[Soil microorganisms and physicochemical properties in marshlands along the Yangtze River basin at different types of land use and their effects on distribution of Oncomelania hupensis snails].

OBJECTIVE: To investigating the microbial communities and physicochemical properties of soil and distribution of Oncomelania hupensis snails in marshlands along the Yangtze River basin at different types of land use, and to examine the effects of soil microorganisms and physicochemical properties on snail distribution, so as to provide insights into snail control and schistosomiasis prevention in marshland along the Yangtze River basin. METHODS: Marshlands with four types of land use were selected along the Yangtze River basin on April 2021, including poplar forest-crops integrated planting, reed areas, agricultural cultivation lands and ditches. The distribution of snails and physicochemical properties of soil were investigated in marshlands with different types of land use, and the V3 to V4 regions of the bacterial 16S ribosomal RNA (16S rRNA) gene, fungal internal transcribed spacer-1 (ITS1) gene and algal ribulose-bisphosphate carboxylase (rbcL) gene in soils were subjected to high-throughput sequencing. The occurrence of frames with living snails and density of living snails were compared in marshland with different types of land use. The associations of soil microorganisms and physicochemical properties with the density of living snails were examined using Pearson correlation analysis, and the contributions of soil microorganisms and physicochemical properties to the density of living snails were evaluated using variance partitioning analysis. RESULTS: In marshlands with four types of land use, the greatest occurrence of frames with living snails [(4.94 ± 2.14)%] and density of living snails [(0.070 ± 0.026) snails/0.1 m2] were seen in ditches, and the lowest were found in [(1.23 ± 1.23)%] agricultural cultivation lands [(0.016 ± 0.019) snails/0.1 m2]. A total of 2 phyla, 5 classes, 8 orders, 9 families and 11 genera of algae were detected in soils at four types of land use, with Chlorophyta as the dominant phylum and Pseudoneochloris as the dominant genus. A total of 44 phyla, 134 classes, 281 orders, 338 families and 516 genera of bacteria were detected in soils at four types of land use, with Proteobacteria and Acidobacteriota as the dominant phyla and uncultured Acidobacterium, MND1, Mitrospira, Haliangium and Sphingomonas as dominant genera. A total of 11 phyla, 41 classes, 108 orders, 223 families and 408 genera of fungi were detected in soils at four types of land use, with phyla Ascomycota, Basidiomycota and Mortierellomycota presenting high relative abundances and genera Cladorrhinum, Mortierella and Humicola presenting high relative abundances. Pearson correlation analysis revealed that the density of living snails correlated negatively with the relative abundance of Proteobacteria (r = -0.965, P < 0.05) and soil electronic conductivity (r = -0.962, P < 0.05) and positively with soil moisture (r = 0.951, P < 0.05). Variance partitioning analysis demonstrated that the physicochemical properties and microorganisms of soil contributed 69% and 10% to the density of living snails, respectively. CONCLUSIONS: The diversity of microbial communities varies in soils at different types of land use in marshland along the Yangtze River basin, and the physicochemical properties and microorganisms of soils may affect the distribution of O. hupensis snails.

Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting one to three genomic sites per cell. We engineer an Acidaminococcus Cas12a (AsCas12a) variant, multiplexed transcriptional interference AsCas12a (multiAsCas12a), that incorporates R1226A, a mutation that stabilizes the ribonucleoprotein-DNA complex via DNA nicking. The multiAsCas12a-KRAB fusion improves CRISPRi activity over DNase-dead AsCas12a-KRAB fusions, often rescuing the activities of lentivirally delivered CRISPR RNAs (crRNA) that are inactive when used with the latter. multiAsCas12a-KRAB supports CRISPRi using 6-plex crRNA arrays in high-throughput pooled screens. Using multiAsCas12a-KRAB, we discover enhancer elements and dissect the combinatorial function of cis-regulatory elements in human cells. These results instantiate a group testing framework for efficiently surveying numerous combinations of chromatin perturbations for biological discovery and engineering.

Higher-order combinatorial chromatin perturbations by engineered CRISPR-Cas12a for functional genomics.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting 1-3 genomic sites per cell. To develop a tool for higher-order ( > 3) combinatorial targeting of genomic sites with CRISPRi in functional genomics screens, we engineered an Acidaminococcus Cas12a variant -- referred to as mul tiplexed transcriptional interference AsCas12a (multiAsCas12a). multiAsCas12a incorporates a key mutation, R1226A, motivated by the hypothesis of nicking-induced stabilization of the ribonucleoprotein:DNA complex for improving CRISPRi activity. multiAsCas12a significantly outperforms prior state-of-the-art Cas12a variants in combinatorial CRISPRi targeting using high-order multiplexed arrays of lentivirally transduced CRISPR RNAs (crRNA), including in high-throughput pooled screens using 6-plex crRNA array libraries. Using multiAsCas12a CRISPRi, we discover new enhancer elements and dissect the combinatorial function of cis-regulatory elements. These results instantiate a group testing framework for efficiently surveying potentially numerous combinations of chromatin perturbations for biological discovery and engineering.

Image-guided Ablative Procedures.

Various image-guided ablative procedures include chemical and thermal ablation techniques and irreversible electroporation. These have been used for curative intent for small tumours and palliative intent for debulking, immunogenicity and pain control. Understanding these techniques is critical to avoiding complications and achieving superior clinical outcomes. Additionally, combination with immunotherapy and chemotherapies is rapidly evolving. There are numerous opportunities in interventional radiology to advance ablation techniques and seamlessly integrate into current treatment regimens for both benign and malignant tumours.

[Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes].

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 µg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 µg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor ß1 (TGF-ß1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-ß1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-ß1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-ß1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-ß1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Prognostic significance of lymphocyte subpopulations for ICU-acquired infections in patients with sepsis: a retrospective study.

AIM: To determine the prognostic value of lymphocyte subpopulations in predicting intensive care unit (ICU)-acquired infections among patients admitted to the ICU with sepsis. METHODS: Data on peripheral blood lymphocyte subpopulations [CD3+ T cells, CD4+ T cells, CD8+ T cells, CD16+CD56+ natural killer (NK) cells and CD19+ B cells] were collected continuously from 188 patients admitted to the study ICUs with sepsis between January 2021 and October 2022. Clinical data collected from these patients, including medical history, number of organ failures, severity of illness scores, and characteristics of ICU-acquired infections, were reviewed. RESULTS: Lymphocyte subpopulation counts were significantly lower in patients who acquired an infection in the ICU compared with those who did not. Univariate analyses showed that the number of organ failures [odds ratio (OR) 3.37, 95% confidence interval (CI) 2.25-5.05], severity of illness scores [Sequential Organ Failure Assessment score - OR 1.69, 95% CI 1.41-2.02; Acute Physiology and Chronic Health Evaluation II score - OR 1.26, 95% CI 0.17-1.36], history of immunosuppressant use (OR 2.41, 95% CI 1.01-5.73) and lymphocyte subpopulations (CD3+ T cells - OR 0.60, 95% CI 0.51-0.71; CD4+ T cells - OR 0.51, 95% CI 0.41-0.63; CD8+ T cells - OR 0.32, 95% CI 0.22-0.47; CD16/CD56+ NK cells - OR 0.41, 95% CI 0.28-0.59; CD19+B cells - OR 0.52, 95% CI 0.37-0.75) were associated with ICU-acquired infections. Multi-factor logistic regression analysis demonstrated that APACHE II score (OR 1.25, 95% CI 1.13-1.38), CD3+ T cells (OR 0.66, 95% CI 0.54-0.81) and CD4+ T cells (OR 0.64, 95% CI 0.50-0.82) were independent significant risk factors for ICU-acquired infections. CONCLUSION: Assessing CD3+ T cells and CD4+ T cells within 24 h of ICU admission may help in identification of patients at risk for developing ICU-acquired infections.

Baicalin Induced Apoptosis of Human Cholangiocarcinoma Cell through Activating AMPK/mTORC1/p70S6K Signaling Pathway.

Baicalin (naturally bioactive flavone compound isolated from Scutellaria baicalensis) has been demonstrated to exert strong anticancer activity against various tumor cells. However, the possibility of using baicalin for the treatment of cholangiocarcinoma and its effectiveness remain unstudied. The effect of baicalin on QBC939 cholangiocarcinoma cell culture was studied by assessing cell viability (CCK-8 test) and expression of the key proteins (Western blotting). Baicalin induced apoptosis of QBC939 cells in culture in a dose- and time-dependent manner. The proapoptotic effect was attributed to inhibition of the mTORC1-p70S6K signaling pathway resulting from baicalin-induced AMPK activation. These findings provide a new approach for cholangiocarcinoma treatment and serve as a basis for developing baicalin-based combination cancer therapy strategies.

[A case of anterior ischemic optic neuropathy after uneventful cataract surgery in a diabetic patient].

A diabetic patient complained of sudden visual field defect on the third day after cataract surgery. The fundus examination showed optic disc edema in the left eye, which was diagnosed as anterior ischemic optic neuropathy by optical coherence tomography and visual field examinations. The optic neuropathy was induced by the excessive application of tropicamide phenylephrine eye drops by herself before cataract surgery. After timely treatment, the patient's vision and visual field recovered well.

[Triptolide increases the radiosensitivity of lung cancer cells by inhibiting DNA repair and inducing apoptosis].

Objective: To investigate the effect of triptolide on radiosensitivity of lung cancer cells and its mechanism. Methods: The lung cancer cells H1299, A549, H157 and H838 were cultured. The strongest radio resistance cell line, H1299 was selected by cell clone formation experiment and for the subsequent experiments. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect the effect of different concentrations of triptolide on the proliferation of H1299 cells. The optimal concentration of triptolide was 50nmol/L, and the optimal treatment time was 48 hours. The H1299 cells were divided into the control group, triptolide group (50 nmol/L), 4 Gy group and triptolide+ 4 Gy group. Flow cytometry was used to detect the apoptosis rate of H1299 cell. Western Blot was used to detect the proteins expression levels of p-Chk2, p-ATM, p-p53, Bcl-2, Bax and cleaved-Caspase 3. Results: The apoptotic rate and protein levels of Bax, cleaved-Caspase 3, p-Chk2, p-ATM and p-p53 in the 4 Gy group were (12.38±1.34)%, 0.42±0.04, 0.38±0.04, 0.98±0.11, 0.73±0.08, 0.95±0.09, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03, 0.32±0.03, 0.21±0.02, 0.25±0.03 in the control group (P<0.05). However, the protein level of Bcl-2 was (0.52±0.05), lower than (0.93±0.09) of the control group (P<0.05). The survival fraction (0.462) and protein level of Bcl-2 (0.44±0.04) in the triptolide group were lower than those of the control group (0.702 and 0.93±0.09, P<0.05). The apoptotic rate and the protein levels of Bax and cleaved-Caspase 3 in the triptolide group were (9.27±1.08)%, 0.45±0.05, 0.41±0.04, respectively, higher than (3.26±2.43)%, 0.22±0.02, 0.23±0.03 in the control group (P<0.05), and the sensitization ratio in the triptolide group was 1.579. The apoptosis rate, Bax and cleaved Caspase 3 protein expression levels in triptolide + 4 Gy group were (26.53±2.19)%, 0.91±0.09 and 0.79±0.08, respectively, higher than (12.38±1.34)%, 0.42±0.04 and 0.38±0.04 in 4 Gy group (P<0.05). The expression level of Bcl-2 protein was (0.21±0.02), lower than (0.52±0.05) in 4 Gy group (P<0.05). Conclusion: Triptolide increases the radiosensitivity of radiation-induced lung cancer cells by inhibiting DNA repair and inducing apoptosis.

Cystatin C alleviates H2O2-induced H9c2 cell injury.

OBJECTIVE: At present, the incidence of acute myocardial infarction is increasing year by year, and it has become one of the diseases with the highest mortality rate in humans. Myocardial ischemia-reperfusion injury (MIRI) is a major problem in the treatment of myocardial infarction, but clinically there is no effective way to treat MIRI. This study used Cystatin C (Cys C) to treat cardiomyocytes and rats to investigate the effect of Cys C on MIRI. MATERIALS AND METHODS: We used H2O2 to induce rat cardiomyocytes (H9c2 cells) injury and stimulated the cells with Cys C. Cell counting kit 8 (CCK8) assay was used to determine the optimal concentration of H2O2 and Cys C to stimulate H9c2 cells. We determined the effects of Cys C on oxidative stress and apoptosis levels in H9c2 cells by measuring the activity of dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), and the expression of apoptosis-related molecules (caspase3/8/9, Bax and Bcl-2). Changes in the activity of the NF-κB signaling pathway in H9c2 cells were also detected. In addition, we made rat MIRI models by ligating the coronary arteries and used Cys C to treat rats to verify the effect of Cys C on MIRI. RESULTS: According to the results of the CCK8 assay, 1000 µM of H2O2 and 15 µM of Cys C were used to stimulate H9c2 cells. Cys C alleviated H2O2-induced H9c2 cell injury, manifested as a decrease in LDH and MDA activity and an increase in SOD activity. Cys C also reduced the apoptosis level in H9c2 cells. The activity of NF-κB signaling pathway in injured H9c2 cells was increased, and stimulation of Cys C could inhibit the NF-κB signaling pathway in H9c2 cells. The application of Cys C in MIRI rats also verified its therapeutic effect on MIRI. CONCLUSIONS: Cys C reduced the oxidative stress and apoptosis levels of cardiomyocytes by inhibiting the activity of NF-κB signaling pathway in cardiomyocytes, thereby reducing cardiomyocyte injury and treating MIRI.

X-ray and neutron scattering measurements of ordering in a Cu46Zr54 liquid.

The structural evolution of the equilibrium and supercooled Cu46Zr54 liquids was investigated with a combination of elastic neutron scattering (with isotopic substitution) and synchrotron x-ray scattering studies. The partial pair correlation functions were determined over a wide temperature range (∼270 °C). These show that the Cu-Cu and Zr-Zr ordering increases as the temperature decreases, while the Cu-Zr ordering decreases. This surprising result is in contradiction with the results from molecular dynamics studies.

[The fundus autofluorescence of retinal astrocytic hamartomas in tuberous sclerosis complex].

Objective: To investigate the autofluorescence findings of retinal astrocytic hamartoma (RAH) in patients with tuberous sclerosis complex (TSC). Methods: It was a retrospective case series study. Twenty-three patients (35 eyes) who were referred to Department of Internal Medicine and Department of Ophthalmology, Peking Union Medical College Hospital between November 2012 and June 2018 with established TSC-associated RAH diagnosis were included. The findings of fundus autofluorescence, fundus photos and spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RAH lesions were classified into three types based on the morphology shown in fundus photos. The fundus autofluorescence features of TSC-associated RAH were described. The Welch's test and Fisher's exact test were used for statistical analysis. Results: The patients were 8 males and 15 females aged (28±9) years old (range, 15-55 years). Seventy-two RAH lesions were examined, including 59 type 1 RAHs, 7 type 2 RAHs and 6 type 3 RAHs. According to fundus autofluorescence, type 1 RAHs could be further divided into reduced, speckled and background autofluorescence patterns, among which the hypoautofluorescence pattern accounted for the majority (69.5%, 41/59), while the speckled pattern was usually accompanied by outer retinal disorganization and discontinuation of photoreceptor outer segment as revealed by SD-OCT. No significant difference was revealed in tumor thickness for reduced, speckled and background autofluorescence patterns of type 1 RAHs [(490.2±97.9) vs. (589.2±221.6) vs. (463.0±76.2) µm respectively, F=1.426, P=0.283]. Among type 1 RAHs, the number of reduced autofluorescence pattern lesions found in perifoveal, peripapillary, inferonasal, inferotemporal, superonasal, superotemporal quadrants were 9, 4, 4, 7, 4, 13 respectively, while that of speckled autofluorescence pattern lesions were 3, 0, 3, 2, 3, 2 and background autoflurorescence pattern lesions 3, 0, 1, 1, 0, 0. No significant difference was revealed in location distribution (P=0.452) either. Type 2 RAHs featured numerous hyperautofluorescent spots or plaques, and calcification in type 2 RAHs varied in autofluorescence intensity. Type 3 RAHs, combining the features of type 1 and 2 RAHs, were characterized by central hyperautofluorescent spots and hypoautoflurescent rim, but the area of hyperautofluorescence was smaller than that of calcification as shown in fundus photos. Conclusions: In TSC, the fundus autofluorescence of RAHs varies from hypoautofluorescence to hyperautofluorescence patterns according to RAH types. The retinal involvement and calcification degree of TSC-associated RAHs could be reflected on the autofluorescence, which was beneficial to the full assessment. (Chin J Ophthalmol, 2020, 56: 211-216).

The prevalence of self-declared sensitive skin: a systematic review and meta-analysis.

BACKGROUND: Sensitive skin is a common cutaneous condition that affects many people. The exact prevalence of sensitive skin remains unknown. OBJECTIVES: We aim to perform a systematic review and meta-analysis of the published literatures to determine the global self-declared prevalence of sensitive skin. METHODS: A systematic review of studies reporting the prevalence of sensitive skin was conducted searching electronic database of PubMed. Data were extracted and proportion meta-analyses were carried out to obtain the pooled prevalence. RESULTS: A total of 26 studies were included representing general population in 18 countries with 51 783 individuals. The pooled proportion of individuals with self-reported sensitive skin to some degrees was 71% [95% confidence interval (CI) 62%-81%] in the general population and 40% (95% CI 32%-47%) among individuals having very or moderately sensitive skin. Sensitive skin affected both women (45%, 95% CI 36%-55%) and men (33%, 95% CI 24%-42%), and women tended to be a risk factor with the development of sensitive skin compared to men (Risk Ratio=1.741, 95% CI 1.38-2.20). The corresponding estimates for prevalence were 38% (95% CI 25%-51%) among America, 35% (95% CI 32%-37%) among South America, 44% (95% CI 39%-50%) among Europe, and 31% (95% CI 16%-45%) among Asia, respectively. The pooled proportion of self-diagnosed facial sensitive skin to some degree was 64% (95% CI 49%-76%). For subjects responded as having very or moderately facial sensitive skin, the pooled proportion was 34% (95% CI 21%-46%). CONCLUSION: Our meta-analysis based on published data showed that the global prevalence of self-declared sensitive skin to some degrees was 71% in the adult population, and 40% among individuals having very or moderately sensitive skin. However, the prevalence of sensitive skin was dependent on the diagnostic method and the prevalence might be over-estimated in the questionnaire-based epidemiological studies.

Evaluation of structural changes and intracellular substance leakage of Escherichia coli O157:H7 induced by ohmic heating.

AIMS: To investigate the effects of ohmic heating (OH) and water bath heating (WB) on the membrane permeability, membrane structure, intracellular organization and leakage of intracellular substances of Escherichia coli O157:H7 at the same inactivation level and at a heating temperature of 72°C. METHODS AND RESULTS: Flow cytometry analysis indicated that membrane permeability of E. coli O157:H7 by OH was comparable to WB at 72°C. Scanning electron microscopy analysis showed that the OH-treated E. coli O157:H7 had greater morphological changes than those of WB-treated ones both at the same inactivation level and the same heating temperature. Transmission electron microscopy analysis showed that both OH and WB caused severe damage on the intracellular organization of E. coli O157:H7 at 72°C. Moreover, OH-treated E. coli O157:H7 had more leakage of intracellular substances than those treated with WB due to the electroporation caused by OH. CONCLUSION: OH presents considerable potential in inactivation of E. coli O157:H7, especially OH at 10 V cm-1 with a much shorter heating time. SIGNIFICANCE AND IMPACT OF THE STUDY: The nonthermal effect of OH had a greater effect on the cell membrane of E. coli O157:H7, resulting in more pores and more leakage of intracellular substances out of the E. coli O157:H7 cells. These results could promote the application of OH in food processing.

Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients.

We applied tandem mass tag (TMT)-based proteomics to investigate protein changes in bone marrow microenvironment of osteoporotic patients undergoing spine fusion. Multiple bioinformatics tools were used to identify and analyze 219 differentially expressed proteins. These proteins may be associated with the pathogenesis of osteoporosis. INTRODUCTION: Bone marrow microenvironment is indispensable for the maintenance of bone homeostasis. We speculated that alterations of some factors in the microenvironment of osteoporotic subjects might influence the homeostasis. This study aimed to investigate the changes in the expression of protein factors in the bone marrow environment of osteoporosis. METHODS: We performed a proteomics analysis in the vertebral body-derived bone marrow supernatant fluid from 8 Chinese patients undergoing posterior lumbar interbody fusion (4 osteoporotic vs. 4 non-osteoporotic) and used micro-CT to analyze the microstructural features of spinous processes from these patients. We further performed western blotting to validate the differential expressions of some proteins. RESULTS: There was deteriorated bone microstructure in osteoporotic patients. Based on proteomics analysis, 172 upregulated and 47 downregulated proteins were identified. These proteins had multiple biological functions associated with osteoblast differentiation, lipid metabolism, and cell migration, and formed a complex protein-protein interaction network. We identified five major regulatory mechanisms, splicing, translation, protein degradation, cytoskeletal organization, and lipid metabolism, involved in the pathogenesis of osteoporosis. CONCLUSIONS: There are various protein factors, such as DDX5, PSMC2, CSNK1A1, PLIN1, ILK, and TPM4, differentially expressed in the bone marrow microenvironment of osteoporotic patients, providing new ideas for finding therapeutic targets for osteoporosis.

Oncogenes expand during evolution to withstand somatic amplification.

Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Results: Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb; P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb; P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0; P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Conclusions: Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic amplification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene amplification and elucidated how cancers have shaped our genome to its present configuration.

The effect of milk consumption on acne: a meta-analysis of observational studies.

BACKGROUND: Acne is a common skin condition in developed countries with western diets. The effect of milk on acne has been highly controversial. To examine the association between milk consumption and acne risk, we conducted a meta-analysis of available data. MATERIALS AND METHODS: We carried out comprehensive databases search of PubMed, Embase, Medline and Cochrane Library and identified four cohort studies and nine case-control or cross-sectional studies, including a total of 71 819 participants. We evaluated the pooled odds ratio (OR) with its 95% confidence interval (CI) using a random effects model. Subgroup analyses on acne severity, milk forms and milk intake levels were performed. RESULTS: Compared with non-consumers, the pooled OR was 1.16 (95% CI 1.09-1.24) for overall milk consumers in all included studies, and 1.17 (95% CI 1.10-1.24) in cohort studies and 1.16 (95% CI 1.09-1.24) in case-control or cross-sectional studies. Subgroup analysis on milk forms determined a stronger association in skim milk consumers (OR = 1.24, 95% CI 1.13-1.37) than in low-fat consumers (OR = 1.14, 95% CI 1.08-1.22) and full-fat consumers (OR = 1.13, 95% CI 1.05-1.21). The pooled OR was greater for high intake level of milk (OR = 1.12, 95% CI 1.01-1.24) than medium intake level of milk (OR = 1.08, 95% CI 1.00-1.17). A subset study of moderate-to-severe acne also found a positive association with milk consumption (OR 1.18, 95% CI 1.01-1.37), while no statistically significant association was found between mild acne risk and milk consumption (OR 1.14, 95% CI 0.86-1.51). CONCLUSION: This meta-analysis provides evidence of a positive association between milk consumption and acne risk.

A possible structural signature of the onset of cooperativity in metallic liquids.

It is widely, although not universally, believed that there must be a connection between liquid dynamics and the structure. Previous supporting studies, for example, have demonstrated a link between the structural evolution in the liquid and kinetic fragility. Here, new results are presented that strengthen the evidence for a connection. By combining the results from high-energy synchrotron X-ray scattering studies of containerlessly processed supercooled liquids with viscosity measurements, an accelerated rate of structural ordering beyond the nearest neighbors in the liquid is demonstrated to correlate with the temperature at which the viscosity transitions from Arrhenius to super-Arrhenius behavior. This is the first confirmation of predictions from several recent molecular dynamics studies.

Comparison of effectiveness and safety between conbercept and ranibizumab for treatment of neovascular age-related macular degeneration. A retrospective case-controlled non-inferiority multiple center study.

PurposeTo compare the efficacy and safety of conbercept and ranibizumab when administered according to a treat-and-extend (TREX) protocol for the treatment of neovascular age-related macular degeneration (AMD) in China.Patients and methodsBetween May 2014 and May 2015, 180 patients were treated in a 1 : 1 ratio using conbercept or ranibizumab from four hospitals. Patients received either conbercept 0.5 mg or ranibizumab 0.5 mg intravitreal injections. Follow-up time was 1 year and treated based on a TREX approach. Main outcomes and measures include best-corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS); number of injections; central retinal thickness (CRT); and leakage of choroidal neovascularization before and after the treatment was analyzed by fluorescein fundus angiography and indocyanine green angiography.ResultsThe 1-year visit was completed by 168 (93.3%) of patients. Mean BCVA was equivalent between two cohorts, and were improved by 12.7±7.770 and 12.3±7.269 letters in the conbercept and ranibizumab cohorts, respectively (P=0.624). There was no significant difference in measured CRT, with a mean decrease of 191.5 µm for conbercept and 187.8 µm for ranibizumab (P=0.773). There was a statistically significant difference (P=0.001) between the drugs regarding the number of treatments: 7.4 for conbercept and 8.7 for ranibizumab. The difference in the distribution of injection intervals was statistically significant between two groups (P=0.011). During the study, there were no cases of endophthalmitis or intraocular inflammation.ConclusionBoth drugs had equivalent effects in visual and anatomic gains at 1 year when administered. In the conbercept group, longer treatment intervals were achieved with more patients.

[The ocular involvement in the transthyretin-related familial amyloid polyneuropathy].

Transthyretin (TTR)-related familial amyloid polyneuropathy (FAP), which is caused by mutant TTR, is a rare but fatal autosomal dominant disease. TTR is synthesized by the liver (95%) , the choroid plexus of the brain and the retinal pigment epithelium. FAP leads to peripheral neuropathy, and the main ocular manifestations are vitreous opacity (yellowish cotton-like), secondary glaucoma and keratoconjunctivitis sicca. Liver transplantation has proven to be the most effective treatment for TTR-FAP. Nowadays, tafamidis is the only drug approved for TTR-FAP (early stage). However, neither liver transplantation nor tafamidis is capable to halt the progression of ocular involvement. Panretinal photocoagulation could damage the retinal pigment epithelium, and thus prevent the progression. Recent investigations on TTR-FAP and its ocular involvement are reviewed in this article. (Chin J Ophthalmol, 2017, 53: 783-785).