Quantitative anatomical analysis of lumbar interspaces based on 3D CT imaging: optimized segment selection for lumbar puncture in different age groups.

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.

[Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome: a Meta-analysis].

Meta-analysis of randomized controlled trials( RCTs) was conducted to clarify the effect of Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome. Databases including CNKI,Wan Fang,VIP,Sino Med,PubMed,EMbase,the Cochrane Library were searched until September,2018. Two reviewers independently assessed study eligibility,extracted data,and evaluated the risk of bias for included trials. Meta-analysis used Review Manager 5. 3 software. Seven RCTs( n = 634) were included.RESULTS: of Meta-analysis indicated that,Bushen Huoxue herbal medicine had advantages on increasing pregnancy rate,lowering LH,T and INS. Bushen Huoxue herbal medicine were not clear on increasing ovulation rate,increasing FSH. No serious adverse reaction appearing from Bushen Huoxue herbal medicine was reported in the including researches. The current Meta-analysis showed a promising effect of Bushen Huoxue herbal medicine in subfertile women with polycystic ovary syndrome,but the quality of current evidence was low and possible publication bias.

[Bushen Huoxue herbal medicine for treating hyperprolactinemia in women: a Meta-analysis].

The clinical efficacy of Bushen Huoxue traditional Chinese medicine( TCM) in the treatment of hyperprolactinemia were systematically evaluated,which provided evidence-based medical evidence for the treatment of hyperprolactinemia with Bushen Huoxue traditional Chinese medicine. The randomized controlled trials on the treatment of hyperprolactinemia with Bushen Huoxue traditional Chinese medicine were comprehensively searched by computer in PubMed,EMbase,Cochrane Library,CNKI,Wan Fang,VIP,CBM and Meta-analysis was performed. The search time is from the time of self-built database to September 28,2018. A total of 816 patients with hyperprolactinemia met the inclusion criteria in 13 clinical studies. The results of Meta-analysis showed that compared with Western medicines,traditional Chinese medicine for tonifying kidney and activating blood circulation had a comparable effect in reducing prolactin and treating infertility,and had obvious advantages in improving of TCM syndromes,disease recurrence and reducing of side effects.

[Research on XOD captured components in Lagotis brevituba based on UPLC-Q-TOF-MS and molecular docking technology].

Potential xanthine oxidase (XOD) inhibitors in Lagotis brevituba were captured by using affinity and ultrafiltration. The structures of the captured components were identified by ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS). The binding intensity and binding mechanism between the captured components and XOD were analyzed by using molecular docking software Autodock 4.2. A total of 17 compounds were identified, including 9 flavonoids, 5 phenolic acids and 3 triterpenes. Molecular docking results showed that all the captured components could be spontaneously bound with XOD mainly via hydrogen bond, Van der Waals' force and hydrophobic interaction. From the perspective of binding energy and scoring function, the collected fractions all had potential prospects for XOD inhibitors, and the flavonoid luteolin-3',7 glucuronide had the best effect. The results also showed that affinity and ultrafiltration, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and molecular docking technology can provide a powerful tool for the analysis of XOD inhibitor components in natural products.

The spectrum of BRCA mutations and characteristics of BRCA-associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next-generation sequencing.

To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

Effects of cyanobacteria- and moss-biocrusts on soil aggregate stability and splash erosion in croplands of the China Mollisols area.

To investigate the effects of biocrusts development on aggregate stability and splash erosion of Mollisols and to understand its function in soil and water conservation, we collected biocrusts (cyano crust and moss crust) samples in croplands during the growing season and measured the differences in aggregate stability between biocrusts and uncrusted soil. The effects of biocrusts on reduction of raindrop kinetic energy were determined and splash erosion amounts were obtained with single raindrop and simulated rainfall experiments. The correlations among soil aggregate stability, splash erosion characteristics, and fundamental properties of biocrusts were analyzed. The results showed that compared to uncrusted soil, the cyano crust and the moss crust decreased the proportion of soil water-stable aggregates <0.25 mm by 10.5% and 21.8%, respectively, while their soil water-stable aggregates 5-10 mm were 4.0 and 8.8 times as that of uncrusted soil. In contrast to uncrusted soil, the macroaggregate content (R0.25), mean weight diameter (MWD), and geometric mean diameter (GMD) of biocrusts were 31.5%, 76.2%, and 33.5% higher, respectively. In addition, biocrusts reduced raindrop kinetic energy by an average of 0.48 J compared to uncrusted soil. The breakthrough raindrop kinetic energy of cyano crust and moss crust were 2.9 and 26.2 times as that of uncrusted soil, while the reduction of raindrop kinetic energy by cyano crust with high biomass was 1.3 and 6.6 times as that of medium and low biomass, respectively. Under the single raindrop and simulated rainfall conditions, biocrusts reduced splash erosion amounts by 47.5% and 79.4%, respectively. The proportion of aggregates >0.25 mm in the splash soil particles of biocrusts (37.9%) was 40.3% lower than that of uncrusted soil, while the proportion of aggregates >0.25 mm decreased as biocrust biomass increased. Moreover, the aggregate stability, splash erosion amount, and fundamental properties of biocrusts were significantly correlated. The MWD of aggregates was significantly and negatively correlated with the splash erosion amount under single raindrop and simulated rainfall conditions, indicating that the improved aggregate stability of surface soil caused by biocrusts accounted for reducing splash erosion. The biomass, thickness, water content, and organic matter content of biocrusts had significant effects on aggregate stability and splash characteristics. In conclusion, biocrusts significantly promoted soil aggregate stability and reduced splash erosion, which had great significance to soil erosion prevention and the conservation and sustainable utilization of Mollisols.

[Characteristics of biocrusts in croplands and their effects on surface soil disintegration in the black soil region of Northeast China]. / ä¸œåŒ—é»‘åœŸåŒºå†œç”°ç”Ÿç‰©ç»“çš®çš„ç‰¹å¾åŠå ¶å¯¹è¡¨å±‚åœŸå£¤å´©è§£çš„å½±å“.

We selected typical croplands in the black soil region of Northeast China to analyze the characteristics of biocrusts during the growing season, including species composition, thickness, coverage, and biomass (chlorophyll content). We collected bareground soil and biocrusts samples with chlorophyll content of 5-15, 15-25, 25-35, and 35-50 mg·g-1, and measured the soil disintegration rate and soil maximum disintegration ratio of each sample using a force gauge in the laboratory. The results showed that: 1) biocrusts dominated by algae and moss were frequently developed in the croplands, with Stigeoclonium and Bryum capillare as the most common species, respectively. The thickness and biomass of algal crusts were significantly lower than moss crusts, with a successional trend from algal crusts to moss crusts. 2) The coverage, thickness, and biomass of biocrusts in croplands were negatively correlated with the frequency and intensity of tillage disturbance. For instance, the values of those characterisitics were only 27.8%, 1.52 mm, and 6.49 mg·g-1 on average, respectively, in traditional tillage croplands, and increased to 83.5%, 2.74 mm, and 34.16 mg·g-1, respectively, in the croplands with conservational tillage. 3) Biocrusts considerably reduced the disintegration of surface soil, particularly in the layer of biocrusts. Compared to the bareground soil, the soil disintegration rate of biocrusts, with four levels of biomass (with chlorophyll content of 5-15, 15-25, 25-35, and 35-50 mg·g-1), was reduced by 43.1%, 50.1%, 55.5%, and 59.8%, respectively, while the soil maximum disintegration ratios were reduced by 11.4%, 17.7%, 33.2%, and 36.6%, respectively. 4) Soil disintegration rate and maximum disintegration ratio were significantly and negatively correlated with the biomass and thickness of biocrusts, indicating that the impacts of biocrusts on soil disintegration were primarily caused by the improvements in physical properties of surface soil. In conclusion, biocrusts were frequently deve-loped in croplands in the black soil region of Northeast China, owing to less disturbance following the conversion from traditional tillage to conservational tillage. They had the potential to protect surface soil against disintegration and improve soil anti-scourability, which was critical for soil conservation in croplands in this region.

Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles.

BACKGROUND: Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty. Up to now, there is no effective treatment for wear particles-induced osteolysis except for the revision surgery, which is a heavy psychological and economic burden to patients. A metabolite of gut microbiota, short chain fatty acids (SCFAs), has been reported to be beneficial for many chronic inflammatory diseases. This study aimed to investigate the therapeutic effect of SCFAs on osteolysis. METHODS: A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium. After two weeks of intervention, the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by Micro-CT analysis and immunohistochemistry staining. In vitro study, lipopolysaccharide (LPS) primed bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate (C2), propionate (C3), and butyrate (C4). Western blotting, Enzyme-linked immunosorbent assay, and immunofluorescence were used to detect the activation of NLRP3 inflammasome. The effects of SCFAs on osteoclasts were evaluate by qRT-PCR, Western blotting, immunofluorescence, and tartrate-resistant acid phosphatase (TRAP) staining. Additionally, histone deacetylase (HDAC) inhibitors, agonists of GPR41, GPR43, and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis. RESULTS: C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits (P < 0.001), higher level of bone volume to tissue volume (BV/TV, P < 0.001), bone mineral density (BMD, P < 0.001), and a lower total porosity (P < 0.001). C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleation-induced oligomerization, suppressing the cleavage of caspase-1 (P < 0.05) and IL-1ß (P < 0.05) stimulated by CoCrMo alloy particles. C3 and C4 also inhibited the generation of Gasdermin D-N-terminal fragment (GSDMD-NT) to regulate pyroptosis. Besides, C3 and C4 have a negative impact on osteoclast differentiation (P < 0.05) and its function (P < 0.05), affecting the podosome arrangement and morphologically normal podosome belts formation. CONCLUSION: Our work showed that C3 and C4 are qualified candidates for the treatment of wear particle-induced osteolysis.

Potential Natural Small Molecular Compounds for the Treatment of Chronic Obstructive Pulmonary Disease: An Overview.

Chronic obstructive pulmonary disease (COPD) is one of the major diseases threatening human life and health. According to the report released by the World Health Organization (WHO) in 2020, COPD has become the third leading cause of death in the world, featuring a sustainable growth of incidence rate as well as population age. The purpose of this review focuses on the advancement of bioactive natural compounds, such as baicalin, quercetin, resveratrol, and curcumin, which demonstrate promising therapeutic/interventional effects on CODP in vitro and in vivo. Information emphasizing on COPD was systematically collected from several authoritative internet databases including Web of Science, PubMed, Elsevier, Wiley Online Library, and Europe PMC, with a combination of keywords containing "COPD" and "natural small molecular compounds". The new evidence indicated that these valuable molecules featured unique functions in the treatment of COPD through various biological processes such as anti-inflammatory, anti-oxidant, anti-apoptosis, and anti-airway fibrosis. Moreover, we found that the promising effects of these natural compounds on COPD were mainly achieved through JAK3/STAT3/NF-κB and MAPK inflammatory signaling pathways, Nrf2 oxidative stress signaling pathway, and TGF-ß1/Smad 2/3 fibrosis signaling pathway, which referenced to multiple targets like TNF-α, IL-6, IL-8, TIMP-1, MMP, AKT, JAK3, IKK, PI3K, HO-1, MAPK, P38, ERK, etc. Current challenges and future directions in this promising field are also discussed at the end of this review. For the convenience of the readers, this review is divided into ten parts according to the structures of potential natural small molecular compounds. We hope that this review brings a quick look and provides some inspiration for the research of COPD.

[Diphenhydramine interferes with MTT reduction assay].

OBJECTIVE: To determine the effects of organic amine diphenhydramine on the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide dye (MTT) reduction assay. METHODS: The primarily cultured cortical astrocytes were incubated with various concentrations of diphenhydramine for 24 h. To analyze the effects of diphenhydramine and other organic amines on the MTT assay, the data obtained from the MTT assay were compared with the results obtained from morphological observation and hoechst 33342 and propidium iodide (PI) nucleus double staining. RESULT: The MTT assay showed that diphenhydramine (10(-4)mol/L), pyrilamine (10 (-4)mol/L) and zolantidine (10 (-5)mol/L) caused a significant increase in MTT reduction in astrocytes. However there was no proliferation, apoptosis or necrosis detected by hoechst and PI nucleus double staining. Light microscopy revealed that exocytosis of formazan granules was inhibited by diphenhydramine. CONCLUSION: Diphenhydramine and other organic amines may enhance MTT reduction by suppression of MTT formazan exocytosis in astrocytes, which may affect the results of cell viability studies.

Nonreciprocal charge transport up to room temperature in bulk Rashba semiconductor α-GeTe.

Nonmagnetic Rashba systems with broken inversion symmetry are expected to exhibit nonreciprocal charge transport, a new paradigm of unidirectional magnetoresistance in the absence of ferromagnetic layer. So far, most work on nonreciprocal transport has been solely limited to cryogenic temperatures, which is a major obstacle for exploiting the room-temperature two-terminal devices based on such a nonreciprocal response. Here, we report a nonreciprocal charge transport behavior up to room temperature in semiconductor α-GeTe with coexisting the surface and bulk Rashba states. The combination of the band structure measurements and theoretical calculations strongly suggest that the nonreciprocal response is ascribed to the giant bulk Rashba spin splitting rather than the surface Rashba states. Remarkably, we find that the magnitude of the nonreciprocal response shows an unexpected non-monotonical dependence on temperature. The extended theoretical model based on the second-order spin-orbit coupled magnetotransport enables us to establish the correlation between the nonlinear magnetoresistance and the spin textures in the Rashba system. Our findings offer significant fundamental insight into the physics underlying the nonreciprocity and may pave a route for future rectification devices.

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

BACKGROUND: Hereditary factors contributed to breast cancer susceptibility. Low BRCA mutation prevalence was demonstrated in previous BRCA mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in. BRCA: negative breast cancers. METHODS: A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations. RESULTS: In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11, 2.9%), PTCH1 (n=7, 1.8%), RET (n=6, 1.6%) and PALB2 (n=5, 1.3%). Other mutant genes included TP53 (n=3, 0.8%), RAD51D (n=2, 0.5%), CHEK2 (n=1, 0.3%), BRIP1 (n=1, 0.3%), CDH1 (n=1, 0.3%), MRE11 (n=1, 0.3%), RAD50 (n=1, 0.3%) and PALLD (n=1, 0.3%). A splicing germline mutation, MUTYH c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer. CONCLUSIONS: Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of BRCA-negative breast cancer patients with high hereditary risk.

Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Acidic preconditioning protects against ischemia-induced brain injury.

Ischemic preconditioning protects against cerebral ischemia. Recent investigations indicated that acidic preconditioning (APC) protects against ischemia-induced cardiomyocytes injury. However, it is not clear whether APC can protect against cerebral ischemia. To address this issue, C57BL/6 mice were exposed 3 times at 10-min intervals to a normoxic atmosphere containing 20% CO(2) for 5 min before being further subjected to bilateral common carotid artery occlusion. APC reversed the ischemia-induced brain injury as revealed by improved performance in passive avoidance experiments and decreased neuron loss in the hippocampal CA1 region. Consistently, both APC-treated brain slices and primary cultured neurons were more resistant to oxygen-glucose-deprivation (OGD)-induced injury, in a pH- and time-dependent manner, as revealed by reversed cell/tissue viability. In addition, the APC treatment prevented OGD-induced mitochondrial transmembrane potential loss and apoptosis, which was inhibited by the mitochondrial permeability transport pore opener atractyloside. Taken together, these findings indicated that APC protects against ischemia-induced neuronal injury. The beneficial effects may be attributed, at least in part, to decreased mitochondria-dependent neuronal apoptosis.

NKT cell defects in NOD mice suggest therapeutic opportunities.

Recent studies have reported that immunoregulatory NKT cells are defective in NOD mice and that treatment of mice with alpha-galactosylceramide that selectively stimulate NKT cells, is anti-diabetogenic. The objective of this study was to document the natural history of changes in NKT cells in various organs in NOD mice in the period up to the time of diabetes onset so that novel intervention therapies could be devised. We found that NKT cell-specific receptor (NKT-TCR) Valpha14Jalpha281 expressions by quantitative (RealTime) RT-PCR in thymus, spleen and liver of NOD male and female mice were low at 1-3 months of life compared to BALB/c and C57BL/6 mice, albeit a transient spike in levels occurred in female NOD livers at 2 months. Female pancreases showed low levels of these transcripts despite their active and destructive insulitis. In contrast, NOD males exhibited high expression of this invariant TCR in pancreas, where their insulitis was less destructive. A survey of NKT-TCR expressions in a battery of congenic, non-diabetes prone NOD strains indicated that this NKT phenotype was quite variable but higher than diabetes prone NOD. Bone marrow transplantation of NOD females from B6.NOD-H2(g7) donors raised their NKT-TCR expressions. Tuberculin administrations in the forms of BCG and CFA in a manner known to protect NOD mice from diabetes both raised NKT-TCR levels, as did the anti-inflammatory PPAR-gamma agonist rosiglitazone. These findings provide exciting therapeutic avenues to be explored in the treatment of human immune mediated type-1 diabetes where there are similar immunoregulatory lesions.