BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to find a light-weight,convenient prediction method through machine learning. METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation. RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the five most important features were acuity,arrival transportation,age,shock index,and respiratory rate. CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

Objective:To investigate the effects of rituximab on lymphocytes and immunoglobulin in the treatment of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).Methods:The subjects were FSGS and MCD patients admitted to Ruijin Hospital affiliated to Shanghai Jiaotong University on July 1, 2014 and July 1, 2019. All the enrolled patients were confirmed by clinical examination and renal biopsy, and received rituximab treatment (4 infusions of 375 mg/m 2 with the interval of 7-14 d). The levels of immunoglobulin IgA, IgG, IgM, and lymphocytes of CD19 +, CD20 +, CD3 +, CD3 +CD4 +, CD3 +CD8 + and natural killer cells (CD56 +CD16 +) were compared between baseline and the third month, the sixth month, the ninth month and the twelfth month after treatment. Results:Ninety-six patients with FSGS or MCD were enrolled in this study. The midian age was 28 years old (14-77 years old). The ratio of men to woman was 1.8∶1. There were 65 cases of MCD and 31 cases of FSGS. After rituximab treatment, the 24 h-proteinuria was significantly lower than that before treatment, and the serum albumin level was increased (both P<0.05). After rituximab treatment of 3 months, 6 months, 9 months and 12 months, CD19 + and CD20 + lymphocyte counts were significantly decreased (all P<0.01), and gradually recovered after 6 months. Compared with baseline, at 3, 6, 9, 12 months after rituximab treatment, the level of blood IgG was significantly increased ( P=0.004,<0.001,<0.001,<0.001, respectively), and the level of blood IgM was significantly decreased ( P<0.001, =0.008, =0.005,<0.001, respectively) but the median level still within the normal range (400-3 450 mg/L). The level of blood IgA was not significantly changed (all P<0.05). T lymphocytes (CD3 +, CD3 +CD4 + and CD3 +CD8 +) and natural killer cells (CD56 +CD16 +) showed no significant difference from baseline (all P>0.05). Conclusions:Rituximab can effectively eliminate CD19 + and CD20 + lymphocytes, and has little influence on peripheral blood lymphocyte count and immunoglobulin level except CD19 + and CD20 + lymphocytes. The standard administration of rituximab is safe for patients with FSGS and MCD.

Peritoneal metastasis is one of the most frequent metastatic patterns of advanced gastric cancer, but the mechanism underlying remains unclear. The 'seed and soil’ theory is now well recognized for peritoneal metastasis of gastric cancer at present. The combination of various cells, extracellular matrix, and ascites components within the abdominal cavity provide a suitable microenvironment for the plantation, infiltra-tion, growth and metastasis of gastric cancer cells. Fully under-standing of peritoneal microenvironment will help to diagnose the peritoneal metastasis of gastric cancer and tumor recurrence, and provide theoretical basis for the development of drugs targeting peritoneal microenvironment. The authors review the main cell formation, ascites and immune microenvironment involved in the formation of the peritoneal microenvironment based on relevant literatures at home and abroad, and investigate the relationship between peritoneal microenvironment and peritoneal metastasis of gastric cancer.

Objective:In combination with 3D printing technology and degradable composite materials, to discuss the preparation method of tissue engineering ossicles for middle ear hearing reconstruction.Methods:Domestic polymer (polylactic acid-glycolic acid copolymer, PLGA) and degradable ceramic material (β-tricalcium phosphate, β-TCP) were selected and prepared by low temperature deposition method according to the design ratio to Program according to the outline design code of the required scaffold to generate appropriate print files, and then the self-developed low-temperature deposition printing device was used to prepare tissue-engineered osseous scaffolds in accordance with the print files in a low-temperature environment. The scaffolds was freeze-dried and sterilized for later use after printing. Light microscopy and scanning electron microscopy were used to observe the apparent characteristics and internal structure of the scaffolds and to check its pore size, porosity and mechanical properties.Results:After printing, a degradable scaffold was obtained. Under the optical microscope, it was a small cylindrical shape with a diameter of 1.5 mm and a length of 6.0 mm, and its surface had micropores. The degradable scaffold had a horizontal and vertical interlaced warp and weft structure, the wire spacing was 1.2 mm, and the pores were connected to each other. The surface could see circular or quadrangular pores with a pore size of about 100-400 μm. The diameter of the inter-pore cross-linked channels was about 50 μm and the diameter of the surrounding circular micropores was about 10-40 μm. β-TCP particles with a size of about 700 nm were attached to the surface of the PLGA material. The average porosity of the whole scaffolds was (83.43±0.01)%, and the content of BMP-2 loaded was about 0.7 μg/mm 3. After freeze-drying, the mechanical strength of the scaffold was moderate, and there was no obvious deformation during stretching and compression, which met the mechanical requirements of tissue engineering ossicles. Conclusions:Using the low-temperature deposition printing method and strictly controlled processes and conditions, a polymer-degradable ceramic ossicle tissue engineering scaffold can be prepared for implantation experiments. The scaffold has suitable porosity and mechanical properties, and can be loaded with osteoinductive factors.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Tanshinones are a class of bioactive components in the traditional Chinese medicine , and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper (bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the bZIP transcription factors involved in tanshinone biosynthesis are unknown. Here, we conducted the first genome-wide survey of the bZIP gene family and analyzed the phylogeny, gene structure, additional conserved motifs and alternative splicing events in A total of 70 SmbZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in . Moreover, seventeen genes underwent alternative splicing events. According to the transcriptomic data, the genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of bZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag treatment quantitative real-time polymerase chain reaction (qRT-PCR), we concluded that and potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate genes, which have the potential to increase tanshinone production.

Objective To investigate the diagnostic value of computer image analysis assisted aroundness measurement of gastric gland lumens in well-differentiated gastric adenocarcinoma.Methods From January 2016 to July 2016,10 hematoxylin-eosin (H-E) stained slides of pathologically diagnosed well-differentiated gastric adenocarcinoma were collected.At the same period,H-E stained slides of gastric epithelial hyperplasia and normal gastric mucosa,six slides of each,were collected as controls.All of them were scanned into high resolution.Digital data roundness,long diameter and short diameter were measured and compared.Kruskal-Wallis rank sum test was used for statistical analysis.Results The median values of lumen roundness of normal gastric mucosa,gastric epithelial hyperplasia and welldifferentiated gastric adenocarcinoma were 79.7°(10.6°),73.0°(12.3°) and 58.6°(15.2°),respectively,and the difference among three groups was statistically significant (H=494.827,P＜0.01).The values of gland roundness of normal gastric mucosa were higher than those of gastric mucosal hyperplasia and welldifferentiated gastric adenocarcinoma,and the differences were statistically significant (T=156.007 and -508.579,both P＜0.01).The value of gland roundness of gastric mucosal hyperplasia was higher than that of well-differentiated gastric adenocarcinoma,and the difference was statistically significant (T=-352.572,P＜0.01).The values of long diameter of gland lumens in normal gastric mucosa,gastric mucosal hyperplasia and well-differentiated gastric adenocarcinoma were 24.1 μm(11.8 μm),43.1 μm (28.8 μm),and 96.0 μm(79.3 μm),respectively,and the difference among three groups was statistically significant (H=744.987,P＜0.01).The values of short diameter of gland lumens in normal gastric mucosa,gastric mucosal hyperplasia and well-differentiated gastric adenocarcinoma were 16.0 μm (8.7 μm),22.7 μm (13.1 μm) and 33.5 μm (38.0 μm),respectively,and the difference among three groups was statistically significant(H=248.170,P＜0.01).Conclusion The roundness of gastric gland lumens can be used as an effective parameter for the differential diagnosis of normal gastric mucosa,gastric mucosal hyperplasia and well-differentiated gastric adenocarcinoma.

Background:As an important catalytic subunit of telomerase,human telomerase reverse transcriptase (hTERT)plays an important role in the development and progression of many cancers including gastric cancer.It has been reported that several single nucleotide polymorphisms (SNPs)of hTERT had varying degrees of association with risk of neoplasms. Aims:To study the correlation between SNPs of hTERT rs2853676 and rs2853677 and susceptibility to gastric cancer. Methods:Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of rs2853676 and rs2853677 of hTERT in 297 gastric cancer patients,105 atrophic gastritis and 402 controls. Helicobacter pylori (Hp)infection was detected by pathological examination and 13 C-urea breath test.Results:Frequency of AA genotype of rs2853676 was significantly higher in gastric cancer group when compared with control group (15.2%vs.6.5%,P =0.01).The risk of gastric cancer in AA genotype carriers increased 2.47-fold (95% CI:1.46-4.16) when compared with GG carriers.No significant differences in the frequencies of CC,TC and TT genotypes of rs2853677 were found among gastric cancer patients,atrophic gastritis patients and controls.Hp infection rates in atrophic gastritis group and gastric cancer group were significantly increased than those in controls (64.8%,56.9% vs.40.3%,P all <0.01),OR were 2.73 (95% CI:1.74-4.26),1.96 (95% CI:1.44-2.67),respectively.Logistic regression analysis showed that there was no significant interaction between Hp infection and gene mutation.Conclusions:Polymorphism of hTERT gene rs2853676 may play a role in susceptibility to gastric cancer,and Hp infection may not be involved in the increase of risk of gastric cancer caused by hTERT gene polymorphism.

Transcription factor is one of the key factors in the regulation of gene expression at the transcriptional level. It plays an important role in plant growth, active components biosynthesis and response to environmental change. This paper summarized the structure and classification of bHLH transcription factors and elaborated the research progress of bHLH transcription factors which regulate the active components in plants, such as flavonoids, alkaloids, and terpenoids. In addition, the possibility of increasing the concentration of active substances by bHLH in medicinal plants was assessed. The paper emphasized great significance of model plants and multidisciplinary research fields including modern genomics, transcriptomics, metabolomics and bioinformatics, providing the contribution to improve the discovery and function characterization of bHLH transcription factors. Accelerating the research in the mechanism of bHLH transcription factors on the regulation of active components biosynthesis will promote the development of breeding and variety improvement of Chinese medicinal materials, also ease the pressure of resources exhaustion of traditional Chinese medicine home and abroad.

The medicinal fungi, which are of great importance in traditional medicine, are facing the problems of wild resources scarcity and low concentration of bioactive compounds. Velvet family and LaeA global regulator play a vital role in secondary metabolism and developmental programs, which are found in a wide variety of fungi ranging from Chytridiomycota to Basidiomycota. This review elaborates the structures and functions between Velvet family and LaeA protein. The Velvet family which shares the Velvet protein domain, including VeA (Velvet), VelB (Velvet like B), VosA (viability of spores A) and VelC (Velvet like C), acts on the regulation function is secondary metabolism and developmental programs such as asexual and sexual development. Furthermore, the function is affected by environmental factors such as light and temperature. LaeA protein which owns S-adenosylmethionine-dependent methyltransferase domain, coordinately regulates development and secondary metabolism by regulating and modifying the Velvet proteins. The regulation of LaeA is mediated by light receptor proteins. Therefore, clarifying the mechanism of Velvet and LaeA proteins in medicinal fungi will pave the way for nurturing medicinal fungi and improving production of bioactive compounds.