Objective: The aim of this study was to analyze the clinical characteristics and prognosis of Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) in a Chinese cohort. Methods: A total of 57 patients diagnosed with EBV+DLBCL from January 1, 2013 to December 31, 2020 were included, and 228 concurrent patients with EBV-DLCBL served as control. The differences between the two groups were compared and the prognosis factors were identified by univariate and multivariate analysis. Results: There were 38 man in the EBV+DLBCL group, with a median age of 56 years (rang, 18 to 88). Tumor cells originated from GCB in 15 patients (26.3%), and from non-GCB in 40 patients (70.2%). There were 34 patients (59.6%) with Epstein Barr virus infection. Compared with EBV-DLCBL patients, patients with EBV+DLBCL had B symptoms, hypoalbuminemia, anemia and extranodal involvement>1 more frequently, as well as higher LDH and β2-Microglobulin levels (P < 0.05 foe all). The most common extranodal sites involved were digestive tract, especially, the stomach, nasopharynx, bone marrow and bone. Immunohistochemical staining showed 24 patients (42.1%) in the EBV+DLBCL group were CD30 positive, compared with xxx in patients with EBV﹣DLCBL (P < 0.001). After treatment with rituximab combined with chemotherapy, the EBV+DLBCL patients had a complete response rate and a overall response rate of 55.5% (30/54) and 83.3% (45/54), respectively. With a median follow-up time of 28 months, 22.2% (10/45) patients relapsed. The overall response rate and recurrent rate were similar between the two groups. In multivariate analysis, increased β2-Microglobulin level and bone marrow invasion were independent risk factors for PFS, while increased β2-Microglobulin level and decreased HB were independent risk factors for OS in patients with EBV+DLBCL. Conclusion: The majority of EBV+DLBCL patients were non-GCB.β2-Microglobulin level and bone marrow invasion were independent risk factors for PFS in patients with EBV+DLBCL, while β2-Microglobulin and HB were independent risk factors for OS in patients with EBV+DLBCL. The therapeutical potentials of targeted medicines, such as CD30 inhibitors and PD-1 inhibitors, deserve to be explored in the future. Keywords：Epstein Barr virus, diffuse large B-cell lymphoma, prognostic factors

BACKGROUND:Colorectal surgery is often associated with a high risk of anastomotic leakage. Intraoperative administration of dexmedetomidine (DEX) can improve postoperative gastrointestinal function. AIM:To investigate the effects of DEX on anastomotic healing in a rat model of intestinal anastomosis (IA). METHODS:Rats were randomly divided into three groups: Sham (underwent abdominal only opening and closure), IA, and IA + DEX. In the IA + DEX group, DEX (5 μg/kg) was administered via tail vein infusion one day before and after anesthesia. Intestinal function, inflammation, and barrier integrity were measured based on intestinal propulsion, anastomotic burst pressure, histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assay, and Western blotting. In vitro, IEC-6 cells faced lipopolysaccharide-induced injury. DEX (4.8 μmol/L) effects on viability, apoptosis, and tight junction proteins were tested with/without the Wnt pathway inhibitor dickkopf-1 (DKK-1) (20 ng/mL). β-catenin, glycogen synthase kinase-3 beta (GSK-3β), claudin-1, and zonula occludens-1 (ZO-1) were assessed by Western blot. RESULTS:Compared with IA, IA + DEX showed a non-significant increase in intestinal propulsion on postoperative day 6 and a significant rise in anastomotic burst pressure on day 7. Histology indicated reduced inflammation and submucosal injury. Serum tumor necrosis factor-alpha and diamine oxidase decreased, while tight junction proteins (claudin-1, ZO-1) increased in IA + DEX. High-throughput sequencing and Western blotting suggested activation of the Wnt/β-catenin pathway as a potential mechanism. In vitro, DEX pretreatment attenuated lipopolysaccharide-induced downregulation of claudin-1 and ZO-1 and reduced apoptosis in IEC-6 cells. These protective effects were reversed by DKK-1, which abolished DEX-mediated Wnt/β-catenin activation (decreased β-catenin, increased GSK-3β) and nullified the benefits of DEX on tight junction protein expression. CONCLUSION:DEX enhances anastomotic healing and barrier function after IA, partly via Wnt/β-catenin activation, indicating therapeutic potential to improve postoperative outcomes.

BACKGROUND:Postoperative gastrointestinal recovery affects hospital stay time and patient's quality of life. Studies suggest that the use of dexmedetomidine during the perioperative period can promote post operational recovery of gastrointestinal function. AIM:To evaluate the efficacy and safety of different doses of dexmedetomidine on postoperative gastrointestinal function recovery after laparoscopic colorectal surgery. METHODS:In this large-sample, retrospective study, 879 patients undergoing laparoscopic colorectal surgery were categorized into three groups: A control group receiving no dexmedetomidine (n = 281), a low-dose group receiving an intraoperative bolus of 0.5 μg/kg dexmedetomidine followed by a continuous infusion of 0.2 μg/kg/hour (n = 313), and a high-dose group receiving a 1.0 μg/kg bolus followed by a 0.5 μg/kg/hour infusion (n = 285). Time to postoperative first flatus, feces, and regular diet, and the intake, feeling nauseated, emesis, physical examination, and duration of symptoms score were evaluated. RESULTS:Multiple linear regression analysis showed that age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities and surgical site were not related to the time to first flatus (all P > 0.05). The times to postoperative first flatus, first feces, and regular diet were earlier in both dexmedetomidine groups than the control group (both P < 0.05). More patients in the control group experienced postoperative gastrointestinal intolerance (both P < 0.05). There was no significant difference between the high- and the low-dose groups (P > 0.05). The incidence of intraoperative bradycardia in the high-dose group was higher than that in the control group (19.15% vs 8.19%, P < 0.05). CONCLUSION:Both low- and high-dose dexmedetomidine regimens enhance postoperative gastrointestinal recovery after laparoscopic colorectal surgery. The low-dose regimen demonstrates superior safety, supporting its integration into multimodal enhanced recovery pathways.

BACKGROUND:Impaction of button batteries (BB) in children is not rare. AIM:To conduct a systematic review of reports of oesophageal injury caused by impaction of BB in children in China. METHODS:The databases of Wanfang, VIP, China National Knowledge Internet, the Chinese Medical Association Journal and PubMed were searched for reports by Chinese authors of BB impaction published between May 2005 and July 2023. The risk factors for complications were analysed by multiple unconditional logistic regression. RESULTS:After excluding 95 articles which did not meet the criteria, 77 remained, with a total of 964 cases of BB impaction. Of 516 cases with complications, 402 were in children (77.9%). The most common complications were oesophageal erosions and ulceration (218/402, 54.2%), followed by oesophageal perforation (88/402, 21.1%), tracheo-oesophageal fistula (69/402, 17.2%), oesophageal stricture (38/402, 9.5%) and peri-oesophagitis (31/402, 7.7%). Regression analysis demonstrated that the duration and location of impaction were the risk factors for complications (OR 13.7 and 11.3, respectively; p < 0.05 for both). CONCLUSION:BB impaction remains common and causes serious oesophageal complications in children. Widespread knowledge of the risks is essential for prevention.

This monthly, peer-reviewed journal includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.

CONTEXT: NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. The Phase II clinical trial shows that intramuscular injection of NL003 in the affected limb of patients with critical limb ischemia (CLI) is safe and could alleviate pain and promote ulcer healing. The purpose of this study was to evaluate the long-term safety and efficacy of NL003. METHODS: A total of 108 participants were evaluated: 32 in the placebo group and 76 in the NL003 group. The primary endpoint was 5-year amputation-free survival and the secondary endpoints were pain, ulcer, and adverse reactions. RESULTS: During a mean follow-up period of 10.4 years, the 5-year amputation-free survival rate was 67.1% (51/76) in the NL003 group and 37.5% (12/32) in the placebo group ( P < 0.05). The median amputation-free survival was 9.53 years in the NL003 group and 4.51 years in the placebo group. There was no significant difference in the rates of major amputation between the two groups (21.1% vs. 21.9%). Pain relief and ulcer healing tended to favor the NL003 group. No serious adverse reactions such as gene integration and tumor were found during the follow-up. CONCLUSIONS: NL003 has a favorable long-term safety profile and may provide long-term benefit for patients with CLI.

Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing. This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics. The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas. The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.

Lipoprotein (a) [Lp (a)] is a complex polymorphic lipoprotein consisting of one low-density lipoprotein particle with one molecule of apolipoprotein B100 and another apolipoprotein (a) linked by a disulfide bond. In recent years, due to its causal role in premature atherosclerotic cardiovascular diseases and calcified aortic stenosis, Lp (a) has attracted more and more attention. Our study aimed to illustrate the trend of Lp (a) research in atherosclerosis (AS) through bibliometric analysis. The Science Citation Index-Expanded was used to locate Lp (a) and AS studies published between December 1, 2012 and December 1, 2022. VOSviewer and CiteSpace bibliometric software packages were used to analyze literature information. LP (a) has seen an overall increase in annual publications. The United States had the highest number of publications worldwide, with 192 publications. The University of California, San Diego, has contributed significantly to Lp (a) with 29 publications and led research collaboration. In the past few decades, there has been close collaboration between countries or regions, institutions, and authors. In addition, the European Heart Journal was the most cited, followed by the Journal of Lipid Research and AS with 2033, 1096, and 806 citations, respectively. Recent studies were on genes and lipid-lowering therapies. Our study comprehensively evaluated the research status and trends of Lp (a) in AS worldwide for the first time and provided a valuable reference for clinical researchers.

Objectives The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in patients with Crohn’s disease (CD). Methods This was an open-label, single-arm clinical trial conducted at Jinling Hospital. Adult patients with complex treatment-refractory CD perianal fistulas (pfCD) were enrolled and received a single intralesional injection of 120 million TH-SC01 cells. Combined remission was defined as an absence of suppuration through an external orifice, complete re-epithelization, and absence of collections larger than 2 cm measured by magnetic resonance imaging (MRI) at 24 weeks after cell administration. Results A total of 10 patients were enrolled. Six patients (60.0%) achieved combined remission at 24 weeks. The number of draining fistulas decreased in 9 (90.0%) and 7 (70.0%) patients at weeks 12 and 24, respectively. Significant improvement in Perianal Crohn Disease Activity Index, Pelvic MRI-Based Score, Crohn Disease Activity Index, and quality of life score were observed at 24 weeks. No serious adverse events occurred. The probability of remaining recurrence-free was 70% at week 52. Conclusion The study demonstrated that local injection of TH-SC01 cells might be an effective and safe treatment for complex treatment-refractory pfCD after conventional and/or biological treatments fail (ClinicalTrials.gov ID, NCT04939337). Trial Registration : The study was retrospectively registered on www.ClinicalTrials.gov (NCT04939337) on June 25, 2021.

在中文文献中,Bromodomain被翻译为溴结构,是因为词中含有Bromo词根.那么Bromodomain中的Bromo是指溴吗?如果是,细胞生物学中并没有提到生命中有溴元素参与,为什么叫溴结构域? 维基百科的注释:The bromodomain was identified as a novel structural motif by John W.Tamkun and colleagues studying the Drosophila gene Brahma/brm,and showed sequence similarity to genes involved in transcriptional activa-tion.The name"bromodomain"is derived from the relationship of this domain with Brahma and is unrelated to the chemical element bromine.

A sensitive quantification method for sufentanil in human milk was developed. Samples were prepared by liquid-phase extraction. Analytes were chromatographically separated. The mobile phase contained 10 mM ammonium formate (A) and methanol (B). The ratios of A to B were 50:50, 10:90, and 50:50 sequentially. For LC-MS-MS detection, transition of the protonated precursor ions to product ions (sufentanil: m/z 387.2→m/z 238.2; internal control fentanil: m/z 337.2→m/z 158.2) was monitored. The linear quantification range of sufentanil concentration was 3.2–400 pg ·mL −1 . The correlation coefficient ( r 2 ) was 0.996. The % RSD was less than 6.0% for intraday and less than 8.68% for interday precision. By this method, sufentanil contents were determined to be very low in the postnatal maternal milk samples.

e21069 Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807 .

ABSTRACT Background: Cecal ligation and perforation (CLP) is currently considered the criterion standard model of sepsis; however, there are some deficiencies, such as low clinical relevance, inconsistency in severity grading, and an unknown proportion of CLP animals meeting the requirements of sepsis-3. Methods: Adult rats were randomly divided into the following three groups: modified CLP (M-CLP) group, CLP group, and sham group. The vital organ function of rats was evaluated 24 hours postoperatively by blood pressure, behavioral testing, histopathology, and blood test. Cytokine levels were determined by enzyme-linked immunosorbent assay, and T-cell suppression was assessed by flow cytometry. The stability of the model was evaluated by comparing the survival rates of repeated experiments in all groups from day 1 to day 14. Results: More rats in the M-CLP group met Sepsis-3 criteria than those in the CLP group 24 hours postoperatively (53.1% vs. 21.9%, P = 0.01). Rats in the M-CLP group developed more serious hepatic, pulmonary, and renal dysfunction. Similar to human sepsis, rats in the M-CLP group demonstrated more serious immunosuppression and systemic inflammation compared with the CLP group. In addition, disease development and severity, which was indicated by the stable survival rates of model animals, were more stable in the M-CLP group. Conclusions: More rats could meet Sepsis-3 criteria with this novel surgical procedure, which may reduce the number of animals needed in preclinical sepsis experiments. This stable M-CLP model may contribute to the development of new therapies.

With the development of linnovative regulations on drug clinical trials in mainland China, the quantity and quality of drug clinical trials have gradually improved over the past decade. Based on the information of the clinical trials from the online drug clinical trial registration platform of National Medical Products Administration, we reviewed the data of drug clinical trials in mainland China from 2009 to 2020. A total of 8,593 clinical trials have been conducted during this period. The annual number of clinical trials has been increasing gradually, and peaked in 2017. There were 2,127, 1,051, 1,551, and 156 phases I, II, III, and IV clinical trials respectively. In addition, there were 3,441 bioequivalence studies. Trials for anti-tumor drugs ranked the highest (19.45%), followed by trials of drugs for infections and infestations (12.96%) and those for cardiovascular diseases (9.00%). Meanwhile the number of the clinical trial sites also increased annually. However, there were only 116 and 130 clinical trials of drugs for children and rare diseases respectively. The geographical distribution of the sites was uneven. This mapping review provides an overall look of clinical trials in China, which may be useful for domestic and international sponsors.

Single tube long fragment read (stLFR) refers to an unseparated long fragment reading technique, which can attach to the read sequencing fragments from the same long DNA molecule with the same molecular label. The library can be prepared by this technology and it may generate short read length (200 ~ 1 000 bp) fragments for sequencing. After co-barcoding analysis, it can splice long fragment sequences. Therefore, it is capable of long fragment analysis similarly to the third-generation sequencing in theory. At present, the technology is mainly used to assemble target samples, and studies have been reported in humans, plants, animals, microorganisms, and so on. However, the technology has not been fully utilized. Therefore, the review of co-barcoding stLFR can provide references for solving the functional study of long genome fragments.

Purpose: The prognosis of head and neck squamous cell carcinoma (HNSCC) is poor. Necroptosis is a novel programmed form of necrotic cell death. The prognostic value of necroptosis-associated lncRNAs expression in HNSCC has not been explored. Methods: We downloaded mRNA expression data of HNSCC patients from TCGA databases. Prognostic lncRNAs were identified by univariate Cox regression. LASSO was used to establish a model with necroptosis-related lncRNAs. Kaplan-Meier analysis and ROC were applied to verify the model. Finally, functional studies including gene set enrichment analyses, immune microenvironment analysis, and anti-tumor compound IC50 prediction were performed. Results: We identified 1,117 necroptosis-related lncRNAs. The Cox regression showed 55 lncRNAs were associated with patient survival (p < 0.05). The risk model of 24- lncRNAs signature categorized patients into high and low risk groups. The patients in the low-risk group survived longer than the high-risk group (p < 0.001). Validation assays including ROC curve, nomogram and correction curves confirmed the prediction capability of the 24-lncRNA risk mode. Functional studies showed the two patient groups had distinct immunity conditions and IC50. Conclusion: The 24-lncRNA model has potential to guide treatment of HNSCC. Future clinical studies are needed to verify the model.

ObjectivePapillary craniopharyngioma (PCP) was previously believed to occur only in adults. Sporadic pediatric PCP (PPCP) confirmed by detection of BRAF V600E mutation has been reported since 2018, but is often misdiagnosed before being diagnosed definitively. We aimed to evaluate PPCP characteristics and propose diagnostic criteria for prompt diagnosis, seeking to reduce patient morbidity and mortality and reduce costs linked to misdiagnosis.MethodsThis study included 5 patients with PPCPs whose data were retrieved retrospectively from among 1032 patients with craniopharyngiomas admitted to Sanbo Brain Hospital Management Group from March 2017 to May 2021. Patients’ demographics, clinical presentation, tumor imaging characteristics, histopathologic results, surgical approaches, and postoperative outcomes were analyzed.ResultsPPCP was misdiagnosed intraoperatively as sellar abscess (n = 4) or Rathke cleft cyst (n = 1). Preoperative magnetic resonance imaging showed that all tumors were under the saddle diaphragm, and the cyst wall was enhanced (n = 5). Computed tomography scans showed scattered high-density signs (n = 4). No recurrence was noted after complete resection. Postoperative hypothalamic dysfunction was mild. BRAF V600E mutation was confirmed in all cases by sequencing and immunohistochemistry. Immunohistochemistry showed granulation and inflammation and MPO, CD3, CD20, CD38, CD68, and CD163 were positively expressed.ConclusionsMisdiagnosis of PPCP is responsible for failed surgical treatment. We propose that prompt diagnosis of PPCP can be achieved if preoperative magnetic resonance images show the tumor under saddle diaphragm with tumor wall enhancement and computed tomography scans show high-density signs scattered in the tumor, which leads to safe, effective tumor resection. Our proposed diagnosis and treatment strategy for PPCP reduces morbidity and mortality.

Background and Aim A worldwide outbreak of coronavirus disease 2019 (COVID-19) has drawn global attention. Several reports have described the gastrointestinal (GI) manifestations in the infected patients. The systematic review was designed to highlight the gaps in our knowledge about the prevalence and clinical significance of GI symptoms in patients with COVID-19.Methods We searched PubMed database and Google articles published in both English and Chinese up to June 3, 2020, using search terms "clinical features," "2019 novel coronavirus," "2019-nCoV," "COVID-19," or "SARS-Cov-2." Observational studies, case reports, or letters describing the clinical features or observational studies regarding the detection and/or isolation of severe acute respiratory syndrome coronavirus 2 viruses in stools were included.Results A total of 22 publications were finally selected. It was reported that GI symptoms occurred in about 3-40.7% of patients. GI manifestations included nausea, diarrhea, anorexia, vomiting, abdominal pain, belching, abdominal distension, and GI hemorrhage. Diarrhea was the most common GI symptom. Infected patients had various degrees of liver dysfunction, and the severity of liver dysfunction was significantly associated with the severity of the disease. Therapy focusing on digestive system like liver supportive therapy or nutrition support or probiotics has been demonstrated to be effective interventions, which greatly improve prognosis. Fecal-oral transmission route is a potential risk for transmission.Conclusions GI symptoms are common in COVID-19. Strengthening the recognition on abnormalities in digestive system of patients with COVID-19 is crucial for early identification and timely treatment, especially for those atypical patients. Hygiene protection and keeping the drainpipe free flowing are necessary for everyone.