Publications by authors named "Chao Zheng"

434 Publications

A rare complication of endoscopic ligation ("loop-and-let-go") for management of a giant colonic lipoma.

Endoscopy 2021 Jul 19. Epub 2021 Jul 19.

Department of Gastroenterology, Shenzhen People's Hospital, Guangdong, P. R. China.

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http://dx.doi.org/10.1055/a-1540-6031DOI Listing
July 2021

Methyl Diet Enhanced Sepsis-Induced Mortality Through Altering Gut Microbiota.

J Inflamm Res 2021 9;14:3107-3121. Epub 2021 Jul 9.

Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, People's Republic of China.

Introduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.

Methods: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or . Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.

Results: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of and , which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.

Discussion: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.
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http://dx.doi.org/10.2147/JIR.S305202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277458PMC
July 2021

Palladium-Catalyzed Dearomative Methoxyallylation of 3-Nitroindoles with Allyl Carbonates​​.

Angew Chem Int Ed Engl 2021 Jul 17. Epub 2021 Jul 17.

Shanghai Inst Org Chem, State Key Lab Organometallic Chem, 345 Lingling Lu, 200032, Shanghai, CHINA.

Herein we report a Pd-catalyzed dearomative methoxyallylation of 3-nitroindoles with readily available allyl carbonates. Good yields (up to 86%) and diastereoselectivity (up to >20:1 dr) are obtained for a wide range of substrates. The compatibility of gram-scale synthesis and the relatively low catalyst loading (down to 1 mol% of [Pd]) enhance the practicality of this method. The kinetic experiments indicate that the rate-determining step of this reaction is the nucleophilic attack of the alkoxide anion.
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http://dx.doi.org/10.1002/anie.202107139DOI Listing
July 2021

Levo-tetrahydropalmatine inhibits α4β2 nicotinic receptor response to nicotine in cultured SH-EP1 cells.

Acta Pharmacol Sin 2021 Jul 12. Epub 2021 Jul 12.

Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.

Nicotine, a major component of tobacco, is highly addictive and acts on nicotinic acetylcholine receptors (nAChRs) to stimulate reward-associated circuits in the brain. It is well known that nAChRs play critical roles in mediating nicotine reward and addiction. Current FDA-approved medications for smoking cessation are the antidepressant bupropion and the nicotinic partial agonist varenicline, yet both are limited by adverse side effects and moderate efficacy. Thus, development of more efficacious medications with fewer side effects for nicotine addiction and smoking cessation is urgently needed. l-Tetrahydropalmatine (l-THP) is an active ingredient of the Chinese medicinal herb Corydalis ambigua that possesses rich neuropharmacological actions on dopamine (DA) receptors in the mesocorticolimbic dopaminergic reward pathway. L-THP has been explored as anti-addiction treatments for drug abuse including nicotine. However, the targets and mechanisms of l-THP-caused anti-nicotine effects are largely unknown. In this study we address this question by elucidating the effects of l-THP on human neuronal nAChRs using patch-clamp recordings. Human neuronal α4β2-nAChRs were heterologously expressed in SH-EP1 human epithelial cells. Bath application of nicotine (0.1-100 μM) induced inward currents, co-application of l-THP (3 μM) inhibited nicotine-induced currents in the transfected cells. L-THP-caused inhibition was concentration-dependent (the EC values for inhibiting the peak and steady-state current were 18 and 2.1 μM, respectively) and non-competitive. Kinetic analysis of the whole-cell currents showed that l-THP slowed rising time and accelerated decay time constants. L-THP specifically modulated α4β2-nAChRs, as it did not affect α7-nAChRs or α1*-nAChRs (muscle type). Interestingly, two putative α4β2-nAChR isoforms, namely sazetidine A-activated, high-sensitive one (α4β2-nAChR) and cytisine-activated, low-sensitive one (α4β2-nAChR) were pharmacologically separated, and the low-sensitive one was more susceptible to l-THP inhibition than the high-sensitive one. In conclusion, we demonstrate that l-THP blocks neuronal α4β2-nAChR function, which may underlie its inhibition on nicotine addiction.
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http://dx.doi.org/10.1038/s41401-021-00709-1DOI Listing
July 2021

Association between atmospheric concentration of particulate matters and inpatient and outpatient visits for chronic respiratory diseases in Xiamen, China.

Chin Med J (Engl) 2021 Feb 25;134(13):1616-1618. Epub 2021 Feb 25.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

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http://dx.doi.org/10.1097/CM9.0000000000001435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280060PMC
February 2021

Arthroscopically Assisted Cannulated Screw Fixation for Treating Type III Tibial Intercondylar Eminence Fractures: A Short-Term Retrospective Controlled Study.

Front Surg 2021 22;8:639270. Epub 2021 Jun 22.

Department of Orthopaedics, Children's Hospital of Chongqing Medical University, Chongqing, China.

This study presents the clinical results from 22 children who underwent minimally invasive arthroscopically assisted screw fixation for the treatment of intercondylar eminence fractures. We retrospectively analyzed the clinical data of 22 children (aged 7.5 to 13.5 years) with type III tibial intercondylar eminence fractures who were treated in our department from March 2007 to September 2019. According to the type of operation, the patients were divided into two groups: group A ( = 12) received arthroscopically assisted cannulated screw fixation, and group B ( = 10) received open reduction and cannulated screw internal fixation. Radiography scans, Lysholm scores, International Knee Documentation Committee (IKDC) 2,000 subjective scores, Tegner scores, range of motion (ROM) of the knee, the anterior drawer test (ADT), the Lachman test, and the pivot-shift test were used to evaluate the clinical efficacy. All 22 children were evaluated over a 12 to 58 month follow-up period (mean: 27.5 months). At the final exam, group A was significantly superior to group B in Lysholm scores (93.33 ± 3.55 vs. 86.20 ± 4.52), IKDC scores (92.06 ± 3.55 vs. 86.07 ± 5.81), and Tegner scores (7.75 ± 0.87 vs. 6.40 ± 0.52) and presented shorter operative times (25.42 ± 3.97 vs. 35.00 ± 5.27). The differences were statistically significant ( < 0.05). All the incisions healed primarily. No complications, such as fracture fragment displacement, delayed epiphyseal growth, or knee joint dysfunction, were observed. The drawer test, Lachman test, and pivot-shift test were negative for all patients. Arthroscopically assisted cannulated screw fixation is effective and safe for the treatment of tibial intercondylar eminence fractures, providing excellent stability and quick recovery of joint function.
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http://dx.doi.org/10.3389/fsurg.2021.639270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259787PMC
June 2021

β-Amyloid Peptides Manipulate Switching Behaviors of Donor-Acceptor Stenhouse Adducts.

Anal Chem 2021 Jul 8;93(28):9887-9896. Epub 2021 Jul 8.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, Charlestown, Boston, Massachusetts 02129, United States.

Molecular switching plays a critical role in biological and displaying systems. Donor-acceptor Stenhouse adducts (DASAs) is a newly re-discovered series of switchable photochromes, and light is the most used approach to control its switching behavior. In this report, we speculated that hydrophobic binding pockets of biologically relevant peptides/proteins could be harnessed to alter its switching behavior without the assistance of light. We designed and synthesized a DASA compound SHA-2, and we demonstrated that the Aβ40 species could stabilize SHA-2 in the linear conformation and decrease the rate of molecular switching via fluorescence spectral studies. Moreover, molecular dynamics simulation revealed that SHA-2 could bind to the hydrophobic fragment of the peptide and resulted in substantial changes in the tertiary structure of Aβ40 monomer. This structural change is likely to impede the aggregation of Aβ40, as evidenced by the results from thioflavin T fluorescence and ProteoStat aggregation detection experiments. We believe that our study opens a new window to alter the switching behavior of DASA via DASA-peptide/protein interactions.
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http://dx.doi.org/10.1021/acs.analchem.1c01957DOI Listing
July 2021

Ag-Catalyzed Asymmetric Dearomatization of Electron-deficient Heteroarenes via Interrupted Barton-Zard Reaction.

Angew Chem Int Ed Engl 2021 Jul 1. Epub 2021 Jul 1.

Shanghai Institute of Organic Chemistry, State Key Laboratory of Organometallic Chemistry, CHINA.

Herein we report a catalytic asymmetric dearomatization reaction of electron-deficient heteroarenes with α -substituted isocyanoacetates through an interrupted Barton-Zard reaction. A range of optically active pyrrolo[3,4- b ]indole derivatives was obtained in good yields (up to 97%) with high stereoselectivities (up to 20:1 dr and 97% ee), using a catalyst system consisting of a cinchona-derived amino-phosphine and silver oxide. This reaction features wide substrate scope and mild conditions, and provides a new strategy for developing asymmetric dearomatization reactions.
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http://dx.doi.org/10.1002/anie.202107767DOI Listing
July 2021

Risk factors and impact on bile leakage in patients with choledochal cysts: a retrospective case-control analysis.

Updates Surg 2021 Jun 23. Epub 2021 Jun 23.

Department of Pediatric General Surgery, Chongqing University Three Gorges Hospital, Chongqing, People's Republic of China.

Although bile leakage is a major postoperative complication after hepatobiliary surgery, the associated risk factors for pediatric patients remain poorly defined. Here, we intend to identify the perioperative risk factors for bile leakage in pediatric patients with choledochal cysts following Roux-en-Y hepaticojejunostomy. A multicenter case-control study investigating the risk factors for bile leakage was conducted among 1179 eligible pediatric patients with choledochal cysts following Roux-en-Y hepaticojejunostomy between January 2009 and December 2019. There were 267 cases with bile leakage, and approximately four control patients were identified for each case. Multivariable logistic regression was performed to identify the risk factors, including perioperative variables. According to univariable analysis, bile leakage was associated with severe cholangitis (p = 0.012), low albumin levels (p = 0.010), anemia (p = 0.002) and laparoscopic surgery (p = 0.004). Multivariable analysis showed that a low level of preoperative albumin (ALB) (odds ratio [OR] = 1.11; 95% CI 1.02-1.19; p = 0.016), worse symptoms (severe cholangitis) (OR = 1.16; 95% CI 1.01-1.26; p < 0.001), and a previous hepatobiliary procedure (OR = 1.32; 95% CI 1.09-1.63; p = 0.036) were independent factors that were associated with bile leakage. This study identified potential risk factors for bile leakage in patients following Roux-en-Y hepaticojejunostomy that should be targeted for interventions to reduce the occurrence of the condition.
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http://dx.doi.org/10.1007/s13304-021-01113-4DOI Listing
June 2021

Fluorine-induced aggregate-interlocking for color-tunable organic afterglow with a simultaneously improved efficiency and lifetime.

Chem Sci 2021 Jan 12;12(10):3580-3586. Epub 2021 Jan 12.

Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications 9 Wenyuan Road Nanjing 210023 China

Designing organic afterglow materials with a high efficiency and long lifetime is highly attractive but challenging because of the inherent competition between the luminescence efficiency and lifetime. Here, we propose a simple yet efficient strategy, namely fluorine-induced aggregate-interlocking (FIAI), to realize both an enhanced efficiency and elongated lifetime of afterglow materials by stimulating the synergistic effects of the introduced fluorine atoms to efficiently promote intersystem crossing (ISC) and intermolecular non-covalent interactions for facilitating both the generation of triplet excitons and suppression of non-radiative decays. Thus, the fluorine-incorporated afterglow molecules exhibit greatly enhanced ISC with a rate constant up to 5.84 × 10 s and suppressed non-radiative decay down to 0.89 s, resulting in efficient organic afterglow with a simultaneously improved efficiency up to 10.5% and a lifetime of 1.09 s. Moreover, accompanied by the efficient phosphorescence emission especially at cryogenic temperature, color-tunable afterglow was also observed at different temperatures. Therefore, tri-mode multiplexing encryption devices by combining lifetime, temperature and color, and visual temperature sensing were successfully established. The FIAI strategy by addressing fundamental issues of afterglow emission paves the way to develop high-performance organic afterglow materials, opening up a broad prospect of aggregated and excited state tuning of organic solids for emission lifetime-resolved applications.
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http://dx.doi.org/10.1039/d0sc06025aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179499PMC
January 2021

Preclinical evaluation of a novel antibody-drug conjugate targeting DR5 for lymphoblastic leukemia therapy.

Mol Ther Oncolytics 2021 Jun 29;21:329-339. Epub 2021 Apr 29.

Yantai Obioadc Biomedical Technology Ltd., Yantai, China.

Acute lymphoblastic leukemia (ALL) is an aggressive hematological neoplasm resulting from immature lymphoid precursors. An antibody-drug conjugate (ADC), coupling a small molecule covalently with a targeting antibody, can specifically kill tumor cells. Death receptor 5 (DR5) is considered as a promising anti-tumor drug target. In this study, we describe the preclinical evaluation of a novel DR5-targeting ADC (Oba01) as a potential therapeutic against ALL. Oba01 utilizes anti-DR5 humanized monoclonal antibody (zaptuzumab) coupled via a cleavable linker to monomethyl auristatin E (MMAE). Oba01 can specifically bind to DR5 on the tumor cells and transfer into lysosome via DR5-mediated endocytosis. It then effectively releases the MMAE, which can bind to the tubulin and prevent its aggregation, thereby leading to a significant inhibition of proliferation and cell death in tumor cells. Additionally, Oba01 displays significant dose-dependent tumoricidal activity in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. More importantly, toxicity analysis of Oba01 showed a favorable safety profile, and pharmacokinetic analysis illustrated an excellent stability and tolerability in rats and cynomolgus monkeys. Taken together, our data conclusively demonstrate that Oba01 is an attractive candidate for further clinical trials in DR5-positive ALL patients.
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http://dx.doi.org/10.1016/j.omto.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173093PMC
June 2021

Atezolizumab-induced anaphylactic shock in a patient with hepatocellular carcinoma undergoing immunotherapy: A case report.

World J Clin Cases 2021 Jun;9(16):4110-4115

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.

Background: Atezolizumab is a programmed death ligand 1 (PD-L1) inhibitor, and its combination with bevacizumab has been proven an effective immunotherapy for unresectable hepatocellular carcinoma (HCC). Treatment with immune checkpoint inhibitors (ICIs) can lead to hypersensitivity reactions; however, anaphylactic shock is rare. We present a case of life-threatening anaphylactic shock during atezolizumab infusion and performed a relevant literature review.

Case Summary: A 75-year-old man was diagnosed with HCC recurrence after hepatectomy. He was administered immunotherapy with atezolizumab plus bevacizumab after an allergy to a programmed death-1 (PD-1) inhibitor. The patient showed a sudden onset of dizziness, numbness, and lack of consciousness with severe hypotension during atezolizumab infusion. The treatment was stopped immediately. The patient's symptoms resolved after 5 mg dexamethasone was administered. Because of repeated hypersensitivity reactions to ICIs, treatment was changed to oral targeted regorafenib therapy.

Conclusion: Further research is necessary for elucidating the hypersensitivity mechanisms and establishing standardized skin test and desensitization protocols associated with PD-1 and PD-L1 to ensure effective treatment with ICIs.
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http://dx.doi.org/10.12998/wjcc.v9.i16.4110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180205PMC
June 2021

Small-molecule probes for fluorescent detection of cellular hypoxia-related nitroreductase.

J Pharm Biomed Anal 2021 Sep 9;203:114199. Epub 2021 Jun 9.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China. Electronic address:

Nitroreductase is a reductase that catalyzes nitro aromatic compounds to aromatic amines. It effectively reduces nitro to hydroxylamine or amino when in the presence of nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate. In terms of tumor, nitroreductase is upregulated in hypoxic tumor cells, and its content is directly related to the degree of hypoxia. Therefore, effective detection of nitroreductase is important not only for the study of cellular hypoxia, but also for the diagnosis and treatment of tumors and related diseases. In this review, we summarized the latest advances in small-molecule fluorescent probes for nitroreductase detection based on different fluorescence mechanisms, with a focus on research conducted between May 2018 and December 2020. The development trends and application prospect in this rapidly developing field were also highlighted.
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http://dx.doi.org/10.1016/j.jpba.2021.114199DOI Listing
September 2021

Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe.

Chem Sci 2020 May 11;11(20):5238-5245. Epub 2020 May 11.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School Room 2301, Building 149, Charlestown Boston Massachusetts 021291 USA

Differentiating amyloid beta (Aβ) subspecies Aβ40 and Aβ42 has long been considered an impossible mission with small-molecule probes. In this report, based on recently published structures of Aβ fibrils, we designed iminocoumarin-thiazole (ICT) fluorescence probes to differentiate Aβ40 and Aβ42, among which Aβ42 has much higher neurotoxicity. We demonstrated that robustly responds to Aβ fibrils, evidenced by turn-on fluorescence intensity and red-shifting of emission peaks. Remarkably, showed different spectra towards Aβ40 and Aβ42 fibrils. results demonstrated that could be used to differentiate Aβ40/42 in solutions. Moreover, our data revealed that could be used to separate Aβ40/42 components in plaques of AD mouse brain slides. In addition, two-photon imaging suggested that was able to cross the BBB and label plaques . Interestingly, we observed that was specific toward plaques, but not cerebral amyloid angiopathy (CAA) on brain blood vessels. Given Aβ40 and Aβ42 species have significant differences of neurotoxicity, we believe that can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.
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http://dx.doi.org/10.1039/d0sc02060eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159352PMC
May 2020

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type.

Clin Exp Immunol 2021 Jun 12. Epub 2021 Jun 12.

Neuroscience Center, Department of Neurology, The First Hospital of Jilin University, Changchun, China.

Guillain-Barré syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of the peripheral nervous system (PNS). Macrophages play a central role in its animal model, experimental autoimmune neuritis (EAN), which has been well accepted. Additionally, nuclear factor (NF)-κB inhibitors have been used to treat cancers and have shown beneficial effects. Here, we investigated the therapeutic effect of M2 macrophage and the NF-κB pathway's correlation with macrophage activation in EAN in C57BL/6 mice. We demonstrate that M2 macrophage transfusion could alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor (BAY-11-7082) could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of proinflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.
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http://dx.doi.org/10.1111/cei.13637DOI Listing
June 2021

New possible silver lining for pancreatic cancer therapy: Hydrogen sulfide and its donors.

Acta Pharm Sin B 2021 May 31;11(5):1148-1157. Epub 2020 Oct 31.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (HS) undertakes essential functions, encompassing various signaling complexes that occupy key processes in human biology. Accumulating evidence indicates that HS exhibits bimodal modulation of cancer development. Thus, endogenous or low levels of exogenous HS are thought to promote cancer, whereas high doses of exogenous HS suppress tumor proliferation. Similarly, inhibition of endogenous HS production also suppresses tumor proliferation. Accordingly, HS biosynthesis inhibitors and HS supplementation (HS donors) are two distinct strategies for the treatment of cancer. Unfortunately, modulation of endogenous HS on pancreatic cancer has not been studied so far. However, HS donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation, inducing apoptosis, arresting cell cycle, and suppressing invasion and migration through exploiting multiple signaling pathways. As far as we know, there is no review of the effects of HS donors on pancreatic cancer. Based on these concerns, the therapeutic effects of some HS donors and NO-HS dual donors on pancreatic cancer were summarized in this paper. Exogenous HS donors may be promising compounds for pancreatic cancer treatment.
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http://dx.doi.org/10.1016/j.apsb.2020.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144891PMC
May 2021

Clinical practice guidelines for pre-operative evaluation of breast cancer: Chinese Society of Breast Surgery practice guidelines 2021.

Chin Med J (Engl) 2021 May 19. Epub 2021 May 19.

Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, China.

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http://dx.doi.org/10.1097/CM9.0000000000001520DOI Listing
May 2021

Strict Surgical Repair for Bile Leakage Following the Roux-en-Y Hepaticojejunostomy.

Front Surg 2021 4;8:641127. Epub 2021 May 4.

Department of Pediatric General and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China.

The optimal bile leakage management strategy in the pediatric population following the initial Roux-en-Y hepaticojejunostomy is still a matter of discussion today. Here, we assessed the roles of bile leakage management and surgical implementation on outcomes for patients with bile leakage. A revised protocol for bile leakage management with restricted surgical intervention was implemented at Chongqing Children's Hospital on March 15, 2013 and Sanxia Hospital on April 20, 2013. We performed a retrospective, historical control analysis for the protocol implementation to compare the short- and long-term outcomes using the corresponding statistical methods. There was a total of 84 patients included in the analysis, including 46 patients in the pre-protocol group and 38 patients in the post-protocol group. No statistical differences for the demographic features were found between the two groups. There was a decrease in redo surgeries in the post-protocol cohort compared to those in the pre-protocol cohort (odds ratio [OR] = 4.48 [95% CI, 1.57-12.77]; = 0.003). Furthermore, patients in the post-protocol group were less likely to be associated with intensive care unit (ICU) admission (OR = 3.72 [95% CI, 1.11-12.49]; = 0.024) compared to patients in the pre-protocol group, respectively. There was no mortality between the two groups. A restrictive surgical intervention strategy can effectively reduce the rate of redo surgery and exhibited promising outcomes for bile leakage in terms of postoperative recovery and hospitalization costs.
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http://dx.doi.org/10.3389/fsurg.2021.641127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130580PMC
May 2021

Predictive value of postoperative C-reactive protein-to-albumin ratio in anastomotic leakage after esophagectomy.

J Cardiothorac Surg 2021 May 17;16(1):133. Epub 2021 May 17.

Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Introduction: Among the many possible postoperative complications, anastomotic leakage (AL) is the most common and serious. Therefore, the purpose of this study was to explore the ability of various inflammatory and nutritional markers to predict postoperative AL in patients after esophagectomy.

Methods: A total of 273 patients were retrospectively evaluated and enrolled into this study. Perioperative, surgery-related, tumor-related and laboratory tests data were extracted and analyzed. The discriminatory ability and optimal cut-off value was evaluated according to the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were performed to access the potential risk factors for AL.

Results: The overall incidence of AL was 12.5% (34/273). C-reactive protein-to-albumin ratio (CRP/ALB ratio) [AUC 0.943 (95% confidence interval (CI) = 0.911-0.976, p <  0.001)] and operation time [AUC 0.747 (95% CI = 0.679-0.815, p <  0.001)] had the greatest discrimination on AL prediction. Multivariate analysis demonstrated that CRP/ALB ratio and operation time were two independent risk factors for AL, and CRP/ALB ratio (OR = 102.909, p <  0.001) had an advantage over operation time (OR = 9.363, p = 0.020; Table 3).

Conclusion: Operation time and postoperative CRP/ALB ratio were two independent predictive indexes for AL. Postoperative CRP/ALB ratio greater than 3.00 indicated a high risk of AL. For patients with abnormal postoperative CRP/ALB ratio, early non-operative treatment or surgical intervention are needed to reduce the serious sequelae of AL.
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http://dx.doi.org/10.1186/s13019-021-01515-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130324PMC
May 2021

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

Aging (Albany NY) 2021 05 7;13(9):13061-13072. Epub 2021 May 7.

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.

Background: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited.

Results: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV.

Conclusions: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV.

Materials And Methods: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.
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http://dx.doi.org/10.18632/aging.202987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148493PMC
May 2021

Enantioselective synthesis of polycyclic pyrrole derivatives by iridium-catalyzed asymmetric allylic dearomatization and ring-expansive migration reactions.

Chem Commun (Camb) 2021 Jun;57(44):5390-5393

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.

Herein, we report an N-alkylation of pyrroles triggered by an unprecedented selective ring-expansive migration of the spiro-2H-pyrrole intermediates obtained via Ir-catalyzed asymmetric allylic dearomatization. The reaction affords a series of tetrahydropyrrolo[1,2-c]pyrimidine derivatives in good yields (up to 88%) with excellent enantioselectivity (up to >99% ee). The proposed reaction mechanism is supported by DFT calculations and the characterization of the key intermediate.
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http://dx.doi.org/10.1039/d1cc01929eDOI Listing
June 2021

Spectroscopy-Assisted Label-free Molecular Analysis of Live Cell Surface with Vertically Aligned Plasmonic Nanopillars.

Small 2021 05 4;17(21):e2100161. Epub 2021 May 4.

Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

A generalized label-free platform for surface-selective molecular sensing in living cells can transform the ability to examine complex events in the cell membrane. While vertically aligned semiconductor and metal-semiconductor hybrid nanopillars have rapidly surfaced for stimulating and probing the intracellular environment, the potential of such constructs for selectively interrogating the cell membrane is surprisingly underappreciated. In this work, a new platform, entitled nano-PROD (nano-pillar based Raman optical detection), enables molecular recording by probing fundamental vibrational modes of membrane constituents of cells adherent on a large-area silver-coated silicon nanopillar substrate fabricated using a precursor solution-based nanomanufacturing process. It is shown that the nano-PROD platform sustains live cells in near-physiological conditions, which can be directly profiled using surface-enhanced Raman spectroscopy due to the confined electromagnetic field enhancement. The experimental results highlight the utility of the platform in probing specific cell surface markers for accurately recognizing the phenotypically identical prostate cancer cells, differing only in prostate-specific membrane antigen expression. Due to its tunability, nano-PROD has the promise to be readily extendable to other applications that can leverage its unique combination of nanoscale topographic features and molecular sensing capabilities, from stain-free cytopathology inspection to understanding spatio-mechanical regulation in membrane receptor function.
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http://dx.doi.org/10.1002/smll.202100161DOI Listing
May 2021

The chromosome-scale genome reveals the evolution and diversification after the recent tetraploidization event in tea plant.

Hortic Res 2020 May 1;7(1):63. Epub 2020 May 1.

Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture and Rural Affairs, Tea Research Institute of the Chinese Academy of Agricultural Science, Hangzhou, 310008, China.

Tea is one of the most popular nonalcoholic beverages due to its characteristic secondary metabolites with numerous health benefits. Although two draft genomes of tea plant (Camellia sinensis) have been published recently, the lack of chromosome-scale assembly hampers the understanding of the fundamental genomic architecture of tea plant and potential improvement. Here, we performed a genome-wide chromosome conformation capture technique (Hi-C) to obtain a chromosome-scale assembly based on the draft genome of C. sinensis var. sinensis and successfully ordered 2984.7 Mb (94.7%) scaffolds into 15 chromosomes. The scaffold N50 of the improved genome was 218.1 Mb, ~157-fold higher than that of the draft genome. Collinearity comparison of genome sequences and two genetic maps validated the high contiguity and accuracy of the chromosome-scale assembly. We clarified that only one Camellia recent tetraploidization event (CRT, 58.9-61.7 million years ago (Mya)) occurred after the core-eudicot common hexaploidization event (146.6-152.7 Mya). Meanwhile, 9243 genes (28.6%) occurred in tandem duplication, and most of these expanded after the CRT event. These gene duplicates increased functionally divergent genes that play important roles in tea-specific biosynthesis or stress response. Sixty-four catechin- and caffeine-related quantitative trait loci (QTLs) were anchored to chromosome assembly. Of these, two catechin-related QTL hotspots were derived from the CRT event, which illustrated that polyploidy has played a dramatic role in the diversification of tea germplasms. The availability of a chromosome-scale genome of tea plant holds great promise for the understanding of genome evolution and the discovery of novel genes contributing to agronomically beneficial traits in future breeding programs.
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http://dx.doi.org/10.1038/s41438-020-0288-2DOI Listing
May 2020

A Sensitive LC-MS/MS Method for the Determination of Afatinib in Human Plasma and Its Application to a Bioequivalence Study.

J Chromatogr Sci 2021 Apr 29. Epub 2021 Apr 29.

BE/Phase I clinical center, The first affiliated hospital of Xiamen university, Xiamen, Fujian 361000, China.

A high performance liquid chromatography-tandem mass spectrometry assay for the determination of afatinib (AFT) in human plasma was established. A simple sample preparation of protein precipitation was used and separation was achieved on a C18 column by the gradient mixture of mobile Phase A of water (containing 0.1% ammonia) and the mobile Phase B of acetonitrile and water (V:V = 95:5, containing 0.2% ammonia). The multiple reaction monitoring mode was used to monitor the precursor-to-production transitions of m/z 486.2 → m/z 371.4 for AFT and m/z 492.2 → m/z 371.3 for AFT-d6 (internal standard) at positive ionization mode. The calibration curve ranged from 0.100 to 25.0 ng·mL-1 and the correlation coefficient was greater than 0.99. The intra- and inter-batch precision was less than or equal to 10.0%. Accuracy determined at four concentrations was in the range of 92.3-103.3%. In summary, our method was sensitive, simple and reliable for the quantification of AFT and was successfully applied to a bioequivalence study.
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http://dx.doi.org/10.1093/chromsci/bmab040DOI Listing
April 2021

Molybdenum-Catalyzed Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds.

Angew Chem Int Ed Engl 2021 Jul 4;60(28):15254-15259. Epub 2021 Jun 4.

State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory of Chemical Biology of Fujian Province, and, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China.

The transition-metal-catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo-catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench-stable 1,2-dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram-scale syntheses, late-stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo-oxo complexes.
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http://dx.doi.org/10.1002/anie.202103429DOI Listing
July 2021

Carnitine palmitoyl transferase 1A is a novel diagnostic and predictive biomarker for breast cancer.

BMC Cancer 2021 Apr 15;21(1):409. Epub 2021 Apr 15.

Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.

Background: Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer.

Methods: Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared.

Results: CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872-0.920; test set, AUC, 0.904, 95% CI, 0.869-0.939) than did CA15-3, CEA, or CA125.

Conclusion: CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.
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http://dx.doi.org/10.1186/s12885-021-08134-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048260PMC
April 2021

Electro-Optic Modulation Using Metal-Free Perovskites.

ACS Appl Mater Interfaces 2021 Apr 15;13(16):19042-19047. Epub 2021 Apr 15.

Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, Ontario M5S 3G4, Canada.

Electro-optic (EO) modulation is of interest to impart information onto an optical carrier. Inorganic crystals-most notably LiNbO and BaTiO-exhibit EO modulation and good stability, but are difficult to integrate with silicon photonic technology. Solution-processed organic EO materials are readily integrated but suffer from thermal degradation at the temperatures required in operating conditions for accelerated reliability studies. Hybrid organic-inorganic metal halide perovskites have the potential to overcome these limitations; however, these have so far relied on heavy metals such as lead and cadmium. Here, we report linear EO modulation using metal-free perovskites, which maintain the crystalline features of the inorganic EO materials and incorporate the flexible functionality of organic EO chromophores. We find that, by introducing a deficiency of cations, we reduce the symmetry in the perovskite crystal and produce thereby an increased EO response. The best-engineered perovskites reported herein showcase an EO coefficient of 14 pm V at a modulation frequency of 80 kHz, an order of magnitude higher than in the nondefective materials. We observe split peaks in the X-ray diffraction and neutron diffraction patterns of the defective sample, indicating that the crystalline structure has been distorted and the symmetry reduced. Density functional theory (DFT) studies link this decreased symmetry to NH deficiencies. This demonstration of EO from metal-free perovskites highlights their potential in next-generation optical information transmission.
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http://dx.doi.org/10.1021/acsami.1c03406DOI Listing
April 2021

The ratio of gastric tube length to thorax length: a vital factor affecting leak after esophageal cervical anastomosis.

Ann Transl Med 2021 Mar;9(6):458

Department of Cardiothoracic Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.

Background: Esophagogastric anastomotic leak (AL) is a severe complication following esophageal resection. This study aims to explore preliminarily whether the ratio of the gastric conduit length to the thorax length can be regarded as a potential prognostic variable for AL, and if so, a cut-off value can be found to divide the patients into distinct risk groups.

Methods: We retrospectively reviewed the clinical data of 273 patients who underwent esophagectomy. The gastric conduit length, the thorax length, and other covariates were collected. Logistic regression was first conducted to probe the rationality of the ratio as a risk indicator of AL. Then the dichotomizing analysis was applied to find the optimal cut-off value.

Results: The incidence of AL was 12.5% (34/273). The coefficient of the ratio in the logistic regression equation was -7.901 with P<0.001, which indicated that the larger the ratio, the smaller the risk of AL. Further smoothed scatter plots revealed that a potential step function of the ratio of AL incidence exists, of which the steep part ranges from 1.74 to 1.90. Results of the accurate cut-off value search through a minimum P value approach give the optimal dichotomization point of 1.79.

Conclusions: The ratio of the gastric conduit length to the thorax length can reflect the tension in the anastomosis. The research proposes that surgeons can control the length of the gastric conduit during reconstruction to reduce the tension in the anastomosis and thus lead to a decrease in the incidence of AL.
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http://dx.doi.org/10.21037/atm-20-6082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039640PMC
March 2021

Advances in Catalytic Asymmetric Dearomatization.

ACS Cent Sci 2021 Mar 22;7(3):432-444. Epub 2021 Feb 22.

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.

Asymmetric catalysis has been recognized as the most enabling strategy for accessing chiral molecules in enantioenriched forms. Catalytic asymmetric dearomatization is an emerging and dynamic research subject in asymmetric catalysis, which has received considerable attention in recent years. The direct transformations from readily available aromatic feedstocks to structurally diverse three-dimensional polycyclic molecules make catalytic asymmetric dearomatization reactions of broad interest for both organic synthesis and medicinal chemistry. However, the inherent difficulty for the disruption of aromaticity demands a large energy input during the dearomatization process, which might be incompatible with the conditions generally required by asymmetric catalysis. In this Outlook, we will discuss representative strategies and examples of catalytic asymmetric dearomatization reactions of various aromatic compounds and try to convince readers that by overcoming the above obstacles, catalytic asymmetric dearomatization reactions could advance chemical sciences in many respects.
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http://dx.doi.org/10.1021/acscentsci.0c01651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006174PMC
March 2021

The prognostic value of modified NUTRIC score for patients in cardiothoracic surgery recovery unit: A retrospective cohort study.

J Hum Nutr Diet 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiothoracic Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.

Background: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited.

Methods: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database.

Results: The optimal cut-off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32-4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan-Meier curve indicated that patients at high nutritional risk have poorer 365-days [hazard ratio (HR) = 1.76, 95% CI = 1.30-2.37, p < 0.001] and 1000-days (HR = 2.30, 95% CI = 1.87-2.83, p < 0.001) overall survival.

Conclusions: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long-term survival in CSRU patients. More well-designed clinical trials are needed to verify and update our findings.
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http://dx.doi.org/10.1111/jhn.12899DOI Listing
March 2021