Primary anaplastic lymphoma kinase-positive large B-cell lymphoma of the left bulbar conjunctiva: A case report

BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar con-junctiva.CASE SUMMARY A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months,accompanied by swelling and pain that had per-sisted for 3 d.Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye.Microscopically,the tumor was com-posed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells.Immunophenotypically,the neoplastic cells were positive for ALK,CD10,CD138,Kappa,MUM1,BOB.1,OCT-2,CD4,CD45,EMA,CD79a,CD38,and AE1/AE3,and negative for CD20,PAX5,Lambda,BCL6,CD30 and all other T-cell antigens.The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearran-gements.Fluorescence in situ hybridization studies did not reveal any BCL2,BCL6 or MYC rearrangements.Furthermore,Epstein-Barr virus was not detected by in situ hybridization in the lesions.Based on the histopathological and imaging examinations,the neoplasm was classified as stage IE ALK-positive LBCL.No further treatments were administered.At the 6,15,and 21 mo postoperative follow-up visits,the patient was in good condition,without obvious discomfort.This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass,which is extremely rare and shares morphological and immunohistochemical features with a variety of other neo-plasms that can result in misdiagnosis.CONCLUSION Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

Ultrasound-guided percutaneous catheter drainage in early treatment of severe acute pancreatitis

Percutaneous catheter drainage （PCD） is a minimally invasive intervation for severe acute pancreatitis （SAP）. This study was undertaken to compare the results of surgery and ultrasound-guided PCD in the treatment of 32 patients with SAP, and to direct clinicians to the most optimal approach for SAP. In the 32 patients, 19 were proved to have deteriorated clinical signs or symptoms, extensive fluid exudation, and necrosis confirmed by computed tomography （CT） and they underwent operative debridement and drainage. For extensive fluid exudation or necrosis, complete liquefaction and safe catheter implantation, the other 13 patients were given PCD. The mortality rate of the surgery group was 26.3%, much higher than that of the PCD group （0%）. There was a significant difference between the two groups （P=0.044）. The mean time for recovery of the serum C-reactive protein （CRP） level was 43.8 days in the surgery group, which was significantly longer than that of the PCD group （23.8 days） （P=0.034）. Early PCD guided by ultrasound could decrease the mortality of patients with severe acute pancreatitis, alleviate life-threatening inflammatory complications, and avoid unnecessary emergency operation.

Clinical Experience of External-route Retinal Detachment Surgery under a Surgical Microscope

Purpose: To evaluate the efficacy of external-route retinal reattachment surgery under a surgical microscope.Methods: A total of 86 patients(86 eyes) with rhegmatogenous retinal detachment underwent external-route retinal detachment surgery under a surgical microscope. Drainage of subretinal fluid, transscleral cryotherapy, scleral buckling, and intravitreal injection of gas were performed intraoperatively.Results: Among 85 patients, 81 achieved postoperative retinal re-attachment after the first surgery and 5 after two surgeries. The visual acuity was elevated in 67 patients, unchanged in15, and decreased in 4.Conclusion: External-route retinal reattachment surgery under a surgical microscope is a convenient procedure for physicians to master and worthy of widespread application in clinical settings.

A systematic review of the effectiveness of clinical nurse specialist interventions in patients with chronic obstructive pulmonary disease(COPD)

Objective： This review aimed to examine the effectiveness of clinical nurse specialist （CNS） interventions in patients with chronic obstructive pulmonary disease （COPD）. COPD significantly affects people＇s health worldwide. With the development in nursing, CNSs are playing increasingly important roles in different departments. However, the studies on the effectiveness of CNSs in COPD are not as well organized as the studies on the effectiveness of CNSs in bronchiectasis and asthma. Therefore, this review aims to find some updated evidence on the CNS interventions for patients with COPD and on whether these interventions are effective.Methods： A narrative analysis of the data was performed for the eligible studies. Four databases were chosen： CINAHL, MEDLINE, British Nursing Index, and Cochrane Library. Other websites such as the National Institute for Health and Clinical Excellence, National Health Service Evidence, Association of Respiratory Nurse Specialists, and National Association of Clinical Nurse Specialist were searched as well. Two reviewers performed study identification independently, and all the retrieved articles were stored using the EndNote X7 software. The risk of bias in the included studies was assessed using the Cochrane Collaboration＇s risk of bias tool. Results： A total of nine studies were included in this review. There were five current interventions by CNSs for patients with COPD. These interventions were home nursing support, CNS]s supported discharge, multidisciplinary cooperation programs, nurse-led care programs, and self-care management education. The effectiveness of these five interventions was evaluated individually. There is low- to moderate-quality evidence indicating that home nursing support interventions may have a positive effect on mortality and quality of life. No significant difference in quality of life has been found between the CNS-supported discharge intervention and the usual service. The multidisciplinary cooperation program probably had a positive effect on quality ot life in patients with COPD. Both nurse-led care and self-care management education intervention had a positive effect on mortality of patients with COPD.Conclusions： The findings of this review provide updated evidence on the effectiveness of CNS interventions for patients with COPD. Although nine trials were included and five types of interventions were identified, there is still lack of high-quality evidence.

Distribution of Microbiota in Fine Particulate Matter Particles in Guangzhou, China

Objective High PM2.5 concentration is the main feature of increasing haze in developing states,but information on its microbial composition remains very limited.This study aimed to determine the composition of microbiota in PM2.5 in Guangzhou,a city located in the tropics in China.Methods In Guangzhou,from March 5th to 10th,2016,PM2.5 was collected in middle volume air samplers for 23 h daily.The 16 S rDNA V4 region of the PM2.5 sample extracted DNA was investigated using high-throughput sequence.Results Among the Guangzhou samples,Proteobacteria,Bacteroidetes,Firmicutes,Cyanobacteria,and Actinobacteria were the dominant microbiota accounting for more than 90%of the total microbiota,and Stenotrophomonas was the dominant gram-negative bacteria,accounting for 21.30%–23.57%.We examined the difference in bacterial distribution of PM2.5 between Beijing and Guangzhou at the genus level;Stenotrophomonas was found in both studies,but Escherichia was only detected in Guangzhou.Conclusion In conclusion,the diversity and specificity of microbial components in Guangzhou PM2.5 were studied,which may provide a basis for future pathogenicity research in the tropics.

Computed tomography perfusion and computed tomography angiography for prediction of clinical outcomes in ischemic stroke patients after thrombolysis

Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis.At present,the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment,with less attention to predictions of outcomes after thrombolysis.Thus,in the present study,we assessed the efficacy of combined computed tomography（CT） perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients.The study included 52 patients who received both CT perfusion and CT angiography.Patients were grouped based on the following criteria to compare clinical outcomes：（1） thrombolytic and non-thrombolytic patients,（2） thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis,（3） thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch,and（4） different CT angiography and CT perfusion results.Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change.Long-term outcome was assessed by the 3-month modified Rankin Scale score.Of 52 ischemic stroke patients,29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment（23 patients）.Patients with both vascular stenosis and blood flow mismatch（13 patients） exhibited the best short-term outcome,while there was no correlation of long-term outcome with CT angiography or CT perfusion findings.These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome,but not long-term outcome,after thrombolysis.

Comparison of conventional and directional freezing for the cryopreservation of human umbilical vein endothelial cells

AIM:To compare conventional slow equilibrium cooling and directional freezing(DF) by gauze package for cryopreservation of human umbilical vein endothelial cells(HUVECs).METHODS:HUVECs were randomly assigned to conventional freezing(CF) and DF by gauze package group. The two groups of HUVECs were incubated with a freezing liquid consisting of 10% dimethylsulfoxide(DMSO), 60% fetal bovine serum(FBS) and 30%Dulbecco’s modified Eagle’s medium(DMEM) and then put into cryopreserved tubes. CF group, slow equilibrium cooling was performed with the following program:precool in 4℃ for 30 min,-20℃ for 1h, and then immersion in-80℃ refrigerator. DF group, the tubes were packaged with gauze and then directional freezing in-80℃ refrigerator straightly. One month later, the vitality of HUVECs were calculated between two groups.RESULTS:There was no significant difference in the survival rate and growth curve between CF and DF groups. The DF group was significantly better than CFgroup in adherent rates, morphological changes and proliferative ability.CONCLUSION:In the conventional cryopreserved method, cells are slow equilibrium cooling by steps(4℃,-20℃ and finally-80℃), which is a complicated and time-consuming process. But the improved DF by gauze package method is better than conventional method, for which is convenient and easy to operate.

Pyogenic arthritis,pyoderma gangrenosum,and acne syndrome in a Chinese family:A case report and review of literature

BACKGROUND Pyogenic arthritis,pyoderma gangrenosum,and acne(PAPA)syndrome is a rare autosomal dominant genetic disease characterized by severe autoimmune inflammation,caused by mutations in the PSTPIP1 gene.Due to PAPA heterogeneous clinical manifestation,misdiagnosis or delayed diagnoses are difficult to avoid.With the use of whole-exome sequencing,we identified a missense mutation in the PSTPIP1 gene in a Chinese family.To the best of our knowledge,this is the first case of PAPA reported in China.CASE SUMMARY A 9-year-old boy suffered from recurrent aseptic pyogenic arthritis triggered by minor trauma or few obvious predisposing causes for more than 3 years.Pyogenic arthritis occurred every 3-5 mo,affecting his knees,elbows,and ankle joints.Treatments,such as glucocorticoids,antibiotics,even surgeries could alleviate joints pain and swelling to some extent but could not inhibit the recurrence of arthritis.Similar symptoms were present in his younger brother but not in his parents.According to the whole-exome sequencing,a missense mutation in exon 11 of the PSTPIP1 gene(c.748G>C;p.E250Q)was detected in the boy,his young-er brother and his father.Taking into account the similar phenotypic features with PAPA syndrome reported previously,we confirmed a diagnosis of PAPA syndrome for the family.CONCLUSION In this case,a missense mutation(c.748G>C;p.E250Q)in PSTPIP1 gene was identified in a Chinese family with PAPA syndrome.Previous studies emphasize the fact that PAPA syndrome is hard to diagnose just through the clinical manifestations owing to its heterogeneous expression.Genetic testing is an effectual auxiliary diagnostic method,especially in the early stages of pyogenic arthritis.Only if we have a deep understanding and rich experience of this rare disease can we make a prompt diagnosis,develop the best clinical treatment plan,and give good fertility guidance.

Overexpression of microRNA-135b-5p attenuates acute myocardial infarction injury through its anti-oxidant and anti-apptotic properties

Objective:Myocardial infarction(MI)remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis.Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI.MicroRNAs(miRNAs,miRs),which regulate target genes at the post-transcriptional level,play a significant role in the regulation of cardiovascular diseases such as MI.MicroRNA-135b(miR-135b)has a protective effect on cardiomyocytes.However,the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification.Methods:We generatedα-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI.MiR-135b mimic and negative control(NC)were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species(ROS)and apoptosis.Results:Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro.MiR-135b inhibited cardiomyocyte apoptosis and ROS generation,downregulated pro-apoptosis proteins(cleaved-caspase-3 and Bax),and increased anti-apoptosis protein(Bcl-2).Moreover,miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4(TRPV4)cation channel.Conclusion:MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.

The alarming link between neonicotinoid insecticides and kidney injury

Neonicotinoid insecticides(NEOs)have been extensively approved for application in agricultural production both in China and globally.Previous studies indicated that human exposure to NEOs would have adverse health effects.However,studies on occurrences of NEOs in kidney injury patients and their association with nephrotoxicity are limited.This study investigates the potential correlation between exposure to NEOs and kidney injury within a subset(n=224)of the population residing in South China.Levels of 8 NEOs and 5 metabolites were quantified in blood samples obtained from both the 110 healthy and 114 kidney injury cohorts in South China.We found that target analytes were frequently detected in samples from the healthy and kidney injury cohorts(61%-100%).Dinotefuran is the predominant NEO in the healthy(42.3%)and kidney injury cohort(49.6%).Significantly positive(p<0.05)associations between blood NEO concentrations and kidney injury were found,indicating that these pollutants may increase the odds of human kidney injury prevalence.Through multilinear regression analysis,it was observed that the concentrations of various NEOs exhibited a significant association(p<0.05)with hematological parameters linked to nephrotoxicity.Our study represents the pioneering investigation examining the relationships between NEOs and kidney injury,thereby offering novel insights into the nephrotoxicity associated with these pollutants.This discovery carries significant implications for public health policies and environmental conservation practices.

First Case Report of Cystic Echinococcosis Caused by G7 Genotype Echinococcus intermedius Confirmed by Genetic Sequencing—Southern China,December 2023

What is already known about this topic?Echinococcosis exhibits a global distribution.In China,the primary endemic area is the northwest region.In December 2023,we documented a case of echinococcosis in an individual lacking any travel or residential history in endemic regions.What is added by this report?This is the first laboratory-confirmed case of hepatic echinococcosis reported in Guangdong Province,associated with the G7 genotype of Echinococcus granulosus(E.granulosus).The most probable mode of transmission is a local infection resulting from E.granulosus introduced from endemic regions.What are the implications for public health practice?As the circulation of agricultural products increases,it is essential to enhance the quarantine and management of livestock from epidemic areas to prevent and control the spread of echinococcosis to non-epidemic regions.

Competing-risks model for predicting the prognosis of patients with regressive melanoma based on the SEER database

Background:The relationship between the regression and prognosis of melanoma has been debated for years.When competing-risk events are present,using traditional survival analysis methods may induce bias in the identified prognostic factors that affect patients with regressive melanoma.Methods:Data on patients diagnosed with regressive melanoma were extracted from the Surveillance,Epidemiology,and End Results(SEER)database during 2000-2019.Cumulative incidence function and Gray's test were used for the univariate analysis,and the Cox proportional-hazards model and the Fine-Gray model were used for the multivariate analysis.Results:A total of 1442 eligible patients were diagnosed with regressive melanoma,including 529 patients who died:109 from regressive melanoma and 420 from other causes.The multivariate analysis using the Fine-Gray model revealed that SEER stage,surgery status,and marital status were important factors that affected the prognosis of regressive melanoma.Due to the existence of competing-risk events,the Cox model may have induced biases in estimating the effect values,and the competing-risks model was more advantageous in the analysis of multipleendpoint clinical survival data.Conclusion:The findings of this study may help clinicians to better understand regressive melanoma and provide reference data for clinical decisions.

Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing.Nowadays, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.

Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue

As a standard cancer treatment method,radiotherapy(RT)has cured or alleviated over half cancer bearing patients worldwide more than 100 years.However,the therapeutic outcome is seriously hindered by the resistant tumor microenvironment(TME).Hypoxia is a critical factor of vicious TME that causes radiation resistance owing to the insufficiency of oxygen for DNA damage maintenance.Moreover,severe vascular dysfunction and pyknomorphic extracellular matrix(ECM)in deep tumor tissues substantially limit radiosensitizer penetration and oxygen diffusion from vessels into tightly packed tumor core.In this study,we develop a hybrid transcytosis nanopomegranate(HTP)with high transcytosis potential in response to TME condition.HTP is architected by self-assembly of small CuS and Au nanoparticles(NPs)at normal physiological condition.HTP can rapidly collapse to transcytosis NPs(CuS and Au NPs)in TME with cationized surface,which enables excellent transcytosis potential and effectively elevates the penetration of CuS and Au into deep tumor tissues.Following the second near-infrared(NIR(II))biowindow laser irradiation,CuS heats the tumor and enhances blood perfusion,eliciting tumor hypoxia alleviation and DNA damage aggravation.Moreover,Au NPs enriched in deep tumor tissues effectively sensitize radio-therapeutic response.Our study provides a new and potential nano-platform to ameliorate tumor hypoxia and sensitize deep tumor tissue radiotherapy.

Research Article Ferric iron coordinated cisplatin prodrug reprograms the immunecold tumor microenvironment through tumor hypoxia relief for enhanced cancer photodynamic-immunotherapy

The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade(ICB)therapy in solid tumors.It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors.In this study,the oxygen(O_(2))self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors.The nanoplatform can produce O_(2)by catalyzing hydrogen peroxide(H_(2)O_(2))in tumor site effectively,showing excellent photodynamic therapy(PDT)performance.Meanwhile,it can further trigger immunogenic cell death(ICD),enhance T cell infiltration,reverse immunosuppression,and reprogram the immune-cold tumor microenvironment.In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect.The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.

Influence of Medial Support Screws on the Maintenance of Fracture Reduction after Locked Plating of Proximal Humerus Fractures

Background： Technical aspects of the correct placement of medial support locking screws in the locking plate for proximal humerus fractures remain incompletely understood. This study was to evaluate the clinical relationship between the number of medial support screws and the maintenance of fracture reduction after locked plating of proximal humerus fractures. Methods： We retrospectively evaluated 181 patients who had been surgically treated for proximal humeral fractures （PHFs） with a locking plate between September 2007 and June 2013. All cases were then subdivided into one of four groups as follows： 75 patients in the medial cortical support （MCS） group, 26 patients in the medial multiscrew support （MMSS） group, 29 patients in the medial single screw support （MSSS） group, and 51 patients in the 11o medial support （NMS） group. Clinical and radiographic evaluations included the Constant-Murley score （CM）, visual analogue scale （VAS）, complications, and revision surgeries. The neck-shaft angle （NSA） was measured in a true anteroposterior radiograph immediately postoperation and at final follow-up. One-way analysis of variance or KruskaI-Wallis test was used for statistical analysis of measurement data, and Chi-square test or Fisher＇s exact test was used for categorical data. Results： The mean postoperative NSAs were 133.46°± 6.01°, 132.39° ± 7.77°. 135.17° ± 10.15°, and 132.41° ± 7.16° in the MCS, MMSS, MSSS, and NMS groups, respectively, and no significant differences were found （F = 1.02, P= 0.387）. In the final follow-up, the NSAs were 132.79° ±6.02°, 130.19° ± 9.25°, 131.28° ± 12.85°, and 127.35° ± 8.50° in the MCS, MMSS, MSSS, and NMS groups, respectively （F = 4.40, P = 0.008）. There were marked differences in the NSA at the final follow-up between the MCS and NMS groups （P = 0.004）. The median （interquartile range [IQR]） NSA losses were 0.0° （0.0-1.0）°, 1.3° （0.0-3.1）°, 1.5° （ 1.0-5.2）°, and 4.0° （ 1.2 -7.1 ）° in the MCS, MMSS, MSSS, and NMS groups, respectively （H = 60.66, P 〈 0.001 ）. There were marked differences in NSA loss between the MCS and the other three groups （MCS vs. MMSS, Z = 3.16, P = 0.002; MCS vs. MSSS, Z = 4.78, P 〈 0.001; and MCS vs. NMS, Z = 7.34, P 〈 0.001）. There was also significantly less NSA loss observed in the MMSS group compared to the NMS group （Z = -3.16, P = 0.002）. However, there were no significant differences between the MMSS and MSSS groups （Z = -1.65, P = 0.225） or the MSSS and NMS groups （Z =- 1.21, P = 0.099）. The average CM scores were 81.35 ± 9.79, 78.04± 8.97, 72.76 ± 10.98, and 67.33 ± 12.31 points in the MCS, MMSS, MSSS, and NMS groups, respectively （F = 18.68, P 〈 0.001）. The rates of excellent and good CM scores were 86.67%, 80.77%, 65.52%, and 43.14% in the MCS, MMSS, MSSS, and NMS groups, respectively （ X^2 = 29.25, P 〈 0.001 ）. The median （IQR） VAS scores were 1 （0-2）, l （0 2）,2 （ 1-3）, and 3 （1-5） points in the MCS, MMSS, MSSS, and NMS groups, respectively （H = 27.80, P 〈 0.001）. Functional recovery was markedly better and VAS values were lower in the MCS and MMSS groups （for CM scores： MCS vs. MSSS, P 〈 0.001 ; MCS vs. N MS. P 〈 0.001; MMSS vs. MSSS, P= 0.031 and MMSS vs. NMS, P 〈 0.001 and for VAS values： MCS vs. MSSS, Z=3.31, P = 0.001： MCS vs. NMS, Z = 4.64, P 〈 0.001; MMSS vs. MSSS, Z = -2.09, P = 0.037： and MMSS vs. NMS, Z=-3.16, P = 0.003）.Conclusions： Medial support screws might help enhance mechanical stability and maintain fracture reduction when used to treat PHFs with medial metaphyseal comminution or malreduction.

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019(COVID-19) due to SARSCoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARSCoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China

Acute myeloid leukaemia(AML) is the most common form of acute leukaemia in adults,with increasing incidence with age and a generally poor prognosis.Almost 20% of AML patients express mutant isocitrate dehydrogenase 2(mIDH2),which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate(2-HG),resulting in poor prognosis.Thus,global institutions have been working to develop mIDH2 inhibitors.SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised.We have conducted a comprehensive study on its pharmacodynamics,pharmacokinetics and safety.First,SH1573 exhibited a strong selective inhibition of mIDH2 R140 Q protein,which could effectively reduce the production of 2-HG in cell lines,serum and tumors of an animal model.It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models.Then,it was confirmed that SH1573 possessed characteristics of high bioavailability,good metabolic stability and wide tissue distribution.Finally,toxicological data showed that SH1573 had no effects on the respiratory system,cardiovascular system and nervous system,and was genetically safe.This research successfully promoted the approval of SH1573 for clinical trials(CTR20200247).All experiments demonstrated that,as a potential drug against mIDH2 R140 Q acute myeloid leukaemia,SH1573 was effective and safe.

Photosensitizer conjugate-functionalized poly(hexamethylene guanidine) for potentiated broad-spectrum bacterial inhibition and enhanced biocompatibility

Pathogen infection is the main cause of human morbidity and death.Traditional antibiotics usually sterilize bacteria in chemical ways,which tends to develop serious antibiotic resistance.Cationic polymers exhibit good bacterial inhibition with less resistance,but often face severe cytotoxicity toward normal cells.The optimization of polymeric antimicrobials for enhanced bactericidal capacity and improved biocompatibility is quite meaningful.In addition,photodynamic therapy(PDT) is a therapeutic modality with less susceptibility to develop resistance.Herein,a typical commercial polymeric antimicrobial,polyhexamethylene guanidine(PHMG) was selected for current proof-of-concept optimization due to its excellent bactericidal capacity but moderate biocompatibility.Eosin-Y(EoS)was copolymerized to afford EoS-labeled polymer conjugates,poly(2-(dimethylamino) ethyl methacrylate-co-eosin),P(DMAEMA-co-EoS),which was conjugated with PHMG to afford a novel polymeric antimicrobial,P(DMAEMA-co-EoS)-b-PHMG-b-P(DMAEMA-co-EoS),noted as PEoS-PHMG.It could efficiently kill broad-spectrum bacteria by physical damage and photodynamic therapy.Compared with PHMG,the bacterial inhibition of PEoS-PHMG was potentiated after the functionalization.Furthermore,PEoS-PHMG exhibited low cytotoxicity and minimal hemolysis,which was demonstrated by cell viability assays toward LO2 cells and RAW 264.7 cells as well as hemolytic assays against red blood cells.These results confirmed that the resultant PEoS-PHMG could act as promising alternative antibacterial materials with excellent broad-spectrum bacterial inhibition and favorable biocompatibility.