Publications by authors named "Jun Zhao"

2,106 Publications

  • Page 1 of 1

Identification of Multi-Target Anti-AD Chemical Constituents From Traditional Chinese Medicine Formulae by Integrating Virtual Screening and Validation.

Front Pharmacol 2021 16;12:709607. Epub 2021 Jul 16.

Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the health of the elderly. At present, no drugs have been proven to cure or delay the progression of the disease. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach provides an innovative and promising idea in search for new drugs against AD. In order to find potential multi-target anti-AD drugs from traditional Chinese medicine (TCM) formulae, a compound database derived from anti-AD Chinese herbal formulae was constructed and predicted by the anti-AD multi-target drug prediction platform established in our laboratory. By analyzing the results of virtual screening, 226 chemical constituents with 3 or more potential AD-related targets were collected, from which 16 compounds that were predicted to combat AD through various mechanisms were chosen for biological validation. Several cell models were established to validate the anti-AD effects of these compounds, including KCl, Aβ, okadaic acid (OA), SNP and HO induced SH-SY5Y cell model and LPS induced BV2 microglia model. The experimental results showed that 12 compounds including Nonivamide, Bavachromene and 3,4-Dimethoxycinnamic acid could protect model cells from AD-related damages and showed potential anti-AD activity. Furthermore, the potential targets of Nonivamide were investigated by molecular docking study and analysis with CDOCKER revealed the possible binding mode of Nonivamide with its predicted targets. In summary, 12 potential multi-target anti-AD compounds have been found from anti-AD TCM formulae by comprehensive application of computational prediction, molecular docking method and biological validation, which laid a theoretical and experimental foundation for in-depth study, also providing important information and new research ideas for the discovery of anti-AD compounds from traditional Chinese medicine.
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http://dx.doi.org/10.3389/fphar.2021.709607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322649PMC
July 2021

Effects of Naodesheng tablets on amyloid beta-induced dysfunction: A traditional Chinese herbal formula with novel therapeutic potential in Alzheimer's disease revealed by systems pharmacology.

Biomed Pharmacother 2021 Jul 22;141:111916. Epub 2021 Jul 22.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Naodesheng (NDS) tablets have been widely used to treat ischemic stroke clinically. NDS relieves neurological function impairment and improve learning and memory in rats with focal cerebral ischemia, suggesting that NDS has potential for Alzheimer's disease (AD) treatment. However, there are no studies about its effective material basis and possible mechanisms. In this study, a systems pharmacology method was applied to reveal the potential molecular mechanism of NDS in the treatment of AD. First, we obtained 360 NDS candidate constituents through ADMET filter analysis. Then, 115 AD-related targets were uncovered by pharmacophore model prediction via mapping the predicted targets against AD-related proteins. In addition, compound-target and target-function networks were established to suggest potential synergistic effects among the candidate constituents. Furthermore, potential targets regulated by NDS were integrated into AD-related pathways to demonstrate the therapeutic mechanism of NDS in AD treatment. Subsequently, a validation experiment proved the therapeutic effect of NDS on cognitive dysfunction in rats with intracerebroventricular injection of Aβ. We found that administration of NDS tablets regulates β-amyloid metabolism, improves synaptic plasticity, inhibits neuroinflammation and improves learning and memory function. In conclusion, this is the first study to provide a comprehensive systems pharmacology approach to elucidate the potential therapeutic mechanism of NDS tablets for AD treatment. We suggest that the protective effects of NDS in neurodegenerative conditions could be partly attributed to its role in improving synaptic plasticity and inhibiting neuroinflammation via NF-κB signaling pathway inhibition and cAMP/PKA/CREB signaling pathway activation.
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http://dx.doi.org/10.1016/j.biopha.2021.111916DOI Listing
July 2021

First-in-human evaluation of a PD-L1-binding peptide radiotracer in non-small cell lung cancer patients with PET.

J Nucl Med 2021 Jul 29. Epub 2021 Jul 29.

Peking University Cancer Hospital and Institute, China.

Ga-NOTA-WL12 is a peptide-based positron emission tomography (PET) imaging agent. We conducted a first-in-human study of Ga-NOTA-WL12 for PET to study the in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying programmed death ligand-1 (PD-L1) expression levels in advanced non-small cell lung cancer (NSCLC) patients. In vitro assessment of the relationship between PD-L1 expression and cellular uptake of Ga-NOTA-WL12 was performed, followed by in vivo evaluation of Ga-NOTA-WL12 uptake in animal models. Nine NSCLC patients with positive PD-L1 expression in lesions were enrolled. Ga-NOTA-WL12 and paired F-FDG PET/CT imaging were performed. The patients were monitored for adverse events. The uptake (SUV/L and kBq/mL) values of tumors and normal organs were obtained. The biodistribution, radiation dosimetry and relationship of tumor uptake and PD-L1 expression were then evaluated. Follow-up F-FDG PET/CT was performed in patients who had undergone treatment with a combination of pembrolizumab with chemotherapy. The cellular and animal experiments demonstrated that PD-L1 expression correlated with the uptake of Ga-NOTA-WL12, and PD-L1-positive tumors exhibited high uptake of Ga-NOTA-WL12. Clinical research showed that Ga-NOTA-WL12 PET imaging is safe with acceptable radiation dosimetry. Physiological tracer uptake was mainly visible in the liver, spleen, small intestine and kidney. High contrast of tumors was observed, particularly in the lungs with a T/lung ratio of 4.45 ±1.89 at 1 h. One hour was a suitable timepoint for image acquisition because no significant differences were noted in the tumor-to-background ratios between 1 and 2 h. Additionally, a strong relationship was found between the tumor uptake (SUVpeak) and PD-L1 immunohistochemistry results (r = 0.9349; = 0.002). Ga-NOTA-WL12 uptake before therapy might indicate the therapeutic efficacy of pembrolizumab plus chemotherapy combination treatment. Our first-in-human findings demonstrate the safety and feasibility of Ga-NOTA-WL12 for noninvasive in vivo detection of the tumor PD-L1 expression levels, indicating potential benefits for clinical PD-L1 therapy.
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http://dx.doi.org/10.2967/jnumed.121.262045DOI Listing
July 2021

Translation and validation of the Chinese version of the MD Anderson symptom inventory for measuring perioperative symptom burden in patients with gynecologic cancer.

BMC Womens Health 2021 Jul 29;21(1):276. Epub 2021 Jul 29.

Nursing Study Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, No. 55, 4Th Section of Renmin South Road, Chengdu, Sichuan, China.

Background: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN.

Methods: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed.

Results: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01).

Conclusions: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.
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http://dx.doi.org/10.1186/s12905-021-01415-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320042PMC
July 2021

Nutrient-Limited Enrichments of Nitrifiers From Soil Yield Consortia of -Affiliated AOA and -Affiliated NOB.

Front Microbiol 2021 12;12:671480. Epub 2021 Jul 12.

Fort Lauderdale Research and Education Center, Department of Microbiology and Cell Science, University of Florida, Davie, FL, United States.

The discovery of ammonia-oxidizing archaea (AOA) and complete ammonia-oxidizing (comammox) bacteria widespread in terrestrial ecosystems indicates an important role of these organisms in terrestrial nitrification. Recent evidence indicated a higher ammonia affinity of comammox bacteria than of terrestrial AOA and ammonia-oxidizing bacteria (AOB), suggesting that comammox bacteria could potentially represent the most low-nutrient adapted nitrifiers in terrestrial systems. We hypothesized that a nutrient-limited enrichment strategy could exploit the differences in cellular kinetic properties and yield enrichments dominated by high affinity and high yield comammox bacteria. Using soil with a mixed community of AOA, AOB, and comammox , we compared performance of nutrient-limited chemostat enrichment with or without batch culture pre-enrichment in two different growth media without inhibitors or antibiotics. Monitoring of microbial community composition via 16S rRNA and gene sequencing showed that batch enrichments were dominated by AOB, accompanied by low numbers of AOA and comammox . In contrast, nutrient-limited enrichment directly from soil, and nutrient-limited sub-cultivation of batch enrichments consistently yielded high enrichments of -affiliated AOA associated with multiple canonical nitrite-oxidizing strains, whereas AOB numbers dropped below 0.1% and comammox were lost completely. Our results reveal competitiveness of sp. under nutrient limitation, and a likely more complex or demanding ecological niche of soil comammox than simulated in our nutrient-limited chemostat experiments.
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http://dx.doi.org/10.3389/fmicb.2021.671480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312096PMC
July 2021

In vitro antimicrobial effect and mechanism of action of plasma-activated liquid on planktonic .

Bioengineered 2021 Dec;12(1):4605-4619

Department of Dermatology, the Second Affiliated Hospital, Anhui Medical University, Hefei, People's Republic of China.

() is highly resistant to treatment, and there is an urgent need for new treatments to alleviate gonococcal resistance caused by antibiotic monotherapy. The antimicrobial effect and mechanism of plasma-activated liquid (PAL) on were evaluated in this study. Upon PAL treatment, extensively analyses on cell culturability, metabolic capacity, intracellular reactive oxygen species (ROS),membrane integrity and nucleic acids for Ng were carried out and significant antimicrobial effects observed.PAL exerted antibacterial effect on and induced bacterial death (6.71-log) following immersion for 30 min and treatment for 120 s. However, bacterial viability test revealed that after immersion in the same PAL, 10.17% of bacteria retained their metabolic capacity. This indicates that bacteria enter a physiological viable but non-culturable state to protect themselves from environmental stress. Confocal fluorescence microscopy and transmission electron microscopy demonstrated that PAL exerts bactericidal effect on and disrupts its morphological structure. PAL may upregulate inflammatory factors and genes to modulate the resistance of and affect the immune status of the host during infection.
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http://dx.doi.org/10.1080/21655979.2021.1955548DOI Listing
December 2021

Postoperative Adjuvant therapy versus Surgery Alone for Stage IIB-III Esophageal Squamous Cell Carcinoma: A Phase III Randomized Controlled Trial.

Oncologist 2021 Jul 26. Epub 2021 Jul 26.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Retrospective studies have shown that adjuvant treatment improves survival of patients with stage IIB-III esophageal squamous cell carcinoma, but there is no evidence from prospective trials so far.

Methods: Patients with pathological stage IIB-III esophageal squamous cell carcinoma were randomly assigned to receive surgery alone (SA), postoperative radiotherapy (PORT), or postoperative concurrent chemoradiotherapy (POCRT). PORT patients received 54 Gy in 27 fractions; POCRT group received 50.4 Gy in 28 fractions, plus concurrent chemotherapy with paclitaxel (135-150 mg/m ) and cisplatin or nedaplatin (50-75 mg/m ) every 28 days. The primary endpoint was disease-free survival (DFS), and secondary endpoint was overall survival (OS).

Results: A total of 172 patients were enrolled (SA, n=54; PORT, n=54; POCRT, n=64). The 3-year DFS was significantly better in PORT/POCRT patients than in SA patients (53.8% vs. 36.7%; p = 0.020); the 3-year OS was also better in PORT/POCRT patients (63.9% vs. 48.0%; p = 0.025). The 3-year DFS for SA, PORT, and POCRT patients were 36.7%, 50.0%, 57.3%, respectively (p = 0.048). The 3-year OS for SA, PORT, and POCRT patients were 48.0%, 60.8%, 66.5%, respectively (p = 0.048).

Conclusion: PORT/POCRT (especially POCRT) may significantly improve DFS and OS in stage IIB-III esophageal squamous cell carcinoma.

Implications For Practice: The results of this phase III study indicated that PORT/POCRT could significantly improve DFS and OS in stage IIB-III esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. In-field and out-of-field recurrences were comparable between the POCRT and PORT groups, which demonstrates the rationality and safety of the radiation field used in our study. The postoperative regimens in this trial might be accepted as a standard treatment options for pathological stage IIB-III esophageal cancer. Larger sample size prospective randomized trials to identify the value are warranted.
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http://dx.doi.org/10.1002/onco.13914DOI Listing
July 2021

Afatinib in EGFR TKI-Naïve Patients with Locally Advanced or Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase IIIb Studies.

Front Oncol 2021 9;11:709877. Epub 2021 Jul 9.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Afatinib is approved for first-line treatment of patients with epidermal growth factor receptor mutation-positive (m+) non-small-cell lung cancer (NSCLC). Here, we report findings from a combined analysis of three phase IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naïve patients.

Methods: EGFR-TKI-naïve patients with m+ NSCLC received afatinib 40 mg/day. Dose reductions were permitted for adverse events (AEs). Efficacy endpoints included progression-free survival (PFS), time to symptomatic progression (TTSP), and tumor response. Subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, age and common/uncommon mutations (plus other factors).

Results: 1108 patients were treated. Median age was 61 years (range, 25-89); 19.2% had baseline brain metastases, 4.4% had ECOG PS ≥2, and 17.9% had tumors harboring uncommon mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 months [95% confidence interval (CI): 12.0-13.8]; median TTSP was 14.8 months (95% CI: 13.9-16.1). Objective response rate (ORR) was 55.0%. Age, presence of baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer in patients with ECOG PS 2 or exon 20 insertion/T790M mutations.

Conclusions: Afatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommon mutations.
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http://dx.doi.org/10.3389/fonc.2021.709877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298067PMC
July 2021

Effects of azithromycin on treating chronic obstructive pulmonary disease with acute exacerbation of chronic bronchitis in the stable phase.

Am J Transl Res 2021 15;13(6):7370-7375. Epub 2021 Jun 15.

Department of Respiratory Medicine, The First People's Hospital of Fuyang Hangzhou Hangzhou 311400, Zhejiang 311400, China.

Objective: To explore the effects of azithromycinon in treatment of chronic obstructive pulmonary disease (COPD) in patients with acute exacerbation (AE) of chronic bronchitis (CB) in the stable phase.

Methods: Totally, 60 COPD patients with AE of CB were divided into control group (CG, 30 cases) and experimental group (EG, 30 cases) using the random number residue method. The CG was administered 250 mg salmeterol-fluticasone powder inhalation twice a day combined with 18 µg tiotropium bromide inhalation once a day. The EG was treated with 250 mg azithromycin tablets once a day in addition to the treatment of the CG. We compared the clinical effect, pulmonary function, and fractional exhaled nitric oxide index between two groups after treated for three-months.

Results: Compared with the CG, the EG showed a better clinical effect with a total effective rate at 86.67% after treatment (<0.05). The EG exhibited better FEV1 and FEV1% than the CG (<0.05). We also observed the difference between clinically FeNO-invalid patients before and after treatment was significant (<0.05). After treatment, this difference among groups was statistically significant (<0.05).

Conclusions: Azithromycin combined with salmeterol-fluticasone powder inhalation and tiotropium bromide inhalation have good effects for treating COPD patients with AE of CB in the stable stage and can improve the pulmonary function. When COPD with AE of CB was exacerbated, the FeNO index increased significantly, indicating a potential increase in the mucosal inflammatory cells and eosinophils of the airway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290734PMC
June 2021

Clinical observation of octreotide combined with diclofenac sodium in preventing ERCP-related pancreatitis.

Am J Transl Res 2021 15;13(6):7179-7185. Epub 2021 Jun 15.

Department of Gastrointestinal Surgery, Nanhua Hospital, Nanhua University Hengyang, Hunan Province, China.

Objective: To elucidate the efficacy of octreotide in combination with diclofenac sodium in the prevention of ERCP-related pancreatitis, and investigate its impact on patients' serum amylase, white blood cell (WBC) count, adverse effects, hyperamylasemia and hemorheology.

Methods: The prospective study was conducted, in which 124 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) in our hospital were evenly divided into 2 groups, the observation group (n=62) and the control group (n=62), via a random number table method. The control group was administered diclofenac sodium lidocaine hydrochloride via injection after ERCP, while the observation group was given octreotide acetate on the basis of the control group. The incidence of pancreatitis, serum amylase level, WBC count, incidence of adverse effects and hyperamylasemia, and hemorheology levels were compared between these two groups of patients.

Results: The incidence of pancreatitis in the observation group was significantly lower than that in the control group (P<0.05). After treatment, the serum amylase level at 24 h post-surgery in the observation group was notably lower than that in the control group (P<0.001). The WBC count at 2 h and 24 h post-surgery in the observation group were both significantly lower than those in the control group (all P<0.001). The incidence of total adverse reactions in the observation group was remarkably lower than that in the control group (P<0.01). The incidence of hyperamylasemia in the observation group was considerably lower than that in the control group (P<0.001). Twenty-four hours post-surgery, the whole blood viscosity at high shear rate, whole blood viscosity at low shear rate, and plasma viscosity in the observation group were all significantly lower than those in the control group (all P<0.001).

Conclusion: The combination of octreotide and diclofenac sodium could effectively prevent the occurrence of ERCP-related pancreatitis, which reduced the incidence of hyperamylasemia, decreased the WBC count and serum amylase level, improved the hemorheology, and lowered the incidence of adverse effects in patients after ERCP. Therefore, this therapeutic strategy is worthy of clinical propagation and application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290821PMC
June 2021

Immune Myocarditis Overlapping With Myasthenia Gravis Due to Anti-PD-1 Treatment for a Chordoma Patient: A Case Report and Literature Review.

Front Immunol 2021 8;12:682262. Epub 2021 Jul 8.

Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Immunotherapy begins to be widely used due to the increasing exploration and gratifying effects in multiple cancers. Chordoma, as a rare bone malignant tumor, often recurs and metastasizes after undergoing surgery and radiotherapy. Therefore, immunotherapy can be explored as an emerging, potentially effective treatment to improve the survival rate and clinical benefit of patients. However, a variety of immune-related adverse events (irAEs) cannot be avoided completely. And the immunotherapy-induced myocarditis, as a rare but fatal irAE, has been increasingly reported. Understanding the mechanism involved in irAEs can inform best practices for side effects management. Here, we firstly reported a case of immune myocarditis and subsequent myasthenia gravis (MG) following anti-PD-1 treatment for chordoma.
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http://dx.doi.org/10.3389/fimmu.2021.682262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297709PMC
July 2021

First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer.

J Immunother Cancer 2021 Jul;9(7)

Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China

Background: Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.

Methods: Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent F-FDG and Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.

Results: Preclinical studies showed that Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of Zr-CTB006 with a mean maximum standardized uptake value (SUV) of 6.63±3.29 (range 1.8-13.8). Tumor tissue was obtained from 18 patients, and Zr-CTB006 uptake in patients with RNAscope scores of 3-4 was significantly higher than that in patients with scores of 0-2. An SUV of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.

Conclusions: Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.
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http://dx.doi.org/10.1136/jitc-2021-002926DOI Listing
July 2021

Comparison of [ Ga]Ga-FAPI-04 and [F]-FDG for the detection of primary and metastatic lesions in patients with gastric cancer: a bicentric retrospective study.

Eur J Nucl Med Mol Imaging 2021 Jul 23. Epub 2021 Jul 23.

PET Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Introduction: The low sensitivity of [F]-fluorodeoxyglucose ([F]-FDG) for the diagnosis of gastric cancer limits its application. In this study, we aimed to investigate the potential advantage of [ Ga]Ga-FAPI-04 over [F]-FDG in the evaluation of gastric cancer.

Methods: This was a bicentric retrospective analysis of a prospective parent study (clinical trial: HS-KY-2020-826 (Huashan Hospital) and DF-2020-102 (Shanghai East Hospital)). Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were included in this study. All of the participants underwent [ Ga]Ga-FAPI-04 and [F]-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The scans were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUV) was calculated. Histopathological findings obtained from biopsy or resected surgical specimens were used as a reference for the final diagnosis.

Results: For the detection of primary gastric cancer, the sensitivities of [ Ga]Ga-FAPI-04 PET and [F]-FDG PET were 100% (38/38) and 82% (31/38), respectively (P = 0.016). Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by [F]-FDG PET. The mean SUV of [ Ga]Ga-FAPI-04 in tumours greater than 4 cm (11.0 ± 4.5) was higher than that in tumours less than 4 cm (4.5 ± 3.2) (P = 0.0015). The mean SUV of [ Ga]Ga-FAPI-04 was higher in T2-4 tumours (9.7 ± 4.4) than in T1 tumours (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of [ Ga]Ga-FAPI-04 PET and [F]-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively.

Conclusion: In this selected cohort, [ Ga]Ga-FAPI-04 PET had a superior detection rate than [F]-FDG PET for primary gastric cancer. [ Ga]Ga-FAPI-04 PET could provide better performance with regard to gastric cancer diagnosis and staging. Prospective clinical trials are warranted.
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http://dx.doi.org/10.1007/s00259-021-05441-wDOI Listing
July 2021

Clinical Observation of Gene Polymorphism of Olanzapine or Aprepitant in Prevention of CINV.

Pharmgenomics Pers Med 2021 15;14:867-875. Epub 2021 Jul 15.

Department of Medical Oncology, Ordos Central Hospital, Ordos, 017000, People's Republic of China.

Objective: The present study aims to investigate the correlation between the gene polymorphisms of the multidrug resistance protein 1 (ABCB1), the intron region of transcriptional factor (GTF2E1) and catechol--methyltransferase (COMT), dopamine receptor (DRD2), and the control of chemotherapy-induced nausea and vomiting (CINV) by olanzapine or aprepitant in a Chinese population under a fractionated cisplatin dosing pattern.

Methods: Antiemetic treatment with 5 mg of olanzapine or aprepitant triplet therapy was conducted in 210 patients with malignancies receiving cisplatin multi-day chemotherapy. The general data on the patients were collected with the evaluation of the rate of complete protection (TP), complete remission (CR), complete control (TC), and time to first vomiting, the functional living index-emesis (FLIE) scale, and side effects in the acute and delayed phases. The DNA mass spectrometry detected the gene polymorphisms of ABCB1, GTF2E1, COMT, and DRD2, and the correlation with TP was analyzed.

Results: 1) There were no statistically significant differences in the TP, CR, TC, time of first vomiting, and FLIE index at different phases between the 5mg of olanzapine group and the aprepitant group (P > 0.05). 2) The main side effect in the olanzapine group was drowsiness (P = 0.00), and in the aprepitant group was constipation (P = 0.02). 3) The distributions of each genotype were in the Hardy-Weinberg (H-W) equilibrium. Univariate analysis showed that in the olanzapine group, delayed-phase TP was correlated with the ABCB1 rs1045642 non-TT (P = 0.01) genotype.

Conclusion: The present study revealed that females and the rs1045642TT genotype were independent risk factors for delayed-phase CINV in the northern Chinese population, which provided a scientific basis for subsequent CINV-related analysis of high-risk factors in Chinese patients.
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http://dx.doi.org/10.2147/PGPM.S317229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289460PMC
July 2021

Unbalanced status and multidimensional influences of municipal solid waste management in Africa.

Chemosphere 2021 Oct 15;281:130884. Epub 2021 May 15.

Department of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China.

The overall status of MSW management in Africa is evaluated systematically, in sight of life cycle indicators such as MSW generation daily per capita, collection and treatment methods. The relations of life cycle indictors with driving factors, including economic level, geographical location, urbanization and solid waste legislation process, are discussed. The results present that the major indicators had obvious regional differences, which can divide Africa into three levels: North Africa and South Africa > West Africa and Central Africa > East Africa. Besides, the disposal methods in North Africa, South Africa and West Africa have evolved from simple open dumping to sanitary landfill, composting and recycle treatment, while opening dumping is still rampant in East Africa. With a combination tool of Principal Component Analysis and Multiple Linear Regression, it was identified that economic growth, urbanization and geographical location are the most critical factors influencing the unbalanced statue of MSW management in Africa. By cluster analysis, unbalance status of MSW management in African countries can be integrated into three grades of MSW management level: good, fair and poor.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130884DOI Listing
October 2021

Sex Differences in Osteomyelitis of the Foot in Persons With Diabetes Mellitus: A Meta-Analysis.

Wound Manag Prev 2021 May;67(5):19-25

Nantong University, Nantong City, Jiangsu Province, China.

Background: Osteomyelitis of the foot is a risk factor for amputation in persons with diabetes mellitus. There is some evidence to suggest that patient sex affects the risk of diabetes-related foot complications.

Purpose: To examine the effect of sex on osteomyelitis risk in patients with diabetic foot disease.

Methods: Systematic searches of PubMed and the China National Knowledge Infrastructure were performed from inception through May 2020 using the terms "diabetic foot" and "osteomyelitis." Original research studies including persons with diabetes mellitus, diabetic foot disease, or ulcers as well as reports of osteomyelitis were included. Study quality was assessed according to the Newcastle-Ottawa Scale. The pooled odds ratio (OR) and 95% confidence interval (CI) for osteomyelitis were calculated by sex.

Results: Nine (9) studies from 6 countries involving 2583 patients met the inclusion criteria for analysis. No significant publication bias was observed. The average age of patients was 65.2 years, and 32.03% of men and 30.0% of women were diagnosed with osteomyelitis. The pooled OR was 1.14 (95% CI, 0.94-1.38; P = .76). Regression analysis (t = -0.61; P > .561) showed no association between the incidence of osteomyelitis and ORs.

Conclusion: This meta-analysis suggests that patient sex does not affect the odds of having osteomyelitis among persons with diabetes and diabetic foot disease or ulcers.
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May 2021

Critical Role of Sc Substitution in Modulating Ferroelectricity in Multiferroic LuFeO.

Nano Lett 2021 Jul 20. Epub 2021 Jul 20.

School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

Understanding how individual dopants or substitutional atoms interact with host lattices enables us to manipulate, control, and improve the functionality of materials. However, because of the intimate coupling among various degrees of freedom in multiferroics, the atomic-scale influence of individual foreign atoms has remained elusive. Here, we unravel the critical roles of individual Sc substitutional atoms in modulating ferroelectricity at the atomic scale of typical multiferroics, LuScFeO, by combining advanced microscopy and theoretical studies. Atomic variations in polar displacement of intriguing topological vortex domains stabilized by Sc substitution are directly correlated with Sc atom-mediated local chemical and electronic fluctuations. The local FeO trimerization magnitude and Lu/Sc-O hybridization strength are found to be significantly reinforced by Sc, clarifying the origin of the strong dependence of improper ferroelectricity on Sc content. This study could pave the way for correlating dopant-regulated atomic-scale local structures with global properties to engineer emergent functionalities of numerous chemically doped functional materials.
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http://dx.doi.org/10.1021/acs.nanolett.1c02123DOI Listing
July 2021

Biological Characteristics of and Strains.

Int J Mol Sci 2021 Jul 1;22(13). Epub 2021 Jul 1.

Team of Crop Verticillium wilt, c/o State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

is a soil-borne plant pathogenic fungus that causes Verticillium wilt on hundreds of dicotyledonous plant species. is considered an asexually (clonal) reproducing fungus, although both mating type idiomorphs ( and ) are present, and is heterothallic. Most of the available information on strains, including their biology, pathology, and genomics comes from studies on isolates with the idiomorph, and thus little information is available on the strains in the literature. We therefore evaluated the growth responses of and   strains to various stimuli. Growth rates and melanin production in response to increased temperature, alkaline pH, light, and HO stress were higher in the strains than in the strains. In addition, the strains showed an enhanced ability to degrade complex polysaccharides, especially starch, pectin, and cellulose. Furthermore, several strains from both potato and sunflower showed increased virulence on their original hosts, relative to their counterparts. Thus, compared to strains, strains derive their potentially greater fitness from an increased capacity to adapt to their environment and exhibit higher virulence. These competitive advantages might explain the current abundance of strains relative to strains in the agricultural and sylvicultural ecosystems, and this study provides the baseline information on the two mating idiomorphs to study sexual reproduction in under natural and laboratory conditions.
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http://dx.doi.org/10.3390/ijms22137148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269371PMC
July 2021

Passivity-based event-triggered control for a class of switched nonlinear systems.

ISA Trans 2021 Jul 8. Epub 2021 Jul 8.

State Key Laboratory of Synthetical Automation for Process Industries, Northeastern University, Shenyang, 110819, China; College of Information Science and Engineering, Northeastern University, Shenyang, 110819, China. Electronic address:

A static output feedback based event-triggered control mechanism for a class of switched nonlinear systems with a passivity property is proposed in this paper. Each subsystem of such a switched system does not necessarily have passivity in the classical sense, while maintaining the passivity property only on the active time intervals. Moreover, passivity is based on multiple storage functions and the storage functions are allowed to increase at switching instants. The proposed event-triggered output feedback controller can not only maintain asymptotic stability but also exclude Zeno behavior under some conditions. Finally, a numerical example is presented to illustrate the effectiveness of the method.
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http://dx.doi.org/10.1016/j.isatra.2021.06.042DOI Listing
July 2021

Assessing the impact of trade openness on CO emissions: Evidence from China-Japan-ROK FTA countries.

J Environ Manage 2021 Jul 12;296:113241. Epub 2021 Jul 12.

School of International Trade and Economics, University of International Business and Economics, Beijing, 100029, China; UIBE Belt & Road Energy Trade and Development Center, University of International Business and Economics, Beijing, 100029, China. Electronic address:

After signing the Regional Comprehensive Economic Partnership trade agreement, China became a proposed signatory to another important trilateral free-trade agreement - the China-Japan-South Korea Free Trade Agreement. In the context of the agreement, we explore the potential effect and internal influencing mechanism of trade openness on this region's carbon emissions from 1970 to 2019. We further detect the impact of the agreement by splitting the full sample into two subsamples, one subperiod before the agreement was signed and the other after it was signed. Then we separately analyze the impacts of imports and exports on carbon emissions and find that: (i) Trade openness positively affects the greenhouse effect, and the signing of the agreement can reduce the promotion effect of trade openness on carbon emissions; (ii) imports contribute to increased carbon emissions while exports significantly reduce carbon emissions in a country; and (iii) expanding trade openness not only directly affects carbon emissions directly, but also has indirect impacts by affecting three main effects (i.e., scale effect, technical effect, and structure effect). Finally, several important policy suggestions are provided to mitigate the greenhouse effect and promote high-quality trade openness.
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http://dx.doi.org/10.1016/j.jenvman.2021.113241DOI Listing
July 2021

Evaluation of Hybrid PET/MRI for Gross Tumor Volume (GTV) Delineation in Colorectal Cancer Liver Metastases Radiotherapy.

Cancer Manag Res 2021 6;13:5383-5389. Epub 2021 Jul 6.

Department of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.

Purpose: Hybrid PET/MRI has been increasingly incorporated into the practice of radiation oncologists since it contains both anatomical and biological data and may bring about personalized radiation plans for each patient. The objective of this study was to evaluate the feasibility of GTV delineation from hybrid PET/MRI compared with that from current-practice MRI during radiotherapy planning in patients with colorectal liver metastases.

Patients And Methods: Twenty-four patients (thirty lesions) with colorectal liver metastases were prospectively enrolled in this study. Three physicians delineated the target volume with the most popular delineating methods-the visual method. First of all, differences among the three observers were assessed. The difference and correlation of GTV values obtained by MRI, PET, and hybrid PET/MRI were subjected to statistical analysis afterwards. Finally, the dice similarity coefficient (DSC) was calculated to assess the spatial overlap. Based on the value of DSC, we also evaluate the correlation between DSC and tumor size. GTV-MRI was set as a reference.

Results: There was no significant difference among observers in GTV-MRI (0.118, 0.889), GTV-PET (0.070, 0.933) and GTV-PET/MRI (0.40, 0.961). 83.33% of GTV-PET/MRI and 63.33% of GTV-PET were larger than the reference GTV-MRI. Statistical analysis revealed that GTV-PET/MRI (0.001) and GTV-PET (0.05) diverged statistically significantly from GTV-MRI. GTV-PET (0.992, 0.001) and GTV-PET/MRI (0.997, 0.001) were significantly related to GTV-MRI. The average DSC value between GTV-MRI and GTV-PET was 0.51 (range 0-0.90) and that between GTV-MRI and GTV-PET/MRI was 0.72 (range 0.42-0.90). There was a positive correlation between the DSC and GTV-MRI (0.851, 0.05).

Conclusion: With the database used, there is good agreement among observers. Hybrid PET/MRI in colorectal liver metastases radiotherapy may affect the GTV delineation. Moreover, the overlap degree between GTV-MRI and GTV-PET/MRI is higher and increases with volume.
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http://dx.doi.org/10.2147/CMAR.S316969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275048PMC
July 2021

Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy.

J Ophthalmol 2021 28;2021:5580595. Epub 2021 Jun 28.

Dr. Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: Based on the differential gene expression analysis for predictive biomarkers with RNA-Sequencing data from Fuchs endothelial corneal dystrophy (FECD) patients, we are aiming to evaluate the efficacy of Library of Integrated Network-based Cellular Signatures (LINCS) perturbagen prediction software to identify novel pharmacotherapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotype in FECD.

Methods: A publicly available RNA-seq dataset was used to compare corneal endothelial specimens from controls and patients with FECD. Based on the differential gene expression analysis for predictive biomarkers, we evaluated the efficacy of LINCS perturbagen prediction software to identify novel therapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotypes in FECD.

Results: The RNA-seq dataset of the corneal endothelial cells from FECD patients revealed the differential gene expression signatures of FECD. Many of the differential expressed genes are related to canonical pathways of the FECD pathogenesis, such as extracellular matrix reorganization and immunological response. The expression levels of genes 2, 18, and 8 were significantly increased in FECD compared with control. Meanwhile, the expression levels of 3, , and 1 were significantly lower in the FECD than in control. We employed LINCS L1000 Characteristic Direction Signature Search Engine (L1000-CDS2) to investigate pathway-based molecular treatment. L1000-CDS2 predicted that small molecule drugs such as histone deacetylase (HDAC) inhibitors might be a potential candidate to reverse the pathological gene expression signature in FECD.

Conclusions: Based on differential gene expression signatures, several candidate drugs have been identified to reverse the disease phenotypes in FECD. Gene expression signature with LINCS small molecule prediction software can discover novel preclinical drug candidates for FECD.
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http://dx.doi.org/10.1155/2021/5580595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260298PMC
June 2021

Epithelial circulating tumor cells with a heterogeneous phenotype are associated with metastasis in NSCLC.

J Cancer Res Clin Oncol 2021 Jul 13. Epub 2021 Jul 13.

State Key Laboratory of Molecular Oncology, Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objectives: To analyze the clinical relevance of heterogeneous phenotypes of peripheral circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC).

Materials And Methods: CTCs in 5 mL venous blood were enriched using the Canpatrol™ CTC technique in 82 NSCLC patients. And then, CTCs were subjected to RNA in situ hybridization with a combination of epithelial (EpCAM and CK8/18/19) and mesenchymal (vimentin and TWIST1) markers.

Results: According to the fluorescent dots, CTCs were classified into three groups, including epithelial CTCs (E-CTC), hybrid epithelial/mesenchymal phenotypes (E/M-CTCs) and mesenchymal CTCs (M-CTCs). In 82 NSCLC cohort, only 2 patients didn't detect CTCs, the overall CTCs detection rate was 97.5% (80/82). For 60 treatment naïve NSCLC, only one patient didn't detect CTCs. The median number of total CTCs, hybrid E/M phenotype CTCs, E-CTCs and M-CTCs per 5 mL blood was 22 (range 1-90), 13 (range 0-83), 1 (range 0-17 and 0-47), respectively. Hybrid E/M CTCs, especially the e = m-CTCs, significantly differed between patients with and without distant metastasis. M-CTCs in advanced NSCLC patients were significantly more than the numbers observed in early stage patients. Patients with pure hybrid E/M-CTCs showed a lower proportion in distant metastasis positive cohort compared to negative ones (7% vs 22%), while patients with E + E/M CTCs (20% vs 9%) and E/M + M CTCs (33% vs 20%) showed a higher proportion. CTCs dynamic changes after treatment in 12 advanced NSCLC patients suggested that hybrid E/M-CTCs were related to the primary tumor size at baseline, while M-CTCs may suggest the progression of NSCLC.

Conclusion: We concluded that E-CTCs with a hybrid E/M phenotype are associated to metastasis in therapy-naïve NSCLC patients.
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http://dx.doi.org/10.1007/s00432-021-03681-9DOI Listing
July 2021

Long noncoding RNA LINC01287 promotes proliferation and inhibits apoptosis of lung adenocarcinoma cells via the miR-3529-5p/RNASEH2A axis under the competitive endogenous RNA pattern.

Environ Toxicol 2021 Jul 13. Epub 2021 Jul 13.

Department of Oncology, Liaocheng People's Hospital, Liaocheng, China.

Lung adenocarcinoma (LUAD) is regarded as the most common type of lung cancer. The molecular targeted therapies for LUAD have being extensively studied. Ribonuclease H2 subunit A (RNASEH2A) is a nucleotide degrading enzyme gene that exerts great influence on cell proliferation, DNA replication and genomic stability. According to bioinformatics analysis, RNASEH2A expression in LUAD tissues is predicted to be upregulated and high expression of RNASEH2A might be related to lower survival rate in LUAD patients. In the present study, we investigated functions of RNASEH2A in LUAD. The mRNA RNASEH2A showed high expression in LUAD cells, and its knockdown inhibited proliferation and induced apoptosis in LUAD cells. RNASEH2A was found to be a target gene of microRNA miR-3529-5p after their expression levels and interaction being examined. Long noncoding RNA LINC01287 upregulated RNASEH2A expression in LUAD cells by combining with miR-3529-5p in a competitive way. Rescue assays revealed that the overexpression of RNASEH2A reversed the suppression of cell proliferation and the promotion of cell apoptosis induced by miR-3529-5p overexpression or LINC01287 knockdown. Finally, forkhead box A1 (FOXA1) interacted with RNASEH2A promoter and LINC01287 promoter to upregulate the expression levels of RNASEH2A and LINC01287 in LUAD cells. Overall, FOXA1-induced LINC01287 serves as a competing endogenous RNA to promote proliferation and inhibit apoptosis of LUAD cells via upregulation of RNASEH2A expression at the posttranscriptional level by competitively combining with miR-3529-5p.
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http://dx.doi.org/10.1002/tox.23325DOI Listing
July 2021

Acute and Sub-chronic Toxicity Study of Recombinant Bovine Interferon Alpha in Rodents.

J Vet Res 2021 Jun 16;65(2):183-192. Epub 2021 May 16.

Department of Microbiology, Anhui Medical University, Hefei, Anhui Province, 230032, P.R. China.

Introduction: Recombinant bovine interferon alpha (rBoIFN-α) has been demonstrated to have antiviral activity. However, no conduct of acute or chronic toxicity tests has been reported.

Material And Methods: Specific pathogen-free Sprague Dawley rats were administered doses at different concentrations through intraperitoneal or intravenous injection. After the administration (single for an acute toxicity test over 14 days or daily for a sub-chronic toxicity test over 30 days), the rats' behaviour and other indicators and the degree of toxic reaction were continuously monitored. Blood was collected for haematological and serum biochemical examinations. At the end of the experiments, the rats were sacrificed for necropsy and histopathological tissue analysis.

Results: The external performance, behaviour characteristics, and changes in body temperature and body weight of the rats in each subgroup were comparable to the normal control subgroup. Except for a few cases, there were no lesions in the viscera's pathological structures, and the blood parameters and biochemical indicators were not noticeably different from those of the control subgroup.

Conclusion: This study suggests that rBoIFN-α seems to be safe for rats, and its use may foster the development of the cattle industry in China by protecting livestock health.
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http://dx.doi.org/10.2478/jvetres-2021-0023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256469PMC
June 2021

Clinical Implementation of Automated Treatment Planning for Rectum Intensity-Modulated Radiotherapy Using Voxel-Based Dose Prediction and Post-Optimization Strategies.

Front Oncol 2021 24;11:697995. Epub 2021 Jun 24.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: This study aims to demonstrate the feasibility of clinical implementation of automated treatment planning (ATP) using voxel-based dose prediction and post-optimization strategies for rectal cancer on uRT (United Imaging Healthcare, Shanghai, China) treatment planning system.

Methods: A total of 180 previously treated rectal cancer cases were enrolled in this study, including 160 cases for training, 10 for validation and 10 for testing. Using CT image data, planning target volumes (PTVs) and contour delineation of the organs at risk (OARs) as input and three-dimensional (3D) dose distribution as output, a 3D-Uet DL model was developed. Based on the voxel-wise prediction dose distribution, intensity-modulated radiation therapy (IMRT) plans were then generated automatedly using post-optimization strategies, including a complex clinical dose target metrics homogeneity index (HI) and conformation index (CI). To evaluate the performance of the proposed ATP approach, the dose-volume histogram (DVH) parameters of OARs and PTV and the 3D dose distributions of the plan were compared with those of manual plans.

Results: By combining clinical post-optimization strategies, the automatically generated treatment plan can achieve better homogeneous PTV coverage and dose sparing for OARs except the mean dose for femoral-head compared with the use of the mean square error objective function alone. Compared with the manual plan, no statistically significant differences in HI, CI or global maximum dose were found. The manual plans perform slightly better than plans with post-optimization strategies in other dosimetric indexes, but these plans are still within clinical requirements.

Conclusions: With the help of clinical post-optimization strategies, the proposed new ATP solution can generate IMRT plans that are within clinically acceptable levels and comparable to plans manually generated by dosimetrists.
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http://dx.doi.org/10.3389/fonc.2021.697995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264432PMC
June 2021

Ga-FAPI-04 Versus F-FDG PET/CT in the Detection of Hepatocellular Carcinoma.

Front Oncol 2021 25;11:693640. Epub 2021 Jun 25.

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: Fibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of Ga-FAPI-04 PET/CT and F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with Ga-FAPI-04 uptake in HCC.

Materials And Methods: Twenty-nine patients with suspiciously HCC who received both F-FDG and Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUV and SUV) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion's SUV divided by background SUV.

Results: A total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. Ga-FAPI-04 PET/CT showed a higher sensitivity than F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% . 57.1%, = 0.002), including in small (≤ 2 cm in diameter; 68.8% . 18.8%, = 0.008) and well- or moderately-differentiated (83.3% . 33.3%, = 0.031) tumors. SUV was comparable between Ga-FAPI-04 and F-FDG (6.96 ± 5.01 . 5.89 ± 3.38, > 0.05), but the TBR was significantly higher in the Ga-FAPI-04 group compared with the F-FDG group (11.90 ± 8.35 . 3.14 ± 1.59, < 0.001). SUV and the TBR in Ga-FAPI-04 positive lesions were associated with tumour size (both < 0.05), but not the remaining clinical and pathological features (all > 0.05).

Conclusions: Ga-FAPI-04 PET/CT is more sensitive than F-FDG PET/CT in detecting HCC lesions, and Ga-FAPI-04 uptake is correlated mainly with tumour size.
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http://dx.doi.org/10.3389/fonc.2021.693640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267923PMC
June 2021

An atlas-guided automatic planning approach for rectal cancer intensity-modulated radiotherapy.

Phys Med Biol 2021 Jul 23;66(15). Epub 2021 Jul 23.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing (BM), and plan fine-tuning (PFT) modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The BM function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the PFT function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms of( = 0.76) and homogeneity index ( = 0.073), respectively. The CI index showed they had a statistically significant difference. But the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1 cGy ( < 0.05) andby 0.9% ( < 0.05), and slightly increased the left and right femoral head mean dose by 70.1 cGy ( < 0.05) and 69.7 cGy ( < 0.05), respectively. This work developed an efficient and automatic approach that could fully automate the IMRT planning process in rectal cancer radiotherapy. It reduced the plan quality dependence on the planner experience and maintained the comparable plan quality with P-auto plans.
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http://dx.doi.org/10.1088/1361-6560/ac127dDOI Listing
July 2021

Peripheral Lung Squamous Carcinoma With ROS1 Rearrangement Sensitive to Crizotinib: A Case Report.

Front Oncol 2021 21;11:703318. Epub 2021 Jun 21.

Department of Respiratory Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

ROS1 rearrangements have been identified as driver mutations, accounting for 1-2% of lung adenocarcinoma, but are extremely rare in case of lung squamous cell carcinoma. In this work, we report a lung squamous cell carcinoma in a patient with peripheral lung cancer radiological manifestation, harboring ROS1 rearrangement, with high sensitivity to crizotinib. Our findings suggest that clinicians should pay more attention toward the occurrence of ROS1 rearrangements and the application of crizotinib for lung squamous cell carcinoma treatment.
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http://dx.doi.org/10.3389/fonc.2021.703318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256165PMC
June 2021

Long Noncoding RNA AATBC Promotes the Proliferation and Migration of Prostate Cancer Cell Through miR-1245b-5p/CASK Axis.

Cancer Manag Res 2021 28;13:5091-5100. Epub 2021 Jun 28.

Department of Urology, East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.

Introduction: Long noncoding RNAs (lncRANs) as suppressive or oncogenic genes have been substantiated in prostate cancer (PCa). In the current study, the role and molecular mechanism of lncRNA AATBC in the progression of PCa was evaluated.

Methods: LncRNA AATBC and miR-1245b-5p expression were evaluated using RT-qPCR. CCK-8, colony-formation, apoptosis and transwell assay were used to analyze the in vitro role. The xenograft model was used to explore the in vivo role. Bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down were used to confirm the interaction between lncRNA AATBC and 1245b-5p, as well as 1245b-5p and CASK.

Results: Firstly, we certified that the expression of AATBC was augmented in PCa, and knockdown of AATBC could significantly inhibit the growth of PCa in vitro and in vivo. Mechanistically, our results manifested that AATBC could directly bind to miR-1245b-5p. In addition, miR-1245b-5p played cancer-suppressive role in PCa cells. Moreover, CASK was attested as the target of miR-1245b-5p, and CASK was demonstrated to exert as oncogene in the progression of PCa. Finally, rescue assays illustrated that miR-1245b-5p downregulation or CASK restoration could greatly resist the restrained effects of AATBC knockdown on PCa progression.

Conclusion: AATBC could accelerate the progression of PCa through regulating miR-1245b-5p/CASK axis, which provided a potential therapeutic target for PCa treatment.
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http://dx.doi.org/10.2147/CMAR.S310529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253982PMC
June 2021
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