阑尾周围炎与溃疡性结肠炎的关联及研究进展

溃疡性结肠炎(ulcerative colitis,UC)在我国的患病率逐年上升,约高达11.6/10万.此疾病的诊断过程极其漫长且复杂,对我国居民的健康造成了极大的影响.UC通常始发于直肠及乙状结肠,当患有远端结肠炎的患者同时合并了阑尾周围炎(periappendiceal inflammation,PAI),这种情况被认为是UC的“跳跃性病变”.这种现象可能与阑尾作为免疫器官以及其与UC发病机制的免疫相关性有关.PAI合并直肠炎可以为UC的诊断提供便利.然而PAI的发病机理,治疗预后及临床意义,目前尚未达成共识,本文综述了近年来的文献,对PAI进行了综合分析.

Alpha-fetoprotein-producing hepatoid adenocarcinoma of the lung responsive to sorafenib after multiline treatment:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) expression.Currently,there is no standardized treatment strategy for advanced HAL and its prognosis is poor.CASE SUMMARY We report a 55-year-old man with unresectable AFP-related HAL.The largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 cm.The patient’s serum AFP level was 9283 ng/m L.The mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy,and serum AFP reached its highest level(71232.2 ng/m L).The patient was treated with sorafenib(400 mg twice daily,per os).Forty days later,the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/m L.The patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response,as well as survival > 13 mo,which is among the longest reported for unresectable stage IV HAL.CONCLUSION This is the first report to document successful treatment of unresectable AFPrelated HAL with single-agent sorafenib after multiline therapy.

Complete response to trastuzumab and chemotherapy in recurrent urothelial bladder carcinoma with HER2 gene amplification: A case report

BACKGROUND Targeted treatments may greatly affect the natural history of urothelial carcinoma based on their pharmacokinetics. A phase II trial has explored the combination of cytotoxic chemotherapy with the anti-HER-2 monoclonal antibody trastuzumab in selected patients with metastatic bladder cancer, but it failed.CASE SUMMARY Here, we report a case of recurrent urothelial bladder carcinoma(UBC) in a patient who has undergone three operations, and further illuminate its diagnosis and treatment. The diagnosis of UBC was rendered according to the pathological indices. Next-generation sequencing on formalin fixed paraffin-embedded(FFPE)tissue was also performed and suggested HER2 gene amplification in the FFPE tissue. Based on HER2 gene amplification in FFPE, the patient was treated with chemotherapy in combination with trastuzumab after his third surgery.Fortunately, the patient got a clinically complete remission to trastuzumab for 34 mo.CONCLUSION There is not enough clinical evidence for incorporating trastuzumab in routine treatment of UBC. This case hinted that recurrent UBC patients with HER2 gene amplification may benefit from targeted trastuzumab. Further studies are needed to further investigate the status of HER2 gene and better determine trastuzumab in the management of UBC.

Idiopathic adulthood ductopenia with elevated transaminase only:A case report

BACKGROUND Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease ofunknown etiology that usually presents as unexplained jaundice. It ischaracterized by adult onset, lack of autoantibodies, inflammatory bowel diseaseand loss of interlobular bile ducts.CASE SUMMARY This case presents a 27-year-old woman with elevation of transaminases andalkaline phosphatase without clinical symptoms. Five years ago, the patient hadabnormal transaminases but no cholestasis. Three months before admission,physical examination revealed an increase in transaminases. Oralhepatoprotective drugs did not show any significant improvement, and she wasadmitted to hospital for further diagnosis and treatment. Liver biopsy confirmedIAD. After about 2 wk of ursodeoxycholic acid treatment, serological andhistological examination showed a significant response.CONCLUSION IAD is a manifestation of cholestasis, but also may be an abnormal increase intransaminase in the early stage.

Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)targeting the programmed death(PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma(m UC);however,the response rate remains low.There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs.Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma.CASE SUMMARY We present a 59-year-old man with m UC harboring ERBB2/3 mutations(in-frame insertion of ERBB2 and ERBB3 amplification),negative PD-ligand 1 expression,and low tumor mutation burden.He received anti-PD-1 antibodies and paclitaxel as second-line treatment.After two cycles of treatment,the lung metastases had significantly shrunk,achieving good partial remission.After six cycles of combination therapy,the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy.At the last follow-up,the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo.CONCLUSION ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of m UC patients who will benefit from ICIs.

Pushing the Boundaries of Molecular Property Prediction for Drug Discovery with Multitask Learning BERT Enhanced by SMILES Enumeration

Accurate prediction of pharmacological properties of small molecules is becoming increasingly important in drug discovery.Traditional feature-engineering approaches heavily rely on handcrafted descriptors and/or fingerprints,which need extensive human expert knowledge.With the rapid progress of artificial intelligence technology,data-driven deep learning methods have shown unparalleled advantages over feature-engineering-based methods.However,existing deep learning methods usually suffer from the scarcity of labeled data and the inability to share information between different tasks when applied to predicting molecular properties,thus resulting in poor generalization capability.Here,we proposed a novel multitask learning BERT(Bidirectional Encoder Representations from Transformer)framework,named MTL-BERT,which leverages large-scale pre-training,multitask learning,and SMILES(simplified molecular input line entry specification)enumeration to alleviate the data scarcity problem.MTL-BERT first exploits a large amount of unlabeled data through self-supervised pretraining to mine the rich contextual information in SMILES strings and then fine-tunes the pretrained model for multiple downstream tasks simultaneously by leveraging their shared information.Meanwhile,SMILES enumeration is used as a data enhancement strategy during the pretraining,fine-tuning,and test phases to substantially increase data diversity and help to learn the key relevant patterns from complex SMILES strings.The experimental results showed that the pretrained MTL-BERT model with few additional fine-tuning can achieve much better performance than the state-of-the-art methods on most of the 60 practical molecular datasets.Additionally,the MTL-BERT model leverages attention mechanisms to focus on SMILES character features essential to target properties for model interpretability.

Characterization of machined surface quality and near-surface microstructure of a high speed thrust angular contact ball bearing

Bearings are one of the most important components in modern industry.Rolling contact fatigue(RCF)initiating from surface and subsurface is the major failure mode.In this paper,a typical high speed thrust angular contact ball bearing was selected,and the machined surface quality and near-surface microstructure of the race-way and rolling ball were systematically characterized by using of a probe surface profiler,white light interferometer,optical microscopy(OM),scanning electron microscopy(SEM),electron backscatter diffraction(EBSD)and transmission electron microscopy(TEM)combined with focused ion beam(FIB).Two kinds of precursor,probably resulting in pitting or spalling during the following rolling contact,were detected.One is the defects on the surface of either the race-way or the rolling ball,such as heavy machining marks,scratches and slag-hole.The other is nano-crystalline layer due to machining,in the outermost layer around the surface of race-way.The results may well lay foundation for our further research on RCF with the real part of such typical rolling bearings.

Quantitative profiles of the mRNAs of ER-α and its novel variant ER-α36 in breast cancers and matched normal tissues

Objective: The novel estrogen receptor-α (ER-α) variant ER-α36 is reported to be functional in the es-trogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-α36 tends to be a favorable factor for survival in patients without tamoxifen therapy. To investigate the mechanisms behind this paradox, we determined the differences between the transcriptional profiles of ER-α36 and full-length ER-α (ER-α66) in breast cancers and matched normal tissues. Methods: We analyzed ER-α36 and ER-α66 messenger RNA ( mRNA) levels in 74 pairs of breast cancers and matched normal tissues using a real-time quantitative polymerase chain reaction (PCR) assay, and correlated the results with their clinicopathological characteristics. Results: Breast cancers expressed lower ER-α36 mRNA levels than matched normal tissues regardless of their ER-α66 expression status. Down-regulation of ER-α36 mRNA was correlated with local progression, lymph node metastasis, and advanced cancer stage. The level of ER-α66 mRNA was lower in ER-α negative breast cancers compared with matched normal tissues. No differences in ER-α66 mRNA levels were observed during cancer progression. Conclusion: Down-regulation of ER-α36 is associated with carcinogenesis and progression of breast cancer.

Core engineering of paired core-shell silver nanoclusters

Unlike the facile modulation of surface structure through protecting ligands,the core shielded by outer shell of silver nanoclusters is still hard to be controlled.Ligand effects may seep into the incipient growth of silver core.However,the comparable cases to validate such hypothesis are currently lacking.Herein,we shed light on two core-shell silver nanoclusters,Ag_(7)S_(6)@Ag_(48)(SD/Ag55b,SD=SunDi)and Ag_(6)S_(6)@Ag_(48)(SD/Ag54b),differing in only one silver atom in the core which varies from a pentagon-bipyramidal Ag_(7)to an octahedral Ag_(6)while keeping the Ag_(48)shielding shell almost the same.Although no direct bonding between alkynes and silver core is observed in them,we propose that the ligand effect still exerts profound influences on the size and geometry of silver core.The solution behaviours and complete ligand-exchange reaction of SD/Ag55b in CH_(2)Cl_(2)are investigated using electrospray ionization mass spectrometry.Due to more and stronger argentophilic interactions,SD/Ag55b exhibits room-temperature phosphorescence with a 40 nm red-shift compared to that of SD/Ag54b in CH_(2)Cl_(2).This work not only presents effective fabrication of silver nanoclusters via synergism of dithiophosphate and alkyne ligands,but also provides us a pair of comparable examples to understand substitution group effect of protecting ligand on the core structures and properties.

Breast metastasis of gastric signet-ring cell carcinoma

乳腺外来源的转移性乳腺癌在所有乳腺癌中所占比例较低,约为0.5%~1.2%,胃印戒细胞癌转移至乳腺更为罕见。本文报道了一例由胃印戒细胞癌转移至乳腺的女性患者,结合相关文献回顾,探讨并总结转移性乳腺癌与原发性乳腺癌在发病机制、临床表现、影像学特点及病理组织和免疫组化中的不同点。本报道旨在提示临床医师在乳腺肿瘤的诊断中,应详细结合患者病史,考虑到乳腺外转移可能,结合病理结果及免疫组化等手段以明确诊断,早期开展后续治疗。此外,随着循环肿瘤细胞和DNA技术的不断发展,对转移性乳腺癌机制的研究更加深入,可能会为此类疾病提供更好的治疗方案。