Publications by authors named "Baojun Wang"

205 Publications

Long-term L-3-n-butylphthalide pretreatment attenuates ischemic brain injury in mice with permanent distal middle cerebral artery occlusion through the Nrf2 pathway.

Heliyon 2022 Jul 8;8(7):e09909. Epub 2022 Jul 8.

Department of Neurology, Baotou Central Hospital, Inner Mongolia, China.

L-3-n-butylphthalide (NBP), which is used for treatment of mild and moderate acute ischemic stroke, exerts its effects by modulating the Nrf2 pathway. However, it has not been established whether NBP exerts its preventive effects in high-risk ischemic stroke patients through the Nrf2 pathway. We investigated whether NBP exerts its preventive effects through the Nrf2 pathway in long-term NBP pretreated dMCAO mice models. Nrf2 wild-type and Nrf2 knockout mice were randomized into the vehicle group (equal volume vegetable oil), NBP-low-dose group (20 mg/kg) and NBP-high-dose group (60 mg/kg). The drug was administered once daily by gavage for a month. Then, a permanent distal middle cerebral artery occlusion model (dMCAO) was established after pretreatment with NBP. Neurological deficits, cerebral infarct volumes, brain water contents, activities of SOD, GSH-Px and MDA levels were determined. Further, axonal injury and demyelination, expression levels of Nrf2, HO-1 and NQO1 in ischemic brains were determined. Long-term NBP pretreatment significantly improved neurological functions, reduced cerebral infarction volumes, reduced brain water contents, increased SOD, GSH-Px activities, decreased MDA contents, reduced neurological injuries, axonal damage as well as demyelination, while increasing Nrf2, HO-1 and NQO1 mRNA as well as protein expressions in dMCAO mice models.
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http://dx.doi.org/10.1016/j.heliyon.2022.e09909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305368PMC
July 2022

Sophoridine Suppresses Herpes Simplex Virus Type 1 Infection by Blocking the Activation of Cellular PI3K/Akt and p38 MAPK Pathways.

Front Microbiol 2022 10;13:872505. Epub 2022 Jun 10.

State Key Laboratory of South Western Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and important human pathogen capable of causing significant clinical diseases ranging from skin damage to encephalitis, particularly in immunocompromised and neonatal hosts. Currently, widely used nucleoside analogs, including acyclovir and penciclovir, have some limitations in their use due to side effects and drug resistance. Herein, we report sophoridine's (SRI) dramatic inhibition of HSV-1 replication . SRI exhibited a remarkable inhibitory influence on HSV-1 virus-induced cytopathic effect and plaque formation, as well as on progeny viruses in Vero and HeLa cells, with selection indexes (SI) of 38.96 and 22.62, respectively. Moreover, SRI also considerably suppressed HSV-1 replication by hindering the expression of viral immediate-early (ICP0 and ICP22), early (ICP8 and TK), and late (gB and gD) genes and the expression of viral proteins ICP0, gB, and gD. We suggest that SRI can directly inactivate viral particles and block some stages in the life cycle of HSV-1 after adsorption. Further experiments showed that SRI downregulated the cellular PI3K/Akt signaling pathway and obstructed HSV-1 replication even more. Most importantly, SRI markedly repressed HSV-1-induced p38 MAPK pathway activation. Collectively, this natural bioactive alkaloid could be a promising therapeutic candidate against HSV-1 the modulation of cellular PI3K/Akt and p38 MAPK pathways.
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http://dx.doi.org/10.3389/fmicb.2022.872505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229184PMC
June 2022

Pilot Study of Effects of Intermittent Pneumatic Compression in the Immediate Peri-Operative Period on Hemodynamic Parameters in Patients After Laparoscopic Gynecologic Surgery.

Front Surg 2022 7;9:896452. Epub 2022 Jun 7.

Department of Anesthesiology, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China.

The randomized controlled study investigated the impacts of immediate peri-operative Intermittent pneumatic compression (IPC) on hemodynamic indicators in patients undergoing laparoscopic gynecologic surgery. Patients scheduled for elective laparoscopic gynecologic surgery were randomized to control (IPC not used), pre-operative IPC, post-operative IPC, and peri-operative IPC (performed both before and after surgery) groups. Systolic blood pressure (SBP), mean blood pressure (MBP) cardiac output (CO), heart rate (HR) and systemic vascular resistance (SVR) were measured at different time points. The results showed that SBP changes not obviously over time in the control and peri-operative IPC group. Compared with values before surgery, the pre-operative IPC group had a lower SBP (< 0.01) at the end of PACU stay, whereas the post-operative IPC group had a higher SBP (< 0.01) after surgery. All groups exhibited little or no variation in HR, CO and SVR. Conclusion is peri-operative IPC has no major adverse effects on hemodynamic parameters.
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http://dx.doi.org/10.3389/fsurg.2022.896452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209646PMC
June 2022

Rare and Common Variants in in Chinese Patients With Intracerebral Hemorrhage.

Front Neurol 2022 27;13:827165. Epub 2022 May 27.

Department of Neurology, Peking University Third Hospital, Beijing, China.

Here, we screened the variants in Chinese intracerebral hemorrhage (ICH) patients to summarize the relationship between the variants and clinical characteristics. Targeted sequencing of a 65-gene panel including was performed to detect all the coding regions and ±10-bp splicing sites. In total, 568 patients were included. Regarding rare nonsynonymous variants with a minor allele frequency (MAF) <0.5%, 6 missense variants and five suspicious splice site variants, absent in 573 healthy controls, were found in 11 patients. The subgroup carrying rare variants did not show specific phenotype compared with non-variant carriers. For the single nucleotide polymorphism (SNP) loci with an MAF> 5%, we did not find a significant association between the allele or genotype distribution of the SNP loci and the risk of ICH. Rs3742207 was nominally associated with death at 1-year follow-up ( = 0.02027, OR 1.857, 95% CI 1.101-3.133) after adjusted by age, hypertension history, hematoma volume and recurrent ICH history. Nevertheless, after the Bonferroni correction, the association was no longer significant. In conclusion, rare nonsynonymous variants in were identified in 1.94% (11/568) of Chinese ICH patients, while rs3742207 maybe indicate a worse prognosis of ICH.
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http://dx.doi.org/10.3389/fneur.2022.827165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196627PMC
May 2022

Progressive Obstruction of Inferior Vena Cava by Ameroid Constrictor: The Canine Model of Revealing Hemodynamic and Compensatory Patterns of Tumor Thrombus Formation at the Renal Hilus Level.

J Endourol 2022 Aug 11;36(8):1119-1125. Epub 2022 Jul 11.

Department of Urology, the Third Medical Center, Chinese PLA General Hospital, Beijing, China.

To develop an efficient and stable canine model of inferior vena cava (IVC) progressive obstruction at the renal hilus level. The model was established in two beagles by encircling an ameroid constrictor (AC) on the IVC at the renal hilus level. Abdominal wall varicosity and animal weight variations were observed weekly after operation. Ultrasound examination was performed weekly after surgery to observe the AC position, the diameter, and the velocity in the IVC. Six weeks after surgery, IVC angiography and CT scan were performed to observe the collateral circulation establishment and internal organ variation. Blood samples were taken regularly to monitor for variation in critical biochemical parameters. Renal biopsy was performed at 0, 2, 4, and 6 weeks after surgery. Superficial varicose veins were observed on the abdominal wall at 2 weeks after surgery. Four weeks after operation, the IVC diameter increased by ∼30%, whereas the IVC velocity decreased by more than 50%. Collateral circulation was observed by IVC angiography at 6 weeks through multiple dilated veins along with neovascularization. CT scan showed congestive alteration in the kidney. The body weight, kidney, and liver function were not significantly affected. Chronic congestive renal injury was detected in the renal tubular epithelium by kidney biopsy after surgery. A canine model of IVC progressive obstruction at the renal hilus level was stably and safely established for the first time by using an AC, which may be helpful for preserving pivotal collateral circulation and nontumor-side kidney function in the IVC thrombus surgery.
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http://dx.doi.org/10.1089/end.2021.0760DOI Listing
August 2022

Loss of cell division cycle‑associated 5 promotes cell apoptosis by activating DNA damage response in clear cell renal cell carcinoma.

Int J Oncol 2022 Jul 1;61(1). Epub 2022 Jun 1.

Department of Urology, The Third Medical Center, Chinese PLA General Hospital/Medical School of Chinese PLA/State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Cell division cycle‑associated 5 (CDCA5) protein, which is involved in cohesion, contributes to cell cycle regulation and chromosome segregation by maintaining genomic stability. Accumulating evidence indicates that CDCA5 expression is upregulated in a number of types of cancer associated with a poor prognosis. However, the biological function of CDCA5 in clear cell renal cell carcinoma (ccRCC) remains largely unknown. In the present study, The Cancer Genome Atlas data mining revealed that CDCA5 was more highly expressed in ccRCC than in adjacent normal tissues. Importantly, such a high expression was associated with a higher risk of distant metastasis and poorer clinical outcomes. Moreover, the clinical and prognostic value of CDCA5 expression was further investigated using immunohistochemistry on tissue microarrays containing paired tumor tissues and adjacent normal tissues from 137 patients with ccRCC. Functional analyses revealed that CDCA5 knockdown significantly inhibited the proliferation and migration of ccRCC cells, and suppressed the growth of xenografts in nude mice. Mechanistically, CDCA5 knockdown induced severe DNA damage with the persistent accumulation of γ‑H2A histone family member X foci, resulting in G2/M cell cycle arrest and finally, in chromosomal instability and apoptosis. CDCA5 knockdown significantly decreased the phosphorylation levels of Stat3 and NF‑κB, suggesting that CDCA5 plays a role in regulating the inflammatory response. Collectively, the findings of the present study indicate that ccRCC cells require CDCA5 for malignant progression, and that CDCA5 inhibition may enhance the outcomes of patients with high‑risk ccRCC.
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http://dx.doi.org/10.3892/ijo.2022.5377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9183765PMC
July 2022

GTSE1 promotes tumor growth and metastasis by attenuating of KLF4 expression in clear cell renal cell carcinoma.

Lab Invest 2022 May 18. Epub 2022 May 18.

Department of Urology, the Third Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC.
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http://dx.doi.org/10.1038/s41374-022-00797-5DOI Listing
May 2022

Are beta blockers effective in preventing stroke-associated infections? - a systematic review and meta-analysis.

Aging (Albany NY) 2022 05 18;14(10):4459-4470. Epub 2022 May 18.

Department of Neurology, Baotou Center Hospital, Inner Mongolia, Baotou, China.

Background: Excessive sympathoexcitation could lead to stroke associated infection. Inhibiting sympathetic excitation may reduce the infection risk after stroke. Thus, the present study aimed to determine the protective effect of beta blockers on stroke associated infection through systematic review and meta-analysis.

Methods: A systematic search of multiple databases were performed up to February 2022. The included studies required beta blockers therapy in stroke patients and assessed the incidence of stroke-associated infections. Outcomes of interest included infections, pneumonia, urinary tract infection and sepsis. Random-effects model was used for analysis. Heterogeneity was evaluated using I2 statistics and publication bias was evaluated by the funnel plot.

Result: A total of 83 potentially relevant publications was identified in the initial search. Six studies met the inclusion criteria for meta-analysis. The risk of bias in the included articles satisfies the quality requirement of meta-analysis. No significant associations between beta blockers therapy and the prevention of stroke associated infection, stroke associated pneumonia and septicemia were found, However, subgroup analyses revealed an association between beta blockers treatment and the increased risk of post-stroke urinary tract infection or stroke associated pneumonia in some stroke patients (OR = 1.69 [1.33, 2.14], < 0.0001; OR = 1.85 [1.51, 2.26], < 0.0001).

Conclusion: Due to the lack of robust evidence, this meta-analysis may not support the preventive effect of beta blockers on stroke associated infection. But beta blockers treatment may be associated with development of post-stroke urinary tract infection and stroke associated pneumonia in some stroke patients.
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http://dx.doi.org/10.18632/aging.204086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186777PMC
May 2022

Design of the ArsR Regulated P Promoter Enables a Highly Sensitive Whole-Cell Biosensor for Arsenic Contamination.

Anal Chem 2022 05 10;94(20):7210-7218. Epub 2022 May 10.

School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, China.

Whole-cell biosensors for arsenic contamination are typically designed based on natural bacterial sensing systems, which are often limited by their poor performance for precisely tuning the genetic response to environmental stimuli. Promoter design remains one of the most important approaches to address such issues. Here, we use the arsenic-responsive ArsR-P regulation system from MG1655 as the sensing element and coupled or as the reporter gene to construct the genetic circuit for characterizing the refactored promoters. We first analyzed the ArsR binding site and a library of RNA polymerase binding sites to mine potential promoter sequences. A set of tightly regulated P promoters by ArsR was designed by placing the ArsR binding sites into the promoter's core region, and a novel promoter with maximal repression efficiency and optimal fold change was obtained. The fluorescence sensor P-P constructed with the optimized P promoter showed a fold change of up to 63.80-fold (with green fluorescence visible to the naked eye) at 9.38 ppb arsenic, and the limit of detection was as low as 0.24 ppb. Further, the optimized colorimetric sensor P-P- with a linear response between 0 and 5 ppb was used to perform colorimetric reactions in 24-well plates combined with a smartphone application for the quantification of the arsenic level in groundwater. This study offers a new approach to improve the performance of bacterial sensing promoters and will facilitate the on-site application of arsenic whole-cell biosensors.
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http://dx.doi.org/10.1021/acs.analchem.2c00055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134189PMC
May 2022

Syngas Conversion to C Species over WC and M/WC (M = Cu or Rh) Catalysts: Identifying the Function of Surface Termination and Supported Metal Type.

ACS Appl Mater Interfaces 2022 May 25;14(17):19491-19504. Epub 2022 Apr 25.

State Key Laboratory of Clean and Efficient Coal Utilization, Taiyuan University of Technology, Taiyuan, Shanxi 030024, PR China.

Improving the selectivity and activity of C species from syngas is still a challenge. In this work, catalysts with monolayer Cu or Rh supported over WC with different surface terminations (M/WC (M = Cu or Rh)) are rationally designed to facilitate C species generation. The complete reaction network is analyzed by DFT calculations. Microkinetics modeling is utilized to consider the experimental reaction temperature, pressure, and the coverage of the species. The thermal stabilities of the M/WC (M = Cu or Rh) catalysts are confirmed by AIMD simulations. The results show that the surface termination and supported metal types in the M/WC (M = Cu or Rh) catalysts can alter the existence form of abundant CH ( = 1-3) monomer, as well as the activity and selectivity of CH monomer and C species. Among these, only the Cu/WC-C catalyst is screened out to achieve outstanding activity and selectivity for CH generation, attributing to that the synergistic effect of the subsurface C atoms and the surface monolayer Cu atoms presents the noble-metal-like character to promote the generation of CH and C species. This work demonstrates a new possibility for rational construction of other catalysts with the non-noble metal supported by the metal carbide, adjusting the surface termination of metal carbide and the supported metal types can present the noble-metal-like character to tune catalytic performance of C species from syngas.
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http://dx.doi.org/10.1021/acsami.2c02217DOI Listing
May 2022

Reprogrammed tracrRNAs enable repurposing of RNAs as crRNAs and sequence-specific RNA biosensors.

Nat Commun 2022 04 11;13(1):1937. Epub 2022 Apr 11.

College of Chemical and Biological Engineering & Hangzhou Innovation Center, Zhejiang University, Hangzhou, 311200, China.

In type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Although tracrRNAs are diverse in sequence and structure across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for Cas9 is not fully understood. Here, we reveal the programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9, and in doing so, redefine the capabilities of Cas9 proteins and the sources of crRNAs, providing new biosensing applications for type II CRISPR systems. By reprogramming the crRNA-tracrRNA hybridized sequence, we show that engineered crRNA-tracrRNA interactions can not only enable the design of orthogonal cellular computing devices but also facilitate the hijacking of endogenous small RNAs/mRNAs as crRNAs. We subsequently describe how these re-engineered gRNA pairings can be implemented as RNA sensors, capable of monitoring the transcriptional activity of various environment-responsive genomic genes, or detecting SARS-CoV-2 RNA in vitro, as an Atypical gRNA-activated Transcription Halting Alarm (AGATHA) biosensor.
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http://dx.doi.org/10.1038/s41467-022-29604-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001733PMC
April 2022

Traditional uses, phytochemical constituents and pharmacological properties of Osmanthus fragrans: A review.

J Ethnopharmacol 2022 Jul 9;293:115273. Epub 2022 Apr 9.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, PR China. Electronic address:

Ethnopharmacological Relevance: Osmanthus fragrans Lour., is a medicinal plant distributed widely in some Asian countries including Japan and Korea and southwestern China. It has been used traditionally for the treatment of weakened vision, halitosis, panting, asthma, cough, toothache, stomachache, diarrhea, rheumatism, physique pain and hepatitis.

Aim Of The Review: Recent advances in traditional uses, botanical characteristics, distribution, taxonomy, phytochemical constituents, biological effects as well as the toxicities of O. fragrans are comprehensively presented and critically evaluated, and the underlying mechanism associated with the bioactivities of extracts, essential oil and components from this plant is also well summarized. In order to provide comprehensive scientific basis for the medical application and help interested researchers discover food and medicinal natural products from O. fragrans.

Materials And Methods: All information was systematically gathered from globally accepted scientific databases by Internet databases, including Elsevier, ScienceDirect, PubMed, Web of Science, Wiley, Springer, SciFinder, ACS Publications, CNKI, WanFang, Google Scholar, Baidu Scholar, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations). All published contributions on O. fragrans different languages were included and cited. The chemical structures of all isolated compounds were drawn by using ChemBioDraw Ultra 14.0 software.

Results: To date, more than 183 compounds were isolated and structurally identified from different plant parts of O. fragrans. Among them, ionone, ionol, flavonoids, polyphenols and iridoids, as the major bioactive substances, have been extensively studied and displayed the best bioactivity. Pharmacological studies demonstrated that O. fragrans and its active components had a wide range of biological activities, such as antioxidant, antitumor, anti-inflammatory, anti-hyperglycemic, anti-thrombotic, anti-melanogenesis, neuroprotective, and hepatoprotective activities, etc. CONCLUSION: O. fragrans, as a food and medicinal resource, has a good health care function and important edible and medicinal value, and thus has good prospects for utilization. However, many studies on biological activities were mainly based on extracts and the bioactive ingredients of this plant, and the mechanism responsible for these extracts and ingredients have not been well identified and there is a gap in research regarding clinical effect and safety. Therefore, the detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more clinical studies are encouraged to be conducted to ensure safety and effectiveness of the plant for human use.
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http://dx.doi.org/10.1016/j.jep.2022.115273DOI Listing
July 2022

Fengreqing Oral Liquid Exerts Anti-Inflammatory Effects by Promoting Apoptosis and Inhibiting PI3K/AKT and NF-κB Signaling Pathways.

Front Pharmacol 2022 14;13:824579. Epub 2022 Mar 14.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of TCM, Chengdu, China.

Fengreqing oral liquid (FOL), a Chinese patent drug frequently used in clinical practice in China, is effective in treating inflammatory diseases of the upper respiratory tract such as colds and flu. However, its anti-inflammatory effects and mechanisms remain to be elucidated. In this study, the anti-inflammatory effects of FOL and its mechanisms on PI3K/AKT and NF-κB signaling pathways in LPS-induced RAW264.7 cells were explored, as well as the regulatory effect of FOL on apoptosis. In addition, the potential of FOL for the treatment of acute lung injury was explored in LPS-induced ALI mice. The results showed that treatment with FOL significantly reduced the levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), nitric oxide (NO), and tumor necrosis factor α (TNF-α) in the supernatant of LPS-induced RAW264.7 cells, and also significantly reduced the phosphorylated protein levels of PI3K and AKT in the PI3K/AKT signaling pathway and also protein levels of NF-κB p50, phosphorylated NF-κB p65, and IκBα in the NF-κB signaling pathway. In addition, the results showed that FOL induced apoptosis in LPS-induced RAW264.7 cells at the level of 80%-90%, and significantly increased the protein expression levels of the pro-apoptotic Bax and cleaved-caspase-3. In LPS-induced ALI mice, FOL administration showed inhibition of IL-1β, IL-6, and TNF-α in Bronchoalveolar lavage fluid (BALF) and decreased protein expression levels of PI3K, AKT, NF-κB p50, and NF-κB p65, and elevated protein expression levels of Bax and cleaved-caspase-3 significantly. These results suggest that FOL may exert anti-inflammatory effects by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and leading to attenuated activation of the NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fphar.2022.824579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967167PMC
March 2022

Use of DWI-FLAIR Mismatch to Estimate the Onset Time in Wake-Up Strokes.

Neuropsychiatr Dis Treat 2022 21;18:355-361. Epub 2022 Feb 21.

Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, People's Republic of China.

Purpose: To compare the MRI characteristics of patients with wake-up ischemic stroke (WUS) and with ischemic stroke with known onset time (clear-onset-time stroke, COS) to clarify the role of diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch in estimating the onset time of WUS patients.

Patients And Methods: Two hundred patients with acute ischemic stroke were selected for complete brain MRI within six hours of symptom onset, including DWI and FLAIR sequences. The patients were divided into WUS (n = 78) and COS (n = 122) groups, based on whether the time of onset was known. The general conditions and imaging characteristics were collected to compare the DWI-FLAIR mismatch features between the two groups at different time intervals.

Results: There was no significant difference in the DWI-FLAIR mismatch on MRI within 2 hour after the first found abnormality between the two groups (50.0% vs 71.8%, p = 0.180). With increasing time, the DWI-FLAIR mismatch decreased substantially in the WUS group, while a higher DWI-FLAIR mismatch presence persisted in the COS group within a four-hour interval from the onset of symptoms to the MRI. The DWI-FLAIR mismatch was significantly lower in the WUS group than in the COS group from symptom identification to MRI at 2-3 h, 3-4 h, and 4-5 h intervals (15% vs 60%, 10.5% vs 48%, 6.7% vs 45.4%; p < 0.01).

Conclusion: Our results suggest that the presence of DWI-FLAIR mismatch within 2 h of the first found abnormality was not significantly different between WUS and COS. Therefore, Patients with WUS within 2 hours after the first detected abnormality may be suitable for intravenous thrombolysis.
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http://dx.doi.org/10.2147/NDT.S351943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881675PMC
February 2022

Comparison of Transperitoneal and Retroperitoneal Robotic Partial Nephrectomy for Patients With Complete Upper Pole Renal Tumors.

Front Oncol 2021 25;11:773345. Epub 2022 Jan 25.

Department of Urology, the Third Medical Centre, Chinese PLA General Hospital, Beijing, China.

Objectives: We compared the outcomes of transperitoneal robotic partial nephrectomy (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN) for complete upper pole renal masses (1 point for the "L" component of the RENAL scoring system).

Material And Methods: We retrospectively reviewed patients who underwent either TRPN or RRPN from 2013 to 2016. Baseline demographics and perioperative, functional, and oncological results were compared. Multivariable analysis was performed to identify factors related to pentafecta achievement (ischemia time ≤25 min, negative margin, perioperative complication free, glomerular filtration rate (eGFR) preservation >90%, and no chronic kidney disease upstaging).

Results: No significant differences between TRPN RRPN were noted for operating time (110 114 min,  = 0.870), renal artery clamping time (19 18 min,  = 0.248), rate of positive margins (0.0% vs. 3.3%,  = 0.502), postoperative complication rates (25.0% 13.3%,  = 0.140). TRPN was associated with a more estimated blood loss (50 40 ml,  = 0.004). There were no significant differences in pathologic variables, rate of eGFR decline for postoperative 12-month (9.0% 7.1%,  = 0.449) functional follow-up. Multivariate analysis identified that only RENAL score (odd ratio: 0.641; 95% confidence interval: 0.455-0.904;  = 0.011) was independently associated with the pentafecta achievement.

Conclusions: For completely upper pole renal masses, both TRPN and RRPN have good and comparable results. Both surgical approaches remain viable options in the treatment of these cases.
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http://dx.doi.org/10.3389/fonc.2021.773345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821917PMC
January 2022

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives.

Drug Des Devel Ther 2022 18;16:191-212. Epub 2022 Jan 18.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People's Republic of China.

Sophoridine is a natural quinolizidine alkaloid and a bioactive ingredient that can be isolated and identified from certain herbs, including , and . In recent years, this quinolizidine alkaloid has gained widespread attention because of its unique structure and minimal side effects. Modern pharmacological investigations have uncovered sophoridine's multiple wide range biological activities, such as anti-cancer, anti-inflammatory, anti-viral, anti-arrhythmia, and analgesic functions, among others. These pharmacological activities and beneficial effects point to sophoridine as a strong potential therapeutic candidate for the treatment of various diseases, including several cancer types, hepatitis B virus, enterovirus 71, coxsackievirus B3, cerebral edema, cancer pain, heart failure, acute myocardial ischemia, arrhythmia, inflammation, acute lung injury, and osteoporosis. The data showed that sophoridine had adverse reactions, including hepatotoxicity and neurotoxicity. Additionally, analyses of sophoridine's safety, bioavailability, and pharmacokinetic parameters in animal models of research have been limited, especially in the clinic, as have been investigations on its structure-activity relationship. In this article, we comprehensively summarize the biological activities, toxicity, and pharmacokinetic characteristics of sophoridine and its derivatives, as currently reported in publications, as we attempt to provide an overall perspective on sophoridine analogs and the prospects of its application clinically.
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http://dx.doi.org/10.2147/DDDT.S339555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784973PMC
March 2022

JFNE-A isolated from Jing-Fang n-butanol extract attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and the NF-κB signaling pathway via promotion of autophagy.

Phytomedicine 2022 Feb 20;96:153891. Epub 2021 Dec 20.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Wenjiang, Chengdu, Sichuan 611137, PR China. Electronic address:

Background: Jing-Fang powder consists of Jingjie (Nepeta tenuifolia Benth, (Lamiaceae)). and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk, (Apiaceae)) Previous studies have revealed that the Jing-Fang powder n-butanol extract (JFNE) has anti-acute lung injury (ALI) and anti-inflammatory properties; however, the active ingredient and mechanism remain unknown.

Purpose: In the present study, we investigated the anti-inflammatory effect of a bioactive fraction obtained from JFNE(JFNE-A) on lipopolysaccharide (LPS)-induced ALI in mice and explored the underlying mechanism.

Study Design: The anti-acute lung injury effect and mechanism of JFNE-A was investigated by prophylactic administration of JFNE-A in mice with LPS-induced acute lung injury.

Methods: The expression levels of myeloperoxidase(MPO) in lung tissues of mice and interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1β, IL-5, interferon (IFN)-γ, monocyte chemotactic protein (MCP)-1, macrophage colony stimulating factor (M-CSF), macrophage inflammatory protein (MIP)-1α, and MIP-1β in bronchi alveolar lavage fluid (BALF) were detected by reagent kit and the histological changes were examined by hematoxylin and eosin (H & E) for general histopathological conditions under a light microscope. In addition, the ultrastructure of the cells in lung tissues were observed and photographed under a transmission electron microscope. The expression levels of protein were detected via Western blotting and the mRNA expression of relative genes were determined of via reverse transcriptase polymerase chain reaction (RT-PCR). What's more, we also further clarified the potential targets of JFNE-A through network pharmacology analysis, which could be utilized in ALI treatment.

Results: Our results showed that pretreatment with JFNE-A for 7 days significantly reduced the lung pathological injury score, alleviated pulmonary edema, and decreased the lung tissue MPO level. Mechanistically, JFNE-A dramatically downregulated the protein levels of IL-6, TNF-α, IL-1β, M-CSF, and IFN-γ in BALF and mRNA expression levels of IL-6, TNF-α, IL-1β, and IFN-γ in lung tissues. JFNE-A also significantly lowered the protein levels of iNOS and phosphorylated NF-κB (p65) and mRNA expression levels of iNOS, Rela, CHUK, and NF-κB1, and also elevated the protein expression levels of Nrf2, HO-1, and SOD1 and the mRNA expression levels of Nrf2, Hmox1, and Keap-1 in the lungs. Moreover, JFNE-A significantly decreased the protein expression of p62 and increased the ratio of LC3II/LC3I. It also upregulated the mRNA expression levels of Atg5 and Beclin-1, whereas it reduced the mRNA expression level of SQSTM1 and increased autophagosome structures.

Conclusion: Overall, treatment with JFNE-A ameliorated LPS-induced ALI in mice by suppressing the NF-κB signaling pathways and promoting Nrf2 signaling pathways by accelerating autophagy.
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http://dx.doi.org/10.1016/j.phymed.2021.153891DOI Listing
February 2022

Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity.

Oncoimmunology 2022 5;11(1):2011673. Epub 2022 Jan 5.

Senior Department of Urology, The Third Medical Center of PLA General Hospital, Beijing, China.

Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells and in xenograft mouse models . In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4 and CD8 T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.
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http://dx.doi.org/10.1080/2162402X.2021.2011673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747516PMC
January 2022

Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211065893

Department of Urology/State Key Laboratory of Kidney Diseases, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Objectives: Never in mitosis gene A-related kinase 2 (NEK2) has been implicated in tumorigenesis in various tissues, but its function in clear cell renal cell carcinoma (ccRCC) tumorigenesis is unclear. We evaluated the correlation between NEK2 expression and ccRCC.

Methods: Immunohistochemistry analysis of NEK2 protein was done on high-density multi-organ Human Cancer tissue microarray derived from the patient samples from clear cell renal cell carcinoma. We used multiple clinical cohorts to analyze the NEK2 immunohistochemical staining expression across human cancers. The cancer genome atlas (TCGA) data analysis of NEK2 was done through UALCAN web servers. Association of NEK2 and Kaplan-Meier survival analysis was done on both of our clinical database and available TCGA datasets.

Results: Using the UALCAN cancer transcriptional data analysis website, we found that NEK2 is overexpressed in ccRCC, and its expression was associated with overall survival. According to the analyses of our own clinical database and immunohistochemical staining, protein levels of NEK2 were elevated in renal carcinoma compared to adjacent normal tissues. Kaplan-Meier survival analysis of both UALCAN and our database showed that high expression of NEK2 was associated with a poor prognosis. Multivariate and univariate analyses showed that NEK2 expression was closely related to a poor prognosis. The findings suggest that NEK2 is associated with ccRCC.

Conclusion: These studies show that NEK2 is over-expressed in clear cell renal cell carcinoma and plays an essential role in cancer cell survival, as such NEK2 could serve as a novel potential target for therapeutic intervention in ccRCC.
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http://dx.doi.org/10.1177/20587384211065893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689635PMC
March 2022

Differences of Sleep Disorders Between Vestibular Migraine and Benign Paroxysmal Positional Vertigo.

Front Psychiatry 2021 18;12:726038. Epub 2021 Nov 18.

Department of Neurology, Baotou Central Hospital, Baotou, China.

Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients. VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month. Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients ( = 0.008) and significantly higher in both the VM group ( < 0.00001) and BPPV group ( = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency ( < 0.001) and N3 ( < 0.001) and the significantly higher time of wake-up after sleep onset ( < 0.001), N1 ( < 0.001), and N2 ( < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome ( = 0.001) and periodic leg movement in sleep ( = 0.016). The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.
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http://dx.doi.org/10.3389/fpsyt.2021.726038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637153PMC
November 2021

Targeted fluorescent imaging of a novel FITC-labeled PSMA ligand in prostate cancer.

Amino Acids 2022 Jan 20;54(1):147-155. Epub 2021 Nov 20.

Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, 100853, China.

In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(-) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.
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http://dx.doi.org/10.1007/s00726-021-03102-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810462PMC
January 2022

Ticagrelor versus Clopidogrel in Loss-of-Function Carriers with Stroke or TIA.

N Engl J Med 2021 12 28;385(27):2520-2530. Epub 2021 Oct 28.

From the China National Clinical Research Center for Neurological Diseases (Yongjun Wang, X.M., A.W., X.X., Y.P., H.L., J.J., J.L., S.N., Yilong Wang, X. Zhao, Z.L., Y.J., W.L., L.L., J.X.), the Department of Neurology (Yongjun Wang, X.M., A.W., X.X., Y.P., H.L., J.J., J.L., S.N., Yilong Wang, X. Zhao, Z.L., Y.J., W.L., L.L., J.X.), and the Advanced Innovation Center for Human Brain Protection (Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, and the Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences (Yongjun Wang), Beijing, the Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai (Q.D.), the Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou (A.X.), the Department of Neurology, Third People's Hospital of Liaocheng (L.C.), and the Department of Neurology, Liaocheng People's Hospital (X. Zhuang), Liaocheng, the Department of Neurology, Second Affiliated Hospital of Harbin Medical University (L.W.), and the Department of Neurology, First Affiliated Hospital of Harbin Medical University (G.L.), Harbin, the Department of Neurology, Weihai Wendeng District People's Hospital (J.Z.), and the Department of Neurology, Weihai Central Hospital (H.M.), Weihai, the Department of Neurology, Second People's Hospital of Huludao, Huludao (Y.F.), and the Department of Neurology, Baotou Central Hospital, Baotou (B.W.) - all in China; Dell Medical School, University of Texas at Austin, Austin (S.C.J.); and the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom (P.M.B.).

Background: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in loss-of-function carriers have not been extensively performed.

Methods: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days.

Results: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.

Conclusions: Among Chinese patients with minor ischemic stroke or TIA who were carriers of loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).
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http://dx.doi.org/10.1056/NEJMoa2111749DOI Listing
December 2021

Sense and sensibility: of synthetic biology and the redesign of bioreporter circuits.

Microb Biotechnol 2022 01 24;15(1):103-106. Epub 2021 Oct 24.

School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK.

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http://dx.doi.org/10.1111/1751-7915.13955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719829PMC
January 2022

Integrated study on the comprehensive magnetic-field configuration performance in the 150 kW superconducting magnetoplasmadynamic thruster.

Sci Rep 2021 Oct 19;11(1):20706. Epub 2021 Oct 19.

Beijing Institute of Control Engineering, Beijing, 100080, China.

Higher magnetic fields are always favoured in the magnetoplasmadynamic thruster (MPDT) due to its superior control of the plasma profile and acceleration process. This paper introduces the world's first integrated study on the 150 kW level AF-MPDT equipped with a superconductive coil. A completely new way of using superconducting magnet technology to confine plasma with high energy and extremely high temperatures is proposed. Using the PIC method of microscopic particle simulation, the plasma magnetic nozzle effect and performance of the MPDT under different magnetic-field conditions were studied. The integrated experiment used demonstrated that, in conjunction with the superconducting coil, greater homogeneity and a stronger magnetic field not only caused more even cathode ablation and improved its lifespan but also improved the performance of the MPDT (maximum thrust was 4 N at 150 kW, 0.56 T). Maximum thrust efficiency reached 76.6% and the specific impulse reached 5714 s.
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http://dx.doi.org/10.1038/s41598-021-00308-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526827PMC
October 2021

Robotic versus Laparoscopic Retroperitoneal Lymph node Dissection for Clinical Stage I Non-seminomatous Germ Cell Tumor of Testis: A Comparative Analysis.

Urol J 2021 Oct 4;18(6):618-622. Epub 2021 Oct 4.

Department of Urology, the Third Medical Center, Chinese PLA General Hospital, Beijing, China.

Purpose: To compare the treatment outcomes of robotic retroperitoneal lymph node dissection (R-RPLND) versus laparoscopic RPLND (L-RPLND) for clinical stage I non-seminomatous germ cell testicular tumors (NSGCTs).

Materials And Methods: We retrospectively reviewed the data of patients with stage I NSGCTs who underwent robotic or laparoscopic RPLND between 2008 and 2017. Perioperative data and oncologic outcomes were reviewed and compared between the two groups. Progression-free survival was analyzed using Kaplan-Meier survival curves and compared between two groups.

Results: A total of 31 and 28 patients underwent R-RPLND and L-RPLND respectively. The preoperative characteristics of the patients were comparable in the two groups. Patients in R-RPLND group had significantly shorter median operative time (140 vs. 175 minutes, P < .001), a shorter median duration to surgical drain removal (2 vs. 4 days, P = .002) and a shorter median postoperative hospital stay (5 vs. 6 days, P = .001). There were no statistical differences in intra- and post-operative complication rate between the groups and the oncologic outcomes were similar in the two groups.

Conclusion: In expert hands, R-RPLND and L-RPLND were comparable in oncological parameter and morbidity rate; R-RPLND showed superiority in operation duration, median days to surgical drain removal and postoperative hospital stay for stage I NSGCTs. Multicenter and randomized studies with good power of study and sufficient follow-up duration are required to validate our result.
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http://dx.doi.org/10.22037/uj.v18i.6629DOI Listing
October 2021

Rational Design and Characterization of Nitric Oxide Biosensors in Nissle 1917 and Mini SimCells.

ACS Synth Biol 2021 10 22;10(10):2566-2578. Epub 2021 Sep 22.

Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, United Kingdom.

Nitric oxide (NO) is an important disease biomarker found in many chronic inflammatory diseases and cancers. A well-characterized nitric sensing system is useful to aid the rapid development of bacteria therapy and synthetic biology. In this work, we engineered a set of NO-responsive biosensors based on the P promoter and its NorR regulator in the operon; the circuits were characterized and optimized in probiotic Nissle 1917 and mini SimCells (minicells containing designed gene circuits for specific tasks). Interestingly, the expression level of NorR displayed an inverse correlation to the P promoter activation, as a strong expression of the NorR regulator resulted in a low amplitude of NO-inducible gene expression. This could be explained by a competitive binding mechanism where the activated and inactivated NorR competitively bind to the same site on the P promoter. To overcome such issues, the NO induction performance was further improved by making a positive feedback loop that fine-tuned the level of NorR. In addition, by examining two integration host factor (IHF) binding sites of the P promoter, we demonstrated that the deletion of the second IHF site increased the maximum signal output by 25% (500 μM DETA/NO) with no notable increase in the basal expression level. The optimized NO-sensing gene circuit in anucleate mini SimCells exhibited increased robustness against external fluctuation in medium composition. The NO detection limit of the optimized gene circuit pPnorVβ was also improved from 25.6 to 1.3 nM in mini SimCells. Moreover, lyophilized mini SimCells can maintain function for over 2 months. Hence, SimCell-based NO biosensors could be used as safe sensor chassis for synthetic biology.
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http://dx.doi.org/10.1021/acssynbio.1c00223DOI Listing
October 2021

Orthogonal paper biosensor for mercury(II) combining bioluminescence and colorimetric smartphone detection.

Biosens Bioelectron 2021 Dec 20;194:113569. Epub 2021 Aug 20.

Department of Chemistry "Giacomo Ciamician", University of Bologna, Via Selmi 2, 40126, Bologna, Italy; Center for Applied Biomedical Research (CRBA), Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi, Bologna, Italy; Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Bologna, Italy. Electronic address:

Mercury contamination in the environment has reached alarming levels. Due to its persistence and bioaccumulation, mercury is one of the most widespread toxic heavy metals found in air, water and food. Thus, it is mandatory to monitor mercury and its compounds, and the availability of sensitive and rapid biosensors is highly valuable. We developed a low-cost biosensor for orthogonal detection of mercury(II) integrating three different biorecognition principles on a three-leaf paper: i) a mercury-specific bioluminescent Escherichia coli bioreporter strain expressing NanoLuc luciferase as reporter protein, ii) a purified β-galactosidase (β-gal) enzyme which is irreversibly inhibited by mercury and other metal ions, and iii) an Aliivibrio fischeri bioluminescent strain which is used to quantitatively assess sample toxicity and correct the analytical signal accordingly. Both sensory elements and substrates, Furimazine for the bioluminescent reporter strain and chlorophenol red-β-D-galactopyranoside for colorimetric detection of β-gal, were integrated in the paper sensor to provide a stable all-in-one disposable cartridge which can be easily snapped into a smartphone with a clover-shaped 3D printed housing. This is the first integration of bioluminescence and colorimetric detection on a smartphone-paper sensor, providing a readout within 15 and 60 min for the colorimetric and bioluminescent detection respectively. The biosensor was applied to water samples spiked with different concentrations of mercury, interferents and toxic chemicals providing a limit of detection for Hg(II) at the ppb levels.
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http://dx.doi.org/10.1016/j.bios.2021.113569DOI Listing
December 2021

A New Accurate, Simple and Less Radiation Exposure Device for Distal Locking of Femoral Intramedullary Nails.

Int J Gen Med 2021 4;14:4145-4153. Epub 2021 Aug 4.

Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

Background: Due to the metal elasticity of intramedullary nails (IMs) and irregularities of the long bone marrow cavity and other reasons, one of the greatest challenges for surgeons is to position the distal locking screw. Therefore, a novel laser guiding navigation device was designed for the distal locking of femoral IMs. The purpose of this study was to compare the effectiveness of the novel device and freehand technique for distal locking of IMs in the femoral model.

Methods: The laser guiding navigation device (laser group) and freehand technique (freehand group) were used in the distal locking of the IMs in the femoral model. All operations were performed by surgeons of the same level. The differences between the two groups were compared in terms of operative time, radiation exposure time, first success rate, deviation angle between ideal trajectory and actual trajectory, and learning curve.

Results: The distal locking of the IMs in the femoral model was performed 40 times in each group. The results showed that the laser group was better than the freehand group in terms of operative time (345±165 VS 212±105 seconds, ), radiation exposure time (164±57 VS 41±15 seconds, ) and first successrate ( =21.36, <0.001). Compared with the freehand group, the actual trajectory of the laser group was closer to the ideal trajectory in coronal and horizontal planes. Furthermore, the learning curve time of the laser group was shorter.

Conclusion: Compared with traditional freehand technique, the novel laser guiding navigation device can shorten the operative time and reduce radiation exposure invitro. In addition, it is easy to master with more accuracy and a higher first success rate in vitro.
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http://dx.doi.org/10.2147/IJGM.S321005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349542PMC
August 2021

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

Pain Ther 2021 Dec 7;10(2):1355-1373. Epub 2021 Aug 7.

Department of Neurology, Guiyang Sixth Hospital, Guiyang, China.

Introduction: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices.

Methods: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded.

Results: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350).

Conclusion: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines.

Trial Registration: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.
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http://dx.doi.org/10.1007/s40122-021-00281-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586277PMC
December 2021
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