Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Medical dilemma:Programmed death 1 blockade(sintilimab)therapy in patients suffering from tumours combined with psoriasis

Tumour immunotherapy represented by immune checkpoint inhibitors(ICIs)has greatly improved the overall prognosis of patients with malignant tumours,and is regarded as an important breakthrough in the field of medicine in recent years.ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic.In order to achieve early clinical prediction and management of immune-related adverse events(irAEs),it is still necessary to perform further research on the mechanisms,risk factors,and predictors of irAE occurrence in the future.Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis.This case provides an important reference for the use of programmed cell death protein-1(PD-1)inhibitors in patients of tumours combined with chronic plaque psoriasis.This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours.PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immunerelated adverse events such as toxic epidermal necrolysis release and psoriasis.Glucocorticosteroids are the first-line agents for irAEs.The incidence of rheumatic irAEs may be higher in reality,which will inevitably become a new challenge for rheumatologists and dermatologists.

晚期支气管腺样囊性癌化疗有效1例

1临床资料患者男性,66岁,患右支气管腺样囊性癌6 年7 个月,为进一步治疗入住河北省唐山市人民医院。患者于2010 年11 月无诱因出现咳嗽、咳少量白痰。痰中有少量暗红色血丝,无胸痛、无呼吸困难、无头痛及头晕等不适,未引起足够重视。

Laparoscopic vs open abdominoperineal resection in the multimodality management of low rectal cancers

AIM: To evaluate the safety and feasibility of laparoscopic abdominoperineal resection compared with the open procedure in multimodality management of rectal cancer.METHODS: A total of 106 rectal cancer patients who underwent open abdominoperineal resection(OAPR) were matched with 106 patients who underwent laparoscopic abdominoperineal resection(LAPR) in a 1 to 1 fashion, between 2009 and 2013 at Fudan University Shanghai Cancer Center. Propensity score matching was carried out based on age, gender, pathological staging of the disease and administration of neoadjuvant chemoradiation. Data regarding preoperative staging, surgical technique, pathologicalresults, postoperative recovery and complications were reviewed and compared between the LAPR and OAPR groups. Perineal closure around the stoma and pelvic floor reconstruction were performed only in OAPR, not in LAPR. Therefore, abdominoperineal resection procedure-specific surgical complications including parastomal hernia and perineal wound complications were compared between the open and laparoscopic procedure. Regular surveillance of the two cohorts was carried out to gather prognostic data. Diseasefree survival was analyzed using Kaplan-Meier estimate and log-rank test. Subgroup analysis was performed in patients with locally advanced disease treated with preoperative chemoradiation followed by surgical resection. RESULTS: No significant difference was found between the LAPR group and the OAPR group in terms of clinicopathological features. The operation time(180.8 ± 47.8 min vs 172.1 ± 49.2 min, P = 0.190), operative blood loss(93.9 ± 60.0 m L vs 88.4 ± 55.2 m L, P = 0.494), total number of retrieved lymph nodes(12.9 ± 6.9 vs 12.9 ± 5.4, P = 0.974), surgical complications(12.3% vs 15.1%, P = 0.549) and pathological characteristics were comparable between the LAPR and OAPR group, respectively. Compared with OAPR patients, LAPR patients showed significantly shorter postoperative analgesia(2.4 ± 0.7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus(57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time(6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission(11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications(perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation.

Death and do-not-resuscitate order in the emergency department:A single-center three-year retrospective study in the Chinese mainland

BACKGROUND:Consenting to do-not-resuscitate(DNR)orders is an important and complex medical decision-making process in the treatment of patients at the end-of-life in emergency departments(EDs).The DNR decision in EDs has not been extensively studied,especially in the Chinese mainland.METHODS:This retrospective chart study of all deceased patients in the ED of a university hospital was conducted from January 2017 to December 2019.The patients with out-of-hospital cardiac arrest were excluded.RESULTS:There were 214 patients’deaths in the ED in the three years.Among them,132 patients were included in this study,whereas 82 with out-of-hospital cardiac arrest were excluded.There were 99(75.0%)patients’deaths after a DNR order medical decision,64(64.6%)patients signed the orders within 24 hours of the ED admission,68(68.7%)patients died within 24 hours after signing it,and 97(98.0%)patients had DNR signed by the family surrogates.Multivariate analysis showed that four independent factors infl uenced the family surrogates’decisions to sign the DNR orders:lack of referral(odds ratio[OR]0.157,95%confi dence interval[CI]0.047–0.529,P=0.003),ED length of stay(ED LOS)≥72 hours(OR 5.889,95%CI 1.290–26.885,P=0.022),acute myocardial infarction(AMI)(OR 0.017,95%CI 0.001–0.279,P=0.004),and tracheal intubation(OR 0.028,95%CI 0.007–0.120,P<0.001).CONCLUSIONS:In the Chinese mainland,the proportion of patients consenting for DNR order is lower than that of developed countries.The decision to sign DNR orders is mainly affected by referral,ED LOS,AMI,and trachea intubation.

Study on the analysis method on ballistic performance of deterred propellant with large web size in large caliber artillery

As for the characteristics of combustibility of deterrent propellant with large web size which is used in large-caliber gun and interior ballistic performance, the combustion characteristics of deterrent propellant are obtained by using closed-bomb experiments. The combustion law of deterrent propellant and the classic interior ballistic model of composite charge are given. By simulation and analysis the results of the artillery firing test, the burning rate variation law and the interior ballistics simulation parameters of propellant A are determined, and the burning rate relationship between propellant A and propellant B obtained from closed-bomb, then the ballistic performance of propellant B is predicted. The results show that the predicted results are in good agreement with the experimental results. The study shows that the burning rate law of deterrent propellant with large web size can be obtained by closed-bomb experiment. Using the method provided in this paper can accurately predict the interior ballistic performance and provide an important basis for improving the accuracy of interior ballistic calculation.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis

Background:In sepsis,vitamin D binding protein(VDBP)has been shown to be low-expressed.The current study examined the relationship between serum VDBP level and liver injury in sepsis patients,as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide(LPS).Methods:The human study included 78 sepsis patients and 50 healthy volunteers.Sepsis patients were categorized into sepsis survivor group(n=43)and sepsis non-survivor group(n=35)based on 28-day mortality for data analysis.Adult male C57BL/6 mice were subjected to cecal ligation and puncture(CLP).Serum samples were collected on day 1,3,5 and 7 to determine the levels of VDBP,25-hydroxyvitamin D[25(OH)D_(3)],1,25-dihydroxyvitamin D[1,25(OH)_(2)D_(3)],interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α).Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.Results:Serum levels of VDBP,25(OH)D_(3),and 1,25(OH)_(2)D_(3)were significantly lower in sepsis patients vs.the healthy control(P<0.001),as well as in the sepsis non-survivor group vs.the sepsis survivor group(P<0.001,P=0.0338,or P=0.0013,respectively).Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation(APACHE)II score(r=−0.2565,P=0.0234)and Sequential Organ Failure Assessment score(r=−0.3522,P=0.0016),but lower serum albumin(ALB,r=0.4628,P<0.001)and total protein(TP,r=0.263,P=0.02).In CLP mice,there was a 5-day period of serum VDBP reduction,followed by return towards the baseline on day 7.VDBP was also decreased in LPS-treated THLE2 cells(P<0.001).VDBP overexpression reduced LPS-induced THLE2 damage.Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.Conclusion:VDBP may be protective against sepsis-induced liver injury.

S-phase arrest after vincristine treatment may promote hepatitis B virus replication

AIM:To observe the effect of vincristine on hepatitis B virus(HBV) replication in vitro and to study its possible mechanisms.METHODS:Vincristine was added to the cultures of two cell lines stably expressing HBV.Then,the levels of hepatitis B surface antigen(HBs Ag),hepatitis B e antigen(HBe Ag),and hepatitis B core antigen(HBc Ag) in the supernatants or cytoplasm were examined using by enzyme-linked immunosorbent assay and Western blot.The HBV pregenome RNA(pg RNA) was detected using reverse transcription-PCR and realtime fluorescent quantitative PCR(RT-q PCR),and viral DNA was detected using Southern blot and RT-q PCR.Cell proliferation after drug treatment was detected using the Brd U incorporation test and the trypan blue exclusion assay.Cell cycle and cell apoptosis were examined using flow cytometry and Western blot.RESULTS:Vincristine up-regulated HBV replication directly in vitro in a dose-dependent manner,and 24-h exposure to 0.1 μmol/L vincristine induced more than 4-fold and 3-fold increases in intracellular HBV DNA and the secretion of viral DNA,respectively.The expression of HBV pg RNA,intracellular HBs Ag and HBc Ag,and the secretion of HBe Ag were also increased significantly after drug treatment.Most importantly,vincristine promoted the cell excretion of HBV nucleocapsids instead of HBV Dane particles,and the nucleocapsids are closely related to the HBV pathogenesis.Furthermore,vincristine inhibited the proliferation of cells stably expressing HBV.The higher the concentration of the drug,the more significant the inhibition of the cell proliferation and the stronger the HBV replication ability in cells.Flow cytometry indicated that cell cycle arrest at S-phase was responsible for the cell proliferation inhibition.CONCLUSION:Vincristine has a strong stimulatory effect on HBV replication and induces cell cycle arrest,and cell proliferation inhibition may be conducive to viral replication.

Laparoscopic segmental colectomy for colonic lymphangiomas: A definitive, minimally invasive surgical option

Colonic lymphangioma is an unusual benign malformation.We herein describe two cases.A 36-year-old woman was admitted with one year of intermittent abdominal pain;colonoscopy,abdominopelvic computed tomography and endoscopic ultrasonography(EUS)revealed enlarged cystic masses at the ascending colon.In another 40-year-old man,colonoscopy and EUS revealed an asymptomatic lobulated cystic mass with four small sessile polyps at the sigmoid colon.Both patients underwent laparoscopic segmental colectomy.Both masses were histologically confirmed as cystic lymphangiomas,and the patients were discharged without complications.The management of colonic lymphangioma depends on the individual situation;close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5 cm in diameter.Surgical intervention can be considered for larger lesions or in patients who develop complication risks.Laparoscopic segmental colon resection may be recommended to excise relatively large submucosal lesions because it is a definitive,minimally invasive intervention with a fast postoperative recovery.

Ticagrelor Protects against Sepsis-Induced Acute Kidney Injury through an Adenosine Receptor-Dependent Pathway

Objective Ticagrelor is a widely used anti-platelet drug.However,the mechanisms by which ticagrelor protects against sepsis-induced acute kidney injury(AKI)have not been clearly demonstrated.We designed this study to explore the protective effect of ticagrelor on sepsis-induced AKI and to explore the underlying mechanisms.Methods C57BL6J mice received oral ticagrelor(20 mg/kg and 50 mg/kg)for 7 days,and then caecal ligation and puncture(CLP)were performed.An adenosine receptor antagonist,CGS15943,was administered(10 mg/kg,intraperitoneal injection)to block the adenosine pathway 2 h before CLP.After 24 h,serum creatinine levels were measured.Periodic acid-Schiff(PAS)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining were employed to analyze pathological changes and cell apoptosis.Serum concentrations of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and mRNA expression of tissue TNF-αand IL-1βwere detected.Western blotting analysis was used to determine AKT and mammalian target of rapamycin(mTOR)protein expression in the kidney.Results PAS staining showed less swelling of renal tubules,and TUNEL staining revealed less cell apoptosis in the ticagrelor group than in the CLP group.Serum creatinine levels were significantly lower in the ticagrelor group than in the CLP group.Moreover,significantly lower serum and kidney levels of TNF-αand IL-1βwere observed in the ticagrelor group.CGS15943 blocked the effects of ticagrelor.Western blotting analysis showed increased phosphorylation of AKT and mTOR in the kidneys of the 50 mg/kg ticagrelor group.The adenosine receptor antagonist inhibited the activation of AKT and mTOR.Conclusion This study demonstrates that the protective effect of ticagrelor on sepsis-induced AKI depends on adenosine receptor activation and the subsequent increase of AKT and mTOR phosphorylation.

Deletion of prominin-1 in mice results in disrupted photoreceptor outer segment protein homeostasis

AIM:To illustrate the underlying mechanism how prominin-1(also known as Prom1)mutation contribute to progressive photoreceptor degeneration.METHODS:A CRISPR-mediated Prom1 knockout(Prom1-KO)mice model in the C57BL/6 was generated and the photoreceptor degeneration phenotypes by means of structural and functional tests were demonstrated.Immunohistochemistry and immunoblot analysis were performed to reveal the localization and quantity of related outer segment(OS)proteins.RESULTS:The Prom1-KO mice developed the photoreceptor degeneration phenotype including the decreased outer nuclear layer(ONL)thickness and compromised electroretinogram amplitude.Immunohistochemistry analysis revealed impaired trafficking of photoreceptor OS proteins.Immunoblot data demonstrated decreased photoreceptor OS proteins.CONCLUSION:Prom1 deprivation causes progressive photoreceptor degeneration.Prom1 is essential for maintaining normal trafficking and normal quantity of photoreceptor OS proteins.The new light is shed on the pathogenic mechanism underlying photoreceptor degeneration caused by Prom1 mutation.

A Novel Trypsin Inhibitor-Like Cysteine-Rich Peptide from the Frog Lepidobatrachus laevis Containing ProteinaseInhibiting Activity

Various bio-active substances in amphibian skins play important roles in survival of the amphibians.Many protease inhibitor peptides have been identified from amphibian skins,which are supposed to negatively modulate the activity of proteases to avoid premature degradation or release of skin peptides,or to inhibit extracellular proteases produced by invading bacteria.However,there is no information on the proteinase inhibitors from the frog Lepidobatrachus laevis which is unique in South America.In this work,a cDNA encoding a novel trypsin inhibitor-like(TIL)cysteine-rich peptide was identified from the skin cDNA library of L.laevis.The 240-bp coding region encodes an 80-amino acid residue precursor protein containing 10 half-cysteines.By sequence comparison and signal peptide prediction,the precursor was predicted to release a 55-amino acid mature peptide with amino acid sequence,IRCPKDKIYKFCGSPCPPSCKDLTPNCIAVCKKGCFCRDGTVDNNHGKCVKKENC.The mature peptide was named LL-TIL.LL-TIL shares significant domain similarity with the peptides from the TIL supper family.Antimicrobial and trypsin-inhibitory abilities of recombinant LL-TIL were tested.Recombinant LL-TIL showed no antimicrobial activity,while it had trypsin-inhibiting activity with aKi of 16.5178 lM.These results suggested there was TIL peptide with proteinase-inhibiting activity in the skin of frog L.laevis.To the best of our knowledge,this is the first report of TIL peptide from frog skin.

Experiment and Simulation for Rolling of Diamond–Cu Composites

We demonstrate an innovative preparation approach of diamond/Cu composites by powder-in-tube technique and rolling. A small copper tube was loaded with Ti- and Cu-coated diamond particles, mad then the diamond particles were combined with Cu matrix by composite rolling. The morphology and element distribution of the interface between diamond and Cu were determined by scanning electron microscopy and energy-dispersive spectrometer. Finite element method （FEM） simulation was used to analyze the rolling process associated with experiment by DEFORM-3D. The final experimental results showed that homogeneous distribution of diamond particles could be observed in the center layer of the composites. According to the contrast experiments, the sample, whose diamond particle size is 0.12-0.15 mm and thickness of pre-rolling is 1.2 mm, showed relatively complete morphologies and homogeneous distribution. Experimental results indicated a poor efficacy of excessive rolling reduction. The thermal conductivity of the composites is about 453 W （m K）-1 by theoretical calculation. For FEM simulation, roiling strain and temperature field of the composites were simulated by DEFORM-3D. Simulation results were interpreted, and numerical results verified the reliability of the model. The simulation predicted that the local area of large strain, indicative of the strain along the thickness direction, could be intensified by adding diamond particles.

The DIRECT consortium and the REST-meta-MDD project:towards neuroimaging biomarkers of major depressive disorder

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder(MDD),repro-ducible findings are lacking,probably reflecting mostly small sample sizes and heterogeneity in analytic approaches.To address these issues,the Depression Imaging REsearch ConsorTium(DIRECT)was launched.The REST-meta-MDD project,pooling 2428 functional brain images processed with a standardized pipeline across all participating sites,has been the first effort from DIRECT.In this review,we present an overview of the moti-vations,rationale,and principal findings of the studies so far from the REST-meta-MDD project.Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network,in whole-brain topological properties,in dynamic features,and in functional lat-eralization.These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research.Following these fruitful explorations,DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations.A state-of-the-art,surface-based preprocessing pipeline has also been introduced to improve sensitivity.Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diag-nosis boundaries.In addition,large-scale longitudinal studies targeting brain network alterations following antidepressant treatment,aggregation of diffusion tensor images,and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway.Through these endeavours,we hope to accelerate the translation of functional neuroimaging findings to clinical use,such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets,while building an open repository for the scientific community.

The application of ECM-derived biomaterials in cartilage tissue engineering

Given the tremendous increase in the risks of cartilage defects in the sports and aging population,current treatments are limited,and new repair strategies are needed.Cartilage tissue engineering(CTE)is a promising approach to handle this burden and several fabrication technologies and biomaterials have been developed these years.The extracellular matrix(ECM)of cartilage consists of a tissue-specific 3D microenvironment with excellent biomechanical and biochemical properties,which regulates cell proliferation,adhesion,migration,and differentiation,thus attracting a great deal of attention to the rapid development of CTE based on ECM components.New generations of biomaterials are being developed rapidly for use as scaffolds to mimic the natural ECM environment.In this review,we discuss such CTE scaffolds based on ECM-derived biomaterials by reviewing the biomaterials for CTE,the applications in different scaffolds and their processing approaches,as well as the current clinical applications of those ECM-based CTE scaffolds.