[The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy: a prospective multicenter study].

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

[Development of a nomogram for predicting the risk of colorectal advanced adenomas].

Objective: To explore the risk factors of colorectal advanced adenomas (AA) and construct a nomogram to predict the risk of colorectal AAs. Methods: Clinical data of patients were retrospectively collected who underwent their first colonoscopy from January 2017 to December 2020 in the First Affiliated Hospital of Nanjing Medical University and were pathologically confirmed harboring colorectal polyps. A credible random split-sample method was used to divide data into training and validation cohorts (split ratio=7∶3). Univariate and multivariate logistic regression analysis were used to identify the predictors of colorectal advanced adenomas, and a nomogram was developed based on the above results. The validation cohort was used for internal validation of the nomogram. The discriminatory value of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The consistency between actual outcomes and predicted probabilities was evaluated by the calibration curve. The clinical validity of the model was evaluated by the decision analysis curve (DCA). Results: A total of 1 936 patients with colorectal polyps were eligible. Including 1 356 patients in the training cohort (840 males and 516 females), and 580 patients in the validation cohort (379 males and 201 females), with the mean ages of (57.4±9.8) and (57.6±9.7) years, respectively. There were 1 502 (77.6%) patients without AAs and 434 [22.4%,1-9 mm 73(16.8%) cases、>9-<20 mm 271(62.5%) cases、≥20 mm 90(20.7%) cases] patients with AAs. The regression analysis found that age (OR=1.018, 95%CI:1.003-1.033), fatty liver (OR=1.870, 95%CI:1.274-2.744), low-density lipoprotein (LDL) (OR=1.378, 95%CI:1.159-1.637), fecal occult blood test (FOBT) (OR=2.597, 95%CI:1.857-3.631), and location of adenomas [proximal (OR=2.869, 95%CI:1.727-4.764), distal (OR=2.791, 95%CI:1.721-4.527)] were identified as predictors of colorectal AAs. The AUC of the nomogram was 0.664 (95%CI:0.630-0.698) in the training cohort and 0.640 (95%CI:0.587-0.693) in the validation cohort. The calibration curve showed good consistency between the predicted and actual risk, and the Hosmer-Lemeshow (H-L) test P value was 0.830 and 0.150 in the training cohort and the validation cohort. DCA demonstrated that the nomogram had a better clinical application value. Conclusions: A nomogram with five predictors, including age, fatty liver, LDL, FOBT, and location of adenomas, helped predict the risk of colorectal AAs in patients with polyps and implemented colorectcal cancer stratified screening strategy for colonoscopy in the high-risk population.

[The application of energy adjustment models in nutritional epidemiology].

The energy adjustment models in nutritional epidemiological studies could substantially reduce the confounding effect of total energy intake from the intake of dietary components, and it could explore the real relationship between the intake of dietary component and research outcomes. Four energy adjustment models were introduced in this article, including the standard multivariate model, multivariate nutrient residual model, energy partition model, and multivariate nutrient density model. The four energy adjustment models were applied to analyze the association between the intake of saturated fatty acids and the risk of all-cause mortality based on the data of the US National Health and Nutrition Examination Survey. The consistent results of different energy adjustment models could indicate that the four models could better control the confounding effect of total energy intake.

The MTase15 regulates reproduction in the wing-dimorphic planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

S-Adenosyl-l-methionine-dependent methyltransferases (SAMMTases) modulate important cellular and metabolic activities in both prokaryotes and eukaryotes. Here, we functionally characterized an SAMMTase gene (MTase15) in the migratory brown planthopper (BPH), Nilaparvata lugens, which is the most notorious rice pest in Asia. The cDNA sequence of MTase15 is 2764 nt in length with an open reading frame of 1218 nt encoding 405 amino acid residues. Quantitative real-time PCR analysis showed that MTase15 was readily detected from egg to adult stages and extensively distributed in various body parts of adult females and males, with slightly high levels in ovary and testis, respectively. In addition, MTase15 was transcriptionally regulated by the insulin signalling pathway in BPH. RNA-interference-mediated knockdown of MTase15 (dsMtase15) resulted in deficiencies in vitellogenin synthesis and oogenesis, and female infertility. Males with Mtase15 knockdown retained the capability of producing sperms with normal viability, but less sperm was transferred to wild-type (wt) females during copulation, and eggs laid by these wt females arrested embryogenesis. These findings not only assign a functional role to MTase15, but also provide a link between the insulin signalling pathway and epigenetic regulation in BPH reproduction.

Effects of tetramethylpyrazine phosphate on pancreatic islet microcirculation in SD rats.

PURPOSES: Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats. METHODS: SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose. The non-radioactive microsphere technique was adopted to measure the organ blood flow. Nitric oxide synthase (NOS) blocker L-NAME was used to address whether NO was involved in mediating the vasoactive effects of TMPP. RESULTS: In the TMPP group, TMPP increased the PBF (pancreatic blood flow), IBF (islet blood flow), and fIBF (fraction of islet blood flow out of pancreatic blood flow) by 57, 76 and 47%, respectively, after 30% glucose infusion, compared with the control, indicating that TMPP could regulate islet microcirculation. Furthermore, TMPP induced a 66% elevation of IBF and 37% of fIBF in the 30% glucose subgroups than the 15% ones. In 30% glucose-treated subgroups, TMPP improved the blood glucose concentration by 10%, compared with the control (19.3 ± 0.64 vs 17.32 ± 0.56 mmol/l, P < 0.05), without influencing the insulin secretion. Blocking NO formation prevented the enhanced PBF and IBF, evoking by TMPP with 30% glucose. CONCLUSIONS: TMPP can regulate the pancreatic islet microcirculation and possess a hypoglycemia effect after glucose infusion through affecting the islet microcirculation.

[Research progress of oral anticoagulants in patients with liver diseases].

Patients with liver disease are at an increased risk of both embolism and bleeding. The optimal anticoagulation strategy remains unclear when associated with venous thromboembolic disease. Moreover, currently approved oral anticoagulant drugs undergo metabolism and elimination in the liver with varying degrees of hepatic dysfunction. Thus, impaired liver function may lead to increased risk of bleeding, making anticoagulant therapy more intricate. This article summarizes the risk of bleeding and thrombosis in patients with liver disease, and the clinical research progress of oral anticoagulants in patients with liver disease to facilitate evidence for choosing oral anticoagulants therapy when required.

[Establishment of DNA Genetic Marker Identification System for Plant Evidence].

OBJECTIVES: To establish a species identification system based on DNA genetic markers for plant evidence. METHODS: Two hundred common plants in Shanghai were collected and identified by morphological characteristics. The primers of gene segments rbcL, matK, and ITS were designed and amplified. The PCR amplicon was detected by agarose gel electrophoresis. After the sequencing, the universality and the identification capacity of the three markers were evaluated. RESULTS: The success rate of amplification was in order of rbcL （99.5%） > matK （92.5%） > ITS （86.0%）. The identification capacity of the combination of rbcL and matK was better than that of rbcL or matK, by which most plant species could be identified to the genus or higher. ITS was not suitable to be a unique marker because of its unstable result, but it still could be a powerful supplement. The identification capacity of the combination of rbcL, matK and ITS was higher than that of rbcL and matK, by which most plant species could be identified to the genus or lower. CONCLUSIONS: The identification system with the combination of rbcL, matK and ITS as markers has excellent universality for plant evidence, which can distinguish most plant species to the genus or lower.

Structure similarity-guided image binarization for automatic segmentation of epidermis surface microstructure images.

Partitioning epidermis surface microstructure (ESM) images into skin ridge and skin furrow regions is an important preprocessing step before quantitative analyses on ESM images. Binarization segmentation is a potential technique for partitioning ESM images because of its computational simplicity and ease of implementation. However, even for some state-of-the-art binarization methods, it remains a challenge to automatically segment ESM images, because the grey-level histograms of ESM images have no obvious external features to guide automatic assessment of appropriate thresholds. Inspired by human visual perceptual functions of structural feature extraction and comparison, we propose a structure similarity-guided image binarization method. The proposed method seeks for the binary image that best approximates the input ESM image in terms of structural features. The proposed method is validated by comparing it with two recently developed automatic binarization techniques as well as a manual binarization method on 20 synthetic noisy images and 30 ESM images. The experimental results show: (1) the proposed method possesses self-adaption ability to cope with different images with same grey-level histogram; (2) compared to two automatic binarization techniques, the proposed method significantly improves average accuracy in segmenting ESM images with an acceptable decrease in computational efficiency; (3) and the proposed method is applicable for segmenting practical EMS images. (Matlab code of the proposed method can be obtained by contacting with the corresponding author.).

A SNP in the 3'-UTR of HSF1 in dairy cattle affects binding of target bta-miR-484.

The heat shock transcription factor 1 gene (HSF1) plays a key role in the heat stress response. We previously found a single nucleotide polymorphism (SNP) in the 3'-untranslated region (g.4693G>T) of HSF1 that was related to thermo tolerance in Chinese Holstein cattle through association analysis. However, it is not known whether other SNPs also affect thermo tolerance.In this study a novel SNP, g.1451G>T, was identified by DNA sequencing and genotyped using creating restriction site-polymerase chain reaction methodology. The g.1451G>T polymorphic site met Hardy-Weinberg equilibrium (P > 0.05). Association analysis demonstrated that this SNP had no effect on thermo tolerance traits in Holstein cattle. Findings of the study compared to the analysis of g.4693 G>T further indicated that g.4693 G>T may play an important role in thermo tolerance, although the mechanism is not clear. RNA hybrid and Targetscan prediction showed that the minimum free energy hybridization of bta-miR-484 with HSF1 3'-UTR was -31.9 kcal/mol and g.4693 G>T was in the seed sequence of bovine HSF1 that binds to bta-miR-484. Analysis by Luciferase assay indicated that HSF1 expression was directly targeted by bta-miR-484 in HEK 293T cells, and the Rluc/luc ratio of wildtype (GG) was lower than that of the mutant (TT) (P < 0.05). These results suggest that g.4693 G>T affects binding of HSF1 to bta-miR-484.

Blockade of S100A3 activity inhibits murine hair growth.

Using mouse gene expression microarray analysis, we obtained dynamic expression profiles of the whole genome in a depilation-induced hair growth mouse model. S100A3 expression increased during the anagen phase and returned to normal during the telogen phase. The effects of S100A3 blockade on the hair growth cycle were examined in mice after subcutaneous injection of an anti-mouse S100A3 antibody. Protein localization of S100A3 was confined to the hair shafts during the anagen phase and the sebaceous glands during the telogen phase. S100A3 blockade delayed hair follicle entry into the anagen phase, decreased hair elongation, and reduced the number of hair follicles in the subcutis, which correlated with the downregulated expression of hair growth induction-related genes in vivo. The present study demonstrates that anti-S100A3 antibody inhibits mouse hair growth, suggesting that S100A3 can be used as a target for hair loss treatment.

Estrogen defines the dynamics and destination of transactivated EGF receptor in breast cancer cells: role of S1P3 receptor and Cdc42.

Sphingosine-1-phosphate (S1P) receptors mediate transactivation of epidermal growth factor receptor (EGFR) by estrogen (E2). Here we report that the amount of intracellular EGFR remains elevated after stimulation of MCF-7 cells with E2 and S1P, although membrane-localized EGFR and S1P3 receptors are quickly internalized. Co-localization of internalized EGFR and LAMP-2 was lower in cells treated with E2/S1P, suggesting that endosomal EGFR might be directed for recycling instead of degradation. In addition, we found that E2/S1P activated Cdc42 and that knockdown of Cdc42 restores fast EGFR degradation after E2/S1P stimulation. Inhibition of S1P3 receptors prevented E2-induced activation of Cdc42, supporting the important role of the S1P receptor in E2 signaling. This is a novel mechanism further defining the effect of E2/S1P on the EGFR transactivation in breast cancer cells.

Tumour budding is a reproducible index for risk stratification of patients with stage II colon cancer.

AIM: High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but it is difficult to identify such a patient group. A robust and reproducible index would be helpful to select the subset of Stage II colon cancer patients at high risk. This study investigated the potential prognostic significance of tumour budding in Stage II colon cancer. METHOD: In all, 135 Stage II colon cancer patients with known outcome were identified. The degree of tumour budding was assessed by two individual observers and was classified, according to the number of tumour buds in the area with the greatest budding intensity on haematoxylin and eosin slides, as high-grade budding (10 or more tumour buds) and low-grade budding (0-9 buds). Inter-observer agreement for two observers was assessed by using the kappa test. Progression-free and cancer-specific survivals were analysed using the Kaplan-Meier method and Cox regression. RESULTS: The 5-year progression-free survival rates for patients with high-grade tumour budding (n = 36) and those with low-grade budding (n = 99) were 57.6% and 89.0% (P < 0.001). The 5-year cancer-specific survival rates were 66.7% vs 92.0% (P < 0.001). Cox regression analyses demonstrated tumour budding as an independent predictor of disease progression (hazard ratio 4.982, P < 0.001) and cancer-related death (hazard ratio 4.142, P = 0.003). The two observers agreed on the classification of tumour budding in 118 cases (87.4%) and the inter-observer agreement was good (κ = 0.692). CONCLUSION: Tumour budding is a strong and reproducible prognostic factor for adverse outcome in Stage II colon cancer, which may serve as a prognostic marker to identify patients with a high risk of recurrence who may benefit from adjuvant therapy.

Stable color-tunable Ca3Y(GaO)3(BO3)4:Bi3+/Tb3+/Eu3+ phosphors for application in n-UV-pumped wLEDs.

For further development of light sources, white light-emitting diodes (wLEDs) have attracted widespread attention as promising next-generation light sources fabricated via the combination of phosphors and LED chips. However, latent defects, such as chemical/thermal instability, low color rendering index (CRI) and high correlated color temperature (CCT), of current mainstream wLEDs seriously hinder their further large-scale implementation. Herein, in order to overcome these limitations, single-phase color-tunable gaudefroyite (Ca3Y(GaO)3(BO3)4 (CYGB)) tridoped with Bi3+/Tb3+/Eu3+ ions was synthesized for the first time and detailed characterisation was performed via high-temperature solid-state reaction and structural/spectral analyses, respectively. Radius difference percentage calculations and Rietveld refinements indicate that dopants occupy both Y3+ and Ca2+ sites but preferably the Y3+ site over the Ca2+ site due to the same valence state. Through subtly regulating the (co)doping contents and skillfully utilizing the energy transfer (ET) strategy from the allowed transition of blue light-emitting Bi to the forbidden transition of green/red light-emitting Tb/Eu, the color hue (including white light) of highly efficient PL can be easily tuned according to the need. Meanwhile, composition/content-optimized white light-emitting CYGB:2%Bi/10%Tb/12%Eu also shows splendid chemical/thermal stability. Finally, as a proof-of-concept experiment, the CYGB:2%Bi/10%Tb/12%Eu phosphor-converted wLED (pc-wLED) was fabricated and encapsulated via the up-to-date remote 'capping' method, which imparted attractive performances. Altogether, the stable CYGB:Bi/Tb/Eu phosphor is a promising candidate for application in lighting/display fields.

[Construction of a model based on multipoint full-layer puncture biopsy for predicting pathological complete response after neoadjuvant therapy for locally advanced rectal cancer].

Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

Structure and luminescence properties of single-component melilite Sr2MgSi2O7:Ce/Tb/Sm for n-UV wLEDs.

Phosphor-converted white light-emitting diodes (pc-wLEDs) have attracted attention in the field of solid-state lighting. Selection and study of suitable single-phase phosphor and packaging modes are currently the main research hotspots. Herein, color-tunable photoluminescence (PL) and thermally stable tri-doped Melitite Sr2MgSi2O7:Ce/Tb/Sm are systematically studied via structural and static/dynamic spectral analyses. All dopants could only be accommodated in the Sr site due to similar ionic radii. Previous studies have concluded that green and red PL could be obtained from singly doped Tb and Sm phosphors with excellent reproduction, and color tunable PL can be achieved from Ce/Tb co-doped phosphors. The forbidden 4f-4f transitions of Tb/Sm cause low efficiency and Ce/Tb co-doping cannot achieve white light emissions. Alternatively, co-doping allowed 5d-4f transition sensitizer with emissions in the UV-blue region (i.e., Ce), color-tunable PL (including the white light); high efficiency of Sr2MgSi2O7:Ce/Tb/Sm could be achieved via energy transfer (ET) from Ce → Tb → Sm. The impossibly direct ET from Ce → Sm is associated with the side metal-metal charge transfer (MMCT) effect. Due to chemically nonequivalent substitutions, two positive Ce(Tb,Sm)Sr and one negative V''Sr were created to maintain the whole charge balance. To reduce the defects and allow more dopants to enter into the Sr site, Na+ was added as a charge balancer to enhance PL efficiency. Furthermore, an alkaline-earth-metal-ions blending strategy via partial replacement of Sr with Ba was investigated to regulate PL owing to the change in crystal field splitting. PL blue-shifted by Ba-co-doping, which could increase the degree of overlapping and enhance ET efficiency. As a proof-of-concept experiment, the pc-wLED fabricated via a combination of the optimal Sr(Ba)2MgSi2O7:Ce/Tb/Sm/Na and an n-UV LED chip based on a remote 'capping' packaging mode shows excellent performances, indicating its strong potential application in the field of solid-state lighting.

Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice.

BACKGROUND: Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an α(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R. METHODS: Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 µg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of α(2) adrenergic antagonist atipamezole 250 µg/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-α) mRNA. RESULTS: Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-α mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-α mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-α mRNA expression level. CONCLUSIONS: Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both α(2) adrenoceptors dependent and independent mechanisms.

Fine structures of embryonic discs of in vivo post-hatching porcine blastocysts at the pre-primitive streak stage.

To date, reports about the ultrastructure of porcine embryonic discs have not shown details of the primitive streak. The main objective of this study was to examine the ultrastructure of interior and exterior embryonic discs in porcine in vivo blastocysts with diameters of 1, 3 and 9 mm using scanning electron microscopy and transmission electron microscopy. For the first time, we revealed the ultrastructure of the unusual group of cells in the pre-primitive streak area of embryonic discs. The cells were 1-2 µm in diameter, had high electron density and contained abundant, free ribosomes and endoplasmic reticulum. These primitive streak cells could represent original embryonic stem cells or represent a stem cell niche. The results also showed three types of cells on the exterior surface of the embryonic discs. Moreover, our results provided morphological evidence of condensed nuclei in the smooth cells on the surface of the embryonic disc.

Metastasis from endometrial carcinoma to bilateral breasts presenting as inflammatory breast lesions.

BACKGROUND: Endometrial carcinoma rarely metastasizes to the bilateral breasts and presents as an inflammatory breast lesion. In this paper, we report a case of bilateral breast metastatic endometrial carcinoma and describe the clinical and pathological features. It is the second case of this kind of disease and the first case report with full clinical data. CASE REPORT: A 56-year-old Chinese woman (G3, P3) with endometrial carcinoma received cytoreductive surgery and chemotherapy. Approximately 22 months later, she presented with pain in the right axillary region and edema of the right breast. The pathology report confirmed multifocal invasive papillary adenocarcinoma of the right mammary gland, consistent with endometrial carcinoma metastasis. Although she received many lines of chemotherapy, the disease still progressed and metastasized to the contralateral breast. Gefitinib (Iressa) improved symptoms temporarily. CONCLUSIONS: Bilateral breasts metastasis of endometrial carcinoma is rare and difficult to treat. Molecular targeted therapy may be an effective treatment for breast metastasis.

A synonymous mutation in IGF-1 impacts the transcription and translation process of gene expression.

Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wild-type (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes.