bluuebunny/crossref_metadata_2025 huggingface dataset:
NUT Carcinoma of the Lung：A Case report and Literature Analysis
Authors: Zhao Rongshuang , Hua Ze , Hu Xiaodong , Zhang Qi , Zhang Jin , Wang Jian
Published: July 2022

NUT carcinoma is a rare, highly aggressive cancer that feature as the rearrangement of the nuclear protein in the testis (NUT) gene on chromosome 15q14, and its pathogenesis and treatment is not yet clear. In this case, we report a 40-year-old male patient who was diagnosed with primary pulmonary NUT carcinoma in The Second Affiliated Hospital of Zhengzhou University. A tumor was found at the right hilus pulmonis when his physical examination with chest pain for half a month. Histopathology confirmed by fluorescence in situ hybridization technique for the NUT carcinoma. After chemotherapy, radiotherapy, immunotherapy, and targeted therapy were given, the patient died. The overall survival time was 4.7 months. Combined with the existing literature, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare lung NUT carcinoma.
Construction and Comparison of Different Models in Detecting Prostate Cancer and Clinically Significant Prostate Cancer
Authors: Zhou Yongheng , Qi Wenqiang , Cui Jianfeng , Zhong Minglei , Lv Guangda , Qu Sifeng , Chen Shouzhen , Li Rongyang , Shi Benkang , Zhu Yaofeng
Published: July 2022

Background

With the widespread adoption of prostatic-specific antigen (PSA) screening, the detection rates of prostate cancer (PCa) have increased. Due to the low specificity and high false-positive rate of serum PSA levels, it was difficult to diagnose PCa accurately. To improve the diagnosis of PCa and clinically significant prostate cancer (CSPCa), we established novel models on the basis of the prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) in the Asian population.

Methods

We retrospectively collected the clinical indicators of patients with TPSA at 4–20 ng/ml. Furthermore, mpMRI was performed using a 3.0-T scanner and reported in the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS). Univariable and multivariable logistic analyses were performed to construct the models. The performance of different models based on PSA derivatives, PHI derivatives, PI-RADS, and a combination of PHI derivatives and PI-RADS was evaluated.

Results

Among the 128 patients, 47 (36.72%) patients were diagnosed with CSPCa and 81 (63.28%) patients were diagnosed with non-CSPCa. Of the 81 (63.28%) patients, 8 (6.25%) patients were diagnosed with Gleason Grade 1 PCa and 73 (57.03%) patients were diagnosed with non-PCa. In the analysis of the receiver operator characteristic (ROC) curves in TPSA 4–20 ng/ml, the multivariable model for PCa was significantly larger than that for the model based on the PI-RADS (p = 0.004) and that for the model based on the PHI derivatives (p = 0.031) in diagnostic accuracy. The multivariable model for CSPCa was significantly larger than that for the model based on the PI-RADS (p = 0.003) and was non-significantly larger than that for the model based on the PHI derivatives (p = 0.061) in diagnostic accuracy. For PCa in TPSA 4–20 ng/ml, a multivariable model achieved the optimal diagnostic value at four levels of predictive variables. For CSPCa in TPSA 4–20 ng/ml, the multivariable model achieved the optimal diagnostic value at a sensitivity close to 90% and 80%.

Conclusions

The models combining PHI derivatives and PI-RADS performed better in detecting PCa and CSPCa than the models based on either PHI or PI-RADS.
The Value of Laparoscopic Simultaneous Colorectal and Hepatic Resection for Synchronous Colorectal Cancer Liver Metastasis: A Propensity Score Matching Study
Authors: Zhou Jiamin , Feng Longhai , Li Xinxiang , Wang Miao , Zhao Yiming , Zhang Ning , Wang Longrong , Zhang Ti , Mao Anrong , Xu Ye , Wang Lu
Published: July 2022

Purpose

The aim of this study is to investigate the value of total laparoscopic simultaneous colorectal and hepatic resection in patients with synchronous colorectal cancer liver metastases (sCRLMs).

Methods

sCRLM patients who underwent simultaneous resection from December 2014 to December 2018 in Shanghai Cancer Center, Fudan University were recruited and analyzed retrospectively. The patients were divided into laparoscopic, open, and hybrid surgery groups. The intraoperative information, postoperative short-term outcome, and long-term survival were compared among the three groups. Propensity score matching (PSM) was performed to balance baselines.

Results

A total of 281 patients were recruited. After PSM, 34 patients were selected from both the laparoscopic and the open surgery group. Forty-seven patients were also selected from both the laparoscopic and the hybrid surgery group. The clinicopathologic baselines between the laparoscopic surgery group and the other two groups were well matched. All the operation-related indicators between laparoscopic surgery and hybrid surgery were similar. However, compared with open surgery, laparoscopic surgery showed significantly longer operation time (229.09 ± 10.94 min vs. 192.24 ± 9.49 min, p = 0.013) and less intraoperative blood loss [100.00 (50.00–300.00) ml vs. 200.00 (150.00–400.00) ml, p = 0.021]. For postoperative morbidity, there was no significant difference between the laparoscopic surgery group and the hybrid or the open surgery group (23.40% vs. 31.91% and 17.65% vs. 26.47%, p = 0.356 and p = 0.380). Long-term survival analysis showed that there were no significant differences in all 1-, 3-, and 5-year overall survival, liver recurrence-free survival (RFS), and whole RFS between laparoscopic surgery and hybrid surgery (p = 0.334, p = 0.286, and p = 0.558) or open surgery (p = 0.230, p = 0.348, and p = 0.450).

Conclusions

Laparoscopic simultaneous resection for sCRLM shows slight advantages in surgical safety and short-term outcome, and does not compromise long-term survival.
Nitrogen Metabolism Disorder Accelerates Occurrence and Development of Lung Adenocarcinoma: A Bioinformatic Analysis and In Vitro Experiments
Authors: Zhang Zexin , Xiahou Zhikai , Wu Wenfeng , Song Yafeng
Published: July 2022

Background

Nitrogen metabolism (NM) plays a pivotal role in immune regulation and the occurrence and development of cancers. The aim of this study was to construct a prognostic model and nomogram using NM-related genes for the evaluation of patients with lung adenocarcinoma (LUAD).

Methods

The differentially expressed genes (DEGs) related to NM were acquired from The Cancer Genome Atlas (TCGA) database. Consistent clustering analysis was used to divide them into different modules, and differentially expressed genes and survival analysis were performed. The survival information of patients was combined with the expressing levels of NM-related genes that extracted from TCGA and Gene Expression Omnibus (GEO) databases. Subsequently, univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression were used to build a prognostic model. GO and KEGG analysis were elaborated in relation with the mechanisms of NM disorder (NMD). Meanwhile, immune cells and immune functions related to NMD were discussed. A nomogram was built according to the univariate and multivariate Cox analysis to identify independent risk factors. Finally, real-time fluorescent quantitative PCR (RT-PCR) and Western bolt (WB) were used to verify the expression level of hub genes.

Results

There were 138 differential NM-related genes that were divided into two gene modules. Sixteen NM-related genes were used to build a prognostic model and the receiver operating characteristic curve (ROC) showed that the efficiency was reliable. GO and KEGG analysis suggested that NMD accelerated development of LUAD through the Wnt signaling pathway. The level of activated dendritic cells (aDCs) and type II interferon response in the low-risk group was higher than that of the high-risk group. A nomogram was constructed based on ABCC2, HMGA2, and TN stages, which was identified as four independent risk factors. Finally, RT-PCR and WB showed that CDH17, IGF2BP1, IGFBP1, ABCC2, and HMGA2 were differently expressed between human lung fibroblast (HLF) cells and cancer cells.

Conclusions

High NM levels were revealed as a poor prognosis of LUAD. NMD regulates immune system through affecting aDCs and type II interferon response. The prognostic model with NM-related genes could be used to effectively evaluate the outcomes of patients.
Disturbances of Vaginal Microbiome Composition in Human Papillomavirus Infection and Cervical Carcinogenesis: A Qualitative Systematic Review
Authors: Wu Ming , Li Huanrong , Yu Hongfei , Yan Ye , Wang Chen , Teng Fei , Fan Aiping , Xue Fengxia
Published: July 2022

Background

Emerging evidence has demonstrated a close association between perturbations in vaginal microbiota composition in women and human papillomavirus (HPV) infection, cervical lesions, and cervical cancer (Ca); however, these findings are highly heterogeneous and inconclusive.

Aim

To perform a comprehensive systematic review of the global disturbance in the vaginal microbiota, specifically in women with HPV-associated cervical diseases, and to further conduct within- and across-disease comparisons.

Method

Twenty-two records were identified in a systematic literature search of PubMed, Web of Science, and Embase up to February 28, 2022. We extracted microbial changes at the community (alpha and beta diversity) and taxonomic (relative abundance) levels. Within- and across-disease findings on the relative abundance of taxonomic assignments were qualitatively synthesized.

Results

Generally, significantly higher alpha diversity was observed for HPV infection, cervical lesions, and/or cancer patients than in controls, and significant differences within beta diversity were observed for the overall microbial composition across samples. In within-disease comparisons, the genera Gardnerella, Megasphaera, Prevotella, Peptostreptococcus, and Streptococcus showed the greatest abundances with HPV infection; Sneathia and Atopobium showed inconsistent abundance with HPV infection, and Staphylococcus was observed in Ca. Across diseases, we find increased levels of Streptococcus and varying levels of Gardnerella were shared across HPV infections, high-grade squamous intraepithelial lesions, and Ca, whereas Lactobacillus iners varied depending on the HPV-related disease subtype.

Conclusions

This systematic review reports that vaginal microbiome disturbances are correlated to the depletion of Lactobacillus, enrichment of anaerobes, and increased abundance of aerobic bacteria in HPV infection and related cervical diseases. Moreover, L. iners may exert either protective or pathogenic effects on different HPV-related diseases.
Genome-wide CRISPR Screening Reveals Pyrimidine Metabolic Reprogramming in 5-FU Chronochemotherapy of Colorectal Cancer
Authors: Niu Ya , Fan Xinyi , Wang Yaping , Lin Jiaxin , Hua Luchun , Li Xiaobo , Qian Ruizhe , Lu Chao
Published: July 2022

Objective

Disruption of the circadian rhythm is associated with cancer occurrence, response to chemotherapy, and poor prognosis. Thus, using internal clock-based chronotherapy to optimize the administration time may improve the therapeutic effects of anticancer drugs while reducing the side effects. Chronotherapy with 5-fluorouracil (5-FU) has been observed in colorectal cancer (CRC) for a long time, but its effect is under controversial and the mechanism remains unclear.

Methods

Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening and RNA-sequencing were combined to identify the potential genes or pathways involved in 5-FU chronochemotherapy. Genetic deletion or overexpression of pyrimidine metabolic pathway genes were conducted to examine cellular viability with or without 5-FU via flow cytometry. Western blotting, qPCR, chromatin immunoprecipitation, gain-of-function and loss-of-function assays of several CRC cell lines in vitro and in vivo were used to elaborate and validate the mechanism of 5-FU chronotherapeutic effects.

Results

Chronochemotherapeutic effects of 5-FU on CRC in vivo were verified. Furthermore, 5-FU chronochemotherapy related genes such as UPP2, UCK2 and UMPS in the pyrimidine metabolic pathway were identified. Disturbance in these genes, especially UMPS, perturbs 5-FU treatment outcomes in CRC cells. Mechanistically, the core circadian gene, brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), extensively regulate gene expression in pyrimidine metabolic pathway by binding to E-box element in the promoter region of key genes such as UMPS and perturb their enzymatic activities, thereby maintain diurnal efficacy of 5-FU in CRC cells.

Conclusion

This study uncovered a new mechanism by which a core circadian gene BMAL1 increases the effectiveness of 5-FU by enhancing the expression and enzymatic activities of key genes in the pyrimidine metabolic pathway in CRC cells. The findings suggest a novel strategy for CRC chemotherapy by targeting chrono-modulated genes of the 5-FU metabolic pathway.
The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients
Authors: Zhang Da-li , Feng Dan-ni , He Xi , Zhang Xiao-feng , Li Li-xin , Li Zhi-jie , Niu Xiao-feng , Zhuang Yun-long , Liu Zhen-wen , Gao Xu-dong , Wang Hong-bo
Published: July 2022

Background

Orthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.

Objective

The study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.

Methods

This retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL.

Results

Among 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P < 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.

Conclusion

Chinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.
Mortality of Hemato-Oncologic Patients Admitted to a Pediatric Intensive Care Unit: A Single-Center Experience
Authors: Pechlaner Agnes , Kropshofer Gabriele , Crazzolara Roman , Hetzer Benjamin , Pechlaner Raimund , Cortina Gerard
Published: July 2022

Introduction

Mortality in children with hemato-oncologic disease admitted to a pediatric intensive care unit (PICU) is higher compared to the general population. The reasons for this fact remain unexplored. The aim of this study was to assess outcomes and trends in hemato-oncologic patients admitted to a PICU, with analytical emphasis on emergency admissions.

Methods

Patients with a hemato-oncologic diagnosis admitted to a tertiary care university hospital PICU between 1 January 2009 and 31 December 2019 were retrospectively analyzed. Additionally, patient mortality 6 months after PICU admission and follow-up mortality until 31 December 2020 were recorded.

Measurements and Main Results

We reviewed a total of 701 PICU admissions of 338 children with hemato-oncologic disease, of which 28.5% were emergency admissions with 200 admissions of 122 patients. Of these, 22 patients died, representing a patient mortality of 18.0% and an admission mortality of 11.0% in this group. Follow-up patient mortality was 25.4% in emergency-admitted children. Multivariable analysis revealed severe neutropenia at admission and invasive mechanical ventilation (IMV) as independent risk factors for PICU death (p = 0.029 and p = 0.002). The total number of PICU admissions of hemato-oncologic patients rose notably over time, from 44 in 2009 to 125 in 2019.

Conclusion

Although a high proportion of emergency PICU admissions of hemato-oncologic patients required intensive organ support, mortality seemed to be lower than previously reported. Moreover, in this study, total PICU admissions of the respective children rose notably over time.
How Well Are Socioeconomic Factors Associated With Improved Outcomes for Infants Diagnosed With Early Childhood Developmental Delay? An Observational Study
Authors: Ji Fang , Sun Yao , Xu Yi , Tang Jian , Hu Jing
Published: July 2022

Purpose

Early childhood developmental delay remains problematic worldwide in terms of weight and the five domains of child development, including gross motor, fine motor, cognition, language, and social domains. Based on the World Health Organization (WHO) guideline and the theoretical domain framework, this study identified five key socioeconomic factors, such as parenting time during hospitalization, parental educational level, medical spending, distance to hospital, and medical insurance coverage, to describe how these five factors are associated with improved outcomes of developmental quotient (DQ) values and the weight of infants in a tertiary hospital.

Methods

In this prospective observational study, clinical and socioeconomic data were collected. Clinical data included the weight and DQ values of infants and other data relevant to the birth of infants. A National Developmental Scale was used to observe infants in five domains and calculate the DQ values of infants. These five domains include gross motor, fine motor, cognition, language, and social domains. Parenting time during hospitalizations was observed by a research nurse. Other socioeconomic factors were reported by parents and verified with system information.

Results

A total of 75 infants' parents were approached, of which 60 were recruited. The age of infants ranged from 75 to 274 days at the first admission. Increments of their weight and DQ values improved from −0.5 to 2.5 kg and from −13 to 63, respectively. More than half of the parents (54.1%) were at the level of minimum secondary education although the results were not statistically significant. However, there was a positive correlation between weight improvement and parenting time during hospitalization (r(58) = 0.258, p < 0.05), medical spending (r(58) = 0.327, p < 0.05), distance to hospital (r(58) = 0.340, p < 0.01), but there was a negative association with medical insurance coverage (r(58) =-0.256, p < 0.05). There was also a significant relationship between the improved DQ value and distance to hospital (r(58)= 0.424, p < 0.01).

Conclusion

Parenting time during hospitalization, medical spending, distance to hospital, and medical insurance coverage are important factors for early childhood developmental delay in relation to possible hospital intervention and improved accessibility to health services for families in rural areas. Therefore, changes in the current medical scheme are needed because a universal medical subsidy among regions will reduce the financial burden of families and provide families with more access to the necessary health services that their children need.
Case Report: Novel TRPM6 Mutations Cause Hereditary Hypomagnesemia With Secondary Hypocalcemia in a Chinese Family and a Literature Review
Authors: Han Yiran , Zhao Yajuan , Wang Hua , Huo Liang
Published: July 2022

Background

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease due to biallelic TRPM6 mutations. Although the reports of HSH caused by TRPM6 mutations are not very rare, the age of onset in previously reported HSH cases were <1 year.

Methods

We collected and analyzed the clinical data of twin brothers with onset age over 1 year old and performed whole exome sequencing in the patients and their parents. Confirmed by Sanger sequencing, missense mutation was analyzed in silico. We also searched Pubmed, and extracted clinical data from case reports and case series with full text in English, reporting original data of patients with TRPM6 mutations.

Results

The twin patients had canonical HSH phenotype with compound novel TRPM6 mutations, p.T87K and c.705dupT, inherited from their father and mother, respectively. T87 is a highly conserved site and T87K is predicted to cause hydrogen bond disruption. We identified 26 articles published between May 28, 2002 to December 31, 2021 which reported a total of 88 patients with TRPM6 mutation. We found that the most common clinical phenotypes were hypomagnesemia, hypocalcemia, and convulsions. However, the age of onset in HSH patients almost always occurred under 12 months old, the twin patients of our study were 18 and 26 months old at onset.

Conclusion

We identified two novel TRPM6 mutations in a Chinses family with HSH, and showed that the age of onset with c.704c-c.705(exon7)insT and c.260(exon4)C>A mutation in TRPM6 was much later than other mutations and would be much less serious.
Case Report: Successful Treatment of a Child With COVID-19 Reinfection-Induced Fulminant Myocarditis by Cytokine-Adsorbing oXiris® Hemofilter Continuous Veno-Venous Hemofiltration and Extracorporeal Membrane Oxygenation
Authors: Phan Phuc H. , Nguyen Dung T. , Dao Nam H. , Nguyen Ha T. T. , Vu An V. , Hoang Son T. , Nguyen Lam V. , Cao Tung V. , Tran Dien M.
Published: July 2022

Background

Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities.

Case Presentation

We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of oXiris® hemofilter continuous venovenous hemofiltration (CVVH) and VA-ECMO. The patient made a full recovery without any sequelae.

Conclusion

We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation.
Pharmacokinetics of Cannabis and Its Derivatives in Animals and Humans During Pregnancy and Breastfeeding
Authors: Monfort Anaëlle , Ferreira Ema , Leclair Grégoire , Lodygensky Gregory Anton
Published: July 2022

Cannabis is one of the most widely used illicit drugs during pregnancy and lactation. With the recent legalization of cannabis in many countries, health professionals are increasingly exposed to pregnant and breastfeeding women who are consuming cannabis on a regular basis as a solution for depression, anxiety, nausea, and pain. Cannabis consumption during pregnancy can induce negative birth outcomes such as reduced birth weight and increased risk of prematurity and admission to the neonatal intensive care unit. Yet, limited information is available regarding the pharmacokinetics of cannabis in the fetus and newborn exposed during pregnancy and lactation. Indeed, the official recommendations regarding the use of cannabis during these two critical development periods lack robust pharmacokinetics data and make it difficult for health professionals to guide their patients. Many clinical studies are currently evaluating the effects of cannabis on the brain development and base their groups mostly on questionnaires. These studies should be associated with pharmacokinetics studies to assess correlations between the infant brain development and the exposure to cannabis during pregnancy and breastfeeding. Our project aims to review the available data on the pharmacokinetics of cannabinoids in adults, neonates, and animals. If the available literature is abundant in adult humans and animals, there is still a lack of published data on the exposure of pregnant and lactating women and neonates. However, some of the published information causes concerns on the exposure and the potential effects of cannabis on fetuses and neonates. The safety of cannabis use for non-medical purpose during pregnancy and breastfeeding needs to be further characterized with proper pharmacokinetic studies in humans feasible in regions where cannabis has been legalized. Given the available data, significant transfer occurs to the fetus and the breastfed newborn with a theoretical risk of accumulation of products known to be biologically active.
Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in Drosophila
Authors: Wang Sitong , Wu Chenxi , Li Yinghong , Ye Bin , Wang Shuai , Li Guowang , Wu Jiawei , Liu Shengnan , Zhang Menglong , Jia Yongsen , Cao Huijuan , Jiang Chunhua , Wu Fanwu
Published: July 2022

Background: Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive.

Purpose: To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion.

Methods: We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the RasV12/lgl−/−-induced Drosophila tumour model to carry out experimental verification.

Results: XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the RasV12/lgl−/− model. Finally, the mRNA level of the transcription complex AP-1 component c-FOS was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model.

Conclusion: The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.
Comparative Pharmacokinetics of Three Bioactive Diterpenoids of Rabdosia serra Extract in Normal and Con A-Induced Liver Injury Rats Using UPLC-MS/MS
Authors: Liu Fangle , Zeng Yun , Dai Pengyu , Huang Kaiwen , Zhang Kaihui , Tao Tao , Wang Meiqi , Zhu Chenchen , Lin Chaozhan
Published: July 2022

Rabdosia serra (Maxim.) Hara (R. serra), one of the source plants of “Xihuangcao”, has been widely used as a Chinese folk herb with the concomitant function of both medicine and foodstuff for the prevention and treatment of liver disease. Diterpenoids were considered as the major bioactive components in R. serra, responsible for their effect on hepatoprotection in previous phytochemical and pharmacological studies, while few comparative pharmacokinetic studies have been conducted under the physiological and pathological conditions. To reveal the difference in the pharmacokinetics process of R. serra extract (RSE) in normal and Con A-induced liver injury rats, a rapid ultra-high-pressure liquid chromatography–tandem mass spectrometry method (total running time: 5 min) was established to simultaneously determine three bioactive diterpenoids (enmein, epinodosin, and isodocarpin) in rat plasma. The results showed significant differences in the pharmacokinetic properties of three analytes between the physiological and pathological states. Compared with normal rats, the AUC of the three analytes was remarkably higher in liver injury rats, while the Tmax, T1/2, and MRT were shortened. It indicated that RSE has higher exposure and quicker elimination in liver injury rats than that in normal rats. Our results suggested that the pharmacokinetics of hepatoprotective medications was affected by liver injury, which prospected to provide essential information for guiding the healthcare and clinical application of R. serra in pathological states.
Nanodrugs Manipulating Endoplasmic Reticulum Stress for Highly Effective Antitumor Therapy
Authors: Xiang Yuting , Liu Min , Yang Yunrong , Wang Yubo , Qiu Yige , Tu Shiqi , Jiang Yitian , Nan Yayun , Zhang Xiaojie , Huang Qiong
Published: July 2022

Cancer is one of the leading causes of death worldwide due to high morbidity and mortality. Many attempts and efforts have been devoted to fighting cancer. Owing to the significant role of the endoplasmic reticulum (ER) in cell function, inducing ER stress can be promising for cancer treatment. However, the sustained activation of cytoprotective unfolded protein response (UPR) presents a tremendous obstacle for drugs in inducing unsolved ER stress in tumor cells, especially small-molecule drugs with poor bioavailability. Therefore, many emerging nanodrugs inducing and amplifying ER stress have been developed for efficient cancer treatment. More importantly, the novel discovery of ER stress in immunogenic cell death (ICD) makes it possible to repurpose antitumor drugs for immunotherapy through nanodrug-based strategies amplifying ER stress. Therefore, this mini-review aims to provide a comprehensive summary of the latest developments of the strategies underlying nanodrugs in the treatment of cancer via manipulating ER stress. Meanwhile, the prospects of ER stress–inducing nanodrugs for cancer treatment are systematically discussed, which provide a sound platform for novel therapeutic insights and inspiration for the design of nanodrugs in treating cancer.
Osteoporosis in Patients With Respiratory Diseases
Authors: Ma Yue , Qiu Shui , Zhou Renyi
Published: July 2022

Climate change, environmental pollution, and virus epidemics have sharply increased the number of patients suffering from respiratory diseases in recent years. Prolonged periods of illness and drug use increase the occurrence of complications in these patients. Osteoporosis is the common bone metabolism disease with respiratory disturbance, which affects prognosis and increases mortality of patients. The problem of osteoporosis in patients with respiratory diseases needs more attention. In this review, we concluded the characteristics of osteoporosis in some respiratory diseases including COPD, asthma, COVID-19, tuberculosis, and lung cancer. We revealed that hypoxia was the common pathogenesis of osteoporosis secondary to respiratory diseases, with malnutrition and corticosteroid abuse driving the progression of osteoporosis. Hypoxia-induced ROS accumulation and activated HIF-1α lead to attenuated osteogenesis and enhanced osteoclastogenesis in patients with respiratory diseases. Tuberculosis and cancer also invaded bone tissue and reduced bone strength by direct infiltration. For the treatment of osteoporosis in respiratory patients, oral-optimized bisphosphonates were the best treatment modality. Vitamin D was a necessary supplement, both for calcium absorption in osteogenesis and for improvement of respiratory lesions. Reasonable adjustment of the dose and course of corticosteroids according to the etiology and condition of patients is beneficial to prevent the occurrence and development of osteoporosis. Additionally, HIF-1α was a potential target for the treatment of osteoporosis in respiratory patients, which could be activated under hypoxia condition and involved in the process of bone remodeling.
How Strigolactone Shapes Shoot Architecture
Authors: Khuvung Khopeno , Silva Gutierrez Federico A. O. , Reinhardt Didier
Published: July 2022

Despite its central role in the control of plant architecture, strigolactone has been recognized as a phytohormone only 15 years ago. Together with auxin, it regulates shoot branching in response to genetically encoded programs, as well as environmental cues. A central determinant of shoot architecture is apical dominance, i.e., the tendency of the main shoot apex to inhibit the outgrowth of axillary buds. Hence, the execution of apical dominance requires long-distance communication between the shoot apex and all axillary meristems. While the role of strigolactone and auxin in apical dominance appears to be conserved among flowering plants, the mechanisms involved in bud activation may be more divergent, and include not only hormonal pathways but also sugar signaling. Here, we discuss how spatial aspects of SL biosynthesis, transport, and sensing may relate to apical dominance, and we consider the mechanisms acting locally in axillary buds during dormancy and bud activation.
Species-Specific Variation in Abscisic Acid Homeostasis and Responses Impacts Important Traits in Crassocephalum Orphan Crops
Authors: Adedeji-Badmus Adebimpe N. , Schramm Sebastian , Gigl Michael , Iwebema Williams , Albertos Pablo , Dawid Corinna , Sieberer Tobias , Poppenberger Brigitte
Published: July 2022

Crassocephalum rubens and Crassocephalum crepidioides are plant species native to Africa, but grow in most tropical and subtropical regions of the world. They are rich in vitamins, minerals, and essential oils and are traditional leafy vegetables and medicinal plants in Sub-Saharan Africa. The plants are still mainly collected from the wild but shall be taken into cultivation and an important aim in the domestication of these species is to improve traits that are relevant for crop production. Here, seed formation and germination capacities in C. crepidioides and C. rubens were investigated, and it was found that C. crepidioides exhibits a higher level of seed dormancy, which could be broken with light, and was correlated with higher amounts of abscisic acid (ABA), a plant hormone that promotes seed dormancy. ABA is also very well-known for its role in abiotic stress tolerance, and it is shown that tetraploid C. crepidioides exhibits a higher level of resistance against drought and heat stress than diploid C. rubens, traits that will benefit the cultivation of these plants, particularly in rain-fed cropping systems. The potential of Crassocephalum to improve nutrition and increase the resilience of marginal cropping systems in Africa is discussed.
Chemical Characterization and Visualization of Progressive Brown Rot Decay of Wood by Near Infrared Imaging and Multivariate Analysis
Authors: Belt Tiina , Awais Muhammad , Mäkelä Mikko
Published: July 2022

Brown rot fungi cause a type of wood decay characterized by carbohydrate degradation and lignin modification. The chemical and physical changes caused by brown rot are usually studied using bulk analytical methods, but these methods fail to consider local variations within the wood material. In this study we applied hyperspectral near infrared imaging to Scots pine sapwood samples exposed to the brown rot fungi Coniophora puteana and Rhodonia placenta to obtain position-resolved chemical information on the fungal degradative process. A stacked-sample decay test was used to create a succession of decay stages within the samples. The results showed that the key chemical changes associated with decay were the degradation of amorphous and crystalline carbohydrates and an increase in aromatic and carbonyl functionality in lignin. The position-resolved spectral data revealed that the fungi initiated degradation in earlywood, and that earlywood remained more extensively degraded than latewood even in advanced decay stages. Apart from differences in mass losses, the two fungi produced similar spectral changes in a similar spatial pattern. The results show that near infrared imaging is a useful tool for analyzing brown rot decayed wood and may be used to advance our understanding of fungal degradative processes.
Effect of Hearing Protection Use on Pianists’ Performance and Experience: Comparing Foam and Musician Earplugs
Authors: Boissinot Elie , Bogdanovitch Sarah , Bocksteal Annelies , Guastavino Catherine
Published: July 2022

Professional musicians are often exposed to high noise levels and thus face the risk of noise-induced hearing loss. Yet, adoption rates for hearing protection among musicians are low. Previous surveys indicate that the chief concern is the effect of hearing protection use on performance. However, few studies have investigated actual changes in performance when wearing hearing protection. We report an experiment investigating differences in pianists’ performance and experience with and without hearing protection. We compare the effect of foam earplugs and musician earplugs, designed to preserve sound quality with a flat frequency response. The analysis revealed that participants performed overall more loudly with the foam earplugs than with the musician earplugs, and in turn performances with the musician earplugs were louder than the open condition, indicating a compensatory effect. However, this effect was stronger for novel excerpts than for familiar excerpts. No effect was observed on dynamic range. Furthermore, we observed an acclimatization effect, whereby the effect of hearing protection use, observed on the first performance, decreased on the second performance. In terms of experience, participants reported changes in coloration, difficulties gauging dynamics and articulation, and increased effort required when performing with hearing protection. These effects were more pronounced when wearing the foam earplugs, and the participants reported finding the musician earplugs more comfortable to wear and play with. In conclusion, hearing protection use affects pianists’ performance particularly in terms of dynamics and their experience more so in terms of coloration. But the effects are less marked for familiar pieces and after repetition, suggesting that pianists can quickly adjust their playing when playing familiar pieces with hearing protection.
Empathy of Marine Aquaculture on Aquatic Products Consumption
Authors: Xilin Le , Wu Yingqi , Zeng Yan , Ma Ting , Wang Yating , Zhang Qingyu
Published: July 2022

The prolonged COVID-19 has caused a global lockdown and greatly impacts the supply chain and consumers’ consumption behavior of aquatic products. Specifically, consumers’ increasing awareness of environmental protection drives the marine aquaculture enterprises to supply green products and establish empathy with consumers in a bid to achieve sustainable consumption. This paper conducts a study on the international green marketing paths of marine aquatic products through PLS-SEM analysis of the 407 valid samples collected from the questionnaire survey. The findings indicate that empathy marketing has a significant positive effect on consumers’ purchase intention; subjective norm has a significant positive effect on consumers’ purchase intention. Additionally, perceived behavior control has a significant mediating effect between consumers’ subjective norm and purchase intention; the consumption environment has a significant positive moderating effect on individual consumption intention. The study suggests that sustainable development can be further propelled by means of coordinating the consumers’ awareness of ecological environment protection and their enhanced consumption intention.
Alcohol Use Among Young Adults in Northern California During the COVID-19 Pandemic—An Electronic Health Records-Based Study
Authors: Metz Verena E. , Palzes Vanessa A. , Chi Felicia W. , Campbell Cynthia I. , Sterling Stacy A.
Published: July 2022

Background

Individuals globally were affected by the COVID-19 pandemic in myriad of ways, including social isolation and economic hardship, resulting in negative impacts on mental health and substance use. Young adults have been subjected to extraordinary challenges such as job loss, virtual school, or childcare issues, but have received limited attention from research so far.

Methods

Using electronic health record data from a large integrated healthcare system in Northern California, this longitudinal observational study examined changes in the prevalence of unhealthy alcohol use (identified via systematic alcohol screening in adult primary care) from pre- (3/1/2019–12/31/2019) to post-COVID onset (3/1/2020–12/31/2020) among young adults (18–34 years). Among the 663,111 and 627,095 young adults who utilized primary care in the pre- and post-COVID onset periods, 342,889 (51.9%) and 186,711 (29.8%) received alcohol screening, respectively. We fit generalized estimating equation Poisson models to estimate the change in prevalence of unhealthy alcohol use from pre- to post-COVID onset among those who were screened, while using inverse probability weighting to account for potential selection bias of receiving alcohol screening. Heterogeneity in the change of prevalence by patient characteristics was also examined.

Results

Overall, the unadjusted prevalence of unhealthy alcohol use slightly decreased from 9.2% pre-COVID to 9.0% post-COVID onset. After adjusting for patient covariates, the prevalence of unhealthy alcohol use decreased by about 2% [adjusted prevalence ratio (aPR) = 0.98, 95% CI = 0.96, 1.00]. The prevalence of unhealthy alcohol use increased among women by 8% (aPR = 1.08, 95% CI = 1.06, 1.11), patients 18–20 years by 7% (aPR = 1.07, 95% CI = 1.00, 1.15), and Latino/Hispanic patients by 7% (aPR = 1.07, 95% CI = 1.03, 1.11). While the prevalence of unhealthy alcohol use decreased among men by 12% (aPR = 0.88, 95% CI = 0.86, 0.90), patients 21–34 years by 2% (aPR = 0.98, 95% CI = 0.96, 0.99), White patients by 3% (95% CI = 0.95, 1.00), and patients living in neighborhoods with the lowest deprivation indices by 9% (aPR = 0.91, 95% CI = 0.88, 0.94), their unadjusted prevalence remained higher than their counterparts post-COVID onset. There was no variation in the change of prevalence by comorbid mental health conditions or drug use disorders.

Conclusions

While changes in unhealthy alcohol use prevalence among young adults were small, findings raise concerns over increased drinking among women, those younger than the U.S. legal drinking age, and Latino/Hispanic patients.
Cortisol, Depression, and Anxiety Levels Before and After Short-Term Intensive Nutritional Stabilization in Patients With Severe Anorexia Nervosa
Authors: Hemmingsen Simone Daugaard , Jensen Nikolai Arndal , Larsen Pia Veldt , Sjögren Jan Magnus , Lichtenstein Mia Beck , Støving René Klinkby
Published: July 2022

Introduction

Depression and anxiety are well-known comorbid conditions in patients with anorexia nervosa (AN). Hypercortisolemia in patients with AN may be pathogenic and contribute to depression and anxiety symptomatology.

Objective

The aim of this study was to investigate short-term changes in cortisol levels and depression and anxiety symptomatology following intensive re-nutrition in patients with severe AN and hospitalized in a specialized unit. Furthermore, we investigated the potential association between cortisol levels and psychometric parameters.

Methods

A total of 36 patients with AN were enrolled in the study. Nine dropped out before follow-up. Patients underwent paraclinical and psychometric examinations at admission and discharge. Measurements included plasma cortisol, cortisol binding globulin (CBG), 24-h urine cortisol, and self-report questionnaires regarding eating disorder, depression, anxiety, and stress symptoms. Patients were hospitalized in the unit for somatic stabilization and intensive re-nutrition. Mean admission length was 41 days. The study was registered at ClinicalTrials.gov (NCT02502617).

Results

Cortisol levels in blood and urine did not change from admission to discharge in patients with severe AN. Symptoms of depression, anxiety, stress, and eating disorder remained elevated at discharge. There were no associations between changes in cortisol levels and changes in psychometrics.

Discussion

Our results suggest that short-term intensive re-nutrition did not alter hypothalamic-pituitary-adrenal axis activity or mental health in patients with severe AN. Long-term stabilization and longer follow-up after hospital discharge may be needed to detect changes in cortisol levels and whether these changes are associated with depression and anxiety symptomatology. Greater knowledge about cortisol levels and mental health in patients with severe AN may help in the development of new treatment choices for the chronically ill patients. Future studies could investigate whether cortisol-lowering drugs have a therapeutic effect on mental health in AN.
An Estimation of the Effect of Green Financial Policies and Constraints on Agriculture Investment: Evidences of Sustainable Development Achievement in Northwest China
Authors: Mei Bingjing , Khan Arshad Ahmad , Khan Sufyan Ullah , Ali Muhammad Abu Sufyan , Luo Jianchao
Published: July 2022

Farming' community actively participating as micro-actors in green finance schemes is critical for regional planning and development. On the basis of the extent to which financial progress and sustainable development are coordinated, in a difference-in-differences approach, this article employed 2350 small investigations to estimate the influence of green-finance strategies on peasants' agriculture investment and developed a mediation effect method. It investigates the role of peasant managerial variability in mediating the influence of financial constraints. The results indicate that the introduction of a financial restriction variable reduces the positive impacts of green-finance regulations on peasants' agricultural investment. Moreover, peasants who participate in non-agricultural management exercises are more inclined to take advantage of green financing regulations and are affected via financial restrictions in mediate means. The building of a green-finance sector in remote regions should accomplish unique positioning and rapid growth.