bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a Nomogram Model for Predicting Peritoneal Dissemination in Gastric Cancer Based on Clinicopathologic Features and Preoperative Serum Tumor Markers
Authors: Bao Dandan , Yang Zhangwei , Chen Senrui , Li Keqin , Hu Yiren
Published: June 2022

Background

Peritoneal dissemination (PD) is the most common mode of metastasis for advanced gastric cancer (GC) with poor prognosis. It is of great significance to accurately predict preoperative PD and develop optimal treatment strategies for GC patients. Our study assessed the diagnostic potential of serum tumor markers and clinicopathologic features, to improve the accuracy of predicting the presence of PD in GC patients.

Methods

In our study, 1264 patients with GC at Fudan University Shanghai Cancer Center and Wenzhou people’s hospital from 2018 to 2020 were retrospectively analyzed, including 316 cases of PD and 948 cases without PD. All patients underwent enhanced CT scan or magnetic resonance imaging (MRI) before surgery and treatment. Clinicopathological features, including tumor diameter and tumor stage (depth of tumor invasion, nearby lymph node metastasis and distant metastasis), were obtained by imaging examination. The independent risk factors for PD were screened through univariate and multivariate logistic regression analyses, and the results were expressed with 95% confidence intervals (CIs). A model of PD diagnosis and prediction was established by using Cox proportional hazards regression model of training set. Furthermore, the accuracy of the prediction model was verified by ROC curve and calibration plots.

Results

Univariate analysis showed that PD in GC was significantly related to tumor diameter (odds ratio (OR)=12.06, p<0.0006), depth of invasion (OR=14.55, p<0.0001), lymph node metastases (OR=5.89, p<0.0001), carcinoembryonic antigen (CEA) (OR=2.50, p<0.0001), CA125 (OR=11.46, p<0.0001), CA72-4 (OR=4.09, p<0.0001), CA19-9 (OR=2.74, p<0.0001), CA50 (OR=5.20, p<0.0001) and CA242 (OR=3.83, p<0.0001). Multivariate analysis revealed that clinical invasion depth and serum marker of CA125 and CA72-4 were independent risk factors for PD. The prediction model was established based on the risk factors using the R program. The area under the curve (AUC) of the receiver operating characteristics (ROC) was 0.931 (95% CI: 0.900–0.960), with the accuracy, sensitivity and specificity values of 90.5%, 86.2% and 82.2%, respectively.

Conclusion

The nomogram model constructed using CA125, CA72-4 and depth of invasion increases the accuracy and sensitivity in predicting the incidence of PD in GC patients and can be used as an important tool for preoperative diagnosis.
Effectiveness of the Sanyin Formula Plus Chemotherapy on Survival in Women With Triple-Negative Breast Cancer: A Randomized Controlled Trial
Authors: Wu Chunyu , Sun Chenping , Liu Guangyu , Qin Yuenong , Xue Xiaohong , Wu Xueqing , Wang Qun , Liu Jin , Ye Zhen , Li Qiong , Qu Wenchao , Wang Yi , Zhang Shuai , Shao Zhiming , Liu Sheng
Published: June 2022

Purpose

To evaluate the efficacy of the Sanyin formula (SYF) plus conventional standard chemotherapy in operable triple-negative breast cancer (TNBC) patients, a randomized controlled trial was implemented at 5 hospitals and cancer centers in China between May 23, 2016, and October 31, 2019.

Materials and Methods

Female patients aged 18 to 80 years with operable TNBC after definitive surgery were screened and enrolled. The exclusion criteria included metastatic disease, other tumors, or locally advanced disease. Patients were randomly divided into groups SYF plus conventional standard chemotherapy and placebo plus conventional standard chemotherapy at a ratio of 1:1. The primary endpoint of the investigation was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity.

Results

A total of 252 operable female TNBC patients were randomized to receive SYF plus conventional standard chemotherapy (N = 127) or a placebo plus conventional standard chemotherapy (N = 125). At a median follow-up of 51 months, 5-year DFS time was longer in those assigned to SYF plus conventional standard chemotherapy compared with placebo plus conventional standard chemotherapy (94.2%vs 85.5%, hazard ratio [HR] = 0.40; 95%CI, 0.17-0.97; P = 0.034). The absolute benefit for 5-year DFS was 8.7% in the SYF plus conventional standard chemotherapy group. No statistically significant difference was observed in OS between the two groups (P = 0.23). Patients with negative node status benefited more from SYF plus conventional standard chemotherapy treatment (HR = 0.21, P-interaction = 0.013) in accordance with the exploratory subgroup analyses of DFS.

Conclusions

The results of the present study suggest that the traditional Chinese medicine SYF plus conventional chemotherapy regimens is an effective alternative adjuvant chemotherapy strategy for female operable TNBC patients.

Clinical Trial Registration

https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR-IPR-16008590.
Self-Managed Non-Pharmacological Interventions for Breast Cancer Survivors: Systematic Quality Appraisal and Content Analysis of Clinical Practice Guidelines
Authors: Tan Jing-Yu (Benjamin) , Zhai Jianxia , Wang Tao , Zhou Hong-Juan , Zhao Isabella , Liu Xian-Liang
Published: June 2022

Background

A growing number of clinical practice guidelines (CPGs) regarding non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistent recommendations, it remains uncertain how best to design and implement non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences.

Aim

To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs.

Methods

CPGs, which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors, were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using The Appraisal of Guidelines for Research and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence.

Results

A total of 14 CPGs were included. Among which, only five were appraised as high quality. The “range and purpose” domain had the highest standardized percentage (84.61%), while the domain of “applicability” had the lowest (51.04%). Five CPGs were rated “recommended”, seven were “recommended with modifications”, and the other two were rated “not recommended”. The content analysis findings summarised some commonly recommended self-managed non-pharmacological interventions in the 14 guidelines, including physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage and acupressure. Physical activity/exercise was the most frequently recommended approach to managing psychological and physical symptoms by the included guidelines. However, significant variations in the level of evidence and grade of recommendation were identified among the included CPGs.

Conclusion

Recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs to guide clinicians in offering high-quality and tailored breast cancer survivorship care.
Differential Gene Expression and Weighted Correlation Network Dynamics in High-Throughput Datasets of Prostate Cancer
Authors: Mohammad Taj , Singh Prithvi , Jairajpuri Deeba Shamim , Al-Keridis Lamya Ahmed , Alshammari Nawaf , Adnan Mohd. , Dohare Ravins , Hassan Md Imtaiyaz
Published: June 2022

Precision oncology is an absolute need today due to the emergence of treatment resistance and heterogeneity among cancerous profiles. Target-propelled cancer therapy is one of the treasures of precision oncology which has come together with substantial medical accomplishment. Prostate cancer is one of the most common cancers in males, with tremendous biological heterogeneity in molecular and clinical behavior. The spectrum of molecular abnormalities and varying clinical patterns in prostate cancer suggest substantial heterogeneity among different profiles. To identify novel therapeutic targets and precise biomarkers implicated with prostate cancer, we performed a state-of-the-art bioinformatics study, beginning with analyzing high-throughput genomic datasets from The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) suggests a set of five dysregulated hub genes (MAF, STAT6, SOX2, FOXO1, and WNT3A) that played crucial roles in biological pathways associated with prostate cancer progression. We found overexpressed STAT6 and SOX2 and proposed them as candidate biomarkers and potential targets in prostate cancer. Furthermore, the alteration frequencies in STAT6 and SOX2 and their impact on the patients’ survival were explored through the cBioPortal platform. The Kaplan-Meier survival analysis suggested that the alterations in the candidate genes were linked to the decreased overall survival of the patients. Altogether, the results signify that STAT6 and SOX2 and their genomic alterations can be explored in therapeutic interventions of prostate cancer for precision oncology, utilizing early diagnosis and target-propelled therapy.
Case Report: Chimeric Antigen Receptor T Cells Induced Late Severe Cytokine Release Syndrome
Authors: He Jinping , Xu Na , Zhou Hongsheng , Zhou Ya , Wu Di , Zhao Ruochong , Lin Tong , Xu Ju , Cao Rui , Li Peng , Liu Qifa
Published: June 2022

Background

Severe cytokine release syndrome (sCRS) has emerged as an adverse complication in the early period of chimeric antigen receptor T cell (CART) therapy, while whether sCRS occurs in the late period remains unknown. Here, we reported two patients with late sCRS.

Case Presentation

Case 1 was a 34-year-old female with refractory Philadelphia chromosome-positive B cell acute lymphoblastic leukemia. She achieved complete remission (CR) but experienced grade III CRS and hemophagocytic lymphohistiocytosis (HLH) 41 days after CD19-targeted CART (CART19) cells and CD22-targeted CART (CART22) cells infusion. Ineffective to tocilizumab and HLH-94 protocol (dexamethasone and etoposide), she died of a cerebral hemorrhage on day 55 after CART therapy. Case 2 was a 38-year-old male with IgG kappa multiple myeloma. He received autologous BCMA-targeted CART (BCMA-CART) therapy 4 months after HLA–matched sibling (sister) donor transplantation and developed grade III CRS 163 days after CART administration, characterized by fever, hypotension, and skin lesions. Effective to methylprednisolone and tocilizumab, his clinical response persisted for over 6.0 months.

Conclusion

Severe CRS could occur in the late period after CART therapy as re-expansion of CART cells possessed the potential risk for late sCRS.
An Applicable Machine Learning Model Based on Preoperative Examinations Predicts Histology, Stage, and Grade for Endometrial Cancer
Authors: Feng Ying , Wang Zhixiang , Xiao Meizhu , Li Jinfeng , Su Yuan , Delvoux Bert , Zhang Zhen , Dekker Andre , Xanthoulea Sofia , Zhang Zhiqiang , Traverso Alberto , Romano Andrea , Zhang Zhenyu , Liu Chongdong , Gao Huiqiao , Wang Shuzhen , Qian Linxue
Published: June 2022

Purpose

To build a machine learning model to predict histology (type I and type II), stage, and grade preoperatively for endometrial carcinoma to quickly give a diagnosis and assist in improving the accuracy of the diagnosis, which can help patients receive timely, appropriate, and effective treatment.

Materials and Methods

This study used a retrospective database of preoperative examinations (tumor markers, imaging, diagnostic curettage, etc.) in patients with endometrial carcinoma. Three algorithms (random forest, logistic regression, and deep neural network) were used to build models. The AUC and accuracy were calculated. Furthermore, the performance of machine learning models, doctors’ prediction, and doctors with the assistance of models were compared.

Results

A total of 329 patients were included in this study with 16 features (age, BMI, stage, grade, histology, etc.). A random forest algorithm had the highest AUC and Accuracy. For histology prediction, AUC and accuracy was 0.69 (95% CI=0.67-0.70) and 0.81 (95%CI=0.79-0.82). For stage they were 0.66 (95% CI=0.64-0.69) and 0.63 (95% CI=0.61-0.65) and for differentiation grade 0.64 (95% CI=0.63-0.65) and 0.43 (95% CI=0.41-0.44). The average accuracy of doctors for histology, stage, and grade was 0.86 (with AI) and 0.79 (without AI), 0.64 and 0.53, 0.5 and 0.45, respectively. The accuracy of doctors’ prediction with AI was higher than that of Random Forest alone and doctors’ prediction without AI.

Conclusion

A random forest model can predict histology, stage, and grade of endometrial cancer preoperatively and can help doctors in obtaining a better diagnosis and predictive results.
Transcutaneous Electrical Acupoint Stimulation Improved Preoperative Blood Pressure in Gynecological Malignant Tumor Patients With Hypertension: A Randomized, Controlled Trial
Authors: Chen Liang , Shen Yang , Liu Shuangmei , Cao Yanyan
Published: June 2022

Objective

Gynecological malignant tumor patients with hypertension, even if blood pressure is well controlled, are prone to hypertension before surgery. We plan to verify the effect of transcutaneous electrical acupoint stimulation (TEAS) on stabilizing blood pressure before operation.

Methods

We enrolled 91 patients and randomly divided them into TEAS group (n=46) and control group (n=45). Patients in TEAS group received TEAS at acupoints Hegu and Neiguan. Patients in control group received transcutaneous electrical stimulation at the nonacupoint position of the upper limbs. After entering the operating room, the blood pressure before and after induction was measured. The main results were the occurrence of preinduction hypertension and postinduction hypotension.

Results

There was no difference in the general information of the two groups. There were four cases (9%) of preinduction hypertension in TEAS group and 13 cases (29%) in control group. The incidence in TEAS group was significantly lower (P=0.013). There were five cases (11%) of postinduction hypotension in TEAS group and eight cases (18%) in control group. There was no significant difference between the two groups (P=0.346). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of the highest blood pressure before induction in TEAS group were lower than those in control group (P=0.002, 0.002, and 0.001). There was no difference in SBP, DBP, or MBP between the two groups on the day before the operation. There was no difference in the lowest blood pressure before operation between the two groups after induction

Conclusion

TEAS can prevent preinduction hypertension in patients with gynecological malignant tumors.

Clinical Trial Registration

http://www.chictr.org.cn/showproj.aspx?proj=143276, identifier ChiCTR2100054336.
CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer
Authors: Yuan Li , Xu Jingli , Shi Yunfu , Jin Zhiyuan , Bao Zhehan , Yu Pengcheng , Wang Yi , Xia Yuhang , Qin Jiangjiang , Zhang Bo , Yao Qinghua
Published: June 2022

The protein encoded by CD3D is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. Previous studies have shown that CD3D is associated with prognosis and treatment response in breast, colorectal, and liver cancer. However, the expression and clinical significance of CD3D in gastric cancer are not clear. In this study, we collected 488 gastric cancer tissues and 430 paired adjacent tissues to perform tissue microarrays (TMAs). Then, immunohistochemical staining of CD3D, CD3, CD4, CD8 and PD-L1 was conducted to investigate the expression of CD3D in gastric cancer and the correlation between the expression of CD3D and tumor infiltrating lymphocytes (TILs) and PD-L1. The results showed that CD3D was highly expressed in gastric cancer tissues compared with paracancerous tissues (P<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (P=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; P=0.046, HR=0.687, 95%CI: 0.474-0.994 for multivariate analyses). In addition, CD3D was negatively correlated with the tumor location, Borrmann type and distant metastasis (P=0.012 for tumor location; P=0.007 for Borrmann type; P=0.027 for distant metastasis). In addition, the expression of CD3D was highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1, and the combination of CD3D with CD3, CD4, CD8 and PD-L1 predicted the best prognosis (P=0.043). In summary, CD3D may play an important regulatory role in the tumor immune microenvironment of gastric cancer and may serve as a potential indicator of prognosis and immunotherapy response.
Neoadjuvant Treatment in Resectable Pancreatic Cancer. Is It Time for Pushing on It?
Authors: Vivarelli Marco , Mocchegiani Federico , Nicolini Daniele , Vecchi Andrea , Conte Grazia , Dalla Bona Enrico , Rossi Roberta , Benedetti Cacciaguerra Andrea
Published: June 2022

Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.
Home-Based EEG Neurofeedback Intervention for the Management of Chronic Pain
Authors: Birch Nick , Graham Jon , Ozolins Christine , Kumarasinghe Kaushalya , Almesfer Faisal
Published: June 2022

Background

Chronic pain and associated symptoms often cause significant disability and reduced quality of life (QoL). Neurofeedback (NFB) as part of a Brain Computer Interface can help some patients manage chronic pain by normalising maladaptive brain activity measured with electroencephalography (EEG).

Objectives

This study was designed to assess the efficacy and safety of a novel home-based NFB device for managing chronic pain by modifying specific EEG activity.

Methods

A prospective, single-arm, proof-of-concept study was conducted between June 2020 and March 2021 among adults with chronic pain (registered with ClinicalTrials.gov NCT04418362). Axon EEG NFB systems for home use were provided to each, and 32–48 NFB training sessions were completed by the participants over 8-weeks. The primary outcome was self-reported pain. Assessment of central sensitisation, sleep quality, affective symptoms, change in QoL, adverse events during use and EEG correlations with symptoms were secondary outcomes.

Results

Sixteen participants were enrolled. Eleven reported pain relief following NFB training, eight reporting clinically significant improvements. Central sensitisation symptoms improved by a third (p < 0.0001), sleep quality by almost 50% (p < 0.001), anxiety reduced by 40% (p = 0.015), and QoL improved at final follow-up for 13 participants. The majority (69%) of participants who upregulated relative alpha reported improved pain, and those who downregulated relative hi-beta reported improved pain, reduced anxiety and depression scores. There were no adverse events during the trial.

Conclusions

Home-based NFB training is well-tolerated and may provide relief for sufferers of chronic pain and its associated symptoms.

Axon, a home-based NFB training device, can positively influence pain and associated symptoms in a proportion of people with chronic pain.
Validation of a Classification Model Using Complete Blood Count to Predict Severe Human Adenovirus Lower Respiratory Tract Infections in Pediatric Cases
Authors: Fan Huifeng , Cui Ying , Xu Xuehua , Zhang Dongwei , Yang Diyuan , Huang Li , Ding Tao , Lu Gen
Published: June 2022

Background

Human adenovirus (HAdV) lower respiratory tract infections (LRTIs) are prone to severe cases and even cause death in children. Here, we aimed to develop a classification model to predict severity in pediatric patients with HAdV LRTIs using complete blood count (CBC).

Methods

The CBC parameters from pediatric patients with a diagnosis of HAdV LRTIs from 2013 to 2019 were collected during the disease’s course. The data were analyzed as potential predictors for severe cases and were selected using a random forest model.

Results

We enrolled 1,652 CBC specimens from 1,069 pediatric patients with HAdV LRTIs in the present study. Four hundred and seventy-four patients from 2017 to 2019 were used as the discovery cohort, and 470 patients from 2013 to 2016 were used as the validation cohort. The monocyte ratio (MONO%) was the most obvious difference between the mild and severe groups at onset, and could be used as a marker for the early accurate prediction of the severity [area under the subject operating characteristic curve (AUROC): 0.843]. Four risk factors [MONO%, hematocrit (HCT), red blood cell count (RBC), and platelet count (PLT)] were derived to construct a classification model of severe and mild cases using a random forest model (AUROC: 0.931 vs. 0.903).

Conclusion

Monocyte ratio can be used as an individual predictor of severe cases in the early stages of HAdV LRTIs. The four risk factors model is a simple and accurate risk assessment tool that can predict severe cases in the early stages of HAdV LRTIs.
Aloperine Ameliorates IMQ-Induced Psoriasis by Attenuating Th17 Differentiation and Facilitating Their Conversion to Treg
Authors: Zhou Hai-Feng , Wang Fa-Xi , Sun Fei , Liu Xin , Rong Shan-Jie , Luo Jia-Hui , Yue Tian-Tian , Xiao Jun , Yang Chun-Liang , Lu Wan-Ying , Luo Xi , Zhou Qing , Zhu He , Yang Ping , Xiong Fei , Yu Qi-Lin , Zhang Shu , Wang Cong-Yi
Published: June 2022

Aloperine is an anti-inflammatory compound isolated from the Chinese herb Sophora alopecuroides L. Previously, our group has reported that the generation of induced Treg was promoted by aloperine treatment in a mouse colitis model. However, the effect of aloperine on effector T cell subsets remains unclear. We therefore carefully examined the effect of aloperine on the differentiation of major subsets of T helper cells. Based on our results, psoriasis, a Th17 dominant skin disease, is selected to explore the potential therapeutic effect of aloperine in vivo. Herein, we demonstrated that topical application of aloperine suppressed epidermal proliferation, erythema, and infiltration of inflammatory cells in skin lesions. Mechanistic studies revealed that aloperine suppressed the differentiation of Th17 cells directly through inhibiting the phosphorylation of STAT3 or indirectly through impairing the secretion of Th17-promoting cytokines by dendritic cells. Moreover, aloperine enhanced the conversion of Th17 into Treg via altering the pSTAT3/pSTAT5 ratio. Collectively, our study supported that aloperine possesses the capacity to affect Th17 differentiation and modulates Th17/Treg balance, thereby alleviating imiquimod (IMQ)-induced psoriasis in mice.
Infusion of Human Albumin on Acute Pancreatitis Therapy: New Tricks for Old Dog?
Authors: Ma Yifei , Yan Tianao , Xu Fengshuo , Ding Jiachun , Yang Bao , Ma Qingyong , Wu Zheng , Lyu Jun , Wang Zheng
Published: June 2022

Objective: Human serum albumin (HSA) infusion is a common administration on acute pancreatitis therapy in the Intensive Care Unit (ICU), but its actual association with patients’ outcomes has not been confirmed. The study is aimed to determine whether the in-hospital prognosis of ICU patients with acute pancreatitis could benefit from HSA.

Methods: 950 acute pancreatitis patients diagnosed in 2008–2019 were extracted from the MIMIC-IV database as our primary study cohort. The primary outcome was in-hospital mortality. We also performed an external validation with a cohort of 104 acute pancreatitis patients after PSM matching from the eICU database.

Results: In MIMIC-IV, 228 acute pancreatitis patients received HSA infusion (Alb group) during their hospitalization, while 722 patients did not (non-Alb group). Patients in the Alb group presented a poorer survival curve than the non-Alb group, while this difference disappeared after PSM or IPTW matching (log-rank test: PSM: p = 0.660, IPTW: p = 0.760). After including covariates, no association was found between HSA infusion and patients’ in-hospital mortality before and after matching (original cohort: HR: 1.00, 95% CI: 0.66–1.52, p = 0.998). HSA infusion also did not benefit patients’ 28-days or ICU mortality, while it was significantly associated with a longer duration of hospital and ICU. In addition, the initial serum albumin levels, infections, the total amount, or the initial timing of infusion did not affect the conclusion. Similarly, in the eICU cohort, HSA infusion was still not a beneficial prognostic factor for patients’ in-hospital prognosis (p = 0.087).

Conclusion: Intravenous human serum albumin infusion could not benefit acute pancreatitis patients’ in-hospital prognosis and was associated with prolonged hospital and ICU duration.
p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)
Authors: Milani Daniela , Caruso Lorenzo , Zauli Enrico , Al Owaifeer Adi Mohammed , Secchiero Paola , Zauli Giorgio , Gemmati Donato , Tisato Veronica
Published: June 2022

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection.
Cattle Bile Arisaema Aqueous Extracts Protect Against Febrile Seizures in Rats Through Regulating Neurotransmitters and Suppressing Neuroinflammation
Authors: Su Fa-Zhi , Bai Chen-Xi , Luo Yumeng , Zhang Wen-Sen , Cui Na , Wang Yang-Yang , Sun Yan-Ping , Zhu Wen-Bo , Zhao Ming-Yang , Yang Bing-You , Kuang Hai-Xue , Wang Qiu-Hong
Published: June 2022

Cattle bile Arisaema (CBA) is a traditional medicine used for the treatment of febrile seizures (FS) for thousands of years in China. However, its application is greatly limited due to cost reasons, and pig bile Arisaema (PBA) is the main commercial product instead. Additionally, the underlying mechanism of CBA for the treatment of FS still remains unknown. In this study, we investigated the anti-convulsant effect and potential mechanism of the CBA aqueous extract for the first time through a hot-water bath-induced FS rat model. Our results showed that pre-treatment with CBA dramatically lowered the incidence rate and generation times and prolonged the latency of FS. In addition, CBA effectively ameliorated neuronal damage and regulated neurotransmitter disorder induced by FS in the rat hippocampus. The enzyme-linked immunosorbent assay, western blotting, immunohistochemical, and qRT-PCR results exhibited that CBA suppressed the expression of GFAP, TLR4, NF-κB, HMGB1, NLRP3, TNF-α, IL-1β, and IL-6 and consequently inhibited the neuroinflammation induced by FS. Interestingly, although the CBA and PBA aqueous extracts possessed the same trend on the changes caused by FS, the improvement of FS by CBA is markedly better than that by PBA. These findings indicate that CBA exerts a protective effect on febrile seizures through regulating neurotransmitter disorder and suppressing neuroinflammation.
Low-Dose Anti-HIV Drug Efavirenz Mitigates Retinal Vascular Lesions in a Mouse Model of Alzheimer’s Disease
Authors: El-Darzi Nicole , Mast Natalia , Buchner David A. , Saadane Aicha , Dailey Brian , Trichonas Georgios , Pikuleva Irina A.
Published: June 2022

A small dose of the anti-HIV drug efavirenz (EFV) was previously discovered to activate CYP46A1, a cholesterol-eliminating enzyme in the brain, and mitigate some of the manifestation of Alzheimer’s disease in 5XFAD mice. Herein, we investigated the retina of these animals, which were found to have genetically determined retinal vascular lesions associated with deposits within the retinal pigment epithelium and subretinal space. We established that EFV treatment activated CYP46A1 in the retina, enhanced retinal cholesterol turnover, and diminished the lesion frequency >5-fold. In addition, the treatment mitigated fluorescein leakage from the aberrant blood vessels, deposit size, activation of retinal macrophages/microglia, and focal accumulations of amyloid β plaques, unesterified cholesterol, and Oil Red O-positive lipids. Studies of retinal transcriptomics and proteomics identified biological processes enriched with differentially expressed genes and proteins. We discuss the mechanisms of the beneficial EFV effects on the retinal phenotype of 5XFAD mice. As EFV is an FDA-approved drug, and we already tested the safety of small-dose EFV in patients with Alzheimer’s disease, our data support further clinical investigation of this drug in subjects with retinal vascular lesions or neovascular age-related macular degeneration.
Anticancer Effects of Amlodipine Alone or in Combination With Gefitinib in Non-Small Cell Lung Cancer
Authors: Fu Bingjie , Dou Xiaojing , Zou Miao , Lu Hao , Wang Kaixuan , Liu Qingxia , Liu Yao , Wang Wei , Jin Meihua , Kong Dexin
Published: June 2022

Amlodipine is a Ca2+ channel blocker commonly used to cardiovascular diseases such as hypertension and angina; however, its anticancer effects in lung cancer A549 cells remain unknown. In the present study, we explored the antitumor effects and molecular mechanisms underlying the action of amlodipine in non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. We observed that amlodipine suppressed the proliferation of A549 lung cancer cells by arresting the tumor cell cycle. Mechanistically, our results revealed that amlodipine could attenuate the phosphoinositide 3 kinase (PI3K)/Akt and Raf/MEK/extracellular signal-regulated kinase (ERK) pathways through epidermal growth factor receptor (EGFR) and modulated cell cycle-related proteins such as cyclin D1, p-Rb, p27, and p21. Subsequently, amlodipine combined with gefitinib could synergistically inhibit cell proliferation by arresting the cell cycle. Moreover, amlodipine combined with gefitinib effectively attenuated the growth of A549 lung cancer xenografts when compared with monotherapy, affording an excellent therapeutic effect. Collectively, our results indicate that amlodipine alone or combined with the novel anticancer drug gefitinib might be a potential therapeutic strategy for NSCLC patients with wild-type EGFR.
Focusing on Formononetin: Recent Perspectives for its Neuroprotective Potentials
Authors: Tian Jiao , Wang Xing-Qin , Tian Zhen
Published: June 2022

Nervous system is the most complex system of the human body, hence, the neurological diseases often lack effective treatment strategies. Natural products have the potential to yield unique molecules and produce integrative and synergic effects compared to standard therapy. Mounting evidence has shown that isoflavonoids contained in traditional medicinal plant or dietary supplementation may play a crucial role in the prevention and treatment of neurological diseases due to their pronounced biological activities correlating to nervous system. Formononetin, a non-steroidal isoflavonoid, is a bioactive constituent of numerous medicinal plants such as red clover (Trifolium pratense) and Astragalus membranaceus. Emerging evidence has shown that formononetin possesses considerable anti-inflammatory, antioxidant and anti-cancer effects. This review intends to analyze the neuropharmacological potential of formononetin on the therapy of nervous system disorders. The neuroprotective properties of formononetin are observed in multiple neurological disorders including Alzheimer’s disease, dementia, cerebral ischemia, traumatic brain injury, anxiety, and depression. The beneficial effects of formononetin are achieved partially through attenuating neuroinflammation and oxidative stress via the related signaling pathway. Despite its evident effects in numerous preclinical studies, the definite role of formononetin on humans is still less known. More well-designed clinical trials are required to further confirm the neuroprotective efficacy and safety profile of formononetin before its application in clinic.
Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine
Authors: Chen Nianzhi , Qi Yulin , Ma Xiao , Xiao Xiaolin , Liu Qingsong , Xia Ting , Xiang Juyi , Zeng Jinhao , Tang Jianyuan
Published: June 2022

In many studies, the extensive and significant anticancer activity of chelerythrine (CHE) was identified, which is the primary natural active compound in four traditional botanical drugs and can be applied as a promising treatment in various solid tumors. So this review aimed to summarize the anticancer capacities and the antitumor mechanism of CHE. The literature searches revolving around CHE have been carried out on PubMed, Web of Science, ScienceDirect, and MEDLINE databases. Increasing evidence indicates that CHE, as a benzophenanthridine alkaloid, exhibits its excellent anticancer activity as CHE can intervene in tumor progression and inhibit tumor growth in multiple ways, such as induction of cancer cell apoptosis, cell cycle arrest, prevention of tumor invasion and metastasis, autophagy-mediated cell death, bind selectively to telomeric G-quadruplex and strongly inhibit the telomerase activity through G-quadruplex stabilization, reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), and PKC. The role of CHE against diverse types of cancers has been investigated in many studies and has been identified as the main antitumor drug candidate in drug discovery programs. The current complex data suggest the potential value in clinical application and the future direction of CHE as a therapeutic drug in cancer. Furthermore, the limitations and the present problems are also highlighted in this review. Despite the unclearly delineated molecular targets of CHE, extensive research in this area provided continuously fresh data exploitable in the clinic while addressing the present requirement for further studies such as toxicological studies, combination medication, and the development of novel chemical methods or biomaterials to extend the effects of CHE or the development of its derivatives and analogs, contributing to the effective transformation of this underestimated anticancer drug into clinical practice. We believe that this review can provide support for the clinical application of a new anticancer drug in the future.
DACPGTN: Drug ATC Code Prediction Method Based on Graph Transformer Network for Drug Discovery
Authors: Yan Chaokun , Suo Zhihao , Wang Jianlin , Zhang Ge , Luo Huimin
Published: June 2022

The Anatomical Therapeutic Chemical (ATC) classification system is a drug classification scheme proposed by the World Health Organization, which is widely used for drug screening, repositioning, and similarity research. The ATC system assigns different ATC codes to drugs based on their anatomy, pharmacological, therapeutics and chemical properties. Predicting the ATC code of a given drug helps to understand the indication and potential toxicity of the drug, thus promoting its use in the therapeutic phase and accelerating its development. In this article, we propose an end-to-end model DACPGTN to predict the ATC code for the given drug. DACPGTN constructs composite features of drugs, diseases and targets by applying diverse biomedical information. Inspired by the application of Graph Transformer Network, we learn potential novel interactions among drugs diseases and targets from the known interactions to construct drug-target-disease heterogeneous networks containing comprehensive interaction information. Based on the constructed composite features and learned heterogeneous networks, we employ graph convolution network to generate the embedding of drug nodes, which are further used for the multi-label learning tasks in drug discovery. Experiments on the benchmark datasets demonstrate that the proposed DACPGTN model can achieve better prediction performance than the existing methods. The source codes of our method are available athttps://github.com/Szhgege/DACPGTN.
Myrtenol Reduces Orofacial Nociception and Inflammation in Mice Through p38-MAPK and Cytokine Inhibition
Authors: Oliveira Janaíne P. , Abreu Fabíula F. , Bispo José Marcos M. , Cerqueira Anderson R. A. , Santos José Ronaldo dos , Correa Cristiane B. , Costa Soraia K. P. , Camargo Enilton A.
Published: June 2022

Orofacial pain is one of the commonest and most complex complaints in dentistry, greatly impairing life quality. Preclinical studies using monoterpenes have shown pharmacological potential to treat painful conditions, but the reports of the effects of myrtenol on orofacial pain and inflammation are scarce. The aim of this study was to evaluate the effect of myrtenol in experimental models of orofacial pain and inflammation. Orofacial nociceptive behavior and the immunoreactivity of the phosphorylated p38 (P-p38)-MAPK in trigeminal ganglia (TG) and spinal trigeminal subnucleus caudalis (STSC) were determined after the injection of formalin in the upper lip of male Swiss mice pretreated with myrtenol (12.5 and 25 mg/kg, i.p.) or vehicle. Orofacial inflammation was induced by the injection of carrageenan (CGN) in the masseter muscle of mice pretreated with myrtenol (25 and 50 mg/kg, i.p.) or its vehicle (0.02% Tween 80 in saline). Myeloperoxidase (MPO) activity and histopathological changes in the masseter muscle and interleukin (IL)-1β levels in the TG and STSC were measured. The increase in face-rubbing behavior time induced by formalin and P-p38-MAPK immunostaining in trigeminal ganglia were significantly reduced by myrtenol treatment (12.5 and 25 mg/kg). Likewise, increased MPO activity and inflammatory histological scores in masseter muscle, as well as augmented levels of IL-1β in the TG AND STSC, observed after CGN injection, were significantly decreased by myrtenol (25 and 50 mg/kg). Myrtenol has potential to treat orofacial inflammation and pain, which is partially related to IL-1β levels in the trigeminal pathway and p38-MAPK modulation in trigeminal ganglia.
Chronic Cervicitis and Cervical Cancer Detection Based on Deep Learning of Colposcopy Images Toward Translational Pharmacology
Authors: Huang Wei , Sun Shasha , Yu Zhengyu , Lu Shanshan , Feng Hao
Published: June 2022

With the rapid development of deep learning, automatic image recognition is widely used in medical development. In this study, a deep learning convolutional neural network model was developed to recognize and classify chronic cervicitis and cervical cancer. A total of 10,012 colposcopy images of 1,081 patients from Hunan Provincial People’s Hospital in China were recorded. Five different colposcopy image features of the cervix including chronic cervicitis, intraepithelial lesions, cancer, polypus, and free hyperplastic squamous epithelial tissue were extracted to be applied in our deep learning network convolutional neural network model. However, the result showed a low accuracy (42.16%) due to computer misrecognition of chronic cervicitis, intraepithelial lesions, and free hyperplastic squamous epithelial tissue with high similarity. To optimize this model, we selected two significant feature images: chronic cervicitis and cervical cancer to input into a deep learning network. The result indicates high accuracy and robustness with an accuracy of 95.19%, which can be applied to detect whether the patient has chronic cervicitis or cervical cancer based on the patient’s colposcopy images.
Optical Coherence Tomography Angiography Parameters Correlated to the Growth of Macular Neovascularization in Age-Related Macular Degeneration
Authors: Arrigo Alessandro , Amato Alessia , Mularoni Cecilia , Saladino Andrea , Aragona Emanuela , Pina Adelaide , Calcagno Francesca , Bandello Francesco , Battaglia Parodi Maurizio
Published: June 2022

Background: To investigate optical coherence tomography angiography (OCTA) quantitative parameters associated with macular neovascularization (MNV) size modifications in age-related macular degeneration.

Methods: Study design was prospective, with 1-year of follow-up. All the included MNV eyes were treated by anti-VEGF intravitreal injections. Quantitative OCTA parameters, including MNV vessel tortuosity (VT) and MNV reflectivity, were calculated. Post-hoc analyses assessed the correlation between quantitative OCTA metrics and MNV size modifications.

Results: A total of 28 MNV eyes of 28 patients were included. Baseline LogMAR BCVA was 0.36 ± 0.21 LogMAR, improved to 0.28 ± 0.22 Log-MAR after 1-year (p < 0.01), with a mean number of 8 ± 3 anti-VEGF injections. Eyes characterized by high MNV VT values group showed worse outcome and higher increases of MNV size. A mean MNV reflectivity value of 101 was associated with a high probability of changes in MNV size. MNV growth was also influenced by the type of MNV, with type 2 and mixed type lesions showing increases in MNV size, unlike type 1 MNV. These factors showed a cumulative effect in determining MNV size modifications. In most of the cases, we observed MNV size increases. Conversely, MNV lesions characterized by low MNV VT values may experience size reductions over the follow-up (34% of cases). The number of intravitreal injections had no significant influence on MNV size changes.

Conclusions: Quantitative OCTA allowed to discriminate highly perfused MNV lesions, providing a basis to predict MNV size modifications and the direction of MNV expansion.
Conditional Regulation of Blood Pressure in Response to Emotional Stimuli by the Central Nucleus of the Amygdala in Rats
Authors: Yamanaka Ko , Waki Hidefumi
Published: June 2022

Humans and animals can determine whether a situation is favorable to them and act accordingly. For this, the autonomic tuning of the cardiovascular system to supply energy to active skeletal muscles through the circulatory system is as important as motor control. However, how the autonomic cardiovascular responses are regulated in dynamically changing environments and the neuronal mechanisms underlying these responses remain unclear. To resolve these issues, we recorded the blood pressure and heart rate of head-restrained rats during dynamically changing appetitive and aversive classical conditioning tasks. The rats displayed various associations between conditioned stimuli and unconditioned stimuli in appetitive (sucrose water), neutral (no outcome), and aversive (air puff) blocks. The blood pressure and heart rate in the appetitive block gradually increased in response to the reward-predicting cue and the response to the actual reward vigorously increased. The reward-predictive response was significantly higher than the responses obtained in the neutral and aversive condition blocks. To investigate whether the reward-predictive pressor response was caused by orofacial movements such as anticipatory licking behavior, we separately analyzed high- and low-licking trials. The conditioned pressor response was observed even in trials with low-licking behaviors. Blood pressure and heart rate responses to the air puff-predicting cue in the aversive block were not significantly different from the responses in the neutral block. The conditioned blood pressure response rapidly changed with condition block switching. Furthermore, to examine the contribution of the amygdala as an emotion center to these conditioned responses, we bilaterally microinjected a GABAA receptor agonist, muscimol, into the central nucleus of the amygdala. Pharmacological inactivation of the central nucleus of the amygdala significantly decreased the reward-predictive pressor responses. These results suggest that the blood pressure is adaptively and rapidly regulated by emotional conditioned stimuli and that the central nucleus of the amygdala participates in regulating the pressor response in dynamically changing situations.