Small cell lung cancer (SCLC), a highly aggressive subtype of lung cancer that originates from pulmonary neuroendocrine cells, accounts for 10% to 15% of all lung cancers. It is characterized by a high rate of early metastasis and extremely poor prognosis, often accompanied by challenges such as drug resistance and recurrence. Related researches indicates that the Notch signaling pathway plays a crucial role in the occurrence and development of SCLC by regulating processes such as cell proliferation, differentiation, and apoptosis. In SCLC, abnormal Notch signaling may promote tumor malignancy and the occurrence of drug resistance. Additionally, the Notch pathway is involved in the epithelial-mesenchymal transition of SCLC and influences immune escape mechanisms through interactions with the tumor immune microenvironment. This article reviews the molecular mechanisms of Notch signaling in SCLC, including the roles of its receptors and ligands, signal transduction processes, and its role in tumorigenesis. It also discusses the research progress of Notch signaling as a potential therapeutic target and looks forward to future research directions in this field.
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Humans ; Receptors, Notch/genetics* ; Signal Transduction ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Animals

Objective:To investigate the risk of hospital death in patients with traumatic hemorrhagic shock combined with multiple organ dysfunction syndrome(MODS)predicted by discriminant analysis.Methods:This study was a single-center retrospective study. From January 2013 to May 2023, patients with traumatic hemorrhagic shock complicated with MODS admitted to Peking University People's Hospital were selected as the research objects. According to the in-hospital survival, the patients were divided into survival group (205 cases) and death group (29 cases). The general condition, injury assessment, laboratory indexes, complications and clinical scores of the two groups were compared. Wilks's Lambda stepwise discriminant analysis was used to establish a discriminant model for in-hospital death in patients with traumatic hemorrhagic shock combined with MODS. the Receiver operating characteristic curve (ROC) was drawn and the Area under the curve (AUC) was calculated. The cross-validation method was used to evaluate the accuracy of the prediction results of the established model.Results:There was a statistical difference between the survival group and the death group in terms of the main bleeding site (limbs), the time from injury to hospital admission, temperature, platelet count, prothrombin time, activated partial thrombin time, fibrinogen, albumin, serum creatinine, estimated glomerular filtration rate, uric acid, cardiac troponin I, procalcitonin, base excess, lactate to albumin ratio, glucose to albumin ratio, acute respiratory distress syndrome, acute kidney injury, acute myocardial injury, traumatic induced coagulopathy, ISS, APACHEⅡ score and SOFA scores. There are four indicators entering the final discrimination model: Prothrombin time, ISS score, estimated glomerular filtration rate, lactate to albumin ratio. The AUC for predicting the risk of death in patients with traumatic hemorrhagic shock combined with MODS was 0.791, and the 95% CI was 0.671 to 0.911. Conclusions:The established discriminant model is highly accurate in predicting the risk of hospital death in patients with traumatic hemorrhagic shock complicated with MODS. Prothrombin time, ISS score, estimated glomerular filtration rate and lactate to albumin ratio were associated with an increased risk of death from traumatic hemorrhagic shock with MODS.

[Objective]To distinguish and analyze the provisions of the word"belly"mentioned in Synopsis of the Golden Chamber,and to explore the similarities and differences in the usage of"belly"and"abdomen"during the period when Synopsis of the Golden Chamber was written,and clarify the specific meanings of"cold in the belly"and"heat in the belly".[Methods]By analyzing the meaning of the articles related to"belly"and verifying the original meaning of the words"belly"and"abdomen"in the era when ZHANG Zhongjing wrote the book,combined with the articles in Treatise on Febrile Diseases and Synopsis of the Golden Chamber that were similar to the diseases"syncope due to pathogenic cold"and"jaundice"described in the articles,the usage of"belly"in the articles was summarized.[Results]Throughout history,there had been various interpretations of"belly",such as considering it as the spleen,a part of the spleen meridian,and a reference to the abdomen.After examining the original meanings of the two characters"belly","abdomen"was first born in"belly",and its meaning and word making ability were higher than"belly"."Belly"was first seen in the Western Han Dynasty,and it mostly referred to the stomach of animals.Through verifying ZHANG Zhongjing's analysis of the principles and methods of"syncope due to pathogenic cold"and"jaundice"diseases,it was found that in Synopsis of the Golden Chamber,"belly"referred to the stomach and intestines,which was applied in the expression of Yangming disease.[Conclusion]The meanings of"belly"and"abdomen"in Synopsis of the Golden Chamber are different,and"belly"is not a mutual use of"abdomen".

Objective: Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. Methods: The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. Results: We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). Conclusion The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods: One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P< 0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.

Objective: To establish the domestic matrix assisted laser desorption/ionisation time of flight mass spectrometry database for identification of clinical mycobacteria and evaluate its accuracy with foreign counterpart. Methods: The establishment of "Chinese Pathogenic Mycobacteria Mass Spectrometry Database" : nineteen American type culture collection strains from 19 species and 183 "standardized" isolates from 42 species were selected and extracted by modified ultrasonic extraction method for spectral acquisition and database establishment based on microTyper MS. Each extract was dropped onto 12 spots and tested twice to generate 24 spectrum, then at least 20 qualified spectrum according to the standard were selected. Subsequently they were composed into one main spectra (MSP) by setting peak number maximum, peak frequency minimum and mass tolerance. Verification of database: Totally 305 mycobacteria from different regions were used for comparison of accuracy and spectral features between microTyper MS based on domestic database and imported MALDI TOF MS base on Mycobacteria Library 3.0 database. Results: The database composed of 202 stains from 42 species was constructed, with an average of 4.8 in each species. The top ten were M. Kansasii(16), M. intracellulare(16), M. gordonae(16), M. fortuitum(16), M. avium(16), M. abscessus(16), M. tuberculosis(15), M. marseillense(11), M. arupense(10), M. yongongens(8). A total of 305 isolates were confirmed belonging to 22 species by sequencing. The accuracy based on this database was 99.67% (304/305), which was better than the Mycobacteria Library 3.0 database (χ²=4.06, P<0.05). Conclusion The construction of the "Chinese Pathogenic Mycobacteria Mass Spectrometry Database" meets the requirement of routine clinical application and was more accurate than its counterpart in terms of domestic comment strains.(Chin J Lab Med, 2018, 41: 519-526)

Objective To compare the diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for solid pancreatic masses performed with three different needle types through the cytological results.Methods All patients with solid pancreatic masses larger than 2cm from December 2010 to May 2011 were enrolled,and divided into two groups according to different access of EUS-FNA,trans-gastric approach with 19-,22-and 25-gauge needles (n =42) and trans-duodenal approach with 22-and 25-gauge needles (n =10).In both groups,EUS-FNA was performed with randomization of needle types.During the puncture,the suction,the number of movements,and the depth of insertion were fixed.At the end of the puncture,a liquid-based cytological (LBC) preparation was used to fix the specimen.One cytopathologists was assigned to make the diagnosis and comparison.Results Technical success was 100％ and no procedure related complications occurred.No statistically significant differences were observed in different needles in terms of all cytological parameters between two groups (P ＞ 0.05).However,the 25-gauge needle showed a trend towards a higher sensitivity,specificity,positive predictive value,negative predictive value and accuracy.Conclusion There is no significant difference in yield of cytological results between different needle types,although 25-gauge needle shows a relative superiority.