Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury:study protocol for a prospective,randomized,controlled trial

Epidural electrical stimulation is a new treatment method for spinal cord injury(SCI).Its efficacy and safety have previously been reported.Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI.Considering that electromyography(EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI,we designed a study protocol for a prospective,randomized controlled trial.In this trial,on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle,patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment.Recovery of muscle strength of key muscles,quality of life,safety and therapeutic effects will be monitored.Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group.The control group will receive conventional rehabilitation treatment.The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment.After rehabilitation treatment,follow up for all patients will occur at 2 weeks and 1,3 and 6 months.The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale.Secondary outcome measures will include modified Barthel Index scores,integrated EMG values,the visual analogue scale,Spinal Cord Independence Measure scores,and modified Ashworth scale scores.The safety indicator will be the incidence of adverse events.This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment.Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation.This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital(Approval No.RKIRB2022-12)on February 15,2022 and was registered with Chinese Clinical Trial Registry(registration number:ChiCTR2200061674;date:June 30,2022).Study protocol version:1.0.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Endoscopic features predictive of gastric cancer in superficial lesions with biopsy-proven high grade intraepithelial neoplasia

AIM:To investigate the macroscopic and clinicopathologic features of gastric cancer in patients with biopsy-suggested high grade intraepithelial neoplasia. METHODS:Patients with biopsy-confirmed gastric high grade intraepithelial neoplasia were reviewed from January 2001 to March 2008.Pathologic sections were re-evaluated by two senior pathologists. Patients with an en-bloc resection of the lesion within two months after the diagnosis of high grade intraepithelial neoplasia were enrolled in the study. Clinical manifestations,endoscopic features,biopsy and surgical pathology of all patients were collected and analyzed.The data acquired were subjected to univariate and multivariate analysis. RESULTS:Seventy-two superficial gastric lesions with a pathologic diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were enrolled. True high grade intraepithelial neoplasia was finally proved in 16 lesions and gastric cancer in the rest 56 lesions,most of which(96.4%)were differentiated carcinomas.The result of univariate analysis indicatedthat the size and the presence of marked ulcer plaque or scar in a superficial lesion were independently associated with gastric cancer(P<0.05),when high grade intraepithelial neoplasia was diagnosed by biopsy pathology.The results of multivariate analysis revealed the size greater than 1.5 cm[odds ratio(OR)18.400,P<0.001]and the presence of 5-odd mm ulcer plaque or scar(OR 10.000,P=0.044)were associated with gastric cancer.Accordingly,the sensitivity,specificity and negative predictive value of multivariate analysis for predicting"true high grade intraepithelial neoplasia" was 87.5%,89.3%and 96.2%,respectively. CONCLUSION:Macroscopic findings are of value in differentiation between high grade intraepithelial neoplasia and superficial gastric cancer.This may simplify patient work-up and save costs for patients and healthcare system.

Combined effect of repetitive transcranial magnetic stimulation and physical exercise on cortical plasticity

Physical exercise can minimize dysfunction and optimize functional motor recovery after stroke by modulating cortical plasticity.However,the limitation of physical exercise is that large amounts of time and effort are necessary to significantly improve motor function,and even then,substantial exercise may not be sufficient to normalize the observed improvements.Thus,interventions that could be used to strengthen physical exercise-induced neuroplasticity may be valuable in treating hemiplegia after stroke.Repetitive transcranial magnetic stimulation seems to be a viable strategy for enhancing such plasticity.As a non-invasive cortical stimulation technique,repetitive transcranial magnetic stimulation is able to induce longterm plastic changes in the motor system.Recently,repetitive transcranial magnetic stimulation was found to optimize the plastic changes caused by motor training,thereby enhancing the long-term effects of physical exercise in stroke patients.Therefore,it is believed that the combination of repetitive transcranial magnetic stimulation and physical exercise may represent a superior method for restoring motor function after stroke.

Pancreatic carcinosarcoma: First literature report on computed tomography imaging

Carcinosarcoma of the pancreas is an extremely rare tumor and has a dismal prognosis. To the best of our knowledge, the histopathological features of the lesion have been illustrated in the literature but to date no reported cases have been documented on imaging characteristics. We report a female case of pancreatic carcinosarcoma presenting as a mucinous cystadenoma on computed tomography(CT). We also summarize the CT characteristics according to the appended CTimages in the reported cases. This is the first report of CT features of pancreatic carcinosarcoma in the English literature.

A randomized,double-blind,placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

AIM: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China. METHODS: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients’ daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs).RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase ≥ 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of ≥ 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%).CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

Value of Evaluating Ovarian Response According to Basal FSH/LH Ratio

Objective To analyze the value of evaluating ovarian response to gonadotrophin stimulation according to patients basal FSH / LH ratio. Methods A total of 134 patients undergoing IVF-ET or ICSI were enrolled using short protocol. We studied their age,basal FSH,bFSH/LH ratio and some indexes which can represent ovarian response. Statistical evaluation was performed using logistic regression analysis and ROC curve to determine odds ratios(OR) and FSH/LH cutoffs. Results Among the patients whose bFSH were less than 8 IU/L,three odds ratios between the ovarian response index and their age,bFSH,bFSH/LH were no significant difference and bFSH/LH cutoff was 3.7. But among the patients those bFSH ≥ 8 IU/L,there were differences among the three OR and bFSH/LH cutoff was 3.3. The highest OR was between bFSH/LH ratio and ovarian response indexes,while the lowest was between bFSH and those indexes . Conclusions Among the patients who has lower ovary reserve (bFSH ≥ 8 IU/L),the ratio of bFSH/LH has superior value to age and basal FSH on evaluating ovarian response.

Novel esophageal squamous cell carcinoma bone metastatic clone isolated by scintigraphy, X ray and micro PET/CT

AIM:To establish a Chinese esophageal squamous cell carcinoma(ESCC)cell line with high bone metastasis potency using99mTc-methylene diphosphonate(99mTcMDP)micro-pinhole scintigraphy,X ray and micropositron emission tomography/computed tomography(PET/CT)for exploring the mechanism of occurrence and development in esophageal cancer.METHODS:The cells came from a BALB/c nu/nu immunodeficient mouse,and oncogenic tumor tissue was from a surgical specimen from a 61-year-old male patient with ESCC.The cell growth curve was mapped and analysis of chromosome karyotype was performed.Approximately 1×106oncogenic cells were injected into the left cardiac ventricle of immunodeficient mice.The bone metastatic lesions of tumor-bearing mice were detected by99mTc-MDP scintigraphy,micro-PET/CT and X-ray,and were resected from the mice under deep anesthesia.The bone metastatic cells in the lesions were used for culture and for repeated intracardiac inoculation.This in vivo/in vitro experimental metastasis study was repeated for four cycles.All of the suspicious bone sites were confirmed by pathology.Real-time polymerase chain reaction was used to compare the gene expression in the parental cells and in the bone metastatic clone.RESULTS:The surgical specimen was implanted subcutaneously in immunodeficient mice and the tumorigenesis rate was 100%.First-passage oncogenic cells were named CEK-Sq-1.The chromosome karyotype analysis of the cell line was hypotriploid.The bone metastasis rate went from 20%with the first-passage oncogenic cells via intracardiac inoculation to 90%after four cycles.The established bone metastasis clone named CEK-Sq-1BM had a high potential to metastasize in bone,including mandible,humerus,thoracic and lumbar vertebrae,scapula and femur.The bone metastasis lesions were successfully detected by micro-pinhole bone scintigraphy,micro-PET/CT,and X-ray.The sensitivity,specificity and accuracy of the micro-pinhole scintigraphy,X-ray,and micro-PET/CT imaging examinations were:89.66%/32%/80%,88.2%/100%/89.2%,and 88.75%/77.5%/87.5%,respectively.Some gene expression difference was found between parental and bone metastasis cells.CONCLUSION:This newly established Chinese ESCC cell line and animal model may provide a useful tool for the study of the pathogenesis and development of esophageal carcinoma.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Leukoaraiosis is associated with clinical symptom severity,poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage:a prospective multi-center cohort study

Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.

RETINOIDS AND THEIR APPLICATIONS IN CLINIC

This review provides an overview of relevant aspects of retinoid physiology and molecular biology, and summarizes the current status of clinical investigations on the use of retinoid for the treatment of malignancies. The mechanism underlying the anticarcinogenic activity of retinoids appears to be associated with the ability of retinoids to modulate the growth and induce differentiation, and apoptosis of normal, premalignant, and malignant cells in vitro and in vivo. Retinoid effects seem to be resulted from changes in gene expression mediated via specific nuclear receptors (termed retinoic acid receptors, RAR-a, -b and -g). Chromosome translocations play an important role in APL pathogenesis. In the classical translocation, RAR a gene is fused with PML gene to form PML-RAR a chimeric gene, which is expressed in over 95% of the APL patients with t (15; 17) (q22; q21). Therefore, PML-RAR a fusion gene is the molecular marker of APL. ATRA can induce relocalization of the PML and restore the normal structure of POD. Furthermore, it could cause a degradation of PML-RAR a. In addition to the very high clinical response rate for APL patients treated with ATRA, clinical responses have been observed for patients with myelodysplastic syndrome, cutaneous T-cell lymphoma and skin cancers. Applications of retinoids are reviewed in different malignancies: including skin cancer, head and neck carcinoma, neuroblastoma, lung cancer, breast cancer, prostate cancer, bladder cancer and ovarian cancer in vivo and in vitro studies. The results indicate that retinoids are potentially useful agents for cancer prevention. RA combined with IFNs or RA combined with G-CSF has synergistic effect in inducing differentiation of cell growth. From current clinical results at least four leads are expected to impact on clinical development of retinoids in future: (1) development of retinoid receptor-selective agents; (2) investigation on cross-talk among members of the steroid superfamily; (3) strategies for attaining sufficient tissue levels of retinoids; (4) combined use with other differentiation or chemotherapeutic agents.

Long term treatment of recurring pathological fractures due to Mccune Albright Syndrome: Case report and literature review

McCune Albright syndrome is a rare genetic disorder which is characterized by café au lait skin pigmentation, precocious puberty and polyostotic fibrous dysplasia. Treating recurring pathological fractures due to Albright syndrome is a very challenging endeavor, and more so when it is accompanied by poor bone quality and deformity. We hereby present the case of a 23-year-old male patient who is treated several times for recurrent pathological fractures of the femur at our center. We analyze the difficulties associated with treating a patient with poor bone quality over several years, discuss our treatment options, review the literature for similar cases and look at what we could have done differently. We weigh in on the difficulties in treating a severely deformed shepherd’s crook, the ways of achieving proper internal fixation and the dangers of using plating instead of an IM nail as suggested in the literature. Our main goal in reporting this case is to bring forth the unusual challenges encountered when treating patients with Albright syndrome and discussing the options of the orthopedic surgeons when treating these types of patients.

Papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer: A case report

BACKGROUND The recognized pattern of cervical lymph node metastasis(CLNM)of papillary thyroid carcinoma involves a stepwise route.Contralateral lymph node skip metastasis is very rare.In addition,the patient in our case report also suffered from a breast carcinoma accompanied by left supraclavicular lymphadenopathy,which made it difficult to distinguish the origin of the CLNM.Based on this case,we recommended that more detailed physical and imaging examinations are needed for patients with uncommon cervical lymphatic metastasis of primary cancer.CASE SUMMARY A 53-year-old women was admitted to the hospital for a neck mass in the left cervical region that had existed for 2 mo.The neck mass was suspected to be an enlarged lateral LN originating from papillary thyroid microcarcinoma of the contralateral thyroid lobe,according to ultrasound and ultrasound-guided fine needle aspiration biopsy.The patient underwent total thyroidectomy and radical cervical LN dissection.Postoperative pathology confirmed the diagnosis of papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis.Unfortunately,a breast cancer was discovered 4 mo later,which was accompanied by ipsilateral supraclavicular LN metastasis.She accepted neoadjuvant chemotherapy and subsequent left modified radical mastectomy for treatment.The patient is currently receiving postoperative radiotherapy,and no local recurrence was observed in the 6-mo follow-up after surgery.CONCLUSIONWe present a rare case of papillary thyroid microcarcinoma with contralateral lymphatic skipmetastasis and breast cancer with supraclavicular lymphatic metastasis.

Anatomical variation of infra-pyloric artery origination： A prospective multicenter observational study (IPA-Origin)

Objective: Infra-pyloric artery(IPA) is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA.Methods: We did this prospective, multicenter, open-label, observational study at gastric surgery departments of34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ~2 tests and Fisher's tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov(No. NCT03071237).Results: Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419(97.7%) patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398(95.0%) patients, including gastroduodenal artery(GDA) in154(36.8%) patients, anterior superior pancreaticoduodenal artery(ASPDA) in 130(31.0%) patients, and right gastroepiploic artery(RGEA) in 114(27.2%) patients. Fifteen(3.6%) patients were identified with multiple IPA and 6(1.4%) patients were identified as IPA absence. The differences in the distribution of surgical approach(P=0.003) and geographic area(P=0.030) were statistically significant. No difference was shown in sex, age,gastrectomy type, tumor location, and clinical T, N and M stage.Conclusions: Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions.Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo

Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour metastasis.SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer.However,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be discovered.Here,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/L.Moreover,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/L.The allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural analyses.Importantly,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver metastasis.To our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic cancer.It not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

Trend in the incidence and geographic variations of acute lymphoblastic leukemia in Shanghai, China from 2002 to 2006

背景大进展在过去的十年在尖锐成淋巴细胞的白血病(所有) 的诊断，分子的致病和治疗被做了。由于大基于人口的研究，在发生的最近的趋势和在上海的所有的地理变化的缺乏，中国很好没被记录。更好理解发生和流行病学的特征都在上海，我们在上海在所有大规模医院里从疾病控制和预防和医药记录( CDC )的上海中心基于数据库进行了回顾的调查，特别有血液学 department.Methods 的那些 30 所主要医院根据从上海 CDC 的数据，与 32 年(变化 1.2-89years )的中部的年龄， 544 个病人都从2002年1月1日作为 de novo 被诊断到12月在男人的发生(0.86/100 000 ) 在女人比那稍微高(0.75/100 000 ) 。成层年龄的发生证明发生是 2.31/100 000 在病人 17 岁， 0.54/100 000 在那些 18-34 岁， 0.46/100 000 在那些 35-59 岁，和 0.94/100 000 在那些 60 岁。而且，在所有的发生有实质的地理变化与在 Chongming 县的发生，在是的上海城市的东方的一个岛 0.60/100 000，比那些低得多另外的区域。French-American-British (FAB ) 和世界健康组织() 分类系统在现在的学习被使用。88 个病人是被诊断 L1 (26.2%) ， 193 L2 (57.4%) ，和 55 L3 (16.4%) 。为有 immunophenotypic 结果的 302 个病人， 242 作为 B 房间起源(80.1%) 被识别， 59 作为 T 房间起源(19.5%) ，并且 1 作为 biphenotype (0.4%) 。在 61 个病人的白血病房间共同表示一或二 myeloid 抗原(20.2%) 。为有细胞发生的结果的 269 个病人， t 的发生( 9 ； 22 )在 10 的病人， 11-17 ， 18-44 ， 第45-59a 60 岁是4.2%，11.4%，19.2%，23.1%和5.3%， respectively.Conclusion 与以前的数据相比，所有的发生在上海被增加，并且有一个地理分发特征。

Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma

Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma(DLBCL).Using whole exome/genome sequencing,RNA-sequencing,and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients,we established a simplified 38-gene algorithm(termed‘LymphPlex’)based on the information on mutations of 35 genes and rearrangements of three genes(BCL2,BCL6,and MYC),identifying seven distinct genetic subtypes:TP53Mut(TP53 mutations),MCD-like(MYD88,CD79B,PIM1,MPEG1,BTG1,TBL1XR1,PRDM1,IRF4 mutations),BN2-like(BCL6 fusion,NOTCH2,CD70,DTX1,BTG2,TNFAIP3,CCND3 mutations),N1-like(NOTCH1 mutations),EZB-like(BCL2 fusion,EZH2,TNFRSF14,KMT2D,B2M,FAS,CREBBP,ARID1A,EP300,CIITA,STAT6,GNA13 mutations,with or without MYC rearrangement),and ST2-like(SGK1,TET2,SOCS1,DDX3X,ZFP36L1,DUSP2,STAT3,IRF8 mutations).Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype.TP53Mut subtype showed poor prognosis,characterized by p53 signaling dysregulation,immune deficiency,and PI3K activation.MCD-like subtype was associated with poor prognosis,activated B-cell(ABC)origin,BCL2/MYC double-expression,and NF-κB activation.BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation.N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell(GCB)-DLBCL,respectively.EZB-like-MYC+subtype was characterized by an immunosuppressive tumor microenvironment,while EZB-like-MYC-subtype by NOTCH activation.ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation.Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy.Collectively,LymphPlex provided high efficacy and feasibility,representing a step forward to the mechanism-based targeted therapy in DLBCL.

Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer

Background:Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy.However,the unique features of the immune microenvironment of triple negative breast cancer(TNBC)compared with other subtypes of breast cancer remain elusive.Therefore,we aimed to depict and compare the immune landscape among TNBC,human epidermal growth factor receptor 2-positive(HER2^(+))breast cancer,and luminal-like breast cancer.Methods:Single-cell RNA sequencing(scRNA-seq)was performed on CD45^(+)immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes.By analyzing the scRNA-seq data,immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC,human HER2^(+)breast cancer,and luminal-like breast cancer.Pseudotime and cell-cell communication analyses were also conducted to characterize the immune microenvironment.Results:ScRNA-seq data of 117,958 immune cells were obtained and 31 immune clusters were identified.A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2^(+)or luminal-like breast cancer,which was characterized by higher proportions of regulatory T cells(Tregs)and exhausted CD8+T cells and accompanied by more abundant plasma cells.Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores.Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC.Cell-cell communication analyses indicated that these unique features are fostered by the diversified T cell-B cell crosstalk in TNBC.Based on the T cell-B cell crosstalk,a prognostic signaturewas established that could effectively predict the prognosis status for patients with TNBC.Additionally,it was found that TNBC had a higher proportion of cytotoxic natural killer(NK)cells,whereas HER2^(+)or luminal-like breast cancer lost this feature,suggesting thatHER2^(+)or luminal-like breast cancer,but not TNBC,may benefit from NK-based immunotherapy.Conclusions:This study identified a distinct immune feature fostered by T cell-B cell crosstalk in TNBC,which provides better prognostic information and effective therapeutic targets for breast cancer.

GPCR信号通路调控微环境的免疫特征和介导EB病毒相关淋巴瘤的发生

EB病毒(EBV)是多种肿瘤的致癌驱动因素.然而,肿瘤发生过程中病毒与肿瘤免疫相互作用的潜在机制仍不清楚.自然杀伤T细胞淋巴瘤(NKTCL)是研究EBV相关淋巴瘤发生的代表性疾病模型.本文整合基因组、转录组和蛋白质组数据,全面报道了NKTCL的蛋白质基因组特征.多组学分析发现EBV基因模式与免疫介导的致癌信号相关.单细胞转录组分析进一步描绘肿瘤微环境的免疫炎症、缺陷和沙漠三种表型特征,与肿瘤-免疫循环的不同设定点相关.EBV与转录因子相互作用引起GPCRome重编程,肿瘤细胞和免疫抑制细胞上CCR1的高表达,从而调控微环境中病毒与肿瘤的相互作用.在NKTCL类器官中,靶向CCR1可清除EBV、激活T细胞和杀伤淋巴瘤细胞,具有潜在的靶向治疗作用.综上,本研究首次发现了一种GPCR介导的肿瘤发生发展机制,将病毒分子的感知效应转化为针对EBV的特异性抗肿瘤疗法.