Potential diagnostic value of PD-1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced skeletal disorder. Bone mineral density (BMD) testing is the gold standard for diagnosing osteoporosis. However, its sensitivity for fracture risk assessment is low. Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule implicated in the pathophysiology of bone remodeling, but its role in osteoporosis has not yet been explored. Thus, this study aimed to assess the expression and diagnostic utility of PD-1 in PMOP. METHODS: A total of 56 patients with PMOP and 37 postmenopausal healthy controls (NC) were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation, and PD-1 expression was measured by quantitative polymerase chain reaction (qPCR). Pearson's correlation test was performed to explore the associations between PD-1 level and clinical variables, while receiver operating characteristic (ROC) curve analysis was used to evaluate the potential diagnostic value of PD-1 in patients with PMOP. RESULTS: We found that PD-1 level was significantly upregulated in the PBMCs of PMOP patients than those of NC (P = .016). PD-1 expression was positively correlated with C-reactive protein (CRP) levels. ROC curve analysis showed that PD-1 had certain diagnostic value for PMOP (area under the curve = 0.65, standard error = 0.06, 95% confidence interval [0.53,0.76], P = .016), with a sensitivity and specificity of 44.64% and 81.08%, respectively. CONCLUSION: Programmed cell death protein 1 is significantly upregulated in the PBMCs of PMOP patients and has certain diagnostic value for PMOP.

Flexible change and cooperation between mitochondrial electron transport and cytosolic glycolysis as the basis for chilling tolerance in tomato plants.

To find if cytosolic glycolysis dynamical metabolism plays a role in mediating respiration homeostasis and its relationship with mitochondrial electron transport chain (miETC) flexibility, we selected two tomato genotypes that differ in chilling tolerance and compared the responses of miETC, cytosolic glycolysis and respiratory homeostasis at 7 °C. Our results showed that the transcripts of both classical and bypass component genes for miETC and glycolysis were comparable for both genotypes when grown at 25 °C. However, there was a rapid global increase in the expression of most respiratory genes in response to chilling at 7 °C for both genotypes. When normally grown plant was set as the control for each genotype, the transcripts of most COX family members, ATP synthase, AOX1b, and UCP are highly up-regulated in chilling-tolerant Zhefen No. 208 plants in contrast to the sensitive Zhefen No. 212 plants. Both genotypes mobilized the energy-saving sucrose synthase pathway for sucrose degradation by cytosolic glycolysis, but this mechanism is evidently more effective in tolerant Zhefen No. 208 plants. Furthermore, only Zhefen No. 208 plants were able to partially switch from low-energy efficiency pathways to ATP conserving pathways to carry out fructose-6-phosphate conversion and pyruvate production. This metabolic flexibility in miETC and cytosolic glycolysis were coupled to higher ATP synthesis and lower ROS accumulation, which may be essential for sustaining the higher leaf respiration and homeostasis of chilling-tolerant plants.

Brassinosteroid-induced CO(2) assimilation is associated with increased stability of redox-sensitive photosynthetic enzymes in the chloroplasts in cucumber plants.

Brassinosteroids (BRs) play important roles in plant growth, development, photosynthesis and stress tolerance; however, the mechanism underlying BR-enhanced photosynthesis is currently unclear. Here, we provide evidence that an increase in the BR level increased the quantum yield of PSII, activities of Rubisco activase (RCA) and fructose-1,6-bisphosphatase (FBPase), and CO(2) assimilation. BRs upregulated the transcript levels of genes and activity of enzymes involved in the ascorbate-glutathione cycle in the chloroplasts, leading to an increased ratio of reduced (GSH) to oxidized (GSSG) glutathione in the chloroplasts. An increased GSH/GSSG ratio protected RCA from proteolytic digestion and increased the stability of redox-sensitive enzymes in the chloroplasts. These results strongly suggest that BRs are capable of regulating the glutathione redox state in the chloroplasts through the activation of the ascorbate-glutathione cycle. The resulting increase in the chloroplast thiol reduction state promotes CO(2) assimilation, at least in part, by enhancing the stability and activity of redox-sensitive photosynthetic enzymes through post-translational modifications.

Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects.

BACKGROUND: The impact of hepatic venous anatomic variations on hepatic resection and transplantation is the least understood aspect of liver surgery. METHODS: A prospective three-dimensional computed tomography study was undertaken on 200 consecutive subjects with normal livers to determine the prevalence of surgically significant hepatic venous anatomic variations. RESULTS: The prevailing pattern of the three hepatic veins in these subjects was a right hepatic vein (RHV) and a common trunk for the middle (MHV) and left (LHV) hepatic veins (122/200, 61%). The remaining patients had the RHV, MHV, and LHV draining independently into the inferior vena cava (IVC). In 39% of patients, the RHV was small and was compensated by a large right inferior hepatic vein (21.0%), an accessory RHV (8.5%) or a well-developed MHV (6.5%). A segment 4 vein was seen in 51.5% of patients. This segment 4 vein joined the LHV (26%), the MHV (17.5%), or the IVC (8%). An umbilical vein and a segment 4 vein were seen in 3.5% of patients. These two veins joined either the LHV (2.0%) or the MHV (1.5%). CONCLUSIONS: Knowing the variations of hepatic veins before surgery is useful during both partial hepatectomy and donor operations for living related liver transplantation.

[Study on the clinical application of abdominal medical image proceeding system in extended hepatectomy].

OBJECTIVE: To study the applied value of abdominal medical image proceeding system (AMIPS) in extended hepatectomy. METHODS: Sixty-four-slice spiral computer tomography (CT) scan data of 32 cases treated from September 2007 to July 2009 (15 male, 17 female; mean age 52 years old) with liver tumor was collected, among which there were 9 cases with huge liver tumor. The data was imported into AMIPS for sequence segmenting and three-dimensional (3D) reconstruction. The reconstructed models were imported into virtual system of AMIPS for digital hepatic segment partition and extended hepatectomy analysis for huge liver tumor of 9 cases. According to the calculated data, suitable modus operandi were selected. RESULTS: In the AMIPS, the 3D models could show the relationships between the lesions to the surrounding tissue more intuitively and the type of blood supply. Digital hepatic segment partition made localize lesions more exactly. It was possible to hepatic segmentectomy and analysis of extended hepatectomy by calculating the relative volume of hepatic segment of huge liver tumor. Huge liver tumor of 9 cases performed different modus operandi, including two cases with right hemi hepatectomies, five cases with hepatic segmentectomy of S6 and S7, two cases with hepatic segmentectomy of S5-7 and part of the S8. There were margin-free tumor cells and no complications such as liver failure in all cases. The average hospitalization time was 21 d. CONCLUSION: AMIPS is helpful in the diagnosis of hepatic disease and in the optimizing surgical plans which can decrease surgical risk and help prevent postoperative hepatic failure.

[The relationship between the level of circulating endothelial progenitor cells CD34+; and carotid artery arteriosclerosis in youth and middle aged patients with essential hypertension].

OBJECTIVE: To explore the relationship between the level of circulating endothelial progenitor cells (EPCs) CD34+ with the Framingham cardiovascular risk factors, or with the carotid artery intima-media thickness (IMT), and to evaluate the value of circulating EPCs CD34+ level as a cytological marker of early vascular lesion in youth and middle aged essential hypertension (EH) patients. METHODS: A total of 62 patients with EH aged between 25 to 45 were enrolled as study group and 20 healthy people were enrolled as control group. EH patients were stratified with cardiovascular risk factors according to Framingham risk factors score into low-risk group with 18 cases, mid-risk group with 14 cases, high-risk group with 17 cases, and extremely high-risk group with 13 cases. The level of circulating EPCs CD34+, carotid artery IMT were respectively measured. The relationship between the level of circulating EPCs CD34+ and Framingham cardiovascular risk factors score, carotid artery IMT was analyzed. RESULTS: The level of circulating EPCs CD34+ was gradually decreased with an increase of the Framingham risk factors score in each hypertensive subgroup [low-risk group: (0.12+/-0.02)%, mid-risk group: (0.07+/-0.03)%, high-risk group: (0.04+/-0.03)%, extremely high-risk group: (0.01+/-0.01)%], and they were significantly lower than that in control group [(0.15+/-0.03)%], and there was a significant difference among hypertensive subgroups (P<0.05 or P<0.01). Carotid artery IMT was significantly thicker among hypertensive subgroups [low- risk group: (0.80+/-0.07) mm, mid-risk group: (1.11+/-0.08) mm, high-risk group: (1.26+/-0.10) mm, extremely high-risk group: (1.45+/-0.09) mm], and there was a significant difference between each hypertensive group and that of control group [(0.73+/-0.08) mm, all P<0.01]. There was also statistical significance among hypertensive subgroups (P<0.05 or P<0.01). There was a negative correlation between the level of circulating EPCs CD34+ and Framingham risk factors score (r=-0.875, P<0.01), and also a negative correlation with carotid artery IMT (r=-0.852, P<0.01). CONCLUSION: There was a significant correlation between the level of circulating EPCs CD34+ with Framingham risk factors score and also carotid artery IMT in EH patients. Circulating EPCs CD34+ could be a cytological marker of early vascular lesion in hypertension patients.

[Application of the medical image three-dimensional visualization system of abdomen in diagnosis and evaluating resectability of pancreatic tumors].

OBJECTIVE: To study the value and the clinical application of the Medical Image three-dimensional Visualization System of Abdomen (MI-3DVS) in diagnosis and evaluating resectability of pancreatic tumor. METHODS: Twelve patients with pancreatic tumor were tested with 64-slice helical CT (64-MSCT) angiography, and the CT data was reconstructed with MI-3DVS from November 2008 to August 2009. The 3D findings were adopted in diagnosis and evaluating resectability, and the results were compared with surgical operation and the pathological finding. There were 7 male and 5 female, aged from 14 to 83 years. Within the 12 cases, there were 4 cases with pancreatic carcinoma, 5 cases with pancreatic solid pseudopapillary tumor, 2 cases with pancreatic serous cystadenoma, 1 case with pancreatic cyst (ductal epithelial papillary hyperplasia). RESULTS: Nine tumors which had been regarded as removable pre-operatively with MI-3DVS were removed successfully. Three patients who were considered unresectable by other hospitals with CT were operated successfully with MI-3DVS. The other 3 patients' tumors were actually not able to be removed as pre-operative evaluation. CONCLUSION: MI-3DVS plays an important role in diagnosis and assessment of resectability of pancreatic tumor.

[Clinical analysis of reconstruction of lateral wall and femoral moment in the treatment of Evans Jensen type V intertrochanteric fracture].

OBJECTIVE: To investigate the clinical effect of proximal femoral nail anti rotation (PFNA) and titanium plate in the treatment of Evans Jensen type V intertrochanteric fractures. METHODS: From October 2013 to March 2016, 30 patients with Evans Jensen type V intertrochanteric fractures were analyzed. According to the operation methods, they were divided into two groups:16 cases of closed reduction and PFNA internal fixation;14 cases of small incision incision reconstruction of titanium plate reconstruction of femoral moment and lateral wall PFNA internal fixation. The operation (blood loss, operation duration), postoperative rehabilitation (postoperative ambulation time, bone healing time), operation related complications (internal fixation fracture, withdrawal, spiral blade cutting out) were observed and compared between the two groups. Harris score of hip joint function was performed 12 months after operation, and the loss degree of cervical trunk angle was observed and compared. RESULTS: All the 30 patients were followed up for 12 to 18 months. The blood loss and operation duration of open reduction group were significantly greater than those of closed reduction group (P<0.05). The postoperative ambulation time, bone healing time, operation related complications, Harris score of hip joint function and loss of cervical trunk angle in the open reduction group were better than those in the closed reduction group(P<0.05). CONCLUSION: Evans Jensen was treated with PFNA intramedullary fixation through reduction and fixation of femoral moment and lateral wall with reconstruction titanium plate Vtype intertrochanteric fracture can restore the support of femoral moment and lateral wall to femoral head and neck, improve the stability of fracture end and internal fixation after operation, and reduce the risk of fracture end displacement, internal fixation loosening, cutting out and even fracture after treatment with PFNA alone. To shorten the bed time of elderly patients and reduce the operation related complications, it provides a new idea and method for the treatment of Evans Jensen type V intertrochanteric fracture.

[Study on the applied value of digital medical technology in diagnosis and treatment of the hepatolithiasis].

OBJECTIVE: To study the value of digital medical technology in diagnosis and treatment of the hepatolithiasis. METHODS: 64-slice spiral computer tomography (CT) scan data of 14 cases (11 female, 3 male; median age, 48 years) with hepatolithiasis admitted from February to September 2008 were collected. The data were imported into medical image proceeding system (MIPS) for sequence segmenting and three-dimensional (3D) reconstruction. The reconstructed models were imported into FreeForm Modeling System for performing simulation surgery with simulation surgical instruments. According to the results of 3D reconstruction and simulation surgery, reasonable operation strategies were chosen. Finally, the value of clinical application of simulation surgery was evaluated according to the findings of clinical operation on hepatolithiasis patients and postoperative T-tube angiography. RESULTS: The 3D reconstructed models of 14 cases with hepatolithiasis revealed 7 cases of left liver hepatolithiasis, 2 cases of right liver hepatolithiasis, 5 cases of bilateral hepatolithiasis, including 6 cases of hepatolithiasis with common bile duct calculi, 6 cases of biliary system models with absolute stricture, 8 cases with relative stricture. The results were of agreement with clinical diagnosis. A variety of operation plans were simulated before operation. Simulation equipment used in process of simulation surgery was a powerful sense of feedback. CONCLUSIONS: Digital medical technology is helpful to understand the calculi distribution, bile ducts stricture and deformity. Through preoperative training, simulation surgery are able to guide for choosing operative strategies. It reduces the operation risks.

The complete chloroplast genome of Torilis scabra (Apiaceae).

Torilis scabra (Thunb.) DC. is widely distributed in China and Japan and has been introduced to North America. In this study, the complete chloroplast genome sequence of the T. scabra was obtained by de novo assembly using the NGS data. The chloroplast genome of T. scabra was 157,855 bp in length and divided into four distinct regions, such as large single-copy region (85,362 bp), small single-copy region (17,993 bp), and a pair of inverted repeat regions (27,250 bp). The genome annotation predicted a total of 127 genes, including 82 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis with reported chloroplast genomes showed that T. scabra has a close genetic relationship with Anthriscus cerefolium.

The complete chloroplast genome of Ageratum conyzoides (Asteraceae).

Ageratum conyzoides L. is an important Chinese medicinal plant. In this study, we reported the complete chloroplast genome of A. conyzoides. The chloroplast genome sequence is 151,309 bp in length and consisted of a large single copy (LSC) region (83,884 bp), a small single copy (SSC) region (17,771 bp), and two inverted repeats (IRs) (24,827 bp). It was composed of 126 genes and they were 81 protein-coding genes, 30 tRNA genes, 8 rRNA genes, and 7 pseudogene. Phylogenetic analysis with reported chloroplast genomes can not only show that A. conyzoides has a close genetic relationship with Centaurea diffusa and Carthamus tinctorius, but also provide new evidence for the identification of Praxelis clematidea and A. conyzoides.

[PFNA combined reconstruction and locking titanium plate for the treatment of comminuted femoral intertrochanteric fractures involving lateral wall].

OBJECTIVE: To investigate the operative effect of PFNA combined with reconstructive locking plate on the treatment of comminuted femoral intertrochanteric fracture which involving the lateral wall. METHODS: A total of 35 patients with comminuted femoral intertrochanteric fractures involving the lateral wall were surgically treated from November 2014 to January 2016. According to whether there was reconstruction of the lateral wall or not and the internal fixation method, the patients were divided into PFNA group (no reconstruction of the lateral wall), PFNA recontruction group (reconstructive locking plate was used to reconstruct the lateral wall, PFNA internal fixation). The clinical curative effect was evaluated by the analysis of operation time, intraoperative blood loss, postoperative activity time, the time of fracture healing, complications, and hip joint Harris score at 12 months after operation. RESULTS: All 35 patients completed the operation successfully. All the incisions were healed by first intention and no incision infection or fat liquefaction occurred. All 35 patients were followed up from 12 to 16 months with an average of 14.4 months. All patients had bone healing. There was no statistical significant in surgery time and intraoperative blood loss between two groups(P>0.05). There were 5 postoperative complications in the PFNA group and 1 in the PFNA combined with reconstructive locking plate group. There was a statistical difference between two groups(P<0.05). The postoperative activity time, bone healing time, complications, and Harris score of PFNA reconstruction group were all superior to PFNA group, there were statistically significant differences between two groups. CONCLUSIONS: Although the operation time and blood loss of PFNA combined with reconstructive locking plate in treatment of comminuted femoral intertrochanteric fracture which involving the lateral wall are more than those in the PFNA group, and the surgical trauma is larger than PFNA, the fracture healing time, postoperative activity time, and hip joint function were all superior to those of the PFNA group, which can effectively shorten the postoperative bed rest time, and reduce bed complications as well as improve hip joint function.

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect.

TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects. However, until now no such compounds with robust glucose-lowering effects were reported, especially in diabetic animal models. Herein, we identify a TGR5 agonist, 26a, which was proven to be intestinally-targeted through pharmacokinetic studies. 26a was used as a tool drug to verify the intestinally-targeted strategy. 26a displayed a robust and long-lasting hypoglycemic effect in ob/ob mice (once a day dosing (QD) and 18-day treatment) owing to sustained stimulation of GLP-1 secretion, which suggested that robust hypoglycemic effect could be achieved with activation of TGR5 in intestine alone. However, the gallbladder filling effect of 26a was rather complicated. Although the gallbladder filling effect of 26a was decreased in mice after once a day dosing, this side effect was still not eliminated. To solve the problem above, several research strategies were raised for further optimization.

[Synthesis and antibacterial activity of ciprofloxacin derivatives].

AIM: To study the synthesis and antibacterial activity of ciprofloxacin derivatives. METHODS: Ciprofloxacin derivatives were synthesized primarily from 2-methyl-5-nitroimidazol and ciprofloxacin through nucleophilic substitution. The antibacterial activity of the synthesized compounds were tested. RESULTS: Nine new compounds were synthesized. The structure of the title compounds were confirmed by 1H NMR, MS and element analysis. CONCLUSION: Compounds II, IVC and IVD showed appreciable antibacterial activity, and were worth further studying.

The role of hydrogen peroxide and nitric oxide in the induction of plant-encoded RNA-dependent RNA polymerase 1 in the basal defense against Tobacco mosaic virus.

Plant RNA-dependent RNA Polymerase 1 (RDR1) is an important element of the RNA silencing pathway in the plant defense against viruses. RDR1 expression can be elicited by viral infection and salicylic acid (SA), but the mechanisms of signaling during this process remains undefined. The involvement of hydrogen peroxide (H2O2) and nitric oxide (NO) in RDR1 induction in the compatible interactions between Tobacco mosaic tobamovirus (TMV) and Nicotiana tabacum, Nicotiana benthamiana, and Arabidopsis thaliana was examined. TMV inoculation onto the lower leaves of N. tabacum induced the rapid accumulation of H2O2 and NO followed by the increased accumulation of RDR1 transcripts in the non-inoculated upper leaves. Pretreatment with exogenous H2O2 and NO on upper leaf led to increased RDR1 expression and systemic TMV resistance. Conversely, dimethylthiourea (an H2O2 scavenger) and 2-(4-carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (an NO scavenger) partly blocked TMV- and SA-induced RDR1 expression and increased TMV susceptibility, whereas pretreatment with exogenous H2O2 and NO failed to diminish TMV infection in N. benthamiana plants with naturally occurring RDR1 loss-of-function. Furthermore, in N. tabacum and A. thaliana, TMV-induced H2O2 accumulation was NO-dependent, whereas NO generation was not affected by H2O2. These results suggest that, in response to TMV infection, H2O2 acts downstream of NO to mediate induction of RDR1, which plays a critical role in strengthening RNA silencing to restrict systemic viral infection.

Hydrogen peroxide functions as a secondary messenger for brassinosteroids-induced CO2 assimilation and carbohydrate metabolism in Cucumis sativus.

Brassinosteroids (BRs) are potent regulators of photosynthesis and crop yield in agricultural crops; however, the mechanism by which BRs increase photosynthesis is not fully understood. Here, we show that foliar application of 24-epibrassinolide (EBR) resulted in increases in CO(2) assimilation, hydrogen peroxide (H(2)O(2)) accumulation, and leaf area in cucumber. H(2)O(2) treatment induced increases in CO(2) assimilation whilst inhibition of the H(2)O(2) accumulation by its generation inhibitor or scavenger completely abolished EBR-induced CO(2) assimilation. Increases of light harvesting due to larger leaf areas in EBR- and H(2)O(2)-treated plants were accompanied by increases in the photochemical efficiency of photosystem II (Φ(PSII)) and photochemical quenching coefficient (q(P)). EBR and H(2)O(2) both activated carboxylation efficiency of ribulose-1,5-bisphosphate oxygenase/carboxylase (Rubisco) from analysis of CO(2) response curve and in vitro measurement of Rubisco activities. Moreover, EBR and H(2)O(2) increased contents of total soluble sugar, sucrose, hexose, and starch, followed by enhanced activities of sugar metabolism such as sucrose phosphate synthase, sucrose synthase, and invertase. Interestingly, expression of transcripts of enzymes involved in starch and sugar utilization were inhibited by EBR and H(2)O(2). However, the effects of EBR on carbohydrate metabolisms were reversed by the H(2)O(2) generation inhibitor diphenyleneodonium (DPI) or scavenger dimethylthiourea (DMTU) pretreatment. All of these results indicate that H(2)O(2) functions as a secondary messenger for EBR-induced CO(2) assimilation and carbohydrate metabolism in cucumber plants. Our study confirms that H(2)O(2) mediates the regulation of photosynthesis by BRs and suggests that EBR and H(2)O(2) regulate Calvin cycle and sugar metabolism via redox signaling and thus increase the photosynthetic potential and yield of crops.

Stress- and pathogen-induced Arabidopsis WRKY48 is a transcriptional activator that represses plant basal defense.

Plant WRKY transcription factors can function as either positive or negative regulators of plant basal disease resistance. Arabidopsis WRKY48 is induced by mechanical and/or osmotic stress due to infiltration and pathogen infection and, therefore, may play a role in plant defense responses. WRKY48 is localized to the nucleus, recognizes the TTGACC W-box sequence with a high affinity in vitro and functions in plant cells as a strong transcriptional activator. To determine the biological functions directly, we have isolated loss-of-function T-DNA insertion mutants and generated gain-of-function transgenic overexpression plants for WRKY48 in Arabidopsis. Growth of a virulent strain of the bacterial pathogen Pseudomonas syringae was decreased in the wrky48 T-DNA insertion mutants. The enhanced resistance of the loss-of-function mutants was associated with increased induction of salicylic acid-regulated PR1 by the bacterial pathogen. By contrast, transgenic WRKY48-overexpressing plants support enhanced growth of P. syringae and the enhanced susceptibility was associated with reduced expression of defense-related PR genes. These results suggest that WRKY48 is a negative regulator of PR gene expression and basal resistance to the bacterial pathogen P. syringae.