[Correlation between femoral offset, rotation center and leg length discrepancy after total hip arthroplasty based on digital analysis].

OBJECTIVE: CT scans combined with Mimics software were used to measure femoral offset (FO), rotation center height (RCH) and lower leg length discrepancy (LLD) following total hip arthroplasty (THA), and the relationship between FO, RCH and LLD after THA is discussed. METHODS: Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022. There were 21 males and 19 females, 18 patients on the left side and 22 patients on the right side, aged range from 30 to 81 years old, with an average age of (58.90 ±14.13) years old, BMI ranged from 17.3 to 31.5 kg·m-2 with an average of (25.3±3.4) kg·m-2. There were 30 cases of femoral head necrosis (Ficat type Ⅳ), 2 cases of hip osteoarthritis (Tönnis type Ⅲ), 2 cases of developmental hip dislocation combined with end-stage osteoarthritis (Crowe type Ⅲ), and 6 cases of femoral neck fracture (Garden type Ⅳ). Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative, and three-dimensional reconstruction model was established after processing by Mimics software. FO, RCH and LLD were measured on the model. The criteria for FO reconstruction were as follows:postoperative bilateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD difference less than 5 mm. RESULTS: Bilateral FO difference was positively correlated with LLD (r=0.744, P<0.001). Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the isometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group (χ2=6.320, P=0.012). The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877, P<0.001). There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD, and the linear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference, y:postoperative bilateral RCH difference; Unit:cm), F=77.993, R2=0.808, P=0.009. CONCLUSION: After THA, LLD increased with the increase of FO and decreased with the increase of RCH. The effect of lower limb isometric length can be obtained more easily by reconstruction of FO. There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD, and the regression equation can provide a theoretical reference for judging LLD.

Resveratrol ameliorates DSS-induced ulcerative colitis by acting on mouse gut microbiota.

OBJECTIVE AND DESIGN: Ulcerative colitis (UC) is a multi-faceted, recurrent immune disorder caused by dextran sulfate sodium (DSS). The intestinal microbiota has multiple functions in the host, so UC requires long-term potent medication. The effect of resveratrol (RSV) has seldom been reported, and this study researched that. Herein, the effect of RSV and Grape seed oil that anti-inflammatory ability in experimental mice was explored, also why RSV altered Gut Microbiota has been researched. MATERIALS AND METHODS: In this experiment, the effects of experimental drugs on colon length in mice with DSS-induced colitis were compared. H&E Staining was performed on serial sections of colon tissues and histological scores were determined for all groups. The expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the colon tissue of mice was detected by immunohistochemical staining. In the end, the α-diversity index, sobs index, and rarefaction curve of the cecal and colon microbiota of different groups of mice were measured. Bray-Curtis-based Venn diagram of PCoA (principal coordinate analysis) and OTUs distribution in mouse gut microbiota were obtained. RESULTS: The results showed that the use of 40 mg/kg RSV (high dose) significantly reduced the severity of UC. The use of 10 mg/kg RSV (low dose) significantly reduced the effect of shortened colon length in DSS mice. Compared with the DSS-treated group, the levels of COX-2 and TNF-α in the colon tissues of RSV + DSS-treated mice were significantly decreased. According to this experiment, 19 mouse gut microbiota species had a relative abundance greater than 0.1%, with Beerella, Bacteroides, Helicobacter, Oscillator, and cecum pylori being more abundant in the colon than in the colon. A higher relative abundance of Lachnospira NK4A136 was observed in DSS and RSV groups compared with the control group, whereas the opposite was observed for Alloprevotella. This proves that resveratrol increases the uniformity and diversity of gut microbes to a certain extent, and has a protective effect on the gut.

Glabridin reduces neuroinflammation by modulating inflammatory signals in LPS-induced in vitro and in vivo models.

OBJECTIVES: Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. METHODS: The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. RESULTS: In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. CONCLUSION: Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.

Geographical distribution and potential distribution prediction of thirteen species of Citrus L. in China.

Using DIVA-GIS software to study the spatial accumulation of Citrus species, an important economic crop in China. Draw the distribution maps of Citrus to concerning altitude and vegetation, and use DIVA-GIS' Bioclim ecological model and maximum information entropy model Maxent software to estimate the potential distribution areas of various Citrus species. The results show that the Citrus genus is located in the south of Qinling Mountains, mainly in the southwest of China and the coast of southeastern China. Sichuan and Chongqing are the most densely distributed regions of Citrus. The distribution of Citrus is closely related to the vegetation type and altitude. The vegetation types in the distribution area is evergreen broad-leaved forest, evergreen shrub, deciduous broad-leaved forest, mixed-leaf forest coverage area, deciduous coniferous forest, farmland, trees, other vegetation coverage, and evergreen coniferous forest. The current potential distribution area of Citrus is mainly in Guizhou, Hubei, Hunan, Guangdong, Guangxi, Yunnan, Sichuan, Chongqing, and other provinces and municipalities and their borders, while the potential distribution area in the future moves northward and enter Henan and southern Gansu. At the same time, climate warming changes the distribution of suitable areas of Citrus, which makes the suitable areas of C. sinensis Osbeck, C. reticulata Blanco, and other crops greatly increased. Planning the planting area will effectively improve the yield and quality in the future. Planning presents new challenges.

Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer.

BACKGROUND: Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear. METHODS: The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo. RESULTS: Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells. CONCLUSIONS: Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.

Geographic distribution and impacts of climate change on the suitable habitats of Glycyrrhiza species in China.

Climate change has a major impact on the growth and distribution of plants. Glycyrrhiza is widely used in the treatment of many diseases in China. However, with the overexploitation and the growing demand for medicinal uses in of Glycyrrhiza plants. The investigation of the geographical distribution of Glycyrrhiza plants and the analysis of future climate change are of great significance for the conservation of Glycyrrhiza. In this study, combined with administrative maps of Chinese provinces, the present and future of geographical distribution and richness of six Glycyrrhiza plants in China were studied by using DIVA-GIS and MaxEnt software. A total of 981 herbarium records of these six species of Glycyrrhiza were collected to research. Results show that the change of climate in the future will lead to an increase in habitat suitability for some Glycyrrhiza species as follows: Glycyrrhiza inflata by 61.6%, Glycyrrhiza squamulosa by 47.5%, Glycyrrhiza pallidiflora by 34.0%, Glycyrrhiza yunnanensis by 49.0%, Glycyrrhiza glabra by 51.7%, and Glycyrrhiza aspera by 65.9%. Glycyrrhiza plants have considerable medicinal and economic value, so it is necessary to adopt targeted development and rational management strategies for it.

Protective effect of bone morphogenetic protein-7 induced differentiation of bone marrow mesenchymal stem cells in rat with acute spinal cord injury.

The principal aim of present study was to assess the therapeutic efficacy of bone morphogenetic protein-7 (BMP-7) induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in a rat acute spinal cord injury (SCI) model. BMSCs were isolated from rats, and then divided into a control and a BMP-7 induction groups. The proliferation ability of BMSCs and glial cell markers were determined. Forty Sprague-Dawley (SD) rats were randomly divided into sham, SCI, BMSC, and BMP7 + BMSC groups (n = 10). Among these rats, the recovery of hind limb motor function, the pathological related markers, and motor evoked potentials (MEP) were identified. BMSCs differentiated into neuron-like cells after the introduction of exogenous BMP-7. Interestingly, the expression levels of MAP-2 and Nestin increased, whereas the expression level of GFAP decreased after the treatment with exogenous BMP-7. Furthermore, the Basso, Beattie, and Bresnahan (BBB) score reached 19.33 ± 0.58 in the BMP-7 + BMSC group at day 42. Nissl bodies in the model group were reduced compared to the sham group. After 42 days, in both the BMSC and BMP-7 + BMSC groups, the number of Nissl bodies increased. This is especially so for the number of Nissl bodies in the BMP-7 + BMSC group, which was more than that in the BMSC group. The expression of Tuj-1 and MBP in BMP-7 + BMSC group increased, whereas the expression of GFAP decreased. Moreover, the MEP waveform decreased significantly after surgery. Furthermore, the waveform was wider and the amplitude was higher in BMP-7 + BMSC group than that in BMSC group. BMP-7 promotes BMSC proliferation, induces the differentiation of BMSCsinto neuron-like cells, and inhibits the formation of glial scar. BMP-7 plays a confident role in the recovery of SCI rats.

sFgl2-Treg Positive Feedback Pathway Protects against Atherosclerosis.

Soluble fibrinogen-like protein 2 (sFgl2), a novel effector of regulatory T cells (Tregs), has been demonstrated to have potent immunosuppressive functions. Multiple studies indicate that Tregs could exert important atheroprotective effects, but their numbers gradually decrease during atherogenesis. The receptor of sFgl2 can be expressed on Treg precursor cells, while the role of sFgl2 on Treg differentiation and atherosclerosis progression remains unclear. Firstly, we detected that the sFgl2 was decreased in humans and mice with atherosclerotic diseases and was especially lower in their vulnerable plaques. Then, we used both Adeno-associated virus-sFgl2 (AAV-sFgl2)-injected ApoE-/- mice, which is systemic overexpression of sFgl2, and sFgl2TgApoE-/- bone marrow cells (BMC)-transplanted ApoE-/- mice, which is almost immune-system-specific overexpression of sFgl2, to explore the role of sFgl2 in atherosclerosis. Our experiment data showed that AAV-sFgl2 and BMT-sFgl2 could reduce atherosclerotic area and enhance plaque stability. Mechanistically, sFgl2 increases the abundance and immunosuppressive function of Tregs, which is partly mediated by binding to FcγRIIB receptors and phosphorylating Smad2/3. Collectively, sFgl2 has an atheroprotective effect that is mainly achieved by forming a positive feedback pathway with Treg. sFgl2 and Treg could synergistically protect against atherosclerosis.

Geographical distribution and predict potential distribution of Cerasus serrulata.

Climate change is closely related to the distribution of plant resources. Cerasus serrulata is an important plant resource in China. The study on the influence of environmental factors on the distribution of suitable areas of C. serrulata is conducive to the protection and development of C. serrulata. In this paper, the distribution information of 238 Chinese Cerasus serrulata plants was processed by DIVA-GIS. The MaxEnt model was used to simulate the current and future distribution, and the ecological distribution and richness of Cerasus were analyzed. The results showed that the Cerasus serrulata was widely distributed in Hebei, Heilongjiang, Shandong, Jiangsu, Zhejiang, Anhui, Jiangxi, Hunan, and Guizhou provinces, mainly in the low and middle elevation areas of 10 to 1200 m. Based on this model, the precipitation of the warmest quarter, the precipitation of the driest month, and the mean temperature of the coldest were the most significant bioclimatic variables affecting the distribution of C. serrulata. In the future, climate change may lead to a slight increase of 2.31% in the area of suitable habitat for Cerasus serrulata, while the optimal habitat will decrease from 20.81 to 14.55%. Therefore, conservation measures should be taken to protect these precious resources.

Geographical distribution and predict potential distribution of Angelica L. genus.

Climate change is very important for the distribution of plant resources, especially for crops. Angelica plants have a long history of use and significant crop resources in China, whose rhizomes are extensively used in medicine and food. In this paper, 1599 georeferenced herbarium records were analyzed using DIVA-GIS, and the ecological distribution and richness of the current and future distribution simulation were analyzed using the MaxEnt model. The results show that they are from 32 provinces in China. Among these provinces, Sichuan, Gansu, and Yunnan have the largest number of herbariums. According to the MaxEnt model simulation, it is found that the precipitation in the warmest season, annual precipitation, and the driest monthly precipitation are the foremost bioclimatic variables that control the distribution of eight selected Angelica plants (A. biserrata, A. gigas, A. laxifoliata, A. likiangensis, A. longicaudata, A. omeiensis, A. polymorpha, and A. valida). It can be seen from the potential distribution map that the suitable growth areas of A. polymorpha and A. valida have increased, while the suitable growth areas of the six species of Angelica have decreased in varying degrees, 18.24%, 20.01%, 9.91%, 53.16%, 10.06%, and 12.64% respectively. Therefore, it is necessary to protect the Angelica plants.

Effects of climate change on the geographical distribution and potential distribution areas of 35 Millettia Species in China.

Climate change has an extremely important impact on the geographic distribution of plants. The genus Millettia is an important plant resource in China and is widely used in medicine and ornamental industries. Due to the continuous changes of climate and the development and utilization of plant resources of the genus Millettia, it is of great significance to systematically investigate the geographic distribution of plants of the Millettia and their potential distribution under climate change. DIVA-GIS software was used to analyze 3492 plant specimens of 35 species of genus Millettia in the herbarium, and the ecological geographic distribution and richness of Millettia were analyzed, and the MaxEnt model was used to analyze the current and potential distribution in the future. The results show that the genus Millettia is distributed in 30 provinces in China, among which Yunnan and Guangdong provinces are the most distributed. Our model determines that precipitation in the driest month and annual temperature range are the most important bioclimatic variables. Future climate changes will increase the suitable habitat area of M. congestiflora by 16.75%, but other cliff beans Suitable habitats for vines will decrease significantly: M. cinereal by 47.66%, M. oosperma by 39.16%, M. pulchra by 36.04%, M. oraria by - 29.32%, M. nitida by 22.88%, M. dielsiana by 22.72%, M. sericosema by 19.53%, M. championii by 7.77%, M. pachycarpa by 7.72%, M. speciose by 2.05%, M. reticulata by 1.32%. Therefore, targeted measures should be taken to protect and develop these precious plant resources.

Anti-inflammatory Study on the Constituents of Angelica sinensis (Oliv.) Diels, Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., Angelica pubescence Maxim and Foeniculum vulgare Mill. Essential Oils.

Umbelliferae plants, which are widely used as traditional Chinese medicine because of their characteristics of relieving rheumatism, alleviating fever, circulating blood and easing pain. This experimental study was based on ear edema model caused by 12-O-tetracycline-propylphenol-13-acetic acid (TPA) in mice and compared with the Ibuprofen (Ib) group. Gas chromatography-mass spectrometry (GC-MS) was used to analyse the composition of the essential oils from the four studied Umbelliferae plants (Angelica sinensis (Oliv.) Diels, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. pubescens Maxim and Foeniculum vulgare Mill.). Biologically active components in volatile oils from the four studied Umbelliferae plants were evaluated. The expression levels of inflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Cyclooxygenase-2 (COX-2), Interleukin-6 (IL-6) and RelA (p65) in mouse skin were determined by immunohistochemical method. The refractive index of the four essential oils was calculated. A total of 239 compounds were identified by GC-MS from the four studied plants, and the main constituents were osthole (44.61%, APEOs), obepin (0.59%, APEOs & 86.58%, FVEOs), undecanol (8.58%, ADEOs), α-muurolene (7.95%, ADEOs) and cis-anethol (9.11%, ADEOs). E-ligustilide (0.14%, APEOs & 81.14%, ASEOs), (-)-spathulenol (0.08%, FVEOs & 1.21%, ASEOs), (-)-terpinen-4-ol (4.91%, FVEOs), 2-butylthiolane (5.76%, APEOs) and α-bisabolol (3.80%, APEOs). This study showed that all the essential oils from the four studied Umbelliferae plants contained various lactones, including ligustrongolactone, trans-anisol and imperatorin. According to the results of the TPA induction test in the mouse ear edema model, the essential oils of four Umbelliferae plants reduced the levels of inflammatory cytokines TNF-α, COX-2, IL-6 and p65. All of them showed extraordinary biological activity in anti-inflammatory, so they have potential application value for biomedical products, pharmaceutical preparations, natural functional nutrients and cosmetic additives.

Aromatic-turmerone ameliorates DSS-induced ulcerative colitis via modulating gut microbiota in mice.

Curcuma longa L. is one of the traditional Chinese herbs in the list of medicinal and food homology. Aromatic-turmerone is the main ingredient in turmeric essential oil. The aim of the present study is to investigate the treatment of Aromatic-turmerone on DSS-included colitis and its regulatory effect on intestinal flora disorder. Male KM mice supplemented with different concentration of aromatic-turmerone and mesalazine are subjected to 2% DSS in drinking water to induce colitis. Colon and cecum contents were collected for colitis lesion evaluation and inflammation-related gene analysis and colon contents for gut microbiota. The results show that treatments with Aromatic-turmerone significantly prevents colon shortening, alleviates the damage of colonic tissue, and reduces colonic inflammatory cytokines TNF-α and COX-2. Furthermore, the 16S rDNA gene sequence data indicate that Aromatic-turmerone improve the abundance of bacterial species, maintain some beneficial bacteria, and reduce harmful bacteria. Aromatic-turmerone downregulates the colonic inflammatory cytokines and modulates the abundance of intestinal flora, which is conductive to ameliorates DSS-induced colitis. Regularly intake of the edible herb may be help to prevent ulcerative colitis-related diseases.

Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus.

BACKGROUND: Sarcopenia is characterized by the age-associated loss of skeletal muscle mass and strength that develops progressively and plays an important role in the disability of the elderly. It has received growing attention over the last decade and has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM). The existence of T2DM could increase the risk of developing sarcopenia through multiple mechanisms including advanced glycation end-product accumulation. Meanwhile, sarcopenia would alter glucose disposal and may contribute to the development and progression of T2DM due to reduced muscle mass. METHODS: We implemented transcriptomic analysis of skeletal muscle biopsy specimens in sarcopenia patients and proliferating myoblasts or differentiated myotubes from individuals with T2DM. Related microarray data were selected from Gene Expression Omnibus (GEO) to screen the genes, which were differentially expressed for sarcopenia and T2DM. Multiple combinatorial statistical methods and bioinformatics tools were used to analyze the common DEGs. Meanwhile, functional enrichment analysis was also carried out. Furthermore, we constructed the protein-protein interaction (PPI), as well as transcription factor (TF)-gene interactions network and TF-miRNA coregulatory network. Finally, based on the common DEGs, drug compounds were speculated using the Drug Signatures database (DSigDB). RESULTS: A total of 1765 and 2155 DEGs of sarcopenia and T2DM were screened, respectively. 15 common genes (LXN, CIB2, PEA15, KANK2, FGD1, NMRK1, PLCB1, SEMA4G, ADARB1, UPF3A, CSTB, COL3A1, CD99, ETV3, FJX1) correlated with sarcopenia and T2DM simultaneously were then identified, and 3 genes (UPF3A, CSTB and PEA15) of them were regarded as hub genes. Functional enrichment analysis revealed several shared pathways between two diseases. In addition, according to the TF-gene interactions network and TF-miRNA coregulatory network, part of TF and miRNA may be identified as key regulator in sarcopenia and T2DM at the same time (e.g., CREM and miR-155). Notably, drug compounds for T2DM and sarcopenia were also suggested, such as coenzyme Q10. CONCLUSION: This study revealed that sarcopenia and T2DM may share similar pathogenesis and provided new biological targets and ideas for early diagnosis and effective treatment of sarcopenia and T2DM.

Variation in Compositions and Biological Activities of Essential Oils from Four Citrus Species: Citrus limon, Citrus sinensis, Citrus paradisi, and Citrus reticulata.

Species of the genus Citrus are cultivated in many regions of China and are widely used for medicinal purposes. In the present study, essential oils (EOs) were extracted from four different Citrus species using steam distillation. The chemical components of these four essential oils were separated using gas chromatography-mass spectrometry, and 52 compounds were confirmed. D-limonene was found to be the most abundant compound. All four essential oils demonstrated varied but remarkable radical scavenging capacity (IC50 ; 0.77-13.9 %). Citrus paradisi essential oil exhibited excellent antioxidant activity. Compared to ibuprofen, topical application of the four Citrus spp. essential oils significantly inhibited ear edema formation in mice. Furthermore, essential oils from the four Citrus species reduced the expression levels of interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear transcription factor kappa B p65 (NF-κB) to different degrees. The cytotoxicity of the four essential oils on BV2 microglial cells was determined using the MTT assay (IC50 ; 321.37-1558.87 µg/mL), wherein Citrus limon essential oil showed the lowest cytotoxicity. The essential oils of Citrus limon, Citrus reticulata, and Citrus paradisi had an inhibitory effect on the lung cancer cell lines H1299 by inducing a G0/G1 cell cycle arrest. Cluster and principal component analyses were used to determine the relationship among the Citrus species. These results suggest that the four Citrus essential oils have potential for use as active ingredients in functional foods or cosmeceutical products.

Corrigendum: The GABAA Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice.

[This corrects the article DOI: 10.3389/fimmu.2021.670153.].

Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review.

Congenital hydrocephalus is frequently caused by mutations in the L1 cell adhesion molecule (L1CAM) gene. The purpose of the present study was to identify possible causes of fetal hydrocephalus in a Chinese family. The samples from the parents and the hydrocephalic fetus were collected. Whole-exome sequencing and in-depth mutation analysis were performed. The identified variant, c.1267C>T.(p.Q423X), is situated on exon 11 of L1CAM gene (chromosome X:153134975). The fetus was confirmed to be hemizygous for the nonsense mutation and the mother was a heterozygous carrier. The mutation turns a glutamine into a premature stop codon at amino acid position 423. In conclusion, in the present study, a nonsense mutation in the L1CAM gene was identified during the prenatal diagnosis of a congenital hydrocephalic fetus from a Chinese family. The diagnosis highlighted the necessity of genetic screening for prenatal diagnosis.

Identification of key genes and immune infiltration modulated by CPAP in obstructive sleep apnea by integrated bioinformatics analysis.

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling, and continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remain elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 was downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.

The GABAA Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice.

Background: Myocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABAA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABAA receptor-mediated macrophage responses in pressure overload-induced heart failure. Methods and Results: C57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABAA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABAA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6Clow macrophages in the heart during POH and circulating Ly6Chigh classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6Clow macrophages toward MHCIIhigh macrophage polarization. As a result, Ly6Clow macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6ClowMHCIIhigh macrophage polarization increased expression levels of osteopontin and TGF-ß, which led to myocardial hypertrophy and fibrosis. Conversely, GABAA receptor blockage with bicuculline reversed these effects. Conclusions: Control of the GABAA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABAA receptor has the potential to improve pressure overload-induced heart failure.

Soluble fibrinogen­like protein 2 levels are decreased in patients with ischemic heart failure and associated with cardiac function.

Soluble fibrinogen­like protein 2 (sFGL2), as a novel effector of regulatory T cells (Tregs), exhibits immune regulatory activity in several inflammatory diseases. Immune activation and persistent inflammation participate in the progression of ischemic heart failure (IHF). The present study aimed to determine serum sFGL2 levels in patients with IHF and explore the relationship between sFGL2 levels and cardiac function. A total of 104 patients with IHF and 32 healthy controls were enrolled. patients with IHF were further split into subgroups according to the New York Heart Association functional classification or left ventricular ejection fraction (LVEF). Serum sFGL2 levels and peripheral Tregs frequencies were analyzed by ELISA and flow cytometry, respectively. The suppressive function of Tregs was measured by proliferation and functional suppression assays. Serum levels of sFGL2 and circulating Tregs frequencies were significantly decreased in patients with IHF compared with healthy controls. In patients with IHF, sFGL2 levels and Tregs frequencies were decreased with the deterioration of cardiac function. Tregs from patients with IHF exhibited compromised ability to suppress CD4+CD25­ T cells proliferation and inflammatory cytokines secretion. Specifically, sFGL2 levels and Tregs frequencies positively correlated with LVEF, whereas negatively correlated with left ventricular end­diastolic dimension and N­terminal pro­brain natriuretic peptide. sFGL2 levels were positively correlated with Tregs frequencies. In conclusion, the reduction of serum sFGL2 levels are associated with the progression of IHF and sFGL2 could be used as a potential indicator for predicting disease severity.