bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels
Authors: Wang Ouxi , Shi Di , Li Yaqi , Zhou Xiaoyan , Yan Haidan , Yao Qianlan
Published: August 2022

Background

Early diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer.

Methods

Based on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR).

Results

A biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes.

Conclusion

We identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer.
A meta-analysis of clinicopathologic features that predict necrosis or fibrosis at post-chemotherapy retroperitoneal lymph node dissection in individuals receiving treatment for non-seminoma germ cell tumours
Authors: Conduit Ciara , Hong Wei , Martin Felicity , Thomas Benjamin , Lawrentschuk Nathan , Goad Jeremy , Grimison Peter , Ahmadi Nariman , Tran Ben , Lewin Jeremy
Published: August 2022

Purpose

Post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) for residual nodal masses is a critical component of care in metastatic testicular germ cell tumour (GCT). However, the procedure is not of therapeutic value in up to 50% of individuals in whom histopathology demonstrates post-treatment necrosis or fibrosis alone. Improved diagnostic tools and clinicopathologic features are needed to separate individuals who benefit from pcRPLND and avoid surgery in those who do not.

Methods

A prospectively registered meta-analysis of studies reporting clinicopathologic features associated with teratoma, GCT and/or necrosis/fibrosis at pcRPLND for metastatic non-seminoma GCT (NSGCT) was undertaken. We examined the effect of various clinicopathologic factors on the finding of necrosis/fibrosis at pcRPLND. The log odds ratios (ORs) of each association were pooled using random-effects models.

Results

Using the initial search strategy, 4,178 potentially eligible abstracts were identified. We included studies providing OR relating to clinicopathologic factors predicting pcRPLND histopathology, or where individual patient-level data were available to permit the calculation of OR. A total of 31 studies evaluating pcRPLND histopathology in 3,390 patients were eligible for inclusion, including two identified through hand-searching the reference lists of eligible studies. The following were associated with the presence of necrosis/fibrosis at pcRPLND: absence of teratomatous elements in orchidectomy (OR 3.45, 95% confidence interval [CI] 2.94-4.17); presence of seminomatous elements at orchidectomy (OR 2.71, 95% CI 1.37-5.37); normal pre-chemotherapy serum bHCG (OR 1.96, 95% CI 1.62-2.36); normal AFP (OR 3.22, 95% CI 2.49–4.15); elevated LDH (OR 1.72, 95% CI 1.37-2.17); >50% change in mass during chemotherapy (OR 4.84, 95% CI 3.94-5.94); and smaller residual mass size (<2 cm versus >2 cm: OR 3.93, 95% CI 3.23-4.77; <5 cm versus >5 cm: OR 4.13, 95% CI 3.26-5.23).

Conclusions

In this meta-analysis, clinicopathologic features helped predict the presence of pcRPLND necrosis/fibrosis. Collaboration between centres that provide individual patient-level data is required to develop and validate clinical models and inform routine care to direct pcRPLND to individuals most likely to derive benefits.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021279699
A combined microinvasive trans-submandibular and nasendoscopy surgical approach to dissect recurrent or radiotherapy-insensitive nasopharyngeal carcinoma
Authors: Zhao Yanming , Fang Jugao , Zhong Qi , Zhang Luo , Wang Chengsuo , Zhang Jiamin , Chen Jiaming , Feng Ling , He Shizhi , Ma Hongzhi , Hou Lizhen , Lian Meng , Shi Qian , Shen Xixi , Yang Yifan , Wang Ru
Published: August 2022

Objective

To investigate a novel combined microinvasive trans-submandibular and nasendoscopy surgical approach for nasopharyngeal carcinoma involving the parapharyngeal space.

Methods

Seven patients diagnosed with nasopharyngeal carcinoma involving the parapharyngeal space between May 2018 and April 2021, two males and five females, aged 37–63 years.Six of the 7 patients underwent submental flap preparation and dissection of the lymph nodes in the upper neck and parapharyngeal space on the lesion side. The nasopharynx lesions and tumor margins were dissected under nasal endoscopy. The medial boundary of internal carotid artery separated by open cervical approach was used as the lateral boundary of the tumor to realize en bloc resection of the tumor.

Results

The patients were preoperatively diagnosed with T2~3N0M0 nasopharyngeal carcinoma, including mucoepidermoid carcinoma (n=2), papillary adenocarcinoma (n=1), and nonkeratinizing squamous cell carcinoma (n=4). The tumors were removed completely, and patients achieved primary healing of the incision. No recurrence and no serious complications were recorded during the 13–48 month follow-up.

Conclusion

Complete resection of the tumor was obtained in the 7 patients without recurrence and serious complications during the follow-up. The findings of this cohort study suggest that, patients with recurrent nasopharyngeal carcinoma after radiotherapy and radiotherapy-insensitive types of nasopharyngeal carcinoma, the combined microinvasive trans-submandibular and nasendoscopy surgical approach may be considered as an surgical options. The results of this study provide an additional option for surgical treatment of NPC in the clinic.
Efficacy and safety of anlotinib plus programmed death-1 blockade versus anlotinib monotherapy as second or further-line treatment in advanced esophageal squamous cell carcinoma: A retrospective study
Authors: Liu Ying , Ge Qingqing , Xu Shuning , Li Ke , Liu Ying
Published: August 2022

Background

Both anlotinib and programmed death-1 (PD-1) blockade have been approved for the second-line treatment of metastatic esophageal squamous cell carcinoma (ESCC). However, the combination of these two therapies has not been evaluated. This study investigated the efficacy and safety of anlotinib, a novel multitarget tyrosine kinase inhibitor targeting tumor angiogenesis, combined with PD-1 blockade as second or further-line treatment for advanced ESCC.

Methods

Between January 2019 and February 2021, 98 advanced ESCC patients receiving anlotinib plus PD-1 blockade or anlotinib monotherapy as second or further-line treatment at Henan Cancer Hospital were retrospectively analyzed. Patients receiving anlotinib plus PD-1 blockade were grouped as cohort A (n=48), while those receiving anlotinib monotherapy were grouped as cohort B (n=50). The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR) and toxicity. Furthermore, independent prognostic factors were identified by Cox regression analysis. A two-sided p-value of <0.05 was considered statistically significant.

Results

Data was collected until May 1, 2021, with a median follow-up time of 9.30 months (8.23–10.37 months) in cohort A and11.10months (7.82–14.38 months) in cohort B. For patients with advanced ESCC, cohort A resulted in significantly longer PFS (5.40 vs. 3.00 months, P<0.001) and higher DCR (71.7% vs. 47.9%, P=0.019) than cohort B. The ORR indicated no significant difference between cohort A (23.9%) and cohort B (10.4%) (P=0.082). Adverse reactions were mainly grade1/2 in the two groups. Compared with cohort B, a significantly higher rate of grade 1–2 hypothyroidism was observed in patients in cohort A (P= 0.034). Three patients (6.3%) developed grade 1/2 immune-related pneumonia. There was no significant difference in the incidence of grade 3-4 toxicities. Multivariable Cox regression analysis showed that the drug regimen (P<0.001), Eastern Cooperative Oncology Group Performance Status (P=0.002), distant organ metastasis (P=0.008), and metastatic sites (P=0.032) were independent prognostic factors for PFS.

Conclusions

Anlotinib plus PD-1 blockade showed promising anti-tumor activity and manageable toxicity as second or further-line treatment of advanced ESCC.
Immune checkpoint inhibitors for PD-1/PD-L1 axis in combination with other immunotherapies and targeted therapies for non-small cell lung cancer
Authors: Mussafi Ofek , Mei Jie , Mao Wenjun , Wan Yuan
Published: August 2022

It has been widely acknowledged that the use of immune checkpoint inhibitors (ICI) is an effective therapeutic treatment in many late-stage cancers. However, not all patients could benefit from ICI therapy. Several biomarkers, such as high expression of PD-L1, high mutational burden, and higher number of tumor infiltration lymphocytes have shown to predict clinical benefit from immune checkpoint therapies. One approach using ICI in combination with other immunotherapies and targeted therapies is now being investigated to enhance the efficacy of ICI alone. In this review, we summarized the use of other promising immunotherapies and targeted therapies in combination with ICI in treatment of lung cancers. The results from multiple animals and clinical trials were reviewed. We also briefly discussed the possible outlooks for future treatment.
Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma
Authors: Xu Liqin , Ma Yuxiang , Fang Chao , Peng Zhuobing , Gao Fangfang , Moll Janne Marie , Qin Shishang , Yu Qichao , Hou Yong , Kristiansen Karsten , Fang Wenfeng , Brix Susanne , Zhang Li
Published: August 2022

Antibodies targeting the programmed cell death protein-1 (PD-1) molecule have been reported to hold promising antitumor activities in patients with nasopharyngeal carcinoma (NPC). However, only a small subset of NPC patients benefits from the anti-PD-1 monotherapy and factors that affect the treatment response need further investigation. This study aimed to examine the impact of multiple genetic and environmental factors on outcome of anti-PD-1 immunotherapy by identifying tumor size, tumor mutation burden (TMB) based on whole exon sequencing, human leukocyte antigen class I (HLA-I) homo-/heterozygosity and supertypes, blood Epstein-Barr virus (EBV) DNA load, T cell proportions, and interferon-γ(IFN-γ) levels in a cohort of 57 NPC patients that received Nivolumab or Camrelizumab treatment. Moreover, we profiled the longitudinal changes in gut microbiota composition using shotgun metagenomics sequencing. We observed that high TMB combined with HLA-I heterozygosity was associated with improved clinical outcomes. In agreement with previous studies, we found that patients with higher plasma EBV DNA load showed worse progression-free survival. We found no evidence for an effect of gut bacterial diversity on the treatment response, but identified a higher abundance of seven specific gut bacteria at baseline of non-responders, including Blautia wexlera and Blautia obeum, as well as four other bacteria belonging to the Clostridiales order, and one Erysipelatoclostridium. Combined, this study provides insight into the influence of several genetic and environmental factors on anti-PD-1 immunotherapy responses in NPC patients.
Post-chemotherapy pneumonia in Chinese patients with diffuse large B-cell lymphoma: Outcomes and predictive model
Authors: Zhao Jinrong , Zhang Yan , Wang Wei , Zhang Wei , Zhou Daobin
Published: August 2022

Pulmonary infections account for a large proportion of life-threatening adverse events that occur after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL); however, data on their influencing risk factors and the effects of infection are relatively limited. A total of 605 patients with DLBCL were newly diagnosed at our institution between March 2009 and April 2017, and 132 of these patients developed pneumonia after treatment (21.8%). There was a significant difference in overall survival (OS) between the pneumonia and non-pneumonia groups (hazard ratio 4.819, 95% confidence interval: 3.109–7.470, p < 0.0001), with 5-year OS of 41% and 82%, respectively. Pulmonary involvement, Eastern Cooperative Oncology Group score > 1, and hypoalbuminemia were identified as independent risk factors for the development of pneumonia. We constructed a prediction model based on these three factors, and the area under the curve was 0.7083, indicating good discrimination. This model may help clinicians develop individualized strategies for preventing and treating post-chemotherapy pneumonia in patients with DLBCL.
Angiogenesis in NENs, with a focus on gastroenteropancreatic NENs: from biology to current and future therapeutic implications
Authors: Lauricella Eleonora , Mandriani Barbara , Cavallo Federica , Pezzicoli Gaetano , Chaoul Nada , Porta Camillo , Cives Mauro
Published: August 2022

Neuroendocrine neoplasms (NENs) are highly vascularized malignancies arising from cells of the diffuse neuroendocrine system. An intricated cross-talk exists between NEN cells and the tumor microenvironment, and three main molecular circuits (VEGF/VEGFR pathway, FGF-dependent signaling and PDGF/PDGFR axis) have been shown to regulate angiogenesis in these neoplasms. Multiple randomized trials have investigated antiangiogenic agents over the past two decades, and sunitinib is currently approved for the treatment of advanced, progressive, G1/G2 pancreatic NENs. In recent years, two phase III clinical trials have demonstrated the efficacy and safety of surufatinib, a multi-tyrosine kinase angioimmune inhibitor, in patients with well-differentiated pancreatic and extrapancreatic NENs, and two studies of this agent are currently underway in Europe and US. The HIF-2α inhibitor belzutifan has recently received regulatory approval for the treatment of tumors arising in the context of Von-Hippel Lindau syndrome including pancreatic NENs, and a study of this drug in patients with sporadic tumors is presently ongoing. Combinations of antiangiogenic agents with chemotherapeutics and targeted drugs have been tested, with accumulating toxicities being a matter of concern. The potential of antiangiogenic agents in fine-tuning the immune microenvironment of NENs to enhance the activity of immune checkpoint inhibitors has been only partially elucidated, and further research should be carried out at this regard. Here, we review the current understanding of the biology of angiogenesis in NENs and provide a summary of the latest clinical investigations on antiangiogenic drugs in this malignancy.
Expression and clinical value of circRNAs in serum extracellular vesicles for gastric cancer
Authors: Xiao Ke , Li Shirong , Ding Juan , Wang Zhen , Wang Ding , Cao Xiangting , Zhang Yi , Dong Zhaogang
Published: August 2022

Objective

At present, there are still no effective diagnosis methods for gastric cancer (GC). Increasing evidences indicate that Extracellular Vesicle circular RNAs (EV circRNAs) play a crucial role in several diseases. However, their correlations with GC are not clarified. This study aims to investigate the expression profile of serum EV circRNAs in GC and evaluate its potential clinical value.

Methods

High-throughput RNA sequencing (RNA-seq) was used to assess circRNA expression profiles between 4 patients with GC and 4 healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed (DE) circRNAs. A circRNA-miRNA-mRNA network was constructed using bioinformatics tools. Reverse transcription-quantitative polymerase chain reaction (RT-q)PCR was used to validate the dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of circRNAs for GC.

Results

A total of 4692 circRNAs were detected in the serum EVs of healthy controls and patients with GC, most of which were novel (98%) and intergenic (52%). 7 circRNAs were upregulated and 4 circRNAs were downregulated (|log2Fold Change| > 2, P < 0.05). GO and KEGG pathway enrichment analyses revealed that DE circRNAs were primarily involved in glutathione metabolism, protein folding, and drug metabolism-cytochrome P450. Of these, 3 circRNAs (Chr10q11, Chr1p11, and Chr7q11) were identified to be significantly overexpressed in patients with GC compared with healthy controls using RT-qPCR. The combination of 3 EV circRNAs and carcinoembryonic antigen (CEA) produced an area under the curve (AUC) of 0.866 (95%CI: 0.803-0.915) with a sensitivity and specificity of 80.4% and 81.8%, respectively. Additionally, the expression levels of 3 EV circRNAs were significantly correlated with tumor size, lymph node metastasis, and TNM stage. The circRNA-miRNA-mRNA network showed that the 3 identified circRNAs were predicted to interact with 13 miRNAs and 91 mRNAs.

Conclusion

Our results illustrate that the panel of EV circRNAs in serum are aberrantly expressed and may act as the suitable biomarkers for gastric cancer.
Evaluation of the Stellae-123 prognostic gene expression signature in acute myeloid leukemia
Authors: Mosquera Orgueira Adrián , Peleteiro Raíndo Andrés , Díaz Arias José Ángel , Antelo Rodríguez Beatriz , López Riñón Mónica , Cerchione Claudio , de la Fuente Burguera Adolfo , González Pérez Marta Sonia , Martinelli Giovanni , Montesinos Fernández Pau , Pérez Encinas Manuel Mateo
Published: August 2022

Risk stratification in acute myeloid leukemia (AML) has been extensively improved thanks to the incorporation of recurrent cytogenomic alterations into risk stratification guidelines. However, mortality rates among fit patients assigned to low or intermediate risk groups are still high. Therefore, significant room exists for the improvement of AML prognostication. In a previous work, we presented the Stellae-123 gene expression signature, which achieved a high accuracy in the prognostication of adult patients with AML. Stellae-123 was particularly accurate to restratify patients bearing high-risk mutations, such as ASXL1, RUNX1 and TP53. The intention of the present work was to evaluate the prognostic performance of Stellae-123 in external cohorts using RNAseq technology. For this, we evaluated the signature in 3 different AML cohorts (2 adult and 1 pediatric). Our results indicate that the prognostic performance of the Stellae-123 signature is reproducible in the 3 cohorts of patients. Additionally, we evidenced that the signature was superior to the European LeukemiaNet 2017 and the pediatric clinical risk scores in the prediction of survival at most of the evaluated time points. Furthermore, integration with age substantially enhanced the accuracy of the model. In conclusion, Stellae-123 is a reproducible machine learning algorithm based on a gene expression signature with promising utility in the field of AML.
Efficacy and safety of the combination of propofol and S(+)-ketamine for procedural sedation in pediatric patients undergoing totally implantable venous access port implantation: A prospective randomized controlled study
Authors: Zhang Yingjun , Ou Chaopeng , Bai Xiaohui , Lai Jielan , Huang Wan , Ouyang Handong
Published: August 2022

Background

Totally implantable venous access port (TIVAP) implantation is usually performed under general anesthesia with endotracheal intubation in children. Procedural sedation without endotracheal intubation has been applied to minor pediatric surgeries like central venous catheter insertion. To explore a more efficient and less invasive anesthesia mode to implant TIVAPs for children, we aimed to evaluate the efficacy and safety of procedural sedation using propofol and S(+)-ketamine compared with general anesthesia.

Methods

Sixty-six patients aged 6 months to 10 years undergoing TIVAP implantation were randomly allocated to two groups. Patients under procedural sedation [S(+)-ketamine-propofol (sketofol) group] were given target-controlled infusion of propofol 4 μg/ml using the Paedfusor model and S(+)-ketamine 0.5 mg/kg as induction, and had target-controlled infusion of propofol 3–4 μg/ml as maintenance. Patients in sketofol group received medium-flow oxygen inhalation through facemasks during surgery. Patients under general anesthesia (control group) were given propofol 2 mg/kg, cisatracurium 0.2 mg/kg, fentanyl 3 μg/kg as induction, and sevoflurane 0.8 minimum alveolar concentration as maintenance after endotracheal intubation. Primary outcome was the postoperative emergence agitation evaluated 5 min after awakening.

Results

Postoperative emergence agitation evaluated 5 min after awakening was lower in sketofol group versus control group [1.0 (0.5, 1.0) vs. 3.0 (2.0, 4.0); median difference (95% CI): 2.0 (1.0, 2.0); P < 0.001]. Time to awakening was significantly lower in sketofol group versus control group [15.0 (5.0, 23.0) vs. 26.0 (20.5, 37.5); median difference (95% CI): 11.0 (7.0, 19.0); P < 0.001], as well as time to discharge from post anesthesia care unit [35.0 (24.0, 45.0) vs. 45.0 (37.5, 59.5); median difference (95% CI): 10.0 (10.0, 23.0); P < 0.001]. Postoperative complications or adverse events were not reported in sketofol group.

Conclusions

Compared to general anesthesia with endotracheal intubation, procedural sedation using propofol and S(+)-ketamine improves the postoperative emergence agitation right after the recovery of consciousness, and has advantage in shortening anesthetic recovery time for pediatric patients undergoing TIVAP implantation.
Pharmacological investigation of brucine anti-ulcer potential
Authors: Noman Muhammad , Qazi Neelum Gul , Rehman Najeeb Ur , Khan Arif-ullah
Published: August 2022

Gastric ulcer is one of the most common chronic gastrointestinal diseases characterized by a significant defect in the mucosal barrier. The current study has been conducted to evaluate the brucine anti-ulcer effect. Brucine has binding energy values ranging from −2.99 to −8.11 kcal/mol against chosen targets, according to in silico research. Brucine exhibits an inhibitory effect against Helicobacter pylori. In vivo findings revealed that brucine (3 mg/kg) showed effective results in healing ethanol-induced ulcer lesions of the gastric region in rats. Brucine showed an inhibitory effect against H+/K+-ATPase. Levels of glutathione, glutathione-s-transferase, and catalase were enhanced in the gastric rat tissue with the use of brucine, while a significant decrease in lipid peroxide levels was seen. Histopathological evaluation showed improvement in cellular architecture and a decrease in inflammatory indicators like cyclooxygenase, tumor necrosis factor, and nuclear factor kappa B expression, validated through immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot techniques. In the reverse transcription–polymerase chain reaction, brucine decreased H+/K+-ATPase mRNA levels. This study reveals that brucine possesses stable binding affinities against selected targets. Brucine exhibits an anti-ulcer effect, mediated via anti-H. pylori, H+/K+-ATPase inhibition, and antioxidant and anti-inflammatory pathways.
Adding Chinese Herbal Medicine to Routine Care is Associated With a Lower Risk of Rheumatoid Arthritis Among Patients With Asthma: A Population-Based Retrospective Cohort Study
Authors: Chang Wei-Chiao , Livneh Hanoch , Chen Wei-Jen , Hsieh Chang-Cheng , Wang Yu-Han , Lu Ming-Chi , Guo How-Ran , Tsai Tzung-Yi
Published: August 2022

Objective: Due to the shared pathogenesis of asthma and rheumatoid arthritis (RA), patients with asthma were found to have a higher risk of RA. While the benefits and safety of Chinese herbal medicine (CHM) for asthma have been reported, the scientific evidence regarding its effect on RA is limited. This longitudinal cohort study aimed to determine the relation between CHM use and RA risk in patients with asthma.

Methods: Using the nationwide claims data, we enrolled 33,963 patients 20–80 years of age who were newly diagnosed with asthma and simultaneously free of RA between 2000 and 2007. From this sample, we utilized propensity score matching to create sets of participants as treatment and control groups, which comprised 13,440 CHM users and 13,440 non-CHM users. The incidence rate and hazard ratio (HR) for RA between the two groups were estimated at the end of 2013. A Cox proportional hazards model was constructed to examine the impact of the CHM use on the risk of RA.

Results: The cumulative incidence of RA was substantially lower in the CHM user group. In the follow-up period, 214 patients in the CHM user group (1.92 per 1,000 person-years) and 359 patients in the non-CHM user group (2.92 per 1,000 person-years) developed RA (adjusted HR = 0.63, 95% confidence interval: 0.54–0.75). Of the commonly-prescribed formulae, nine CHM products were associated with a lower RA risk: Xiao-Qing-Long-Tang, Ma-Xing-Gan-Shi-Tang, Ding-Chuan-Tang, Xin-Yi-Qing-Fei-Tang, Bei Mu, Jie Geng, Xing Ren, Da Huang, and San Chi.

Conclusion: This study found that patients with asthma who received CHM treatment, in addition to the conventional therapy, had a lower risk of RA. Use of CHM treatment may be integrated into conventional therapy to reduce subsequent RA risk among asthma patients.
Formation of pre-metastatic bone niche in prostate cancer and regulation of traditional chinese medicine
Authors: Chen Chiwei , Huang Renlun , Zhou Jianfu , Guo Lang , Xiang Songtao
Published: August 2022

Prostate cancer with bone metastasis has a high cancer-specific mortality. Thus, it is essential to delineate the mechanism of bone metastasis. Pre-metastatic niche (PMN) is a concept in tumor metastasis, which is characterized by tumor-secreted factors, reprogramming of stromal cells, and immunosuppression by myeloid-derived suppressor cells (MDSC), which is induced by bone marrow-derived cells (BMDC) in the target organ. However, PMN does not explain the predilection of prostate cancer towards bone metastasis. In this review, we discuss the initiation of bone metastasis of prostate cancer from the perspective of PMN and tumor microenvironment in a step-wise manner. Furthermore, we present a new concept called pre-metastatic bone niche, featuring inherent BMDC, to interpret bone metastasis. Moreover, we illustrate the regulation of traditional Chinese medicine on PMN.
Prophylactic administration of tranexamic acid combined with thromboelastography-guided hemostatic algorithm reduces allogeneic transfusion requirements during pediatric resective epilepsy surgery: A randomized controlled trial
Authors: Zhang Ting , Feng Hua , Xiao Wei , Li Jingsheng , Liu Qinghai , Feng Xuexin , Qi Dezhou , Fan Xiaotong , Shan Yongzhi , Yu Tao , Zhao Guoguang , Wang Tianlong
Published: August 2022

Background:Intraoperative bleeding and allogeneic transfusion remain common problems in pediatric resective epilepsy surgery. Tranexamic acid (TXA) is a widely recommended antifibrinolytic drug that reduces blood loss and transfusion requirements for bleeding patients. Thromboelastography (TEG)-guided hemostatic algorithm is commonly used in bleeding management. This trial was designed to validate the efficacy of a multimodal coagulation therapy involving continuous TXA infusion with TEG-guided hemostatic algorithm in reducing allogeneic exposure risk in pediatric resective epilepsy surgery.

Methods:Eighty-three children undergoing resective epilepsy surgery were randomized into a treatment group (Group T;n= 42) and a control group (Group C;n= 41). Group T received prophylactic TXA (10 mg/kg followed by 5 mg/kg/h) with TEG-guided hemostatic algorithm, whereas Group C received conventional coagulation management. The primary outcome was allogeneic transfusion rate during surgery, and the secondary outcomes were intraoperative blood loss, incidence of postoperative seizures, and thromboembolic events during hospitalization.

Results:The incidence of intraoperative allogeneic transfusion reduced by 34.7% with the use of a multimodal coagulation therapy (19.0% in Group T vs. 53.7% in Group C; RR 0.355, 95% CI 0.179–0.704;p= 0.001). This was mainly triggered by a significant reduction (44.1%) in intraoperative plasma transfusion (7.1% in Group T vs. 51.2% in Group C; RR 0.139, 95% CI 0.045–0.432;p= 0.000). The risk of intraoperative RBC transfusion was lower in Group T than in Group C, but the difference was not statistically significant (14.3% in Group T vs. 29.3% in Group C; RR 0.488, 95% CI 0.202–1.177;p= 0.098). No platelets were transfused in both groups. Further, 19 (45.2%) patients in Group T received fibrinogen concentrates guided by TEG data, whereas 1 (2.4%) patient in Group C received fibrinogen concentrates empirically. There were no significant differences in estimated blood loss and postoperative seizures between the two groups, and no thromboembolic events were observed after surgery.

Conclusion:Prophylactic administration of TXA combined with TEG-guided hemostatic algorithm can be an effective multimodal coagulation strategy for reducing allogeneic transfusion requirements during pediatric resective epilepsy surgery.

Clinical Trial Registration:www.chictr.org.cn/index.aspx, identifier ChiCTR1800016188.
Activin receptor-like kinase 7 promotes apoptosis of vascular smooth muscle cells via activating Smad2/3 signaling in diabetic atherosclerosis
Authors: Cao Shengchuan , Yuan Qiuhuan , Dong Qianqian , Liu Xilong , Liu Weikang , Zhai Xiaoxuan , Zhang Chuanxin , Liu Han , Tang Mengxiong , Wei Shujian , Chen Yuguo
Published: August 2022

Vascular smooth muscle cells (VSMCs) is a vital accelerator in the late phase of diabetic atherosclerosis, but the underlying mechanism remains unclear. The aim of our study was to investigate whether activin receptor-like kinase 7 (ALK7)-Smad2/3 pathway plays an important role in VSMC apoptosis of diabetic atherosclerosis. It was shown that ALK7 expression was obviously elevated in the aorta of ApoE−/− mice with type 2 diabetes mellitus. Inhibition of ALK7 expression significantly improved the stability of atherosclerotic plaques and reduced cell apoptosis. Further experiments showed that ALK7 knockdown stabilized atherosclerotic plaques by reducing VSMC apoptosis via activating Smad2/3. Our study uncovered the important role of ALK7-Smad2/3 signaling in VSMCs apoptosis, which might be a potential therapeutic target in diabetic atherosclerosis.
Anti-NMDA receptor encephalitis and vaccination: A disproportionality analysis
Authors: Martin Salomé , Azzouz Brahim , Morel Aurore , Trenque Thierry
Published: August 2022

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis is an auto-immune neurological disorder characterized by the presence in the cerebrospinal fluid (CSF) of antibodies against the GluN1 subunit of NMDA receptors in the brain. The etiology of the disease remains largely unknown. In this study, we aimed to investigate the possible existence of pharmacovigilance signals relating to a link between vaccination and the occurrence of anti-NMDAR encephalitis. We performed a case/non-case study using data from the World Health Organization pharmacovigilance database (VigiBase) up to 31 December 2021. All individual case study reports (ICSRs) linked to a vaccine and coded with the MedDRA Lower Level Term (LLT) “anti-NMDA receptor encephalitis” were analysed. We calculated the Reporting Odds Ratio (ROR) and 95% Confidence Interval (CI) for each type of vaccine. A total of 29,758,737 ICSRs were registered in VigiBase, of which 70 were coded under the selected LLT, and 29/70 (41.4%) involved a vaccine. Of these cases, 53.8% involved children aged younger than 15 years. The median time to onset of anti-NMDAR encephalitis after vaccination was 4 days (range 0–730). The highest RORs were observed for the diphtheria/polio/tetanus/pertussis vaccine [54.72 (95% CI 26.2–114.3)], yellow fever vaccine [50.02 (95% CI 15.7–159)] and human papillomavirus vaccine [32.89 (15.8–68.7)]. All cases were coded as serious; 13 patients did not recover, or were left with permanent sequelae. Nine patients recovered without sequelae or are on the path to recovery, and one patient died. In summary, pharmacovigilance signals were observed for anti-NMDAR encephalitis and vaccination. Clinicians need to be aware of this potential risk, and encourage to report any case of anti-NMDAR encephalitis occurring after vaccination.
Evaluating the therapeutic role of selected active compounds in Plumula Nelumbinis on pulmonary hypertension via network pharmacology and experimental analysis
Authors: Xiao Xinghua , Luo Fangmei , Fu Minyi , Jiang Yueping , Liu Shao , Liu Bin
Published: August 2022

Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are critical factors leading to vascular remodeling in pulmonary hypertension (PH). This study aimed to explore the effect and potential mechanism of Plumula Nelumbinis on PH by using network pharmacology and experimental analysis. Network pharmacology and molecular docking results indicated that the potential active components of Plumula Nelumbinis against PH were mainly alkaloid compounds, including neferine, liensinine, and isoliensinine. Subsequently, by constructing a Su5416 plus hypoxia (SuHx)-induced PH rat model, we found that the total alkaloids of Plumula Nelumbinis (TAPN) can reduce the right ventricular systolic pressure, delay the process of pulmonary vascular and right ventricular remodeling, and improve the right heart function in PH rats. In addition, TAPN can effectively reverse the upregulation of collagen1, collagen3, MMP2, MMP9, PCNA, PIM1, and p-SRC protein expression in lung tissue of PH rats. Finally, by constructing a hypoxia-induced PASMCs proliferation and migration model, we further found that TAPN, neferine, liensinine, and isoliensinine could inhibit the proliferation and migration of PASMCs induced by hypoxia; reverse the upregulation of collagen1, collagen3, MMP2, MMP9, PCNA, PIM1 and p-SRC protein expression in PASMCs. Based on these observations, we conclude that the alkaloid compounds extracted from Plumula Nelumbinis (such as neferine, liensinine, and isoliensinine) can inhibit the abnormal proliferation and migration of PASMCs by regulating the expression of p-SRC and PIM1, thereby delaying the progression of PH.
Investigation into the in vivo mechanism of diosmetin in patients with breast cancer and COVID-19 using bioinformatics
Authors: Wang Jin , Ma Shanbo , Li Long , Chen Yuhan , Yang Qian , Wang Feiyan , Zheng Meiling , Miao Shan , Shi Xiaopeng
Published: August 2022

Patients with breast cancer are prone to SARS-CoV-2 infection [the causative virus of coronavirus disease (COVID-19)] due to their lack of immunity. In the current study, we examined the mechanism of action of Diosmetin, a flavonoid with anti-inflammatory properties, in patients with BRCA infected with SARS-CoV-2.We used bioinformatics technology to analyze the binding ability, biological function, and other biological characteristics of Diosmetinin vivo and examine the core target and potential mechanism of action of Diosmetin in patients with patients with breast cancer infected with SARS-CoV-2. A prognostic model of SARS-COV-2–infected breast cancer patients was constructed, and the core genes were screened out, revealing the correlation between these core genes and clinicopathological characteristics, survival rate, and high-risk and low-risk populations. The docking results revealed that Diosmetin binds well to the core genes of patients with breast cancer with COVID-19. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that Diosmetin inhibited inflammation, enhanced immune function, and regulated the cellular microenvironment in patients with BRCA/COVID-19. For the first time, we reveal the molecular functions and potential targets of Diosmetin in patients with breast cancer infected with SARS-CoV-2, improving the reliability of the new drug and laying the foundation for further research and development.
A novel clinical-radiomics model predicted renal lesions and deficiency in children on diffusion-weighted MRI
Authors: Kang Weijie , Ji Min , Zhang Huili , Shi Hua , Xiang Tianchao , Li Yaqi , Fang Ye , Qi Qi , Wang Junbo , Shen Jian , Tang Liangfeng , Liu Xiaoxiong , Ye Yingzi , Ge Xiaoling , Wang Xiang , Xu Hong , Qiao Zhongwei , Shi Jun , Rao Jia
Published: August 2022

Background: Assessment of renal lesions and deficiency accurately remains critical in the diagnosis of congenital anomalies of the kidneys and urinary tracts (CAKUT) in children. Advanced imaging such as Magnetic resonance Imaging (MRI) and Diffusion weighted Imaging (DWI) allows structural and functional insufficiency to be detected. Currently, radiomics machine learning models are being explored as full-automated diagnostic tools. We aimed to develop a machine learning integrated radiomics model to predict renal anomalies and deficiency in children.

Methods: A retrospective study of 280 children with MRI/DWI were enrolled between 2018 and 202 at a children’s hospital. A total of 1,037 radiomics features were extracted from the DWI images of each participant, which were divided into training set and test set (8:2 split). Using 5-fold cross-validated method, multiple machine learning algorithms were employed to predict renal lesions and deficiency when compared with the radiologist’s diagnosis based on DWI, 99mTc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy or 99mTc-labeled diethylenetriamine pentaacetate (DTPA) renal scan.

Results: For detecting the kidney lesions, the LASSO + Random Forest algorithm outperformed other classifiers with an accuracy of 0.750 (95% confidence interval, 0.734–0.766) and area under the curve (AUC) of 0.765 (95% confidence interval, 0.700–0.831). The performance of classifiers did not show a significant difference (p > 0.05) in detecting bilateral or unilateral kidney lesions by DWI scanning. The classifiers performed significantly better in bilateral kidney deficit than in unilateral kidney deficit (p < 0.05). We next built prediction models for renal deficiency using the radiomics signature and clinical features compared to renal scintigraphy. The ensemble model had a high-test accuracy of 80.9% ± 4.2% and a sensitivity of 91.7% ± 7.1% with a moderate calibration.

Conclusion: An ensemble model integrated with DWI-radiomic and clinical features can be utilized to predict renal lesions and deficiency in children with CAKUT.
Effects of individual heterogeneity and multi-type information on the coupled awareness-epidemic dynamics in multiplex networks
Authors: Chen Peiyu , Guo Xudong , Jiao Zengtao , Liang Shihao , Li Linfeng , Yan Jun , Huang Yadong , Liu Yi , Fan Wenhui
Published: August 2022

Awareness of epidemics can influence people’s behavior and further trigger changes in epidemic spreading. Previous studies concentrating on the coupled awareness-epidemic dynamics usually ignore the multi-type information and the heterogeneity of individuals. However, the real-world cases can be more complicated, and the interaction between information diffusion and epidemic spreading needs further study. In this article, we propose an individual-based epidemics and multi-type information spreading (IEMIS) model on two-layered multiplex networks considering positive and negative preventive information and two types of heterogeneity: 1) heterogeneity of aware individual’s state which leads to differences in aware transmission capacity and 2) heterogeneity of individual’s node degree which affects the epidemic infection rate. Based on Micro-Markov Chain approach (MMCA), we derive the theoretical epidemic threshold for the proposed model and validate the results by those obtained with Monto Carlo (MC) simulations. Through extensive simulations, we demonstrate that for epidemics with low infectivity, promoting the diffusion of positive preventive information, enhancing the importance ratio of neighbors who are aware of positive information, and increasing social distance among individuals can effectively suppress epidemic spreading. However, for highly infectious diseases, the influence of these factors becomes limited.
Effect of 12 weeks of complex training on occupational activities, strength, and power in professional firefighters
Authors: Liu Meng , Zhou Kaixiang , Li Bin , Guo Zhenxiang , Chen Yan , Miao Guozhen , Zhou Limingfei , Liu Haoyang , Bao Dapeng , Zhou Junhong
Published: August 2022

Objective: This study examined the effects of 12-week complex training (CT) programs on professional firefighters’ occupational activities, strength, and power.

Methods: Thirty men professional firefighters were randomly assigned to the CT group (n = 15) and control group (n = 15). The CT group performed complex training and the control group completed resistance training (RT) twice a week over 12 weeks. The occupational activities, strength, and power were assessed at baseline and immediately after the intervention by measuring the performance of 100 m load-bearing run (100 m LR), 60 m shoulder ladder run (60 m SLR), 5 m × 20 m shuttle run (5 m × 20 m SR), 4th-floor climbing rope (4th-floor CR), countermovement jump with arm swing (CMJas), seated medicine-ball throw (SMT), one-repetition maximum bench press (1RM BP), and one-repetition maximum back squat (1RM BS).

Results: The results showed that compared to RT, CT induced significantly greater improvements in 60 m SLR (p = 0.007), 4th-floor CR (p = 0.020), CMJas (p = 0.001), and SMT (p < 0.001).

Conclusion: These findings suggest that CT is a novel intervention with great promise of improving professional firefighters’ occupational activities, strength, and power.
Identifying the natural reserve area of Cistanche salsa under the effects of multiple host plants and climate change conditions using a maximum entropy model in Xinjiang, China
Authors: Shao Minghao , Fan Jinglong , Ma Jinbiao , Wang Lei
Published: August 2022

Cistanche salsa (C. A. Mey.) G. Beck, a holoparasitic desert medicine plant with multiple hosts, is regarded as a potential future desert economic plant. However, as a result of excessive exploitation and poaching, its wild resources have become scarce. Thus, before developing its desert economic value, this plant has to be protected, and the identification of its natural reserve is currently the top priority. However, in previous nature reserve prediction studies, the influence of host plants has been overlooked, particularly in holoparasitic plants with multiple hosts. In this study, we sought to identify the conservation areas of wild C. salsa by considering multiple host–plant interactions and climate change conditions using the MaxEnt model. Additionally, a Principal Component Analysis (PCA) was used to reduce the autocorrelation between environmental variables. The effects of the natural distribution of the host plants in terms of natural distribution from the perspective of niche similarities and extrapolation detection were considered by filtering the most influential hosts: Krascheninnikovia ceratoides (Linnaeus), Gueldenstaedt, and Nitraria sibirica Pall. Additionally, the change trends in these hosts based on climate change conditions combined with the change trends in C. salsa were used to identify a core protection area of 126483.5 km2. In this article, we corrected and tried to avoid some of the common mistakes found in species distribution models based on the findings of previous research and fully considered the effects of host plants for multiple-host holoparasitic plants to provide a new perspective on the prediction of holoparasitic plants and to provide scientific zoning for biodiversity conservation in desert ecosystems. This research will hopefully serve as a significant reference for decision-makers.