Steel bar penetrating cervical spinal canal without neurological injury:A case report

BACKGROUND We report a rare case of cervical spinal canal penetrating trauma and review the relevant literatures.CASE SUMMARY A 58-year-old male patient was admitted to the emergency department with a steel bar penetrating the neck,without signs of neurological deficit.Computed tomography(CT)demonstrated that the steel bar had penetrated the cervical spinal canal at the C6–7 level,causing C6 and C7 vertebral body fracture,C6 left lamina fracture,left facet joint fracture,and penetration of the cervical spinal cord.The steel bar was successfully removed through an open surgical procedure by a multidisciplinary team.During the surgery,we found that the cervical vertebra,cervical spinal canal and cervical spinal cord were all severely injured.Postoperative CT demonstrated severe penetration of the cervical spinal canal but the patient returned to a fully functional level without any neurological deficits.CONCLUSION Even with a serious cervical spinal canal penetrating trauma,the patient could resume normal work and life after appropriate treatment.

Unsatisfied methodological qualities assessment of systematic reviews/Meta-analyses on Chinese medicine for stroke and their risk factors

Background:Stroke is not only high in morbidity and mortality but also poses a great burden of disease and it is also the most reported disease in Chinese medicine systematic reviews.Therefore,the quality of such evidence couldn’t be ignored.This study aims to use a measurement tool to assess systematic reviews(AMSTAR)to assess the methodological qualities of SR/Meta-analyses of Chinese medicine on stroke.Methods:Systematic searching of seven electronic databases and PROSPERO registration platform was carried out.Two researchers separately selected studies,extracted bibliographical characteristics and scored every included study independently after training.Total score and the proportion of each item completion were explored in different subgroup comparisons.Spearman rank correlation and multivariable logistic regression were used to measure the association between bibliographical characteristics and total score or each item.Results:Total average score of AMSTAR 1.0 checklists of 234 systematic reviews/Meta-analyses was 4.47(95%CI 4.27–4.68)and the qualities were unsatisfied especially in terms of priori setting(2.14%),grey literature inclusion(5.13%),providing a list of excluded studies(2.14%)and conflict of interest(0.00%).No improvement was found in 3 years even after the publication of AMSTAR.Chinese or nonregistered systematic reviews/Meta-analyses showed even worse methodological qualities(P<0.01).Positive correlation was found between individual items and number of pages,number of authors,research questions,languages or Meta-analyse separately(P<0.05).Conclusion:The methodological qualities of systematic reviews/Meta-analyses of Chinese medicine on stroke are poor especially Chinese studies,non-registered studies,brief studies and studies without Meta-analyse or cooperation.There is no obvious improvement over these years even after the publication of AMSTAR tool,so it is urgent to promote the use of AMSTAR or develop other efficient methods to control the quantity and monitor the quality in future.

Sarcomatoid intrahepatic cholangiocarcinoma mimicking liver abscess: A case report

Sarcomatoid intrahepatic cholangiocarcinoma(SICC)is an extremely rare and highly invasive malignant tumor of the liver.To our knowledge,the imaging findings of sarcomatous cholangiocarcinoma have been rarely reported;and radiological features of this tumor mimicking liver abscess have not yet been reported.CASE SUMMARY We present a case of SICC mimicking liver abscess.The patient,a 43-year-old male,complained of repeated upper right abdominal discomfort and intermittent distension over a period of one month.Radiology examination revealed a huge focal lesion in the right liver.The lesion was hypointense on computed tomography with honeycomb enhancement surrounded by enhanced peripheral areas.It showed a hypo-signal on non-contrast T1-weighted images and a hypersignal on non-contrast T2-weighted images.Radiologists diagnosed the lesion as an atypical liver abscess.The patient underwent a hepatectomy.After surgery,he survived another 2.5 mo before passing away.A search of PubMed and Google revealed 43 non-repeated cases of SICC reported in 20 published studies.The following is a short review in order to improve the diagnostic and therapeutic skills in cases of SICC.CONCLUSION This report presents the clinical and radiological features of SICC and imaging features which showed hypovascularity and progressive enhancement.SICC can present as a multilocular cyst on radiological images and it is necessary to distinguish this lesion from an atypical abscess.Simple surgical treatment is not the best treatment option for this disease.

Chordin-like 2 influences the differentiation fate of retinal pigment epithelium cells by dynamically regulating BMP pathway

AIM:To explore the functions of Chordin-like 2,which is encoded by CHRDL2,in the process of retinal pigmented epithelium(RPE)differentiation and damage repair.METHODS:The fetal RPE cells(f RPE)was obtained from aborted fetus which obeyed medical ethics.Real-time quantitative polymerase chain reaction was used to measure expression quantity of CHRDL2 and other functional genes expression.Knocking down and overexpression was used to analyze the functions about Chordin-like 2.Enzyme-linked immunosorbent assay(ELISA)was used to detect the secretion of bone morphogenetic proteins 4(BMP4).Flow cytometry was used to analyze cell cycle.Cell morphology was observed by phase contrast microscope(PCM).RESULTS:In normal RPE cells,CHRDL2 was firstly upregulated and followed a downregulation but eventually,it was expressed higher than the cells which undergone epithelial-mesenchymal transition(EMT).After knocking down CHRDL2,the secretion of BMP4 was decreased,RPErelated genes(OTX2,MITF,RPE65)were downregulated while EMT-related genes(SNAI1,VIM)were upregulated.However,the expression of these related genes after overexpression of CHRDL2 had contrary results.Chordin-like 2 also regulated the cell cycle by regulating BMP pathway.When CHRDL2 was knocked down,more f RPE cells stayed in S phase of cell cycle,while adding BMP4 reduced the proportion of the cells in S phase.However,overexpression of CHRDL2 increased more BMP4 secretion,this effect decreased the number of cells in S phase,but exogenous BMP inhibitor also could change this effect.At last,in the process of RPE cells differentiation,adding BMP4 at early stage could intervene normal RPE differentiation.Compared with BMP4,inhibiting BMP pathway had no significant negative effect at early stage,but suppressed differentiation at late stage.CONCLUSION:BMP pathway can be activated in a correct temporal order,otherwise,the cells have incorrect differentiation orientation.And Chordin-like 2 plays a role in dynamic regulation of BMP pathway and it also regulates the differentiation of RPE cells.Therefore,this research enlightens a new direction to inhibit EMT and promote cell redifferentiation after injury.

Risk Factors of Post-Operative Extracorporeal Membrane Oxygenation Support after Lung Transplantation: A Retrospective Analysis

Background: Extracorporeal membrane oxygenation (ECMO) is an effective adjuvant therapy for cardiopulmonary support during the period of lung transplantation (LTx). However, factors associated with the application of ECMO after LTx remain controversial. The purpose of this study is to clarify the risk factors of post-operative ECMO support and to evaluate the outcomes. Methods: It was a hospital, single-center, retrospective study. 266 patients underwent LTx supported by ECMO were included. According to whether or not the patients received continourly ECMO support after the surgery, the enrolled patients were further divided into intra-operative ECMO group (group I, 105 cases) and post-operative ECMO group (group P, 161 cases). The peri-operative data of the donors and recipients were collected. The independent risk factors associated with post-operative ECMO support during LTx were identified. The relationship between primary graft dysfunction (PGD)/post-operative survival and duration of ECMO support was also analyzed. Results: Prolonged donor ventilation ≥ 5 days, pre-operative recipient mechanical ventilation, bilateral lung transplantation (BLT), veno-venous (V-V) ECMO and PGD in recipient were independent risk factors for post-operative ECMO support. The risk of PGD and post-operative death increased along with the increase of ECMO bypass time, and the mortality risk in group P was 2.33 (95% confidence interval: 1.16 - 4.67) times as that in group I. Conclusions: Mechanical ventilation for donor ≥ 5 days, pre-operative mechanical ventilation, BLT, V-V-ECMO and PGD in recipient were independent risk factors for post-operative ECMO support after LTx, and post-operative ECMO could not reduce recipients’ hospital mortality.

Residential energy transition and chronic respiratory diseases

Obtaining clean energy is of prime importance for planetary health and sustainable development.We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases.Using data from the Global Health Observatory and Global Burden of Diseases,Injuries,and Risk Factors Study,we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale.In the China Health and Retirement Longitudinal Study,we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use,residential energy transition,duration of solid fuel use,and the risk of chronic respiratory diseases.Despite great progress,huge disparities in access to clean energy persist globally.Residential energy transition was associated with a lower risk of chronic respiratory diseases.In the period of 2011–2013,compared with persistent solid fuel users,both participants who switched from solid to clean fuels(adjusted risk ratio[RR]0.78,95%confidence interval[CI]0.62–0.98)and persistent clean fuel users(adjusted RR 0.71,95%CI 0.57–0.89)had significantly lower risk of chronic respiratory diseases(p<0.001 for trend).Consistent associations were observed in the period of 2011–2015 and 2011–2018.Household energy transition from solid to clean fuels could reduce the risk of chronic respiratory diseases.This is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits,particularly in low-and middle-income countries.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization

Background and Aims:To validate prognostic performance of the China liver cancer(CNLC)staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer(BCLC)staging system for Chinese hepatocellular carcinoma(HCC)treated with transarterial chemoembolization(TACE).Methods:This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals.Based on overall survival(OS),the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination[C statistic and Akaike information criterion(AIC)],monotonicity of the gradient(linear trend chi-square test),homogeneity(likelihood ratio chisquare test),and calibration(calibration plots).A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes.Results:Median OS was 19.1(18.2–20.0)months,with significant differences in OS between stages defined by the CNLC and BCLC observed(p<0.001).The CNLC performed better than the BCLC regarding model discrimination(C-index:0.661 vs.0.644;AIC:10,583.28 vs.10,583.72),model monotonicity of the gradient(linear trend chi-square test:66.107 vs.57.418;p<0.001),model homogeneity(159.2 vs.158.7;p<0.001).Both staging systems had good model calibration.Similar results were observed in the prospective cohort.Conclusions:Combining model discrimination,gradient monotonicity,homogeneity,and calibration,the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy

Immune checkpoint inhibitors(ICI)targeting PD-1/PD-L1 have been approved for the treatment of a variety of cancers.However,the efficacy of antibody-based ICIs could be further improved by mitigating anti-drug antibodies,proteolytic cleavage,and on-target off-tumor toxicity.One strategy for accomplishing this is through the use of extracellular vesicles(EVs),cell derived submicron vesicles with many unique properties.We constructed an engineered MDA-MB-231 cell line for harvesting EVs.This was accomplished by overexpressing a high-affinity variant human PD-1 protein(havPD-1),while simultaneously knocking out intrinsic PD-L1 and beta-2 microglobulin.The engineered havPD-1 EVs reduced PD-L1 overexpressing cancer cell proliferation and induced cellular apoptosis.Moreover,the EVs were shown to efficiently block PD-L1 mediated T cell suppression.Meanwhile antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not observed.The havPD-1 EVs treatment resulted in robust anti-tumor activity in both preventative co-implantation and therapeutic xenograft tumor models reconstituted with human T cells.The efficacy of the havPD-1 EVs was shown to be comparable to clinical anti-PD1 monoclonal antibodies.Additionally,loading the havPD-1 EVs with a potent PARP inhibitor was shown to further augment treatment efficacy.In brief,the engineered universal EVs harboring havPD-1 proteins can be used for cancer concurrent immunotherapy and chemotherapy.

Small extracellular vesicles in cancer

Extracellular vesicles(EV)are lipid-bilayer enclosed vesicles in submicron size that are released from cells.A variety of molecules,including proteins,DNA fragments,RNAs,lipids,and metabolites can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells.In tumors,through such intercellular communication,EVs can regulate initiation,growth,metastasis and invasion of tumors.Recent studies have found that EVs exhibit specific expression patterns which mimic the parental cell,providing a fingerprint for early cancer diagnosis and prognosis as well as monitoring responses to treatment.Accordingly,various EV isolation and detection technologies have been developed for research and diagnostic purposes.Moreover,natural and engineered EVs have also been used as drug delivery nanocarriers,cancer vaccines,cell surface modulators,therapeutic agents and therapeutic targets.Overall,EVs are under intense investigation as they hold promise for pathophysiological and translational discoveries.This comprehensive review examines the latest EV research trends over the last five years,encompassing their roles in cancer pathophysiology,diagnostics and therapeutics.This review aims to examine the full spectrum of tumor-EV studies and provide a comprehensive foundation to enhance the field.The topics which are discussed and scrutinized in this review encompass isolation techniques and how these issues need to be overcome for EV-based diagnostics,EVs and their roles in cancer biology,biomarkers for diagnosis and monitoring,EVs as vaccines,therapeutic targets,and EVs as drug delivery systems.We will also examine the challenges involved in EV research and promote a framework for catalyzing scientific discovery and innovation for tumor-EV-focused research.

脊髓P2X7受体参与链脲佐菌素诱导的小鼠糖尿病早期机械痛性神经病变

目的:探讨嘌呤能离子通道型受体7(P2X7R)在链脲佐菌素(STZ)诱导的1型糖尿病(T1DM)小鼠早期发生的机械痛性神经病变中的作用。创新点:探讨脊髓P2X7R在T1DM产生痛性神经病变的早期阶段所起的作用,将有望为研究糖尿病痛性神经病变药物提供新的靶点。方法:本实验采用健康雄性C57BL小鼠与P2X7RKO小鼠(体重20~23克,从20点至次日8点隔夜禁食12小时)为研究对象,连续三天腹腔注射STZ(浓度为100 mg/kg),从而制备T1DM动物模型。如果空腹血糖>11.1 mmol/L且三周后小鼠机械痛阈值明显下降,则表示模型制备成功。在小鼠机械痛阈下降的对应时间点,取腰段脊髓背角,采用蛋白质印迹法(western blot)和免疫组化方法测定P2X7R的表达情况。同时,在发生机械痛阈值下降的第3周时间鞘内给予其拮抗剂A740003,并进行机械刺激从而观察其痛阈值的变化。结论:STZ诱导的T1DM动物模型在早期表现为显著的机械诱发痛,并伴随脊髓背角P2X7R表达上调;在痛阈下降期鞘内给予其拮抗剂A740003可抑制糖尿病小鼠的痛行为。与腹腔注射STZ形成T1DM的C57BL/6小鼠相比,P2X7R基因敲除的糖尿病小鼠早期机械痛阈值下降的时间延迟,程度减轻。因此,我们推测P2X7R可能参与了STZ诱导的糖尿病小鼠早期机械痛性神经病变。

CX3CL1受体参与1型糖尿病机械痛的形成

目的:趋化因子(CX3CL1)在神经性疼痛中起重要的生理病理作用,然而其在糖尿病神经病理痛中的作用还有待研究。本实验主要研究了在糖尿病小鼠痛阈下调的时间窗内,脊髓背角中趋化因子CX3CL1/趋化因子受体(CX3CR1)在触诱发痛发生与发展中的作用。创新点:主要探讨CX3CR1在链脲佐菌素(STZ)诱导的1型糖尿病(T1DM)小鼠早期发生的机械痛性神经病变中的作用。方法:本实验采用健康雄性C57BL/6小鼠与CX3CR1KO小鼠,体重20~23 g,隔夜禁食12 h(20点至次日8点),并连续三天腹腔注射100 mg/kg的STZ制备T1DM模型。以空腹血糖浓度>11.1 mmol/L且三周后小鼠机械痛阈值明显下降的情况视为T1DM模型制备成功。在小鼠机械痛阈下降的对应时间点,取腰段脊髓背角,采用蛋白质印迹法(westernblot)和免疫组化法测定CX3CL1及CX3CR1的表达情况。同时,在发生机械痛阈值下降的第三周时间鞘内给予CX3CR1的中和抗体,进行机械刺激并观察其痛阈值的变化。结论:STZ诱导的T1DM动物模型在早期表现为显著的机械诱发痛,并伴随脊髓背角CX3CL1/CX3CR1表达上调;在痛阈下降期鞘内给予CX3CR1的中和抗体可抑制糖尿病小鼠的痛行为。与腹腔注射STZ形成T1DM的C57BL/6小鼠相比,CX3CR1基因敲除的糖尿病小鼠机械痛阈值下降的时间延迟,程度减轻。因此,我们推测CX3CL1/CX3CR1可能参与T1DM机械痛的形成与发展。