Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of ...Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of abnormally hyperphosphorylated tau proteins in the brain. Autophagy is a conserved degradation pathway that eliminates abnormal protein aggregates and damaged organelles. Previous studies have suggested that autophagy plays a key role in the production and clearance of Aβ peptides to maintain a steady-state of Aβ peptides levels.However, a growing body of evidence suggests that autophagy is significantly impaired in the pathogenesis of AD, especially in Aβ metabolism. Therefore, this article reviews the latest studies concerning the mechanisms of autophagy, the metabolism of Aβ peptides, and the defective autophagy in the production and clearance of Aβpeptides. Here, we also summarize the established and new strategies for targeting autophagy in vivo and through clinical AD trials to identify gaps in our knowledge and to generate further questions.展开更多
White matter hyperintensities(WMHs) that arise with age and/or atherosclerosis constitute a heterogeneous disorder in the white matter of the brain. However, the relationship between age-related risk factors and the p...White matter hyperintensities(WMHs) that arise with age and/or atherosclerosis constitute a heterogeneous disorder in the white matter of the brain. However, the relationship between age-related risk factors and the prevalence of WMHs is still obscure. More clinical data is needed to confirm the relationship between age and the prevalence of WMHs. We collected 836 patients, who were treated in the Renmin Hospital, Hubei University of Medicine, China from January 2015 to February 2016, for a case-controlled retrospective analysis. According to T2-weighted magnetic resonance imaging results, all patients were divided into a WMHs group(n = 333) and a non-WMHs group(n = 503). The WMHs group contained 159 males and 174 females. The prevalence of WMHs increased with age and was associated with age-related risk factors, such as cardiovascular diseases, smoking, drinking, diabetes, hypertension and history of cerebral infarction. There was no significant difference in sex, education level, hyperlipidemia and hyperhomocysteinemia among the different age ranges. These findings confirm that age is an independent risk factor for the prevalence and severity of WMHs. The age-related risk factors enhance the occurrence of WMHs.展开更多
Transcutaneous auricular vagus nerve stimulation(ta-VNS)is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve.There have been recent reports that ta-V...Transcutaneous auricular vagus nerve stimulation(ta-VNS)is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve.There have been recent reports that ta-VNS combined with conventional rehabilitation training promotes the recovery of neurological function of patients with acute stroke.However,these were small-sample-sized studies on the recovery of neurological function in patients after percutaneous vagus nerve stimulation in the subacute and chronic phases after stroke.This double-blinded randomized controlled trial involved 60 acute ischemic or hemorrhagic stroke patients aged 18-80 years who received treatment in the Second Affiliated Hospital of Chongqing Medical University.The subjects were randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training.The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses compared with sham ta-VNS combined with conventional rehabilitation training.There were no obvious side effects.These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or hemorrhagic stroke patients is safe and effective.展开更多
The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry.However,the clinical application of nanocrysta...The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry.However,the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin,which have potential toxicity risks including hemolysis and allergies.Here,we designed an amorphous nanocrystal drug complex(IHNC),which is stabilizer-free and composed of indocyanine green(ICG)framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin(HCPT).Considering the possibility of industrial manufacturing,IHNC was simply prepared with the assistance of ferric ion(III)via supramolecular assembly strategy.The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III)framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio.The IHNC was stable at physiological pH,with excellent PTT/PDT efficacy,and in vivo probing characteristics.The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo.Moreover,such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%.These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.展开更多
Objective:For patients with early acute cerebral infarction(ACI),transcranial Doppler ultrasound was used in the clinical examination,and its application effect was observed and analyzed.Methods:This study was carried...Objective:For patients with early acute cerebral infarction(ACI),transcranial Doppler ultrasound was used in the clinical examination,and its application effect was observed and analyzed.Methods:This study was carried out between October 2018 and October 2019.50 patients with ACI included as the research object was evaluated by transcranial Doppler and CT examination,and the application of the two examination methods was compared.Results:The results of transcranial Doppler examination showed that the abnormal rate of blood flow velocity and the ratio of both sides(VACA)in patients with early ACI was higher than that of CT examination.Conclusion:With the impact on the location and area of vascular occlusion in patients,VACA can effectively reflect the status and effectiveness of the collateral circulation function of the patient’s pia vessels during cerebral infarction.展开更多
Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patien...Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.展开更多
Objective:To explore the effect of TCD foaming test in screening patent foramen ovale in migraine patients,as well as in the treatment effect.Methods:From September 2019 to August 2020,236 patients with migraine and 3...Objective:To explore the effect of TCD foaming test in screening patent foramen ovale in migraine patients,as well as in the treatment effect.Methods:From September 2019 to August 2020,236 patients with migraine and 362 patients with normal physical examination were treated in our hospital.According to the random number table method,60 patients with migraine were selected as the observation group,and 60 patients with normal physical examination were selected as the control group.48 cases of PFO were confirmed by TCD foaming test Among the patients with migraine,36 patients received interventional occlusion therapy.The therapeutic effect and VAS score of the two groups were analyzed.Results:Through TCD foaming test,the proportion of PFO in the observation group was 80%,and that in the control group was 13.33%.The proportion of PFO in the observation group was significantly higher than that in the control group,and the difference was statistically significant(χ^(2)=53.5714,P<0.01);The symptoms disappeared in 30 patients and improved in 4 patients;Among the 36 patients who received interventional occlusion therapy,the VAS score of patients before and after the operation was significantly changed,and the proportion of patients whose pain disappeared after the operation was 83.33%,which was significantly lower than that before the operation,and the difference was comparable(χ^(2)=51.4286,P<0.01).Conclusion:TCD foaming test for PFO screening has strong applicability,not only safe and convenient,will not cause trauma to patients,and through interventional occlusion treatment,can significantly improve the clinical symptoms of migraine patients and cure patients.展开更多
Background:Synovectomy has been introduced into total knee arthroplasty(TKA)with the aim of relieving pain and inflammation of the synovium.However,there are no long-term,comparative data to evaluate the effect of syn...Background:Synovectomy has been introduced into total knee arthroplasty(TKA)with the aim of relieving pain and inflammation of the synovium.However,there are no long-term,comparative data to evaluate the effect of synovectomy in TKA.This study was aimed at assessing pain,function,and complications in patients undergoing synovectomy during TKA for osteoarthritis(OA)at long-term follow-up.Methods:This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA.Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA.The overall efficacy of both strategies was evaluated by determination of blood loss,the Knee Society score(KSS),and knee inflammation conditions during a 3-month postoperative period.The postoperative pain,range of motion(ROM),and complications were sequentially evaluated to compare the two groups until 10 years after surgery.Results:At the 10-year follow-up,both groups had a similarly significantly improved ROM(114.88±9.84°vs.114.02±9.43°,t=0.221,P=0.815)and pain relief with no differences between the two groups(1.0[1.0]vs.1.0[1.5],U=789.500,P=0.613).Similar changes in total blood loss,KSS,and knee inflammation were found in both groups during 3 months postoperatively(P>0.05).Additionally,there was no significant difference regarding complications and satisfaction between the two groups(P>0.05).Conclusions:Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain,ROM,and satisfaction during a 10-year follow-up.In addition,it may not result in more blood loss and increased incidence of long-term complications.Based on our long-term findings,it should not be performed routinely.Trial registration:Chinese Clinical Trial Registry,ChiCTR-INR-16008245;https://www.chictr.org.cn/showproj.aspx?proj=13334.展开更多
Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.How...Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.However,the underlying mechanism in genetic compensation remain unsolvable.The initial concept of genetic compensation has been studied in model organisms when there was a discrepancy between knockout-mediated and knockdown-mediated phenotypes.In the zebrafish model,several studies have reported that zebrafish mutants did not exhibit severe phenotype as shown in zebrafish morphants for the same genes.This phenomenon in zebrafish mutants but not morphants is due to the response of genetic compensation.In 2019,two amazing works partially uncovered genetic compensation could be triggered by the upregulation of compensating genes through regulating NMD and/or PTC-bearing mRNA in collaboration with epigenetic machinery in mutant zebrafish.In this review,we would like to update the recent advances and future perspectives of genetic compensation studies,which including the hypothesis of time-dependent involvement and addressing the discrepancy between knockout-mediated and knockdown-mediated to study gene function in the zebrafish model.At last,the study of genetic compensation could be a potential therapeutic strategy to treat human genetic disorder related diseases.展开更多
As a necessary process of modern drug development,finding a drug compound that can selectively bind to a specific protein is highly challenging and costly.Exploring drug‐target interaction strength in terms of drug‐...As a necessary process of modern drug development,finding a drug compound that can selectively bind to a specific protein is highly challenging and costly.Exploring drug‐target interaction strength in terms of drug‐target affinity(DTA)is an emerging and effective research approach for drug development.However,it is challenging to model drug‐target interactions in a deep learning manner,and few studies provide interpretable analysis of models.This paper proposes a DTA prediction method(mutual transformer‐drug target affinity[MT‐DTA])with interactive learning and an autoencoder mechanism.The proposed MT‐DTA builds a variational autoencoders system with a cascade structure of the attention model and convolutional neural networks.It not only enhances the ability to capture the characteristic information of a single molecular sequence but also establishes the characteristic expression relationship for each substructure in a single molecular sequence.On this basis,a molecular information interaction module is constructed,which adds information interaction paths between molecular sequence pairs and complements the expression of correlations between molecular substructures.The performance of the proposed model was verified on two public benchmark datasets,KIBA and Davis,and the results confirm that the proposed model structure is effective in predicting DTA.Additionally,attention transformer models with different configurations can improve the feature expression of drug/protein molecules.The model performs better in correctly predicting interaction strengths compared with state‐of‐the‐art baselines.In addition,the diversity of drug/protein molecules can be better expressed than existing methods such as SeqGAN and Co‐VAE to generate more effective new drugs.The DTA value prediction module fuses the drug‐target pair interaction information to output the predicted value of DTA.Additionally,this paper theoretically proves that the proposed method maximises evidence lower bound for the joint distribution of the DTA prediction model,which enhances the consistency of the probability distribution between actual and predicted values.The source code of proposed method is available at https://github.com/Lamouryz/Code/tree/main/MT‐DTA.展开更多
Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question i...Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question in these patients.Here,we developed a novel approach to assess true splenic volume more precisely.Methods:High-quality thin-slice computed tomography data of 112 cirrhotic patients with PHT were obtained and reviewed.Both the conventional measurement and a novel formula obtained from 3-dimensional reconstruction software were used to estimate splenic volume,and the accuracy was compared and verified.Results:In PHT patients,the splenic volume calculated using the conventional method was significantly less than that calculated using the 3-dimensional software.We found that the splenic volume was significantly positively correlated with splenic indices of length(L),thickness(T),and width(W)and also the diameter of the splenic vein.Using these indices,we propose 2 novel formulas using the software to estimate the splenic volume more accurately:SV=69.686 L+53.077 W+103.525 T+314.510 diameter of splenic vein 2266.209(p<0.01,R^(2)=0.805).And a more practical simplified formula:SV'=0.504× L× W×T+319.762 diameter of splenic vein 81.66(p<0.01,R^(2)=0.784).Conclusion:Although the conventional formula has been widely used for years,it is not suitable for an enlarged spleen.We developed 2 novel formulas for estimating splenic volume from clinical data that were more appropriate for cirrhotic patients with PHT.展开更多
Background:Tuberculosis(TB)is one of the most debilitating diseases worldwide.Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis,but clinical t...Background:Tuberculosis(TB)is one of the most debilitating diseases worldwide.Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis,but clinical trials reported inconsistent results.Therefore,we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy.Methods:We systematically searched PubMed,Embase,and the Cochrane Central Register of Controlled Trials from their inception to February 8th,2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy.The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture.The secondary outcomes were clinical response to treatment and adverse events.A random-effects model was used to pool studies.Data were analyzed using RevMan 5.3 software.Results:Five studies with a total of 1126 participants were included in our meta-analysis.Vitamin D supplementation did not shorten the time to sputum culture and smear conversion(hazard ratio[HR]1.04,95%confidence interval[CI]0.89–1.23,P=0.60;HR 1.15,95%CI 0.93–1.41,P=0.20,respectively)and did not lead to an increase in the proportion of participants with negative sputum culture(relative risk[RR]1.04,95%CI 0.97–1.11,P=0.32).However,it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype(HR 8.09,95%CI 1.39–47.09,P=0.02)and improved the multidrug-resistant(MDR)TB sputum culture conversion rate(RR 2.40,95%CI 1.11–5.18,P=0.03).There was no influence on secondary outcomes.Conclusions:Vitamin D supplementation had no beneficial effect on anti-TB treatment,but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.展开更多
The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life ...The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.展开更多
Low back pain,mainly caused by intervertebral disc degeneration(IVDD),is a common health problem;however,current surgical treatments are less than satisfactory.Thus,it is essential to develop novel non-invasive surgic...Low back pain,mainly caused by intervertebral disc degeneration(IVDD),is a common health problem;however,current surgical treatments are less than satisfactory.Thus,it is essential to develop novel non-invasive surgical methods for IVDD treatment.Here,we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage(ECM-Gels)that are loaded with cartilage endplate stem cells(CESCs).After loaded with CESCs overexpressing Sphk2(Lenti-Sphk2-CESCs)and injected near the cartilage endplate(CEP)of rats in vivo,ECM-Gels produced Sphk2-engineered exosomes(Lenti-Sphk2-Exos).These exosomes penetrated the annulus fibrosus(AF)and transported Sphk2 into the nucleus pulposus cells(NPCs).Sphk2 activated the phosphatidylinositol 3-kinase(PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs,ultimately ameliorating IVDD.This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.展开更多
The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spec...The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spectrum antiviral drugs by targeting the viral polymerases.However,the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood.Here,we reveal that Favipiravir,as a pyrazine derivative,could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides.This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs,different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products.We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARSCoV-2 in the pre-catalytic state.This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase,and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides.These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.展开更多
The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and sta...The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.展开更多
Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role...Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.展开更多
Objective:The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms(pNENs)undergoing surgery in China.Methods:This is a multicenter ...Objective:The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms(pNENs)undergoing surgery in China.Methods:This is a multicenter cross-sectional study performed in China.Data from patients with pNENs undergoing surgery at 33 high-volume medical centers,where the number of pancreatectomies exceeds 20 cases per year,were collected and analyzed between March 1,2016 and February 28,2017.Results:In total,392 patients with pNENs were enrolled.The male to female ratio was 1.4.The majority of patients were aged between 40 and 70 years.65.6%of the patients had non-functional tumors.Among those with functional tumors,the percentages of insulinomas,gastrinomas,glucagonomas,and vasoactive intestinal peptide-secreting tumors were 94.8%,1.5%,2.2%,and 1.5%,respectively.Multidisciplinary team(MDT)discussion was conducted for 39.0%of the patients.Minimally invasive surgery was performed on 31.1%of the 392 patients.The incidence of grade B/C pancreatic fistula formation was 4.4%.A total of 89.0%of the surgeries achieved R0 resection,and 41.6%of the tumors were well differentiated.Lymph node metastasis was present in 8.9%of the patients.The percentages of patients with grades G1,G2,and G3 disease were 49.2%,45.7%,and 5.1%,respectively.Conclusion:This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China.MDT consultation for pNENs has not been widely implemented in China.Although the incidence of surgical complications is relatively low,minimally invasive procedures should be further promoted.This study shows us how to improve the outcomes of these patients.展开更多
The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreat...The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.展开更多
基金supported by the Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission affiliated unit (2019NLTS001)-ZS03174operating grant to Chongqing Key Laboratory of Neurodegenerative Diseases (Grant No. 1000013)+2 种基金Chongqing Talent Project [2000062]Overseas Students entrepreneurial fund (Grant No. 2000079)Plan for High-level Talent Introduction (Grant No. 2000055)。
文摘Alzheimer’s disease(AD) is the most prevalent neurodegenerative disorder. The major pathological changes in AD progression are the generation and accumulation of amyloid-beta(Aβ) peptides as well as the presence of abnormally hyperphosphorylated tau proteins in the brain. Autophagy is a conserved degradation pathway that eliminates abnormal protein aggregates and damaged organelles. Previous studies have suggested that autophagy plays a key role in the production and clearance of Aβ peptides to maintain a steady-state of Aβ peptides levels.However, a growing body of evidence suggests that autophagy is significantly impaired in the pathogenesis of AD, especially in Aβ metabolism. Therefore, this article reviews the latest studies concerning the mechanisms of autophagy, the metabolism of Aβ peptides, and the defective autophagy in the production and clearance of Aβpeptides. Here, we also summarize the established and new strategies for targeting autophagy in vivo and through clinical AD trials to identify gaps in our knowledge and to generate further questions.
基金supported by the Natural Science Foundation of Hubei Province of China,No.2015CFB260the Health and Family Planning Scientific Research Project of Hubei Province of China,No.WJ2015MB219(to WBH and ZYC)
文摘White matter hyperintensities(WMHs) that arise with age and/or atherosclerosis constitute a heterogeneous disorder in the white matter of the brain. However, the relationship between age-related risk factors and the prevalence of WMHs is still obscure. More clinical data is needed to confirm the relationship between age and the prevalence of WMHs. We collected 836 patients, who were treated in the Renmin Hospital, Hubei University of Medicine, China from January 2015 to February 2016, for a case-controlled retrospective analysis. According to T2-weighted magnetic resonance imaging results, all patients were divided into a WMHs group(n = 333) and a non-WMHs group(n = 503). The WMHs group contained 159 males and 174 females. The prevalence of WMHs increased with age and was associated with age-related risk factors, such as cardiovascular diseases, smoking, drinking, diabetes, hypertension and history of cerebral infarction. There was no significant difference in sex, education level, hyperlipidemia and hyperhomocysteinemia among the different age ranges. These findings confirm that age is an independent risk factor for the prevalence and severity of WMHs. The age-related risk factors enhance the occurrence of WMHs.
基金supported by the Medical Scientific Research Project of Chongqing Municipal Health Commission of China,Nos.2018ZDXM022,2019MSXM017 and 2020MSXM106a grant from Chongqing General Hospital of China,No.2019ZDXM03(all to LCN and JXM).
文摘Transcutaneous auricular vagus nerve stimulation(ta-VNS)is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve.There have been recent reports that ta-VNS combined with conventional rehabilitation training promotes the recovery of neurological function of patients with acute stroke.However,these were small-sample-sized studies on the recovery of neurological function in patients after percutaneous vagus nerve stimulation in the subacute and chronic phases after stroke.This double-blinded randomized controlled trial involved 60 acute ischemic or hemorrhagic stroke patients aged 18-80 years who received treatment in the Second Affiliated Hospital of Chongqing Medical University.The subjects were randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training.The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses compared with sham ta-VNS combined with conventional rehabilitation training.There were no obvious side effects.These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or hemorrhagic stroke patients is safe and effective.
基金supported by the National Key Research and Development Program of China(2021YFD1800900)National Natural Science Foundation of China(82073790)Science and Technology Research Project of Chongqing Education Commission(KJQN202100229)。
文摘The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry.However,the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin,which have potential toxicity risks including hemolysis and allergies.Here,we designed an amorphous nanocrystal drug complex(IHNC),which is stabilizer-free and composed of indocyanine green(ICG)framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin(HCPT).Considering the possibility of industrial manufacturing,IHNC was simply prepared with the assistance of ferric ion(III)via supramolecular assembly strategy.The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III)framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio.The IHNC was stable at physiological pH,with excellent PTT/PDT efficacy,and in vivo probing characteristics.The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo.Moreover,such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%.These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.
文摘Objective:For patients with early acute cerebral infarction(ACI),transcranial Doppler ultrasound was used in the clinical examination,and its application effect was observed and analyzed.Methods:This study was carried out between October 2018 and October 2019.50 patients with ACI included as the research object was evaluated by transcranial Doppler and CT examination,and the application of the two examination methods was compared.Results:The results of transcranial Doppler examination showed that the abnormal rate of blood flow velocity and the ratio of both sides(VACA)in patients with early ACI was higher than that of CT examination.Conclusion:With the impact on the location and area of vascular occlusion in patients,VACA can effectively reflect the status and effectiveness of the collateral circulation function of the patient’s pia vessels during cerebral infarction.
基金supported by Improving the Ability of Diagnosis and Treatment of Difficult Diseases (ZLYNXM202009)。
文摘Granulomatous lobular mastitis(GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence.Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions,etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology.The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidencebased consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.
文摘Objective:To explore the effect of TCD foaming test in screening patent foramen ovale in migraine patients,as well as in the treatment effect.Methods:From September 2019 to August 2020,236 patients with migraine and 362 patients with normal physical examination were treated in our hospital.According to the random number table method,60 patients with migraine were selected as the observation group,and 60 patients with normal physical examination were selected as the control group.48 cases of PFO were confirmed by TCD foaming test Among the patients with migraine,36 patients received interventional occlusion therapy.The therapeutic effect and VAS score of the two groups were analyzed.Results:Through TCD foaming test,the proportion of PFO in the observation group was 80%,and that in the control group was 13.33%.The proportion of PFO in the observation group was significantly higher than that in the control group,and the difference was statistically significant(χ^(2)=53.5714,P<0.01);The symptoms disappeared in 30 patients and improved in 4 patients;Among the 36 patients who received interventional occlusion therapy,the VAS score of patients before and after the operation was significantly changed,and the proportion of patients whose pain disappeared after the operation was 83.33%,which was significantly lower than that before the operation,and the difference was comparable(χ^(2)=51.4286,P<0.01).Conclusion:TCD foaming test for PFO screening has strong applicability,not only safe and convenient,will not cause trauma to patients,and through interventional occlusion treatment,can significantly improve the clinical symptoms of migraine patients and cure patients.
基金1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18039)Sichuan Province Regional Innovation Cooperation Project(No.2021YFQ0028)West China Nursing Discipline Development Special Fund Project,Sichuan University(No.HXHL20003)
文摘Background:Synovectomy has been introduced into total knee arthroplasty(TKA)with the aim of relieving pain and inflammation of the synovium.However,there are no long-term,comparative data to evaluate the effect of synovectomy in TKA.This study was aimed at assessing pain,function,and complications in patients undergoing synovectomy during TKA for osteoarthritis(OA)at long-term follow-up.Methods:This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA.Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA.The overall efficacy of both strategies was evaluated by determination of blood loss,the Knee Society score(KSS),and knee inflammation conditions during a 3-month postoperative period.The postoperative pain,range of motion(ROM),and complications were sequentially evaluated to compare the two groups until 10 years after surgery.Results:At the 10-year follow-up,both groups had a similarly significantly improved ROM(114.88±9.84°vs.114.02±9.43°,t=0.221,P=0.815)and pain relief with no differences between the two groups(1.0[1.0]vs.1.0[1.5],U=789.500,P=0.613).Similar changes in total blood loss,KSS,and knee inflammation were found in both groups during 3 months postoperatively(P>0.05).Additionally,there was no significant difference regarding complications and satisfaction between the two groups(P>0.05).Conclusions:Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain,ROM,and satisfaction during a 10-year follow-up.In addition,it may not result in more blood loss and increased incidence of long-term complications.Based on our long-term findings,it should not be performed routinely.Trial registration:Chinese Clinical Trial Registry,ChiCTR-INR-16008245;https://www.chictr.org.cn/showproj.aspx?proj=13334.
基金supported by the National Natural Science Foundation of China(No.31971242,12032007,and 31771599)Key grants from Chongqing Science and Technology Bureau,China(No.cstc2019jcyj-zdxmX0028)+1 种基金the State Key Project Specialized for Infectious Diseases,China(No.2017ZX10201201-001-005,and 2017ZX10201201-002-005)as well as Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education,China(No.CQKLBST-2020-007).
文摘Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.However,the underlying mechanism in genetic compensation remain unsolvable.The initial concept of genetic compensation has been studied in model organisms when there was a discrepancy between knockout-mediated and knockdown-mediated phenotypes.In the zebrafish model,several studies have reported that zebrafish mutants did not exhibit severe phenotype as shown in zebrafish morphants for the same genes.This phenomenon in zebrafish mutants but not morphants is due to the response of genetic compensation.In 2019,two amazing works partially uncovered genetic compensation could be triggered by the upregulation of compensating genes through regulating NMD and/or PTC-bearing mRNA in collaboration with epigenetic machinery in mutant zebrafish.In this review,we would like to update the recent advances and future perspectives of genetic compensation studies,which including the hypothesis of time-dependent involvement and addressing the discrepancy between knockout-mediated and knockdown-mediated to study gene function in the zebrafish model.At last,the study of genetic compensation could be a potential therapeutic strategy to treat human genetic disorder related diseases.
基金supported by Cooperation Project Between Undergraduate Universities in Chongqing and Institutions Affiliated to the Chinese Academy of Sciences(No.HZ2021018)the National Natural Science Foundation of China(Grant 62276037)Special key project of Chongqing technology innovation and application development:CSTB2022TIAD‐KPX0039.
文摘As a necessary process of modern drug development,finding a drug compound that can selectively bind to a specific protein is highly challenging and costly.Exploring drug‐target interaction strength in terms of drug‐target affinity(DTA)is an emerging and effective research approach for drug development.However,it is challenging to model drug‐target interactions in a deep learning manner,and few studies provide interpretable analysis of models.This paper proposes a DTA prediction method(mutual transformer‐drug target affinity[MT‐DTA])with interactive learning and an autoencoder mechanism.The proposed MT‐DTA builds a variational autoencoders system with a cascade structure of the attention model and convolutional neural networks.It not only enhances the ability to capture the characteristic information of a single molecular sequence but also establishes the characteristic expression relationship for each substructure in a single molecular sequence.On this basis,a molecular information interaction module is constructed,which adds information interaction paths between molecular sequence pairs and complements the expression of correlations between molecular substructures.The performance of the proposed model was verified on two public benchmark datasets,KIBA and Davis,and the results confirm that the proposed model structure is effective in predicting DTA.Additionally,attention transformer models with different configurations can improve the feature expression of drug/protein molecules.The model performs better in correctly predicting interaction strengths compared with state‐of‐the‐art baselines.In addition,the diversity of drug/protein molecules can be better expressed than existing methods such as SeqGAN and Co‐VAE to generate more effective new drugs.The DTA value prediction module fuses the drug‐target pair interaction information to output the predicted value of DTA.Additionally,this paper theoretically proves that the proposed method maximises evidence lower bound for the joint distribution of the DTA prediction model,which enhances the consistency of the probability distribution between actual and predicted values.The source code of proposed method is available at https://github.com/Lamouryz/Code/tree/main/MT‐DTA.
基金by the Ethical Committee of Tangdu Hos-pital(approval number:K202001-07).
文摘Background and aims:Splenomegaly often occurs in cirrhotic patients with portal hypertension(PHT),and therefore,the efficacy and accuracy of conventional methods for measuring splenic volume are a matter of question in these patients.Here,we developed a novel approach to assess true splenic volume more precisely.Methods:High-quality thin-slice computed tomography data of 112 cirrhotic patients with PHT were obtained and reviewed.Both the conventional measurement and a novel formula obtained from 3-dimensional reconstruction software were used to estimate splenic volume,and the accuracy was compared and verified.Results:In PHT patients,the splenic volume calculated using the conventional method was significantly less than that calculated using the 3-dimensional software.We found that the splenic volume was significantly positively correlated with splenic indices of length(L),thickness(T),and width(W)and also the diameter of the splenic vein.Using these indices,we propose 2 novel formulas using the software to estimate the splenic volume more accurately:SV=69.686 L+53.077 W+103.525 T+314.510 diameter of splenic vein 2266.209(p<0.01,R^(2)=0.805).And a more practical simplified formula:SV'=0.504× L× W×T+319.762 diameter of splenic vein 81.66(p<0.01,R^(2)=0.784).Conclusion:Although the conventional formula has been widely used for years,it is not suitable for an enlarged spleen.We developed 2 novel formulas for estimating splenic volume from clinical data that were more appropriate for cirrhotic patients with PHT.
文摘Background:Tuberculosis(TB)is one of the most debilitating diseases worldwide.Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis,but clinical trials reported inconsistent results.Therefore,we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy.Methods:We systematically searched PubMed,Embase,and the Cochrane Central Register of Controlled Trials from their inception to February 8th,2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy.The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture.The secondary outcomes were clinical response to treatment and adverse events.A random-effects model was used to pool studies.Data were analyzed using RevMan 5.3 software.Results:Five studies with a total of 1126 participants were included in our meta-analysis.Vitamin D supplementation did not shorten the time to sputum culture and smear conversion(hazard ratio[HR]1.04,95%confidence interval[CI]0.89–1.23,P=0.60;HR 1.15,95%CI 0.93–1.41,P=0.20,respectively)and did not lead to an increase in the proportion of participants with negative sputum culture(relative risk[RR]1.04,95%CI 0.97–1.11,P=0.32).However,it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype(HR 8.09,95%CI 1.39–47.09,P=0.02)and improved the multidrug-resistant(MDR)TB sputum culture conversion rate(RR 2.40,95%CI 1.11–5.18,P=0.03).There was no influence on secondary outcomes.Conclusions:Vitamin D supplementation had no beneficial effect on anti-TB treatment,but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.
基金This work was supported by the National Natural Science Foundation of China(Nos.51803170,51803171 and 81703424)China Agricultural Research System(No.CARS-18-ZJ0102)Fundamental Research Funds for the Central Universities(2020CDJQY-A041).
文摘The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.
基金supported by the National Natural Science Foundation of China(Grant Number:81874028,81702182)the Research Program of Foundation Science and Application Technology of Chongqing(Grant Number:cstc2018jcyjAX0598)Basic Medical College Foundation of Army Medical University(2019JCZX10).
文摘Low back pain,mainly caused by intervertebral disc degeneration(IVDD),is a common health problem;however,current surgical treatments are less than satisfactory.Thus,it is essential to develop novel non-invasive surgical methods for IVDD treatment.Here,we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage(ECM-Gels)that are loaded with cartilage endplate stem cells(CESCs).After loaded with CESCs overexpressing Sphk2(Lenti-Sphk2-CESCs)and injected near the cartilage endplate(CEP)of rats in vivo,ECM-Gels produced Sphk2-engineered exosomes(Lenti-Sphk2-Exos).These exosomes penetrated the annulus fibrosus(AF)and transported Sphk2 into the nucleus pulposus cells(NPCs).Sphk2 activated the phosphatidylinositol 3-kinase(PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs,ultimately ameliorating IVDD.This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.
基金We thank all staff members in the Center of Biological Imaging(CBI),the Institute of Biophysics(IBP),and the Chinese Academy of Sciences(CAS)for assistance with data collection.This study was supported by the Strategic Priority Research Program of CAS(XDB29010000)the National Science and Technology Major Project(2018ZX10101004)+3 种基金the National Key Research and Development Program of China(2020YFC0845900)the National Natural Science Foundation of China(NSFC)(82041016,81871658,and 81802010)a grant from the Bill&Melinda Gates Foundation,and is partially supported by the Yanqi Lake Meeting organized by the Academic Divisions of CAS.M.W.is supported by the National Science and Technology Major Project(2018ZX09711003)the National Natural Science Foundation of China(NSFC)(81802007).R.P.is supported by the Young Elite Scientist Sponsorship Program(YESS)by the China Association for Science and Technology(CAST)(2018QNRC001).Y.S.is also supported by the Youth Innovation Promotion Association of CAS.
文摘The outbreak of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has developed into an unprecedented global pandemic.Nucleoside analogs,such as Remdesivir and Favipiravir,can serve as the firstline broad-spectrum antiviral drugs by targeting the viral polymerases.However,the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood.Here,we reveal that Favipiravir,as a pyrazine derivative,could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides.This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs,different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products.We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARSCoV-2 in the pre-catalytic state.This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase,and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides.These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.
基金This study was supported by grants from the National Natural Science Foundation of China(No.31800763 to Y.Z.)Special Grant from Postdoctoral Science Foundation of China(No.2020T130791 to Y.Z.)the National Key Research and Development Plan of China(No.2016YFA0502202 to L.Y).
文摘The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.
文摘Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.
基金Chinese Academy of Medical Sciences(CAMS)Initiative for Innovative Medicine(CAMS-I2M)2017-I2M-1-001 supported this study.
文摘Objective:The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms(pNENs)undergoing surgery in China.Methods:This is a multicenter cross-sectional study performed in China.Data from patients with pNENs undergoing surgery at 33 high-volume medical centers,where the number of pancreatectomies exceeds 20 cases per year,were collected and analyzed between March 1,2016 and February 28,2017.Results:In total,392 patients with pNENs were enrolled.The male to female ratio was 1.4.The majority of patients were aged between 40 and 70 years.65.6%of the patients had non-functional tumors.Among those with functional tumors,the percentages of insulinomas,gastrinomas,glucagonomas,and vasoactive intestinal peptide-secreting tumors were 94.8%,1.5%,2.2%,and 1.5%,respectively.Multidisciplinary team(MDT)discussion was conducted for 39.0%of the patients.Minimally invasive surgery was performed on 31.1%of the 392 patients.The incidence of grade B/C pancreatic fistula formation was 4.4%.A total of 89.0%of the surgeries achieved R0 resection,and 41.6%of the tumors were well differentiated.Lymph node metastasis was present in 8.9%of the patients.The percentages of patients with grades G1,G2,and G3 disease were 49.2%,45.7%,and 5.1%,respectively.Conclusion:This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China.MDT consultation for pNENs has not been widely implemented in China.Although the incidence of surgical complications is relatively low,minimally invasive procedures should be further promoted.This study shows us how to improve the outcomes of these patients.
文摘The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.
