Parametric Control via the Algebraic Expression of Lotus-Type Pore Shapes in Metals.

Lotus-type porous metals, characterized by low densities, large surface areas, and directional properties, are contemporarily utilized as lightweight, catalytic, and energy-damping materials; heat sinks; etc. In this study, the effects of dimensionless working parameters on the morphology of lotus-type pores in metals during unidirectional solidification were extensively investigated via general algebraic expressions. The independent dimensionless parameters include metallurgical, transport, and geometrical parameters such as Sieverts' law constant, a partition coefficient, the solidification rate, a mass transfer coefficient, the imposed mole fraction of a solute gas, the total pressure at the top free surface, hydrostatic pressure, a solute transport parameter, inter-pore spacing, and initial contact angle. This model accounts for transient gas pressure in the pore, affected by the solute transfer, gas, capillary, and hydrostatic pressures, and Sieverts' laws at the bubble cap and top free surface. Solute transport across the cap accounts for solute convection at the cap and the amount of solute rejected by the solidification front into the pore. The shape of lotus-type pores can be described using a proposed fifth-degree polynomial approximation, which captures the major portions between the initial contact angle and the maximum radius at a contact angle of 90 degrees, obtained by conserving the total solute content in the system. The proposed polynomial approximation, along with its working parameters, offers profound insights into the formation and shape of lotus-type pores in metals. It systematically provides deep insights into mechanisms that may not be easily revealed with experimental studies. The prediction of a lotus-type pore shape is thus algebraically achieved in good agreement with the available experimental data and previous analytical results.

Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer.

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.

Molecular Regulatory Network of Anthocyanin Accumulation in Black Radish Skin as Revealed by Transcriptome and Metabonome Analysis.

To understand the coloring mechanism in black radish, the integrated metabolome and transcriptome analyses of root skin from a black recombinant inbred line (RIL 1901) and a white RIL (RIL 1911) were carried out. A total of 172 flavonoids were detected, and the analysis results revealed that there were 12 flavonoid metabolites in radish root skin, including flavonols, flavones, and anthocyanins. The relative concentrations of most flavonoids in RIL 1901 were higher than those in RIL 1911. Meanwhile, the radish root skin also contained 16 types of anthocyanins, 12 of which were cyanidin and its derivatives, and the concentration of cyanidin 3-o-glucoside was very high at different development stages of black radish. Therefore, the accumulation of cyanidin and its derivatives resulted in the black root skin of radish. In addition, a module positively related to anthocyanin accumulation and candidate genes that regulate anthocyanin synthesis was identified by the weighted gene co-expression network analysis (WGCNA). Among them, structural genes (RsCHS, RsCHI, RsDFR, and RsUGT75C1) and transcription factors (TFs) (RsTT8, RsWRKY44L, RsMYB114, and RsMYB308L) may be crucial for the anthocyanin synthesis in the root skin of black radish. The anthocyanin biosynthesis pathway in the root skin of black radish was constructed based on the expression of genes related to flavonoid and anthocyanin biosynthesis pathways (Ko00941 and Ko00942) and the relative expressions of metabolites. In conclusion, this study not only casts new light on the synthesis and accumulation of anthocyanins in the root skin of black radish but also provides a molecular basis for accelerating the cultivation of new black radish varieties.

Controllable Crystal Growth and Improved Photocatalytic Activity of Porous Bi2O3-Bi2S3 Composite Sheets.

Porous Bi2O3-Bi2S3 composite sheets were constructed through a combinational methodology of chemical bath deposition and hydrothermal reaction. The Na2S precursor concentration in the hydrothermal solution was varied to understand the correlation between the vulcanization degree and structure evolution of the porous Bi2O3-Bi2S3 composite sheets. The control of the etching rate of the Bi2O3 sheet template and the regrowth rate of Bi2S3 crystallites via suitable sulfide precursor concentration during the hydrothermal reaction utilizes the formation of porous Bi2O3-Bi2S3 sheets. Due to the presence of Bi2S3 crystallites and porous structure in the Bi2O3-Bi2S3 composites, the improved visible-light absorption ability and separation efficiency of photogenerated charge carriers are achieved. Furthermore, the as-synthesized Bi2O3-Bi2S3 composite sheets obtained from vulcanization with a 0.01M Na2S precursor display highly enhanced photocatalytic degradation toward methyl orange (MO) dyes compared with the pristine Bi2O3 and Bi2S3. The porous Bi2O3-Bi2S3 sheet system shows high surface active sites, fast transfer, high-efficiency separation of photoinduced charge carriers, and enhanced redox capacity concerning their constituent counterparts. This study affords a promising approach to constructing Bi2O3-based Z-scheme composites with a suitable microstructure and Bi2O3/Bi2S3 phase ratio for photoactive device applications.

HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms.

Triple-negative breast cancer (TNBC) is a great detriment to women's health due to the lack of effective therapeutic targets. In this study, we employed an integrated genetic screen to identify a pivotal oncogenic factor, heterogeneous nuclear ribonucleoprotein U (HNRNPU), which is required for the progression of TNBC. We elucidated the pro-oncogenic role of HNRNPU, which can induce the proliferation and migration of TNBC cells via its association with DEAD box helicase 5 (DDX5) protein. Elevated levels of the HNRNPU-DDX5 complex prohibited the intron retention of minichromosome maintenance protein 10 (MCM10) pre-mRNA, decreased nonsense-mediated mRNA decay, and activated Wnt/ß-catenin signalling; on the other hand, HNRNPU-DDX5 is located in the transcriptional start sites (TSS) of LIM domain only protein 4 (LMO4) and its upregulation promoted the transcription of LMO4, consequently activating PI3K-Akt-mTOR signalling. Our data highlight the synergetic effects of HNRNPU in RNA transcription and splicing in regulating cancer progression and suggest that HNRNPU may act as a potential molecular target in the treatment of TNBC.

Crystal Design and Photoactivity of TiO2 Nanorod Template Decorated with Nanostructured Bi2S3 Visible Light Sensitizer.

In this study, TiO2-Bi2S3 composites with various morphologies were synthesized through hydrothermal vulcanization with sputtering deposited Bi2O3 sacrificial layer method on the TiO2 nanorod templates. The morphologies of decorated Bi2S3 nanostructures on the TiO2 nanorod templates are controlled by the duration of hydrothermal vulcanization treatment. The Bi2S3 crystals in lumpy filament, nanowire, and nanorod feature were decorated on the TiO2 nanorod template after 1, 3, and 5 h hydrothermal vulcanization, respectively. Comparatively, TiO2-Bi2S3 composites with Bi2S3 nanowires exhibit the best photocurrent density, the lowest interfacial resistance value and the highest photodegradation efficiency towards Rhodamine B solution. The possible Z-scheme photoinduced charge separation mechanism and suitable morphology of Bi2S3 nanowires might account for the high photoactivity of TiO2 nanorod-Bi2S3 nanowire composites.

Clinicopathological Characteristics and Survival Outcomes of Mammary Paget's Disease: A Retrospective Study Based on a Chinese Population.

BACKGROUND: Mammary Paget's disease (PD) is a rare type of breast cancer. Most cases of PD are presented with underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IDC). This study aimed to investigate the clinicopathological characteristics and survival outcomes of PD patients. MATERIALS AND METHODS: A total of 406 patients diagnosed with PD with IDC/DCIS at Fudan University Shanghai Cancer Center (FUSCC) were recruited as the PD group, 1218 patients diagnosed with IDC/DCIS alone during the same period were selected as the non-PD group, and the clinicopathological results of these two groups were compared. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the clinicopathological features between PD and non-PD patients for validation. RESULTS: Compared with the non-PD group, the PD group was much more likely to have larger (≥2 cm: 43.1% vs 35.5%, P < 0.001), less hormone receptor (HR)-positive (68.5% vs 26.6%, P < 0.001), more human epidermal growth factor receptor-2 (HER-2)-positive (70.7% vs 27.5%, P < 0.001) and higher Ki-67 proportion (51.5% vs 42.5%, P < 0.001) tumors. The HER-2 overexpression subtype accounted for the largest proportion in the PD-IDC group and the lowest proportion in the non-PD-IDC group (54% vs 8%, P < 0.01). Moreover, the PD group had significantly worse disease-free survival (DFS) than the non-PD group (5-year DFS: 91.8% vs 97.3%, P = 0.001), and the SEER database showed a similar trend. Univariate and multivariate Cox regression analyses demonstrated that PD was an independent poor-risk factor. Our matched study showed that the PD group had worse survival than the non-PD group after excluding age, HR, HER-2, tumor size and lymph node status. CONCLUSION: PD with IDC/DCIS is associated with more aggressive tumor characteristics and worse survival outcomes. More than half of PD breast cancers are HER-2 overexpression subtype. PD is an independent poor-risk factor for breast cancer survival.

Clinical features and survival of pregnancy-associated breast cancer: a retrospective study of 203 cases in China.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is an aggressive disease, and since Chinese authority began to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. METHODS: Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled. Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. RESULTS: Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it's 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P < 0.001) as follows: in the PABC patients, Luminal B 38.4%, Triple negative breast cancer (TNBC) 30.1%, Human Epidermal Growth Factor Receptor 2 (HER-2) overexpression 15.8%, and Luminal A 10.8%; in the non-PABC patients, Luminal A 50.9%, Luminal B 20.1%, TNBC 17.4%, and HER-2 overexpression 8.0%. The 3-year disease free survival (DFS) of all PABC patients was 80.3%. The 3-year DFS of the patients in the first-pregnancy group was 78.4%, and that of the patients in the non-first-pregnancy group was 83.7% (P = 0.325). CONCLUSIONS: Our study proved that the proportion of women who developed PABC during the second or third pregnancy was extremely high relative to the newborn populations. The patients in the PABC population tended to present more luminal B and TNBC breast cancer than the non-PABC patients.

Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25-100 µM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg-1 ·d-1, sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD.

The clinical significance of Msi1 gene and its biological role in colon cancer / 医学研究生学报

Objective　At present, the clinical significance and biological function of Msi1 (Musashi1) in colon cancer are still not very clear. So, a comprehensive understanding of the expression and role of Msi1 in colon cancer has important clinical and theoretical significance. This study is to investigate the clinical significance of Msi1 gene and its biological role in colon cancer by lentiviral vector to interfere with Msi1 gene expression in colon cancer SW480 cells.　Methods　20 colon cancer specimens were collected from the Second Surgery Department of the Fourth Hospital of Hebei Medical University from October 2013 to May 2014. Each specimen was collected from the cancer tissue and the adjacent intestinal wall tissue. Western blot was performed to determine the protein expression of Msi1 in tumor tissues and adjacent normal tissues from colon cancer patients. The relationship between Msi1 protein expression and clinical characteristics was further analyzed. The lentiviral vector was used to construct a stable SW480 cell line with low expression of Msi1. The lentivirus containing two different interference sequences (shmsi1-1 and shmsi1-2) was transfected into the target cells, and the colon cancer cells were divided into control group (without any treatment), shMsi1-1 group (transfected shMsi1-1) and shMsi1-2 group (transfected shMsi1-2). The two lentivirus silencing effects were detected by Western blot. Cell proliferation was detected by CCK-8 assay, Clone formation assay was conducted to detect the colony forming ability, and Flow cytometry analysis was used to examine the apoptosis rate.　Results　The protein expression of Msi1 in colon cancer tissue(0.863±0.208) was significantly higher than that in adjacent normal tissues(0.272±0.078), and the difference was statistically significant(P<0.001). The relative expression of Msi1 protein in shMsi1-1 and shMsi1-2 groups (0.299±0.111 and 0.207±0.087) was significantly lower than that in the control group (1.000±0.149) (P<0.001). The proliferation rate of shMsi1-1 and shMsi1-2 at 48 h and 72 h was significantly lower than that of the control group (P<0.01). Compared with the control group (296.33±64.04), shMsi1-1 group (92.00±43.31) and shMsi1-2 group (78.67±32.87) were significantly decreased (P<0.01). Compared with the control group [(4.01±0.26) %], the apoptosis rate of shMsi1-1 group, shMsi1-2 group [(10.22±1.04) %, (10.87±1.27) %] was significantly increased (P<0.001).　Conclusion　Interference with Msi1 gene expression inhibits proliferation of colon cancer SW480 cells and promotes tumor cell apoptosis. This finding provides a new intervention target for the clinical treatment of colon cancer.

Application of indocyanine green in complex upper urinary tract repair surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery.@*METHODS@#This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty.@*RESULTS@#All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal.@*CONCLUSION@#The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.

Application of 3D printing in the flipped classroom in practice teaching of otolaryngology-head and neck surgery / 中华医学教育探索杂志

Objective To investigate the application of 3D printing in the flipped classroom in the practice teaching of otolaryngology-head and neck surgery. Methods A total of 68 medical undergraduates of the Grade 2013 in Air Force Medical University were divided into experimental group and control group, with 34 undergraduates in each group. The undergraduates in the experimental group received the teaching method of 3D printing in the with flipped classroom , and those in the control group received traditional teaching. The teaching effect was evaluated by questionnaire and examinations of basic knowledge and clinical skills, Independent-samples t test was used for between-group comparison with SPSS 20.0. Results Compared with the control group , the experimental group had significantly higher scores in theoretical examinations (34.79 ±2.20 vs. 31.73 ±3.12, t=4.676, P=0.000) and clinical skill examination (50.06 ±2.98 vs. 45.82 ±4.68, t=4.449, P=0.000). The questionnaire survey showed that among the 34 undergraduates in the experimental group, 31(91.2％) thought that the new teaching method could increase their learning interest, 33 (97.0％) believed it could improve learning efficiency, 25 (73.5％) believed the models obtained by 3D printing had good quality, 32 (94.1％) felt that it could improve clinical skills, 28 (82.4％) thought it could enhance the interaction between students and teachers, and 29(85.3％) thought it did not bring extra burden. Conclusion The teaching method of 3D printing combined with flipped classroom in the practice teaching of otolaryngology-head and neck surgery can improve students' learning interest, academic scores, and clinical skills, and therefore, it holds promise for application in teaching.

Application of 3D printing in the flipped classroom in practice teaching of otolaryngology-head and neck surgery / 中华医学教育探索杂志

Objective@#To investigate the application of 3D printing in the flipped classroom in the practice teaching of otolaryngology-head and neck surgery.@*Methods@#A total of 68 medical undergraduates of the Grade 2013 in Air Force Medical University were divided into experimental group and control group, with 34 undergraduates in each group. The undergraduates in the experimental group received the teaching method of 3D printing in the with flipped classroom, and those in the control group received traditional teaching. The teaching effect was evaluated by questionnaire and examinations of basic knowledge and clinical skills, Independent-samples t test was used for between-group comparison with SPSS 20.0.@*Results@#Compared with the control group, the experimental group had significantly higher scores in theoretical examinations (34.79±2.20 vs. 31.73±3.12, t=4.676, P=0.000) and clinical skill examination (50.06±2.98 vs. 45.82±4.68, t=4.449, P=0.000). The questionnaire survey showed that among the 34 undergraduates in the experimental group, 31(91.2%) thought that the new teaching method could increase their learning interest, 33(97.0%) believed it could improve learning efficiency, 25(73.5%) believed the models obtained by 3D printing had good quality, 32(94.1%) felt that it could improve clinical skills, 28 (82.4%) thought it could enhance the interaction between students and teachers, and 29(85.3%) thought it did not bring extra burden.@*Conclusion@#The teaching method of 3D printing combined with flipped classroom in the practice teaching of otolaryngology-head and neck surgery can improve students' learning interest, academic scores, and clinical skills, and therefore, it holds promise for application in teaching.

Transcription profiling and identification of infection-related genes in Phytophthora cactorum.

Phytophthora cactorum, an oomycete pathogen, infects more than 200 plant species within several plant families. To gain insight into the repertoire of the infection-related genes of P. cactorum, Illumina RNA-Seq was used to perform a global transcriptome analysis of three life cycle stages of the pathogen, mycelia (MY), zoospores (ZO) and germinating cysts with germ tubes (GC). From over 9.8 million Illumina reads for each library, 18,402, 18,569 and 19,443 distinct genes were identified for MY, ZO and GC libraries, respectively. Furthermore, the transcriptome difference among MY, ZO and GC stages was investigated. Gene ontology (GO) and KEGG pathway enrichment analyses revealed diverse biological functions and processes. Comparative analysis identified a large number of genes that are associated with specific stages and pathogenicity, including 166 effector genes. Of them, most of RXLR and NLP genes showed induction while the majority of CRN genes were down-regulated in GC, the important pre-infection stage, compared to either MY or ZO. And 14 genes encoding small cysteine-rich (SCR) secretory proteins showed differential expression during the developmental stages and in planta. Ectopic expression in the Solanaceae indicated that SCR113 and one elicitin PcINF1 can trigger cell death on Nicotiana benthamiana, tobacco (N. tabacum) and tomato (Solanum lycopersicum) leaves. Neither conserved domain nor homologues of SCR113 in other organisms can be identified. Collectively, our study provides a comprehensive examination of gene expression across three P. cactorum developmental stages and describes pathogenicity-related genes, all of which will help elucidate the pathogenicity mechanism of this destructive pathogen.

Establishment and verification of fluctuation of reference intervals for biochemistry parameters in routine physical examina-tion / 临床检验杂志

Objective To establish and verify the fluctuation of reference intervals for biochestry parameters in routine physical exami-nation. Methods The results of biochemistry parameters,i.e., total protein (TP), albumin (Alb), total bilirubin (T-Bil), alanine aminotransferase (ALT), glucose (Glu), urea (Urea), creatinine (Cr), uric acid (UA), triacylglycerol (TG) and total cholesterol ( TC) from 2 089 healthy subjects in routine physical examination during consecutive 2014, 2015 and 2016 were randomly collected, in which all the results were within the reference range. The ratio (λ1) of the results of 2015 to those of 2014, and ratio (λ2) of the re-sults of 2016 to those of 2015 were calculated. λ1was analyzed statistically to establish the fluctuation of reference interval (CIλ). CIλ was verified by λ2.The personalized reference interval (CIp) was established by multiplying each result of 2015 and the upper and low-er limits of CIλ. The CIpwas verified by the results of 2016. The ratios of CIpto the upper and lower limits of conventional reference in-terval were calculated. Results The values of CIλwere as follows: TP: 0.91 to 1.08, Alb: 0.91 to 1.08, T-Bil: 0.58 to 1.74, ALT:0.49 to 1.99, Glu: 0.84 to 1.20, Urea: 0.67 to 1.50, Cr: 0.82 to 1.22, UA: 0.77 to 1.32, TG: 0.51 to 1.98 and TC: 0.80 to 1.26. Compared with conventional reference interval, the ratio of the upper and lower limits of CIp was lessened. Conclusion The personal-ized reference interval (CIp) which may increase the sensitivity of conventional reference intervals was established and verified.

Renal protective effect of Ganoderma lucidum / 中国药理学与毒理学杂志

OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho-logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel-lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha-ride peptide (GLPP) has therapeutic effect on NAFLD. METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic path-ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato-cytes induced by oleic acid and palmitic acid. CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.

Establishment and verification of personalized reference interval of blood cells / 临床检验杂志

Objective To establish and verify the personalized reference interval of blood cells.Methods The results of blood cells from 2 089 health subjects in 2014,2015 and 2016 were collected.The ratio of the later results to the previous results was defined as the fluctuation (λ).The ratio (λ1) of the results of 2015 to the results of 2014 was calculated and λ1 was analyzed statistically to establish the fluctuation reference interval (CIλ).The ratio (λ2) of the results of 2016 to the results of 2015 was calculated.λ2 was used to verify λ2.The personalized reference interval (CIp) was established by multiplying each result of 2015 and CIλ.CIp was verified by results of 2016.The ratio of the upper and lower limits of CIp was calculated.The ratio of the upper and lower limits of the reference interval (WS/T 405) was calculated.Results The values of CIλ were as follows:WBC (0.66 to 1.53),L(0.67 to 1.51),M (0.50 to 2.00),N(0.56 to 1.78),E(0.4 to 2.51),PLT(0.76 to 1.32),RBC(0.92 to 1.12),Hb(0.92 to 1.11),Hct(0.91 to 1.12),MCV(0.95 to 1.07),MCH(0.95 to 1.05)and MCHC(0.94 to 1.06).The validation tests of CIλ and CIp showed that both CIλ and CIp were suitable for this laboratory.Compared with the reference interval of professional criteria,the ratio of the upper and lower limits of the CIp was smaller than that of traditional criteria.Conclusion CIp for this laboratory was established and verified.Compared with traditional criteria,CIp should be more personalized and highly sensitive.

Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sj(o)gren's syndrome: a case report / 北京大学学报(医学版)

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung.The underlying pathogene sis of ILDs is complex and associated with multiple rheumatologic conditions,such as systemic sclerosis,rheumatoid arthritis,pollymyositis and dermatomyositis,Sjt(o)gren's syndrome,and systemic lupus erythematosus.As the disease progresses,excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function.The common methods to diagnose ILDs,such as clinical manifestations,pulmonary function test,and radiological examinations are not specific for ILDs and not able to diagnose ILDs at the early stage due to their low sensitivity.So,the easy way is important to diagnose ILDs.One important biomarker for ILDs is the high-molecular-weight glycoprotein,Krebs von den Lungen-6 (KL-6).KL-6 encoded by the MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed predominantly on the cell surface of type Ⅱ alveolar epithelial cells,and is detectable in the serum of patients with ILDs.We here report a case of ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome.A 60-year-old woman was admitted to our hospital with the chief complaints of debilitation,dry mouth,dyspnea and astasia.ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome was diagnosed clinically when the following criteria were satisfied:(1) development of dyspnea within 2 months of presentation,(2) pulmonary dispersion dysfunction,(3) bilateral infiltrative shadows on chest high resolution computed tomography (HRCT).She was treated with prednisone 50 mg/d prior to admission,but the result of therapy was not good.In our hospital she was treated with intravenous methylprednisolone and cyclophosphamide and oral hydroxychloroquine sulfate.Subsequently,her serum KL-6 levels gradually decreased after treatment,pulmonary diffuse function improved,and the improvement in the clinical manifestation and HRCT findings were observed.Nevertheless,the combination treatment of glucocorticoid and cyclophosphamide had contributed to the favourable outcomes.In conclusion,detection of serum KL-6 levels in ILDs associated with connective tissue diseases may be beneficial to making a definitive diagnosis,predicting the prognosis and monitoring the disease activity,which would be of great help in clinical practice.However,a well-designed clinical study with more patients and a longer follow-up period are required to arrive at a more conclusive judgment on the role of serum KL-6 in patients with ILDs.

A retrospective study on post-operative hearing of middle ear cholesteatoma patients with labyrinthine fistula.

CONCLUSIONS: There is no significant change in bone conduction threshold after operation, so the tympanoplasty can be done to maintain hearing when conditions allow. OBJECTIVE: To study the impact of surgical treatment on hearing of cholesteatoma patients with labyrinthine fistula. METHODS: The clinical data of 35 patients (35 ears) with labyrinthine fistula, which were caused by cholesteatoma, were analyzed retrospectively. The hearing of 21 patients was followed up. RESULTS: Three months to 5 years follow-up of 21 patients were accomplished by pure tone audiometry and other details. There was no recurrent cholesteatoma in the patients. Compared with pre-operative average bone conduction at 0.5, 1, 2, 4, and 8 kHz, 12 cases had a difference less than 5 dB, three patients' hearing improved (more than 10 dB), and five cases declined (more than 10 dB). One patient received cochlear implantation 3 months after the surgery. The average bone and air conduction thresholds at 0.5, 1, 2, 4, and 8 kHz had no obvious change (p > 0.05) in 11 patients managed by a canal wall down mastoidectomy with tympanoplasty.

Bioconjugated persistent luminescence nanoparticles for Föster resonance energy transfer immunoassay of prostate specific antigen in serum and cell extracts without in situ excitation.

A novel Föster resonance energy transfer (FRET) immunoassay based on persistent luminescence nanoparticles (PLNP) was established for prostate specific antigen (PSA) detection in serum and cell extracts without in situ excitation. The specific FRET behavior allows highly selective and sensitive ratiometric photoluminescent detection of PSA in biological samples.