Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

δ^(13)C_(org) perturbations preserved by the interglacial Datangpo Formation in South China with implications for stratigraphic correlation and carbon cycle

Palaeoclimatic and palaeoenvironmental reconstructions of the Cryogenian Period have attracted attention in relation to the debated“Snowball Earth”hypothesis and the early evolution of metazoan life.The carbon cycle and redox conditions of the Sturtian-Marinoan non-glacial interval have been subjected to much controversy in the past decades because of the lack of a high-resolution stratigraphic correlation scheme.As one of the typical Sturtian-Marinoan interglacial deposits,the Datangpo Formation was widely distributed in South China with shales continuously deposited.The previous zircon dating data of the Datangpo Formation provide important ages for global constrain of the Sturtian-Marinoan non-glacial interval.Here we present a high-resolution straitigraphic study of the organic carbon isotopes of the Datangpo Formation from a drill core section in northern Guizhou Province.Based on measured episodicδ^(13)C_(org) perturbations,three positive shifts and three negative excursions are identified.Aδ^(13)C_(org)-based chemostratigraphic correlation scheme is proposed herein that works well for the Datangpo Formation regionally.Meanwhile,theδ^(13)C_(org) vertical gradients changed dynamically throughout the formation.This discovery implies that a significant ocean circulation overturn might have occurred in the upper Datangpo Formation,coinciding with the potential oxygenation.

脾多肽对非小细胞肺癌患者化疗后骨髓造血功能的影响

目的观察脾多肽对非小细胞肺癌患者化疗后造血功能的影响及其最佳剂量。方法回顾性分析152例进行化疗的非小细胞肺癌患者,按有无使用脾多肽,分为对照组和治疗组。对照组给予常规化疗,治疗组在常规化疗基础上联合使用脾多肽注射液≥7 d。观察两组患者血细胞下降的最低值,重组人粒细胞集落刺激因子(G-CSF)药物使用量及不良反应。结果两组化疗后白细胞、血小板最低值比较,差异无统计学意义(P>0.05);两组化疗后中性粒细胞最低值比较,差异有统计学意义(P<0.05)。以不同脾多肽注射液剂量分为2 ml、4 ml、6 ml、10 ml组,脾多肽注射液10 ml组白细胞、中性粒细胞最低值高于其他剂量组及对照组(P<0.05);各组血小板最低值比较,差异无统计学意义(P>0.05)。脾多肽注射液10 ml组G-CSF的使用时间较对照组减少(P<0.05)。各组患者不良反应发生率比较,差异无统计学意义(P>0.05),主要为恶心呕吐及神经毒性。结论大剂量脾多肽对非小细胞肺癌患者化疗后骨髓造血功能有保护作用,其最佳剂量可能为10 ml。

Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients

AIM To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract(UPGI) tract.METHODS Patients who underwent routine esophagogastroduodenoscopy(EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between january 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients' demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analyseddifferences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period.RESULTS A total of 21 patients out of 98746 patients(0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was(55.3 ± 17.2) years, and 11 patients were male(52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach(including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps(8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period(38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group(22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028).CONCLUSION Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.

Combined fascia iliaca compartment block and monitored anesthesia care for geriatric patients with hip fracture: Two case reports

BACKGROUND Major hip surgery usually requires neuraxial or general anesthesia with tracheal intubation and may be supplemented with a nerve block to provide intraoperative and postoperative pain relief.CASE SUMMARY This report established that hip surgical procedures can be performed with a fascia iliaca compartment block(FICB)and monitored anesthesia care(MAC)while avoiding neuraxial or general anesthesia.This was a preliminary experience with two geriatric patients with hip fracture,American Society of Anesthesiologists status III,and with many comorbidities.Neither patient could be operated on within 48 h after admission.Both general anesthesia and neuraxial anesthesia were high-risk procedures and had contraindications.Hence,we chose nerve block combined with a small amount of sedation.Intraoperative analgesia was provided by single-injection ultrasound-guided FICB.Light intravenous sedation was added.Surgical exposure was satisfactory,and neither patient complained of any symptoms during the procedure.CONCLUSION This report showed that hip surgery for geriatric patients can be performed with FICB and MAC,although complications and contraindications are common.The anesthetic program was accompanied by stable respiratory and circulatory system responses and satisfactory analgesia while avoiding the adverse effects and problems associated with either neuraxial or general anesthesia.

Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy

Objective Melatonin has been reported to suppress inflammation and alleviate liver fibrosis,but its effect on autophagy in liver fibrosis has not been studied.This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell(HSC)-T6 cell line.Methods The model was established in rats through carbon tetrachloride treatment,and melatonin was administered at three doses(2.5,5.0,and 10.0 mg/kg).Haematoxylin and eosin staining and Van Gieson’s staining were performed to examine the pathological changes of liver.The expression of alpha-smooth muscle actin(α-SMA)and Beclin1 in liver tissues was detected by immunohistochemical staining.The protein levels ofα-SMA,Beclin1 and LC3 in the animal model were detected by Western blot analysis,and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR(qRT-PCR)in the animal model.HSC-T6 cells were activated by platelet-derived growth factor-BB(PDGF-BB).The expression ofα-SMA,Beclin1 and collagen I was detected by Western blot analysis,and the gene expression of Beclin1 and LC3 was detected by qRT-PCR.Results Melatonin reduced the expression ofα-SMA,Beclin1 and LC3 in liver tissues.In addition,melatonin inhibited the activation of HSC-T6 cells and the expression ofα-SMA,Beclin1 and LC3 in these cells.These results revealed that melatonin could inhibit autophagy and HSC activation.Conclusion Melatonin might ameliorate liver fibrosis by regulating autophagy,suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

Rate Constants for Reaction Between Hydroxyl Radical and Dimethyl Sulfide Under Real Atmospheric Condition

The rate constants of the reaction between hydroxyl radical （OH-） and dimethyl sulfide （DMS） were investigated by using the relative methods in air, N2, and 02. Strong influences of ground state oxygen O（3p） on DMS consumption were found by the photolysis of HONO and CH3ONO as OH. sources, and the rate constants obtained in these systems varied significantly. The rate constants of the reaction between DMS and OH- （generated by photolysis of H2 O2） at room temperature were 8.56 × 10^-12, 11.31× 10^-12, and 4.50× 10^-12 cm3/（molecule.s）, in air, O2, and N2, respectively. The temperature dependence of the rate constants for OH- with DMS over the temperature range of 287-338 K was also investigated in nitrogen and air, and the Arrhenius expression was obtained as follows： kaire=（7.24±0.28）× 10^-13exp[（770.7±E97.2）/T], kN2 =（3.40±0.15） × 10^-11 exp[-- （590.3±165.9）/T].

Gastrointestinal bleeding caused by jejunal angiosarcoma: A case report

BACKGROUND Angiosarcoma is a rare disease with a poor prognosis.Its occurrence in the small intestine is low,and gastrointestinal bleeding caused by small intestinal angiosarcoma is unusual.CASE SUMMARY Here,we report the case of a 57-year-old man who presented with hematochezia for 1 mo.The patient had a medical history of chronic viral hepatitis B for 15 years.The causes of gastrointestinal bleeding were initially diagnosed as esophagogastric variceal bleeding or portal hypertensive gastropathy before endoscopy.However,after a complicated diagnostic and therapeutic process,including gastroendoscopy,colonoscopy,contrast-enhanced computed tomographic(CT),positron emission computed tomography/CT,capsule endoscopy,and pathological and immunohistochemical examinations,small intestinal angiosarcoma was diagnosed.Arrest of bleeding was achieved after surgical treatment.Furthermore,the patient had lung cancer with bone and adrenal metastases.At the follow-up 10 mo after the operation,the patient was alive.CONCLUSION Gastroenterologists should maintain strong vigilance to small intestinal angiosarcoma,which is necessary for the early identification of this infrequent but fatal disease.

Scaphoid metastasis as the first sign of occult gastroesophageal junction cancer:A case report

BACKGROUND Metastatic tumors of the hand are very rare.They are usually late manifestations of massive advanced malignancies.However,a small portion of acrometastases are indications of occult primary cancer.Here,we report an extremely rare case in which a scaphoid bone lesion was the initial manifestation and was found to be a metastasis from gastroesophageal junction(GEJ)cancer.CASE SUMMARY A 57-year-old male patient presented with ongoing left wrist pain and swelling after trauma.He was initially misdiagnosed with infection of the scaphoid bone and treated with antibiotics and anti-inflammatory drugs.Further radiographic investigations showed a scaphoid pathological fracture,indicating a metastatic tumor derived from the GEJ and/or right lung malignancies.Gastroscopy failed to identify the pathology of the mass at the GEJ,which grew in an exophytic pattern.A lung puncture biopsy was not performed because the patient refused the procedure.To relieve his wrist pain and obtain a definite pathology,we resected the scaphoid lesion.Based on the clinical and pathological results,the patient was finally diagnosed with multiple metastases of advanced GEJ adenocarcinoma.He underwent chemotherapy and died 6 mo after his initial presentation.CONCLUSION Despite the rareness of the disease,orthopedic surgeons should consider the possibility of metastasis to the bones of the hand when patients complain of persistent and progressive pain in the hand.

Prediction for permeability index of blast furnace based on VMD-PSO-BP model

The permeability index is one of the important production indicators to monitor the operation of blast furnace.It is crucial to grasp the trends of changes in the new permeability index in time.For the complex vibration spectrum of the permeability index,a prediction model of the permeability index based on the VMD-PSO-BP(variational mode decomposition-particle swarm optimization-back propagation)method was proposed.Firstly,the key factors that affect the permeability index of blast furnace were studied from multiple perspectives.Then,the permeability index was divided into multiple sub-modes based on the difference of frequency bands by the VMD algorithm,and a PSO-BP prediction model was established for each sub-mode.Finally,the prediction results of each sub-mode were summed to obtain the final one.The results show that the composite prediction accuracy by using the VMD algorithm is 3%higher than that of the traditional prediction method,which has better applicability.

鉴定最重QED原子的新方法

QED atoms are composed of unstructured and point-like lepton pairs bound together by the electromag-netic force.The smallest and heaviest QED atom is formed by a τ^(+)τ^(-)pair.Currently,the only known atoms of this type are the e^(+)e^(-)and μ^(+)e^(-)atoms,which were discovered 64 years ago and remain the sole examples found thus far.We demonstrate that the J_(τ)(τ^(+)τ^(-) atom with J^(PC)=1^(--))atom signal can be observed with a significance larger than 5o including both statistical and systematic uncertainties,via.the process e^(+)e^(-)→X^(+)Y^(-)E(X,Y=e,μ,π,K,or ρ,and E is the missing energy due to unobserved neutri-nos)with 1.5 ab^(-1)data taken around the τ pair production threshold.The τ lepton mass can be measured with a precision of 1 keV with the same data sample.This is within one year's running time of the pro-posed super tau-charm facility in China or super charm-tau factory in Russia.

m^6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2

N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.

Dissipativity of Multistep Runge-Kutta Methods for Nonlinear Volterra Delay-integro-differential Equations

This paper is concerned with the numerical dissipativity of multistep Runge-Kutta methods for nonlinear Volterra delay-integro-differential equations. We investigate the dissipativity properties of （k, l）- algebraically stable multistep Runge-Kutta methods with constrained grid and an uniform grid. The finite- dimensional and infinite-dimensional dissipativity results of （k, /）-algebraically stable Runge-Kutta methods are obtained.

CRYSTALLIZATION BEHAVIOR, THERMAL AND MECHANICAL PROPERTIES OF PHBV/GRAPHENE NANOSHEET COMPOSITES

Biodegradable poly（3-hydroxybutyrate-co-3-hydroxyvalerate） （PHBV）/graphene nanosheet （GNS） composites were prepared via a solution-casting method at low GNS loadings in this work. Transmission electron microscopy revealed that a fine dispersion of GNSs was achieved in the PHBV matrix. The thermal properties of the nanocomposites were investigated by thermogravimetric analysis, and the results showed that the thermal stability of PHBV was significantly improved with a very low loading of GNSs. Nonisothermal melts crystallization behavior, spherulitic morphology and crystal structure of neat PHBV and the PHBV/GNSs nanocomposites were investigated, and the experimental results indicated that crystallization behavior of PHBV was enhanced by the presence of GNSs due to the heterogeneous nucleation effect; however, the two-dimensional （2D） GNSs might restrict the mobility of the PHBV chains in the process of crystal growing. Dynamic mechanical analysis studies showed that the storage modulus of the PHBV/GNSs nanocomposites was greatly improved.

Trimetazidine in angina and poor muscle function: protocol for a randomized controlled study

Background: Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study. Methods: This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study. Discussion: This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.

国企混改、高管持股与企业绩效——基于中国上市公司的经验检验

本文以沪深A股国有上市公司2009—2017年的数据为样本,实证检验了我国国有企业混合所有制改革对企业绩效的影响,以及在此过程中高管持股所发挥的中介机制作用。研究发现:国企混改力度的增强能够显著提升企业绩效;高管持股在国企混改影响企业绩效过程中发挥着中介机制作用。此结论有助于深化国企混改的经济结果研究,也为实施和推行员工持股计划提供了部分实证支持。