trends and influencing factors of the. By using the radial basis function (RBF), neural network model, geographic information system (GIS), and the comprehensive index method, this paper predicted the land ecological changes of Henan Province from 2007 to 2025 based on a comprehensive evaluation of the system. The results show that the TEH of Henan Province exhibited a general trend of improvement from 2007 to 2025. The predictions exhibited a tendency to fluctuate and increase, from “severe warning” to “moderate warning” and even to “no warning” state. The early warning index of the subsystem showed a fluctuating upward trend except for the press subsystem, which fluctuated between “extraordinary warning” and “heavy warning” states. The overall TEH level is improving but is largely dependent on effective corresponding measures. The health status of the land ecosystem in Henan Province is guaranteed to be stable due to improvements in rural residential incomes, mechanization levels of cultivated land, domestic sewage treatment rates, and the numbers of scientific and technological personnel per unit of land. The TEH is mainly restricted by the population densities, urbanization levels, inputs of fertilizers and pesticides, and average wastewater load factors of the land. To improve the health level of the land ecosystem, it is necessary to reduce the use of fertilizers and pesticides and to control the urbanization rate. At the same time, improving the level of forest coverage and the effective irrigation rate play a positive role in improving ecosystem health. The results provide a reference for land-use planning and management decisions.

Background/Aim: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). Methods: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. Results: Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3ʹ-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. Conclusion: Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo.

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. [ABSTRACT FROM AUTHOR]