Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and metaanalysis

BACKGROUND Lung cancer is a major cause of death among patients,and non-small cell lung cancer(NSCLC)accounts for more than 80%of all lung cancers in many countries.AIM To evaluate the clinical benefit(CB)of COX-2 inhibitors in patients with advanced NSCLC using systematic review.METHODS We searched the six electronic databases up until December 9,2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC.Overall survival(OS),progression free survival(PFS),1-year survival rate(SR),overall response rate(ORR),CB,complete response(CR),partial response(PR),stable disease(SD),and toxicities were measured with more than one outcome as their endpoints.Fixed and random effects models were used to calculate risk estimates in a meta-analysis.Potential publication bias was calculated using Egger’s linear regression test.Data analysis was performed using R software.RESULTS The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS,progression free survival,1-year SR,CB,CR,and SD.However,there was a difference in overall response rate for patients with advanced NSCLC.In a subgroup analysis,significantly increased ORR results were found for celecoxib,rofecoxib,first-line treatment,and PR.For adverse events,the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia,thrombocytopenia,and cardiovascular events.CONCLUSION COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.

Subcutaneous angiolipoma in the scrotum: A case report

BACKGROUND Angiolipoma has been reported in many cases,and it often occurs in the skin of the trunk and limbs.However,angiolipoma in the scrotum is a rare disease with unknown etiology.This condition is difficult to diagnosis with other lumps in the scrotum.CASE SUMMARY A 32-year-old man presented to the urinary department with a history of an enlarged left scrotum with increasing discomfort for about 5 years.Physical examination revealed that there were a palpable mass measuring about 7.0 cm×6.5 cm in the left scrotum,with smooth surfaces but without tenderness or adhesion to the skin.Ultrasound showed that there was a hyperechoic mass under the skin of the top scrotum,about 72 mm×64 mm×21 mm in size,with clear borders,uneven internal echo,and abundant blood flow signals.Serum human chorionic gonadotropin and alpha-fetoprotein were in normal level.Subcutaneous mass resection at the bottom of the left scrotum was performed under local anesthesia with 1%lidocaine.Postoperative pathological examination resulted in a diagnosis of subcutaneous angiolipoma of the scrotum.No evidence of recurrence was found at 6 mo after surgery and there were no complaints of discomfort.CONCLUSION Angiolipoma is an extremely rare type of benign tumor extremely rarely found in the scrotum,but needs to be considered when evaluating scrotal masses especially when the mass is solid.According to the characteristics of angiolipoma,surgical resection is the best treatment strategy and it is not prone to recurrence after resection.

Application of Mammary Gland Endoprosthesis without a Shell in Modern Oncomammological Practice

Immediate and late follow-up results of oncomammological application of novel Ukrainian endoprosthesis “Nubiplant”, made of one piece of polyacrylamide gel, for mammary gland malignancies (MGM) radical treatment with reconstruction were analyzed. This endoprosthesis have proved its unique complex of favorable surgical and oncological properties, such as the shape and size accommodation for mammary gland plasty purposes, absence of shell and textured surface. Of 184 patients, operated on radically for initial stages of MGM, using "Nubiplant" endoprosthesis, postoperative complications have had occur in 18 (9,8%): the wound seroma in 12 (6,5%) and partial necrosis of cutaneous edge of postoperative wound – in 6 (3,8%). The seromas were successfully treated by their punctures and local necrosis - using excision with secondary suture placement. Late follow-up results were obtained in 112 (60,9%) patients: three-year period have had survived 104 (92,6±2,4%), and a five-year one – 84 (75,0±4,0%) of them. A contracture capsule was revealed in 3 (2,6%) patients, and excised with the endoprosthesis change. “Nubiplant” endoprosthesis have advantages over most popular worldwide kinds of such products. It may be used securely and effectively for total or partial reconstruction of mammary gland, including cases with hypoplasia, and is more resistant to trauma, radiation therapy and local complications occurrence, including contracture capsule formation. Its property to absorb the water may be used for purposes of plastic surgery. Prophylaxis of specific immediate surgical complications is trustworthy in MGM patients, using modified endoprosthesis “Nubiplant”, containing insulin, antihistamine and antiseptic medicines.

Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

GSH-responsive camptothecin prodrug-based hybrid micellar nanoparticles enable antitumor chemo-immunotherapy by PD-L1 knockdown

The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L1 via inhibiting novo production of PD-L1 will overcome the innate and adaptive PD-L1 expression during chemotherapy,thus enable sustained and efficient immune checkpoint blockade(ICB)to active antitumor immune response.Herein,we designed a glutathione(GSH)-responsive camptothecin(CPT)prodrug-based hybrid micellar nanoparticles(siPD-L1@HM-CPT)to achieve synergistic antitumor chemoimmunotherapy by PD-L1 knockdown.siPD-L1@HM-CPT derived from the one-step loading PD-L1 siRNA(siPD-L1)into the CPT prodrug-based hybrid micelles(HM-CPT)which were co-assembled from biodegradable polyphosphoesters-based prodrug CPT-ss-PAEEP15 and stabilizer DSPE-PEG,showed high loading efficiency,GSH-responsive drug release,and excellent stability and biosafety.siPD-L1@HM-CPT achieved simultaneously the co-delivery of CPT and siPD-L1 in vitro and in vivo,high accumulation at the tumor sites,and rapid intracellular release to promote antitumor efficacy via sensitizing CPT chemotherapy,inducing strong immunogenic cell death(ICD)and sustained ICB to improve intratumoral CD8+T cells infiltration.In addition,the antitumor immunity response limited by the differentiated immunogenicity,intrinsic PD-L1 expression,and intracellular GSH level was facilitated by efficient ICD and ICB from silencing PD-L1 and synergistic CPT chemosensitization in our experimental B16-F10 and 4T1 tumor models.Our study might offer a perspective on designing novel co-delivery nanoparticles by convenient and controllable preparation for antitumor chemo-immunotherapy.

Effects of Metal Cations and Counter Anions on the Structural Stability of Isoquinoline-Based Metallo-Supramolecular Cages

Metallo-supramolecular architectures that are constructed by coordination-driven self-assembly have received tremendous attention on account of their diverse yet molecular-level precise structures and broad applications.Of particular,metal cations and counter anions are fundamentally important in terms of self-assembly,characterization and property;however,their effects on the structural stabilities of metallo-supramolecular architectures have seldom been investigated.To address this issue,herein,a series of octahedral metallo-cages that are capable of tolerating with five metal cations(Pd^(2+),Cu^(2+),Ni^(2+),Co^(2+)and Zn^(2+)),and five counter anions(ClO_(4)^(–),OTf^(–),BF_(4)^(–),NTf_(2)^(–)and NO_(3)^(–))are constructed by the coordination-driven self-assembly of a well-designed tritopic isoquinoline-based ligand with corresponding metal salts.Structural stability studies show that metal cations and counter anions play a critical role in the stability of the resulting cages depending on their coordination abilities and stacking manners.This work provides deep insights in the ever-diversifying field of metallo-supramolecular chemistry,and will enable us to design more sophisticated assembled structure with desired function.

Luminescent terpyridine-based metallo-supramolecular systems:from design to applications

Luminescent metallo-supramolecules have received tremendous attention in recent years owing to their diverse yet well-defined structures,tunable luminescent properties,and broad applications.In this context,the development of terpyridine(tpy)-based luminescent metallo-supramolecular systems has seen rapid growth.This review aims to summarize the recent progress of luminescent metallo-supramolecular assemblies from tpy ligands with metal ions,with a focus on discrete metallo-supramolecular architectures and metallo-supramolecular polymers.The design strategies and common approaches for tuning the luminescence properties are detailed along with representative applications.Finally,the pitfalls and unmet challenges regarding the structural characterization and practical applications of tpy-based metallo-supramolecules are discussed followed by our perspectives on the future directions of this field.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Objective:To select potential molecules that can target viral spike proteins,which may potentially interrupt the interaction between the human angiotension-converting enzyme 2(ACE2)receptor and viral spike protein by virtual screening.Methods:The three-dimensional(3D)-coordinate file of the receptor-binding domain(RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared.Secondly,approximately 15,000 molecular candidates were prepared,including US Food and Drug Administration(FDA)-approved drngs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology(TCMSP),for the docking process.Then,virtual screening was performed and the binding energy in Autodock Vina was calculated.Finally,the top 20 molecules with high binding energy and their Chinese medicine(CM)herb sources were listed in this paper.Results:It was found that digitoxin,a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores.Interestingly,two of the CM herbs containing the natural compounds that had relatively high binding scores,Forsyfh/ae frucft/s and/saf/d/s racWx,are components of Lianhua Qingwen(莲花清痕),a CM formula reportedly exerting activity against severe acute respiratory syndrome(SARS)-Cov-2.Moreover,raltegravir,an HIV integrase inhibitor,was found to have a relatively high binding score.Conclusions:A class of compounds,which are from FDA-approved drugs and CM natural compounds,that had high binding energy with RBD of the viral spike protein.Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection,and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

Multidimensional Mass Spectrometry Assisted Metallo-Supramolecular Chemistry

Metallo-supramolecular chemistry based on the reversible,directional,and predictable noncovalent interaction of metal–ligand coordination has been widely applied in constructing a myriad of two-and threedimensional supramolecules with sophisticated structures.The development of metallo-supramolecular chemistry highly relies on facile characterization methods.For advancement of structural complexity with desired functions,however,conventional crystallographicandspectroscopiccharacterizationsarelimited by crystal growth,sample purity,and severe signal overlaps.With high sensitivity and low requirement for purity,multidimensional mass spectrometry(MS),including electrospray ionization-MS(ESI-MS),tandem MS(MS2),and ion mobility-MS(IM-MS),is emerging as an essential analytical tool for characterization of the chemical compositions,connectivity,stability,shape,and size of metallo-supramolecules,as well as kinetic and thermodynamic features of self-assembly processes.Thus,this review mainly focuses on the recentdevelopment ofmultidimensionalMSinmetallosupramolecular characterization and discusses how ESI-MS,MS2,and IM-MS assist the development of metallo-supramolecular chemistry.