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Introduction. Thumb fingertip injuries, often combined with phalanx fracture or torn ligament, are very common. The focus of treatment is on how to rebuild the function and shape of the thumb. Single thumb fingertip pulp injury is more common. However, due to the diverse type of injury, no uniform treatment guideline is described in the literature. Case report. A patient with extensive thumb fingertip pulp incisions, which looked like multiple parallel wounds, was admitted to our Emergency Department. We used the method of bundling to maintain the shape of the fingertip. A single suture to pass through all the incisions was performed and then the suture was tied outside the skin. After that, we bandaged them with sterile bandages. Finally, good contour and fingertip function were restored. Conclusion. We successfully used the bundling method to treat patient with extensive thumb fingertip pulp incisions.

Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are linked to intracranial aneurysm (IA) formation and progression. Long antisense noncoding RNA in the INK4 locus (ANRIL) has been reported to regulate VSMC functions in several cardiovascular diseases. However, little is known about how ANRIL influences VSMC proliferation and apoptosis during IA pathogenesis. The expression level of ANRIL in the plasma and arterial wall tissues of patients with IA was detected by real-time quantitative polymerase chain reaction. The functional role of ANRIL in the regulation of VSMC proliferation and apoptosis and its downstream regulatory mechanism were determined using Cell Counting Kit 8, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated UTP nick end labeling, western blotting, luciferase reporter assay, and RNA immunoprecipitation assay. ANRIL was downregulated in the plasma and arterial wall tissues of patients with IA, when compared with control groups. Overexpression of ANRIL significantly promoted VSMC proliferation and blocked cell apoptosis. Mechanistic studies demonstrated that ANRIL directly bound to microRNA-7 (miR-7) and that overexpression of miR-7 overturned the increased cell proliferation and decreased cell apoptosis, which was induced by ANRIL restoration. Besides, further study showed that ANRIL positively regulated fibroblast growth factor 2 (FGF2) expression via targeting miR-7. These results suggested that ANRIL affects VSMC proliferation and apoptosis via regulation of the miR-7/FGF2 pathway in IA, which provided a potential novel strategy for the treatment of IA.

Knee osteoarthritis-associated bone marrow edema-like lesions (KOA-BMLs) is a common MRI imaging feature, which is mainly manifested as abnormal bone marrow hyperintensity in subchondral bone on T2 imaging. The formation of KOA-BMLs may be related to the abnormality of lower limb force line and subchondral bone perfusion, and related histopathological studies showed that the remodeling of bone and bone marrow in these damaged areas was abnormally increased. In KOA patients, the size of BMLs can fluctuate or even disappear in a relatively short period of time, and was closely related to pain, subchondral bone cyst formation, and the progression of KOA. However, the current treatment methods for KOA-BMLs are limited, and there is no uniform guideline or expert consensus, mainly includingmedication, physical therapy and surgical treatment. This article reviews the research progress of the disease characteristics and treatment of KOA-BMLs in order to provide guidance for the clinical diagnosis and treatment of KOA-BMLs.

The most common nongranular fillers are sheet and fiber. When they are distributed along the heat flux direction, the thermal conductivity of the composite increases greatly. Meanwhile, the filler contact also has a large effect on the thermal conductivity. However, the effect of filler contacts on the thermal conductivity of the composite with directional fillers has not been investigated. In this paper, combined effects of the filler contact, content, and orientation are investigated. The results show that the effect of filler orientations on the thermal conductivity is greater than filler contacts in the low filler content, and the exact opposite in the high filler content. The effect of filler contacts on fibrous and sheet fillers is far greater than cube and sphere fillers. This rule is affected by the filler contact. The filler content of 8% is the ideal percolation threshold of composites with fibrous and sheet fillers. It is lower than cube filler and previous reports. The space for the thermal conductivity growth of composites with directional fillers is still very large. The effect of the interfacial thermal resistance should be considered in predicting the thermal conductivity of the composite under high interfacial thermal resistances (>10−4).

Background: To observed the effect of autophagy in tibial growth plate chondrocytes on apoptosis in chronic renal insufficiency(CRI) rats.Method: Male 4-week-old Sprague Dawley(SD) rats were randomly divided into two groups (n=20/per group): (1) the normal group was intragastrically administered distilled water; and (2) the CRI group was given a 150 mg/(kg·d) adenine suspension. All rats were sacrificed after continuous gavage for 6 weeks. The tibial length and the width of the tibial growth plate were measured using micro-CT. The width of the tibial growth plate was also measured in histological sections at both 4 w and 10 w. The level of the autophagy marker Beclin-1 in chondrocytes was measured by immunofluorescence. The level of glycogenin-1, a marker of intracellular glycogen accumulation, was measured by immunohistochemistry in chondrocytes in vivo and in vitro. The apoptosis rate of chondrocytes was measured by the TUNEL method in vivo and in vitro.Results: The results showed that the length of tibia was shorter and the width of tibia growth plate was narrower in CRF young rats. Autophagy level of chondrocytes in tibial growth plate decreased, and accumulation of glycogen granules in chondrocytes increased significantly. Meanwhile, the apoptosis rate of chondrocytes in tibial growth plate increased.Conclusion: When CRF occurred in young rats, the autophagy level of chondrocytes in tibial growth plate decreased significantly.As a result, there are not enough autophagic vesicles to swallow glycogen granules in chondrocytes and degrade them into glucose for energy supply, which leads to chondrocyte apoptosis.Autophagy of chondrocytes is at least partly involved in energy metabolism of cells.

Background The aim of our study was to observe the quantitative changes in tibial plateau chondrocytes in the proliferation process from normal Gottingen pigs in vitro and compare them with the Fibonacci sequence.Methods Chondrocytes from normal Gottingen pig tibial plateau cartilage were isolated and cultured to the third generation, and the number of chondrocytes was measured to determine whether the chondrocyte growth was at the logarithmic growth phase. Chondrocytes were added to cell culture bottles at very a low density to allow full separation and allow each chondrocyte to grow as independently as possible. Thirty single chondrocytes were selected, and the number of chondrocyte colonies were observed and recorded every day. Results Among the 30 chondrocyte colonies, the changes in the numbers of 16 chondrocyte colonies were 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, 233, 377, 610, and 987, which conformed to the numbers of the Fibonacci sequence.The number of other chondrocyte colonies was lower than corresponding numbers of the Fibonacci sequence at the same time point.Conclusion The numbers of normal Gottingen pig tibial plateau chondrocytes during the proliferation process were in line with the numbers of the Fibonacci sequence.Alignment to the Fibonacci sequence may be the fastest way for changes in the numbers of normal chondrocytes during the proliferation process in vitro.

Objective The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. Design Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group, and a 3-methyladenine (3-MA) group. Intracellular glycogen accumulation and chondrocyte apoptosis were assessed by altering the level of autophagy in chondrocytes in vivo. Results When spontaneous OA occurred in guinea pigs, autophagy levels in tibial plateau chondrocytes decreased, while intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the level of autophagy in tibial plateau chondrocytes in guinea pigs with OA, intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased, while inhibiting autophagy had the opposite effects. Conclusion The results indicate that the function of autophagy in chondrocytes may at least partly involve the catabolism of glycogen. In guinea pigs with OA, the level of autophagy in tibial plateau chondrocytes decreased, and chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for chondrocytes and increased apoptosis.

Increasing evidence suggests that triggering receptor expressed on myeloid cells 2 (TREM2) is implicated in the pathophysiology of neuroinflammation. The aim here was to investigate the neuroprotective role of TREM2 and its regulatory mechanism after subarachnoid hemorrhage (SAH). TREM2 siRNA was administered to measure the detrimental role of TREM2 in mediating microglial polarization in vivo and in vitro after experimental SAH. The relationship between Toll-like receptor 4 (TLR4) signaling and TREM2 was further explored. The soluble TREM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The results showed that TREM2 mainly located in the microglia and presented a markedly delayed elevation after SAH. TREM2 knockdown triggered increased pro-inflammatory productions, aggravated microglial activities, and further exacerbated neurological dysfunction after SAH. Significantly, TLR4 knockout increased the expression of TREM2, accompanied by ameliorated neuroinflammation and improved neurological function. Corresponding to different clinical Hunt–Hess grades, obviously enhanced accumulation of soluble TREM2 was detected in the CSF of patients with SAH. TREM2 played a pivotal role in mediating microglial polarization after SAH, and the neuroprotective effect of TREM2 might be potentially suppressed by the hyperactive TLR4 in the early phase of SAH. Pharmacological targeting of TREM2 may be a promising strategy for SAH therapy.

Objective: To observe the significance of subchondral bone microfracture in the human osteoarthritic tibial plateau on cartilage tidemark drift.Methods: Human knee tibial plateau cartilage samples with different OARSI grades were obtained, and the numbers of cartilage tidemarks and microfracture lines were determinedafter safranin O staining and compared among groups. Osteogenesis caused by microfracture in subchondral bone was observed and staged according to biological properties.Immunohistochemistry, western blotting, PCR and laser microdissection were performedto detect the biological properties of osteogenic areas caused by microfractures.The accompanying relationship between the ossification process and new tidemark formation inosteogenic areas caused by microfractures was then evaluated.Results: With the increase in OARSI grade, the numbers of cartilage tidemarks and subchondral bone microfracture lines in human knee tibial plateau cartilage tissue samples showed increasing trends.The subchondral bone microfracture line was observed toextend as far asthe basal area of hyaline cartilage and cause endochondral osteogenesis.The endochondral osteogenesis caused by subchondral microfracture was categorized into chondrocyte,calcareous sedimentary and ossification stages. A new tidemark appeared in the osteogenic region near the hyaline cartilage when the ossification process of the osteogenic region was completed.Conclusions:Endochondral osteogenesis canoccur at the base of hyaline cartilage induced by microfractures in the tibial plateau subchondral bone. A new cartilage tidemark can form on the side of the osteogenic tissue close to hyaline cartilage when the process of osteogenesis is completed.There is a positive correlation between the degree of cartilage tissue degeneration and the number of tidemarks in articular cartilage.

Nearly 10% of patients undergoing primary total knee arthroplasty (TKA) have valgus deformity (VD) of the knee. For severe VD of the knee, a more lateral structural release is needed to achieve balance between medial and lateral space and neutral femorotibial mechanical axis (FTMA), which is challenging and technical.To introduce a new surgical technique of resection, soft tissue release, and FTMA for Ranawat type-II VD with a 5-year follow-up.A retrospective study was conducted on patients who underwent TKA from December 2011 to December 2014. Hip-knee-ankle (HKA), range of motion (ROM), Oxford knee score (OKS), and knee society score (KSS) were used to assess the joint activity of patients in the new theory TKA group (NT-TKA) and were compared with those of the conventional TKA group (C-TKA).A total of 103 people (103 knees) were included in this study, including 42 patients with an average follow-up period of 83 mo in the C-TKA group and 61 patients with an average follow-up period of 76 mo in the NT-TKA group. Six patients had constrained prosthesis, one had common peroneal nerve injury, and two had joint instability in the C-TKA group, but none of these occurred in the NT-TKA group. There were significant statistical differences in constrained prosthesis usage and complications between the groups (Adopting 5°-7° valgus cut angle for VD and sacrificing 2° neutral FTMA for severe VD which cannot be completely corrected during TKA can reduce the need for soft tissue release, maintain early joint stability, reduce the use of constrained prostheses, and minimize postoperative complications.

Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.

Contact of a flammable liquid and water can cause hazardous boilover because of their different boiling points. The dependence of the initial boilover point of a flammable liquid on atmospheric pressure was studied at different geographic locations with different altitudes, i.e., at HeFei (alt., 0 m; P, 101 kPa) and on Lhasa plateau (alt., 3650 m; P, 64 kPa). The temperatures in the bulk and at the interface of the flammable liquid and water, flame temperature, thermal radiation, sound level, and mass loss at ambient temperature were experimentally measured using identical transparent quartz pans for each measurement. The experimental results showed that boilover was delayed or diminished at low pressure and disappeared completely at pressures lower than a certain critical value for this pan surface area. The pan size was shown not to affect the boilover onset or intensity.

Background: To observe the effect of high expression of the tyrosine kinase Fyn on chondrocyte differentiation in the tibial growth plate of young rats with chronic renal failure (CRF) and to explore the related molecular mechanism. Methods: The level of Fyn, the levels of the key Wnt/β-catenin pathway protein β-catenin and its phosphorylated form, p-β-catenin (Tyr142), and the level of the chondrocyte differentiation marker collagenX were observed in the CRF group in vivo and in vitro. The direct effect of Fyn and p-β-catenin in the cytoplasm of chondrocytes of rats with CRF was observed by using coimmunoprecipitation (co-IP). The levels of p-β-catenin (Tyr142), β-catenin and collagenX were observed after altering the Fyn levels in the chondrocytes of rats with CRF. Results: When CRF occurred in young rats, the level of Fyn in chondrocytes increased, the levels of p-β-catenin (Tyr142) and β-catenin in the Wnt/β-catenin pathway increased, and the level of the chondrocyte differentiation marker collagenX increased. The levels of p-β-catenin (Tyr142), β-catenin and collagenX were obviously increased when the Fyn level was increased in the chondrocytes of rats with CRF. In contrast, the levels of p-β-catenin (Tyr142), β-catenin and collagenX significantly decreased when the Fyn level was decreased. The Fyn protein and the p-β-catenin (Tyr142) protein directly interacted in the cytoplasm of the chondrocytes from the CRF group. Conclusion: The level of the tyrosine kinase Fyn in the tibial growth plate chondrocytes of young rats with CRF significantly increased, and the levels of the wnt/β-catenin pathway-related protein β-catenin and its phosphorylated form, p-β-catenin (Tyr142), significantly increased. Fyn could promote β-catenin phosphorylation (Tyr142) and cause it to be released from the α-catenin and cadherin complex and enter the cytoplasm of chondrocytes. p-β-catenin (Tyr142) could be transformed into β-catenin by dynamic equilibrium in the cytoplasm of chondrocytes, or p-β-catenin (Tyr142) could enter the nucleus of chondrocytes from the cytoplasm, thus activating the wnt/β-catenin pathway and accelerating the differentiation of chondrocytes. Funding: This work was supported by grants from the China Postdoctoral Science Foundation (2020M680910), Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (no.20210019),the Natural Science Foundation of Shanxi Province of China (no. 201701D121161) and the Key Research and Development Projects of Shanxi Province (no. 201803D31160). Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethics Committee of Shanxi Medical University [Approval number:SXMUE(2019004)] (Tai Yuan,China).

During the development of knee osteoarthritis(OA), chondrocyte colony-like clusters occur in cartilage tissue. However, the significance of chondrocyte colony-like cluster formation in cartilage tissue remains unclear. In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee OA,and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue. The resulte showed that chondrocyte colony-like clusters mainly formed in the OARSI grades 3 and 4 cartilage tissue,which could divide into four stages according to the quantity and biological properties of the chondrocytes inside the cluster.The chondrocyte colony-like clusters in cartilage tissue could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration. To understand this, we further clarified the development of this disease and provided a new direction for the treatment of knee OA.

BACKGROUND: Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow. OBJECTIVE: To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients. DESIGN: Randomized community intervention trial. PARTICIPANTS: The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China. MAIN MEASURES: Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention. KEY RESULTS: BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P

Background To observe the sequence of chondrocyte degeneration and matrix degradation in the superficial surface cartilage of the tibial plateau in guinea pigs with spontaneous knee osteoarthritis (OA). Methods Sixty guinea pigs were euthanized at the ages of 8 months (n = 20),10 months (n = 20) and 12 months (n = 20) respectively. The degree of degeneration of the tibial plateau cartilage was evaluated by Osteoarthritis Research Society International (OARSI) score. The levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the chondrocytes were detected by immunohistochemistry (IHC). The serum concentration of CTX-II was measured and compared. Western blot analysis was used to detect the levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the cartilage tissue. Results The OARSI scores both in 8-month-old group and 10-month-old group were lower than that in the 12-month-old group. The levels of Aggrecan in articular chondrocyte were higher both in 8-month-old group and 10-month-old group than that in 12-month-old group. The level of Collagen X increased with the age of guinea pigs. And the levels of MMP-13 and caspase-3 both in 10-month-old group and 12-month-old group were higher than those in 8-month-old group. The concentration of CTX-II in serum increased significantly in 12 months old group. Conclusion The superficial chondrocytes of the tibial plateau first appeared to be hypertrophic and then apoptotic, and the matrix was further degraded when spontaneous knee osteoarthritis occurred in guinea pigs. Changes in the physiological state of chondrocytes are the initiating factors in the pathogenesis of knee OA.

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR‐483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA‐seq and bioinformatics analyses showed that miR‐483 targets several PAH‐related genes, including transforming growth factor‐β (TGF‐β), TGF‐β receptor 2 (TGFBR2), β‐catenin, connective tissue growth factor (CTGF), interleukin‐1β (IL‐1β), and endothelin‐1 (ET‐1). Overexpression of miR‐483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF‐β, TGFBR2, β‐catenin, CTGF, IL‐1β, and ET‐1. In contrast, inhibition of miR‐483 increased these genes in ECs. Rats with EC‐specific miR‐483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR‐483. These results indicate that PAH is associated with a reduced level of miR‐483 and that miR‐483 might reduce experimental PH by inhibition of multiple adverse responses., This study reveals a protective role for miR‐483 in the development of pulmonary arterial hypertension (PAH). Overexpression of miR‐483 in endothelial cells (ECs) inhibits inflammatory and fibrogenic responses and leads to ameliorated pulmonary hypertension phenotypes in rats.

Rhodamine B (RhB), widely used as an industrial dye, is a toxic organic that is hazardous to human health and can cause water pollution. In this study, the removal rate of RhB was investigated by the following methods: hydrodynamic cavitation (HC) operated individually, and HC combined with oxidants H

Background: To observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. Methods: Fifty 2-month-old female Hartley guinea pigs were divided into a normal group, which was euthanized after 7 months, and an OA group, ten of which were euthanized after 10 months. Immunohistochemistry, PCR and western blotting were used to evaluate the level of autophagy, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group and a 3-MA group. Intracellular glycogen accumulation and chondrocyte apoptosis were observed by changing the level of autophagy in chondrocytes in vivo. Findings: When spontaneous OA occurred in the guinea pigs, the level of autophagy in tibial plateau chondrocytes decreased,and intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the autophagy level of tibial plateau chondrocytes in OA guinea pigs, the intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased. When the autophagy level of the chondrocytes was weakened, intracellular glycogen accumulation was further increased, and the apoptosis rate was higher. Interpretation: The autophagy function of chondrocytes may be at least partly involved in the catabolism of glycogen in chondrocytes. In OA guinea pigs, the autophagy level in tibial plateau chondrocytes decreased, and the chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for the chondrocytes and increased apoptosis. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (no. 81572098), Natural Science Foundation of Shanxi Province of China (no.201701D121161) and Key Research and Development Projects of Shanxi Province (no.201803D31160). Declaration of Interests: None declared. Ethics Approval Statement: This study was approved by the Ethics Committee of Shanxi Medical University (approval number: SXMUE2019004). All experiments were performed in accordance with the Public Health Service Policy and the Guide to the Care and Use of Laboratory Animals.

Th2 response is implicated in the pathogenesis of PAH. Chen et al. demonstrate that CRTH2-mediated Th2 activation is exaggerated in patients with PAH and mouse PAH models, and pharmacological inhibition of CRTH2 attenuates experimental PAH by suppression of IL-4 and IL-13., Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary artery (PA) remodeling. T helper 2 cell (Th2) immune response is involved in PA remodeling during PAH progression. Here, we found that CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cell) expression was up-regulated in circulating CD3+CD4+ T cells in patients with idiopathic PAH and in rodent PAH models. CRTH2 disruption dramatically ameliorated PA remodeling and pulmonary hypertension in different PAH mouse models. CRTH2 deficiency suppressed Th2 activation, including IL-4 and IL-13 secretion. Both CRTH2+/+ bone marrow reconstitution and CRTH2+/+ CD4+ T cell adoptive transfer deteriorated hypoxia + ovalbumin–induced PAH in CRTH2−/− mice, which was reversed by dual neutralization of IL-4 and IL-13. CRTH2 inhibition alleviated established PAH in mice by repressing Th2 activity. In culture, CRTH2 activation in Th2 cells promoted pulmonary arterial smooth muscle cell proliferation through activation of STAT6. These results demonstrate the critical role of CRTH2-mediated Th2 response in PAH pathogenesis and highlight the CRTH2 receptor as a potential therapeutic target for PAH.

Background Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. Method A single subcutaneous injection of monocrotaline (MCT) (60 mg kg− 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. Results Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. Conclusion The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.

Aim: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. Materials & methods: Prospective randomized trials were included. p-score was used to rank treatment effects. Results: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79–0.95). Combination therapy had more grade 3–5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. Conclusion: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.

Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8-9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.

Use the mobile platform (taking Chaoxing APP as an example) to assist the teaching of principles and equipment of medical imaging course. Then evaluate the teaching effect by measurement data, questionnaire survey and interview. The results indicate that, this teaching mode with mobile platform is applicable not only in principles and equipment of medical imaging course, but also in providing a reference value in teaching reform in medical universities, for its function of improving students’ subjective initiative and strengthening the communication between teachers and students.

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. The genetic basis of IPAH needs further investigation.To identify novel IPAH susceptibility genes other than BMPR2.This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018.PTGIS rare variants.Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing. Functional assessments were conducted to analyze the effects of identified genetic variants on transcript splicing, enzymatic activity, and endothelial cell phenotypes.Among 230 patients with IPAH (164 female [71.3%]; mean [SD] age, 34 [18] years), an enrichment of rare variants in a gene encoding prostacyclin synthase (PTGIS) was identified in the discovery cohort. The association of PTGIS rare variants with IPAH was confirmed in the replication cohort. In the combined data set, PTGIS rare variants were found in 14 of 230 cases (6.1%) and 8 of 968 controls (0.8%) (odds ratio, 7.8; 95% CI, 3.2-18.8; P = 5 × 10-6, logistic regression). Compared with patients without PTGIS variants, inhaled iloprost induced a more significant decrease of pulmonary vascular resistance (difference in the least square mean, -21.7%; 95% CI, -31.4% to -12.0%; P .001, linear regression model) and an increase of cardiac index (difference in the least square mean, 18.3%; 95% CI, 8.8%-27.8%; P .001, linear regression model) in patients with PTGIS variants. The minigene assay indicated that the c.521 + 1GA variant resulted in aberrant messenger RNA transcripts. The functional studies showed that the 2 missense rare variants (R252Q and A447T) resulted in a decrease in prostacyclin production and increased cell death of pulmonary microvascular endothelial cells.This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.

Background: Epstein–Barr virus-associated gastric cancer (EBVaGC) has unique clinicopathologic features and our present understanding of its treatment outcome is limited. Here, we investigated the clinical outcomes of resectable and metastatic EBVaGC cases with regards to their respective treatment. Methods: We retrieved the data of EBVaGC patients treated at our center from October 2014 to June 2019. The primary endpoint was overall survival (OS). Secondary endpoints were disease-free survival (DFS) for stage I–III patients, progression-free survival (PFS) and objective response rate (ORR) for stage IV patients. Results: Patients classified as stage I–III accounted for 83.7% of the total 197 cases analyzed. Two patients had mismatched repair-deficiency. The 5-year OS rate of the entire cohort was 63.51% [95% (confidence interval (CI): 52.31–72.76%]. Tumor-node-metastasis (TNM) stage and gastric stump cancer were identified as independent prognostic factors for OS. The 3- and 5-year DFS rate for stage I–III patients were 83.72% (95% CI: 75.86–89.19%) and 73.83% (95% CI: 60.39–83.32%), respectively. TNM stage III, neural invasion, lymphovascular invasion, and baseline plasma EBV-DNA positive were correlated with shorter DFS. The ORR and disease control rate (DCR) for metastatic EBVaGC patients to first-line therapy were 29.0% and 90.3% (median PFS: 9.8 months), respectively, and to second-line therapy were 25.0% and 75.0%, respectively. Seven patients received anti-PD1 therapy and had an ORR of 28.5% and a median PFS of 2.8 months. Conclusions: EBVaGC patients have few metastases, long DFS, and high DCR. TNM stage and gastric stump cancer were independent prognostic factors for OS.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases.We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function.The gene encoding human bone morphogenetic protein 9 (We identify

Sanger sequencing, the traditional “gold standard” for mutation detection, has been wildly used in genetic testing of pulmonary artery hypertension (PAH). However, with the advent of whole-exome sequencing (WES), few studies have compared the accuracy of WES and Sanger sequencing in routine genetic testing of PAH. PAH individuals were enrolled from Fu Wai Hospital and Shanghai Pulmonary Hospital. WES was used to analyze DNA samples from 120 PAH patients whose bone morphogenetic protein receptor type 2 (BMPR2) mutation statuses had been previously studied using Sanger sequencing. The Sanger sequencing and WES agreement was 98.3% (118/120) with near-perfect agreement (κ coefficient = 0.848). There was no significant difference between the two methods on the McNemar–Bowker test ( P > 0.05). Twenty-one BMPR2 mutation carriers and 99 non-carriers were detected by Sanger sequencing. Among the 21 BMPR2 carriers detected by Sanger sequencing, one variant (c.1040 T > A) was not found by WES. Among the 99 BMPR2 non-carriers, WES detected an extra mutation carrier (c.76 + 1 G > C) missed by Sanger sequencing. Both false-positive and false-negative results were highly conserved and were re-analyzed by Sanger sequencing. WES improved the accuracy of Sanger sequencing and detected 1% (1/99) false-positive and 4.8% (1/21) false-negative results of Sanger sequencing. No false-positive and false-negative results of WES were identified in our analysis. WES is non-inferior to Sanger sequencing and may play a more important role in genetic testing of PAH patients in the future.

Polymeric heat exchangers are widely used in various industries. However, their low thermal conductivity has limited their practical applications. Adding fillers with high thermal conductivity to the base materials has been recognized as an efficient way to increase the thermal conductivity of polymers. Filler contents have great impacts on the overall effective thermal conductivity of composite materials. Increasing filler content is the most direct and efficient way to prepare materials of super-high thermal conductivity. Previous researches were confined to volumetric filler content less than 20%. Higher filler contents were not considered due to possible filler aggregation. In this study, the effects of filler contents higher than 20% are investigated, with simultaneous considerations of random distribution of fillers in the base material and fillers aggregation. The interactions between the fillers, and between the fillers and the base material, are studied to predict the effective thermal conductivi...

Background The human phenome has been widely used with a variety of genomic data sources in the inference of disease genes. However, most existing methods thus far derive phenotype similarity based on the analysis of biomedical databases by using the traditional term frequency-inverse document frequency (TF-IDF) formulation. This framework, though intuitive, not only ignores semantic relationships between words but also tends to produce high-dimensional vectors, and hence lacks the ability to precisely capture intrinsic semantic characteristics of biomedical documents. To overcome these limitations, we propose a framework called mimvec to analyze the human phenome by making use of the state-of-the-art deep learning technique in natural language processing. Results We converted 24,061 records in the Online Mendelian Inheritance in Man (OMIM) database to low-dimensional vectors using our method. We demonstrated that the vector presentation not only effectively enabled classification of phenotype records against gene ones, but also succeeded in discriminating diseases of different inheritance styles and different mechanisms. We further derived pairwise phenotype similarities between 7988 human inherited diseases using their vector presentations. With a joint analysis of this phenome with multiple genomic data, we showed that phenotype overlap indeed implied genotype overlap. We finally used the derived phenotype similarities with genomic data to prioritize candidate genes and demonstrated advantages of this method over existing ones. Conclusions Our method is capable of not only capturing semantic relationships between words in biomedical records but also alleviating the dimensional disaster accompanying the traditional TF-IDF framework. With the approaching of precision medicine, there will be abundant electronic records of medicine and health awaiting for deep analysis, and we expect to see a wide spectrum of applications borrowing the idea of our method in the near future.

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15–70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend