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To comprehensively evaluate the effect of accelerated rehabilitation surgical care on perioperative wound infections and complications in patients undergoing lung cancer surgery. A comprehensive computerised search for randomised controlled trials (RCTs) of accelerated rehabilitative surgical care applied to patients undergoing lung cancer surgery was conducted using the Web of Science, PubMed, Cochrane Library, Embase, Wanfang and China National Knowledge Infrastructure databases from inception to September 2023. The literature was screened and evaluated by two investigators, and data were extracted from the final included literature. Stata software (version 17.0) was used for data analysis. Overall, 21 RCTs involving 2187 patients were included, including 1093 cases in the accelerated rehabilitation surgical care group and 1094 cases in the conventional care group. The analyses revealed that patients with lung cancer surgery who implemented accelerated rehabilitation surgical care were significantly less likely to develop postoperative wound infections (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.17-0.49, p < 0.001) and postoperative complications (OR = 0.26, 95% CI: 0.20-0.34, p < 0.001) and shortened the hospital length of stay (standardised mean differences [SMD] = -1.93, 95% CI: -2.32 to -1.53, and p < 0.001) compared with conventional care. The effect of accelerated rehabilitation surgical care intervention in the perioperative period of lung cancer surgery patients is remarkable, as it can effectively reduce the incidence of wound infection and complications, shorten hospitalisation time and promote patient recovery., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

In the present study, a novel and green temperature-responsive deep eutectic solvent (TRDES) system was developed and applied for the simultaneous extraction and separation of different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill. The TRDES, consisting of amino alcohols and phenolic compounds, was chosen as the switching medium, and an upper critical solution temperature (UCST) type switchable solvent was obtained by adding an inorganic salt solution. The switchable phase diagram was plotted based on the relationship between the phase change temperature, the concentration and the amount of sodium chloride solution. Under optimal parameters, the yields with TRDES for different polar active phytochemicals (lignanoids and polysaccharides) from the dried fruit of Schisandra chinensis (DFSC) were 1.62 ∼ 1.17-fold and 1.39-fold to those with conventional solvents. Also, the TRDES system was still effective on extraction of DFSC lignanoids and polysaccharides after four cycles of extraction. The separated polysaccharides and lignanoids both had strong antioxidant activities with IC 50 values of 1.92 mg/ mL and 0.10 mg/ mL against 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), respectively. The extraction mechanism of TRDES was postulated by Density functional theory (DFT) calculations the hydrogen bonding in TRDES was the main factor to the higher extraction yield. This temperature-responsive deep eutectic solvent could be widely used for the efficient extraction and separation of multi-polar components. As a green and recyclable solvents, TRDES has great potential for the lower cost production from plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective : Astragaloside IV (AS-IV) is the primary bioactive component purified from Astragalus membranaceus which is one of the traditional Chinese medicines. Research studies found that AS-IV has significant pharmacological effects on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver cirrhosis, and diabetic nephropathy, but little is known about the effects of AS-IV on nonalcoholic fatty liver disease (NAFLD). In this study, we investigated whether AS-IV has beneficial effects on NAFLD in rats and its potential mechanisms. Methods : Male SD rats were fed with high-fat diet (HFD) for 12 weeks to establish NAFLD rat model, and then, the rats were divided into five groups. The control group rats were fed with normal diet for 12 weeks and then were given normal saline (1.0 ml kg -1 day -1 ) by intragastric administration for 4 weeks. The model group rats were fed with HFD for 12 weeks and then were given normal saline (1.0 ml kg -1 day -1 ) by intragastric administration for 4 weeks. The AS-IV-L, AS-IV-M, and AS-IV-H groups were treated with 20, 40, and 80 mg kg -1 day -1 of AS-IV by intragastric administration for 4 weeks and given HFD diet. Then, we detected serum transaminase (ALT, AST), blood lipid (TG, TC), inflammatory cytokines (IL-6, IL-8 and TNF-α), liver histology(NAFLD activity score), TLR4/MyD88 signaling pathway in liver tissue. Results : We found AS-IV significantly reduced serum levels of AST, ALT, TG, TNF-α, IL-6, and IL-8 in NAFLD rats and downregulate the expression of TLR4 mRNA, MyD88 mRNA, NF-κB mRNA, and proteins in liver tissue. Moreover, AS-IV could significantly reduce the NAFLD activity score of NAFLD rat liver. Conclusion : In this study, we demonstrated that AS-IV have a protective effect on NAFLD by inhibiting TNF-α, IL-6 and IL-8 levels and down-regulating TLR4, MyD88 and NF-κB expression in rat liver tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Zhang, Wang, Fu, Han, Zhang and Wang.)

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro . Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

Objective: To investigate the effect of Na(+)/K(+)-ATPase inhibitor ouabain on the proliferation and division of liver cancer HepG2 cells, and to explore the anticancer mechanism. Methods: HepG2 cells were exposed with different concentrations of ouabain (0.1, 1, 10 μmol/L) for 24 h, the proliferation ability was appraised using CCK-8, and the HepG2 cells was as a control group. The status of chromosome separation was detected with cell immunofluorescence (ICC) coupled to confocal microscope. The expression levels of AURKA, mTOR, p-mTOR, ERK and p-ERK protein were analyzed using western blot. Results: After treating with 0.1, 1 and 10 μmol/L of ouabain for 24 h, the inhibitory rate of cells were (23.5±4.57)%, (49.80±5.32)%, and (72.10±5.62)%, respectively. Ouabain could significantly inhibit the proliferation of HepG2, and presented in a dose-dependent manner( F= 32.8, P< 0.05). The ICC results showed that the chromosome separation disorders occurred in HepG2 cells treated with 1 μmol/L for 24 h, and the spindle diameter of HepG2 cells with ouabain treatment was decreased significantly compared with the control group( t= 9.58, P< 0.05). The results of western blot showed that the expression levels of AURKA, p-mTOR and p-ERK expressions in HepG2 cells treated with 1 μmol/L of ouabain were significantly decreased compared with the control group( F= 16.26, 8.32, 33.59, P< 0.05). Ouabain inhibited the growth of hepatocellular carcinoma cells in nude mice( F= 370.20, P< 0.05). Conclusion: Ouabain can induce chromosome division disorder and inhibit the proliferation in liver cancer HepG2 cells by inhibiting AURKA signaling pathway.

Rationale : Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods : Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results : Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B -knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B . Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B ( P < 0.001) in 60 human CRC tissues. Conclusion : These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B , thus driving the malignancy of CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the etiology and risk factors for unintentional injuries in children admitted to the pediatric intensive care unit (PICU), and to provide a basis for preventing these injuries and decreasing the mortality rate., Methods: A retrospective analysis was performed on the clinical data of children with unintentional injuries admitted to the PICU from December 2012 to December 2017., Results: A total of 102 children with unintentional injuries were admitted to the PICU, which accounted for 3.30% (102/3 087) of the overall PICU patients. The top three causes of unintentional injuries were food or drug poisoning, drowning, and foreign body ingestion and aspiration. The proportion of unintentional injuries in boys was significantly higher than in girls (P<0.05). The younger children had a significantly higher proportion of unintentional injuries (P<0.05). The cause of unintentional injuries was also related to age, and the common causes of unintentional injuries varied between different age groups. The proportion of unintentional injuries was not significantly different between children from urban and rural areas (P>0.05). The logistic regression analysis showed that the number of organs with dysfunction after unintentional injuries, especially respiratory, cardiac, neurological, renal and hematological involvement, was closely associated with the mortality rate of children with unintentional injuries (P<0.05); however, it is not an independent risk factor (P>0.05)., Conclusions: Prevention is the key to decreasing the incidence of childhood unintentional injuries. Preventive measures should be taken based on patient's sex and age and the cause of unintentional injuries. The spread of first aid knowledge, improvement in emergency transportation, and more attention to organ protection may be useful for decreasing the mortality rate of children with unintentional injuries.

For hydrogel patches, the laboratory tests could not fully reveal the existing problems of full scale of industrial production, and there are few studies about the preparation technique for the industrial manufacturing process of hydrogel patches. So, the purpose of this work was to elucidate the effects of mainly technological operation and its parameters on the performance of hydrogel patches at the industrial-scale production. The results revealed the following: (1) the aqueous phase was obtained by polyvinylpyrrolidone (PVP) along with tartaric acid dissolved in purified water, then feeding this into a vacuum mixer as a whole in one batch, thus extended the crosslinking reaction time of hydrogel paste (matrix) and allowed the operation of coating/cutting-off to be carried out easily, and there was no permeation of backing layer; (2) the gel strength of the hydrogel patches increased with the increase of working temperature, however, once the temperature exceeded 35 ± 2 °C, the hydrogel paste would lose water severely and the resultant physical crosslinking structure which has lower gel/cohesive strength would easily bring gelatinization/residues during application; (3) the relative humidity (RH) of the standing-workshop was dynamically controlled (namely at 35 ± 2 °C, keeping the RH at 55 ± 5% for 4 days, then 65 ± 5% for 2 days), which would make patches with satisfactory characteristics such as better flexibility, higher adhesive force, smooth flat matrix surface, and without gelatinization/residues and warped edge during the using process; (4) the aging of the packaged hydrogel patches was very sensitive to storage temperature, higher temperature, higher gel strength and lower adhesiveness. The storage temperature of 10 ± 2 °C could effectively prevent matrix aging and adhesion losing, which would also facilitate the expiration date of patches extended obviously. In conclusion, this work provides an optimized and feasible preparation technique for the industrial production of the hydrogel patches and establishes the hydrogel patches as a novel carrier for transdermal drug delivery.

Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13 C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.

Objectives: The histone methylation and acetylation pathway genes regulate cell growth and survival. Aberrations in this pathway are implicated in a variety of cancers. This study aimed to identify germline genetic variants in histone methylation and acetylation pathway genes that may contribute to risk in eight types of cancers and to explore the relation between the whole pathway and their risks in these types of cancers., Methods: Germline genetic variants in 89 genes in the histone methylation and acetylation pathway were explored. Gene-based and pathway-based associations with eight types of cancers were analyzed using logistic regression models and the permutation-based adaptive rank-truncated product method, respectively., Results: Gene-level associations revealed that genetic variants in 45 genes were significantly associated with the risk of cancer. The total histone methylation and acetylation pathway was significantly associated with the risk of esophageal squamous cell carcinoma (P = 0.0492) and prostate (P = 0.0038), lung (P = 0.00015), and bladder cancer (P = 0.00135), but not with breast (P = 0.182), pancreatic (P = 0.336) and gastric cancer (P = 0.347) and renal cell carcinoma (P =0.828)., Conclusions: Our study suggested there is an association between germline genetic variation at the overall histone methylation and acetylation pathway level and some individual genes with cancer risk. Further studies are needed to validate these relations and to explore relative mechanisms., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Metabolic stress is a common phenomenon in solid tumors. Compensatory mechanisms to overcome metabolic stress (glucose deprivation) are vital to tumor cell survival. The histone demethylase Jumonji domain-containing protein 2B (JMJD2B) is vital for the growth and progression of various cancers. However, the role of JMJD2B during glucose deprivation remains unclear. Our aim was to examine the function of JMJD2B in glucose-deprived colon cancer cells and the involvement of extracellular signal-regulated kinase (ERK) and glucose transporter 1 (GLUT1). Our study demonstrated that JMJD2B expression was upregulated via ERK phosphorylation during glucose deprivation. Further, the cell viability assay showed that the effect of p-ERK on the viability of colon cancer cells was at least partly dependent on JMJD2B expression. Glucose deprivation increased interaction between JMJD2B and p-ERK, as demonstrated by the co-immunoprecipitation and fluorescence assays. Glucose deprivation also resulted in phosphorylation of JMJD2B by p-ERK, as shown by the immunoprecipitation assay and western blotting analysis. In addition, the phosphorylation of JMJD2B via p-ERK at Thr305, Ser352, Ser566 and Thr1065 contribute to JMJD2B stability. p-ERK stabilizes the JMJD2B protein level by protecting JMJD2B from ubiquitination and proteasome degradation. We found that knockdown of JMJD2B significantly impaired colon cancer cell viability, which is accompanied by a significant reduction in glucose uptake and lactate production. Furthermore, knockdown of JMJD2B after glucose deprivation caused decreased level of GLUT1 through increasing H3K9 tri-methylation levels on its promoter, demonstrated by chromatin immunoprecipitation assay. Moreover, targeting JMJD2B in xenograft tumors also decreased the GLUT1 level. Finally, a positive correlation was observed between p-ERK, JMJD2B and GLUT1 expression in 85 human colon cancer tissue specimens. These results indicated that p-ERK-mediated phosphorylation and stabilization of JMJD2B during glucose deprivation contributes to its role in glucose uptake and cell viability, which may be modulated through epigenetically upregulation of GLUT1.

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer‑associated deaths worldwide. It has previously been demonstrated that microRNAs (miRNAs) are actively involved in the pathogenesis of gastric cancer. Therefore, miRNAs have been proposed as promising therapeutic targets in gastric cancer patients. MiR‑744 is aberrantly expressed in different types of human cancer. However, the expression pattern and biological roles of miR‑744 in gastric cancer remain unknown. The present study demonstrated that miR‑744 expression was low in gastric cancer tissues and cell lines. Low expression levels of miR‑744 was significantly correlated with lymph node metastasis, invasive depth and TNM staging in gastric cancer patients. The restoration of miR‑744 expression inhibited cell proliferation and invasion in vitro. Bioinformatic prediction, luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis verified that brain‑derived neurotrophic factor (BDNF) is a direct target of miR‑744 in gastric cancer cells. Furthermore, BDNF was upregulated in gastric cancer tissues and inversely correlated with miR‑744 expression. Furthermore, enforced BDNF expression reversed the tumor‑suppressing effects of miR‑744 on the proliferation and invasion of gastric cancer cells, indicating that BDNF is a functional mediator of miR‑744 in gastric cancer. The present study suggests that miR‑744 is a potential prognostic biomarker and treatment target in gastric cancer patients.

The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.

Background: Colon Cancer-Associated Transcript 2 (CCAT2) has been demonstrated associated with clinical outcomes in various tumors. However, the results from each study were unfortunately insufficient and not completely consistent. Therefore, we conduct a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis. Methods: A meta-analysis was performed using data obtained through a systematic search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang database and VIP database. The pooled odds ratio (OR) and hazard ratio (HR) with 95% Confidence interval (CI ) using random-effect were used to identify the relationship of CCAT2 with clinical outcome of cancer patients. Subgroup analysis and sensitivity analysis were performed. Results: A total of 867 patients from eight studies were finally included. Patients with high CCAT2 expression underwent an increased risk of lymph node metastasis (LNM) (OR=3.09, 95% CI: 1.53-6.26) and distant metastasis (DM) (OR=7.70, 95% CI: 3.26-18.17). CCAT2 was also significantly correlated with overall survival (OS) (HR=2.19, 95%CI: 1.70-2.82) and progression-free survival (PFS) (HR=2.59, 95% CI: 1.78-3.76). Moderate heterogeneity was observed in meta-analysis for LNM. However, the results remained robust in multiple sensitivity analyses. Conclusions: High expression of CCAT2 was linked with poor clinical outcome. CCAT2 can serve as a potential molecular marker for prognosis in different types of cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

A highly efficient alkenylation reaction of arylglyoxals with 3-vinylindoles catalyzed by chiral calcium phosphate is described. Structurally diverse allylic alcohols bearing indole and carbonyl units are prepared in excellent yields, good diastereoselectivities, and high to excellent enantioselectivities. These products are good building blocks for the synthesis of polysubstituted chiral tetrahydrocarbozol-2-ones. The mechanism study indicates that the most likely role of the catalyst is to activate the hydrate of arylglyoxal and control the stereoselectivity via desymmetric coordination.

A simple Brønsted acid catalyzed tandem reaction, including intermolecular nucleophilic addition, substitution and intramolecular cyclization, in a one-pot manner is described. Thirty two 2-indolyl substituted carbazoles are generated in good to excellent yields. Based on this tandem reaction strategy, the poly(1,4-carbazole) is prepared for the first time. Preliminary studies indicate that the poly(1,4-carbazole) has good thermostability and optical properties.

The 3-vinyl indole is used as a nucleophile to react with aromatic and aliphatic imines. Chiral 3-substituted indoles bearing multiple functional groups are produced with up to 99% yield, a 98:2 E/Z ratio, and 97% ee. A possible mechanism is proposed to explain the observed stereoselectivities. This strategy provides an efficient way for the preparation of novel chiral 3-substituted indoles.

Objective: To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers., Methods: The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and β C-terminal telopeptide of type Ⅰ collagen (β-CTX) were monitored regularly in the two years following treatment in 66 cases., Results: (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum β2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of β-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 μg/L, 60.95 vs 43.47 μg/L, both P<0.05). The ratio of β-CTX /tPINP in group B was higher than that in group A (median 0.017 vs 0.012, P<0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both group A and group B (both P>0.05), the level of β-CTX decreased significantly compared with that before treatment in both groups(median 0.16 vs 0.42 μg/L, 0.26 vs 0.78 μg/L, both P<0.05); the ratio of β-CTX /tPINP decreased significantly compared with that before treatment in both group A and in group B(median 0.008 vs 0.012, 0.011 vs 0.017, both P<0.05). There were no differences in the level of β-CTX, tPINP and β-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that after 3 months in both group A and group B (all P>0.05). (4)All patients were divided into two groups according to the therapeutic effect: effective group included patients who reach the effect of partial remission or better remission(n=48), while ineffective group included patients who did not reach the effect of partial remission(n=18). Before treatment there were no differences in the level of β-CTX, tPINP and β-CTX/tPINP ratio between the effective groupand the ineffective group (all P>0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both effective group and ineffective group (all P>0.05), but the level of β-CTX decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.24 vs 0.60 μg/L, 0.44 vs 0.95 μg/L, both P<0.05). The ratio of β-CTX /tPINP decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.005 vs 0.012, 0.005 vs 0.011, both P<0.05). There were no differences in the level of β-CTX, tPINP and β-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that for 3 months both in effective group and ineffective group (all P>0.05)., Conclusions: Pain in bones, osteolysis and pathological fracture are the most common clinical manifestations in myeloma-related bone disease. The severity of bone disease can reflect the tumor load, but may not affect the therapeutic effect and the overall survival. The bone metabolic markers tPINP and β-CTX can be used to evaluate the severity of myeloma-related bone disease at diagnosis and to monitor the effect of treatment for bone disease.

The purpose of this work was to develop and characterize the fibrauretine (FN) loaded propylene glycol-embodying deformable liposomes (FDL), and evaluate the pharmacokinetic behavior and safety of FDL for vaginal drug delivery applications. FDL was characterized for structure, particle size, zeta potential, deformability and encapsulation efficiency; the ability of FDL to deliver FN across vagina tissue in vitro and the distribution behavior of FN in rat by vaginal drug delivery were investigated, the safety of FDL to the vagina of rabbits and rats as well as human vaginal epithelial cells (VK2/E6E7) were also evaluated. Results revealed that: (i) the FDL have a closed spherical shape and lamellar structure with a homogeneous size of 185±19nm, and exhibited a negative charge of -53±2.7mV, FDL also have a good flexibility with a deformability of 92±5.6 (%phospholipids/min); (ii) the dissolving capacity of inner water phase and hydrophilicity of phospholipid bilayers of deformable liposomes were increased by the presence of propylene glycol, this may be elucidated by the fluorescent probes both lipophilic Nile red and hydrophilic calcein that were filled up the entire volume of the FDL uniformly, so the FDL with a high entrapment capacity (were calculated as percentages of total drug) for FN was 78±2.14%; (iii) the permeability of FN through vaginal mucosa was obviously improved by propylene glycol-embodying deformable liposomes, no matter whether the FN loaded in liposomes or not, although FN loaded in liposomes caused the highest permeability and drug reservoir in vagina; (iv) the FN mainly aggregated in the vagina and uterus, then the blood, spleen, liver, kidney, heart and lungs for vaginal drug delivery, this indicating vaginal delivery of FDL have a better 'vaginal local targeting effect'; and (v) the results of safety evaluation illustrate that the FDL is non-irritant and well tolerated in vivo, thereby establishing its vaginal drug delivery potential. These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The highly efficient, regioselective, and enantioselective transfer hydrogenation of α-keto ketimines and reductive amination of diketones by Brønsted acid catalysis is described. A series of chiral α-amino ketones is prepared in high yields (up to >99%), excellent regioselectivities (up to >99:1), and enantioselectivities (up to 98% ee). This method has broad substrate scope.

This work describes an efficient α-alkylation reaction of α-amino aldehydes with 3-indolylmethanols. In the promotion of catalyst 3f, the target products were obtained in high yields (up to 99%), good diastereoselectivities (up to 88:12), and excellent enantioselectivities (up to 96% ee). The direct alkylation products can be readily converted into other tryptophan derivatives without the loss of stereoselectivities.

Objective: To investigate the molecular mechanism of colorectal cancer (CRC) cell apoptosis induced by the Jumonji domain containing 2B (JMJD2B) silencing., Methods: Both HCT116 and LoVo CRC cell lines were used for analyses. Cell apoptosis after JMJD2B silencing was determined by flow cytometry. JC-1 fluorescence probe was applied to measure the mitochondrial outer membrane permeabilization by flow cytometry and fluorescence microscopy. Immunofluorescence was used to detect cytochrome C translocation from mitochondria to cytosol after JMJD2B silencing. The efficacy of JMJD2B silencing on the protein levels of Bcl-2 family, caspase proteins, CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were detected by Western blot., Results: JMJD2B silencing induced CRC cell apoptosis via a decrease of the anti-apoptotic gene Bcl-2 family expression, leading to the translocation of Bak and Bax proteins and the promotion of mitochondrial membrane disruption, resulting in the release of cytochrome C from mitochondria and subsequent caspase-9 and caspase-3 cleavage. It also increased the amount of cleaved caspase-8 involved in the death receptor-related apoptotic pathway. Bcl-2 homology 3 interacting-domain death agonist (Bid), a specific caspase-8 substrate involved in the Fas signaling pathway, subsequently induced cleavage via caspase-8 activation. However, levels of CHOP and GRP78 remained unchanged after JMJD2B silencing., Conclusions: JMJD2B silencing induced CRC cell apoptosis via both mitochondria-related and death receptor-related pathways. The cleavage of Bid activated by caspase-8 might serve as a crosstalk mediator between these two pathways in CRC., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Corky split vein caused by boron (B) deficiency in 'Newhall' Navel Orange was studied in the present research. The boron-deficient citrus exhibited a symptom of corky split vein in mature leaves. Morphologic and anatomical surveys at four representative phases of corky split veins showed that the symptom was the result of vascular hypertrophy. Digital gene expression (DGE) analysis was performed based on the Illumina HiSeq™ 2000 platform, which was applied to analyze the gene expression profilings of corky split veins at four morphologic phases. Over 5.3 million clean reads per library were successfully mapped to the reference database and more than 22897 mapped genes per library were simultaneously obtained. Analysis of the differentially expressed genes (DEGs) revealed that the expressions of genes associated with cytokinin signal transduction, cell division, vascular development, lignin biosynthesis and photosynthesis in corky split veins were all affected. The expressions of WOL and ARR12 involved in the cytokinin signal transduction pathway were up-regulated at 1(st) phase of corky split vein development. Furthermore, the expressions of some cell cycle genes, CYCs and CDKB, and vascular development genes, WOX4 and VND7, were up-regulated at the following 2(nd) and 3(rd) phases. These findings indicated that the cytokinin signal transduction pathway may play a role in initiating symptom observed in our study.

Background: Detecting small breast tumors is difficult for conventional ultrasound. The goal of this study was to assess the value of ultrasound elastography in characterizing small breast tumors and to compare its sensitivity, specificity and accuracy with conventional ultrasound., Methods: A total of 308 breast tumors less than 2 cm in size from 283 in-hospital patients examined with both conventional ultrasound and ultrasound elastography were retrospectively analyzed. The results were compared to surgical pathology., Results: There were 104 malignant and 204 benign lesions. The sensitivities of sonography and sonoelastography were similar (P < 0.05), and the sensitivity of the two modalities combined improved remarkably to 97.1%. The mean elastic score of malignant and benign tumors less than 2 cm were 3.76 ± 1.01 and 1.73 ± 0.99, respectively (P < 0.05), and the mean elastic score of the false-negative lesions on conventional ultrasound was 3.61 ± 1.14., Conclusions: Ultrasound elastography in combination with conventional ultrasound can improve the sensitivity for detecting small breast tumors. It is also valuable in detecting small malignant tumors which are difficult to diagnose with conventional ultrasound. Ultrasound elastography can be a useful adjunct to conventional ultrasound in diagnosing small breast tumors.

Objective: To study the chemical constituents of Rhizoma Imperatae and their anti-complementary activity., Methods: By the hemolysis test, the petroleum extraction, ethyl acetate extraction, n-butanol extraction and the water extraction was tested for anti-complementary activity. Compounds were isolated and purified by silica gel column chromatography, Sephadex LH-20 and reversed-phase column chromatography. The structures were identified by the various spectroscopic data of ESI-MS, 1H-NMR, 13C-NMR. The compounds were evaluated for anti-complementary activity in vitro., Results: The petroleum extraction, ethyl acetate extraction showed significant anti-complementary activity. Ten compounds were isolated from the petroleum and EtOAc soluble fractions and identified as cylindrin (1), arundoin (2), friedelin (3), beta-sitosterol (4), siderin (5), ethyl p-hydroxybenzoate (6), 5-methoxyflavone (7), vanillic acid (8), trans-p-coumaric acid (9), 5-hydroxymethylfurfural (10)., Conclusion: Compounds 6, 7, 8, and 10 are isolated from the genus for the first time, and compounds 3, 8 and 9 inhibited the complement system towards the classical pathway.

Purpose: Rhesus monkeys reared with restricted visual environment during their first few months of life develop large ocular misalignment (strabismus). The purpose of this study was to describe 'A and V' patterns and DVD in these animals during fixation and eye movements and suggest that this form of rearing produces animals that are suitable model to study the mechanisms that might cause 'A/V' pattern incomitant strabismus and dissociated vertical deviation (DVD) in humans., Methods: Eye movements were recorded during fixation, smooth-pursuit and saccades using binocular search coils in one monkey with esotropia, three monkeys with exotropia and one normal monkey., Results: 1) Monkeys reared with Alternating Monocular Occlusion or Binocular deprivation (tarsal plates intact) showed both horizontal and vertical misalignment during monocular and binocular viewing. 2) Large 'A' patterns were evident in 2 out of 3 exotropes while a 'V' pattern was observed in the esotrope. 3) Similar 'A/V' patterns were observed with either eye viewing and during fixation or eye movements. 4) The vertical misalignment, which consisted of the non-viewing eye being higher than the fixating eye, appeared to constitute a DVD., Conclusion: Visual sensory deprivation methods that induce large strabismus also induce 'A/V' patterns and DVD similar to certain types of human strabismus. The source of pattern strabismus could be central, i.e., altered innervation to extraocular muscles from motor nuclei, or peripheral, i.e., altered location of extraocular muscle pulleys.

Objective: To study the alkaloids from Armeniaca mume Sieb., Methods: The alkaloids were extracted with chloroform from 80% alcoholic extract and concentrated. Then they were transferred into aqueous solution and absorbed by macroporous cation exchange resin. The concentrated total eluent was extracted with chloroform. The alkaloids were purified by recrystallization with petroleum ether and sublimation. Then they were determined by Fourier Transform Infrared spectroscopy, Mass spectrometry and Nuclear magnetic resonance etc methods., Result: Two alkaloids were separated and their structures were elucidated as 2,2,6,6-tetramethyl-4-piperidone and tert-butylurea on the basis of spectral evidence., Conclusion: They are new alkaloids from A. mume.

Aim: To report the long-term effect of stent placement in 115 patients with Budd-Chiari syndrome (BCS)., Methods: One hundred and fifteen patients with BCS were treated by percutaneous stent placement. One hundred and two patients had IVC stent placement, 30 patients had HV stent placement, 17 of them underwent both IVC stent and HV stent. All the procedures were performed with guidance of ultrasound., Results: The successful rates in placing IVC stent and HV stent were 94% (96/102) and 87% (26/30), respectively. Ninety-seven patients with 112 stents (90 IVC stents, 22 HV stents) were followed up. 96.7% (87/90) IVC stents and 90.9% (20/22) HV stents remained patent during follow up periods (mean 49 months, 45 months, respectively). Five of 112 stents in the 97 patients developed occlusion. Absence of anticoagulants after the procedure and types of obstruction (segmental and occlusive) before the procedure were related to a higher incidence of stent occlusion., Conclusion: Patients with BCS caused by short length obstruction can be treated by IVC stent placement, HV stent placement or both IVC and HV stent placement depending on the sites of obstruction. The long-term effect is satisfactory. Anticoagulants are strongly recommended after the procedure especially for BCS patients caused by segmental occlusion.

Aim: To study the effects of non-cytotoxic concentrations of docetaxel on some important angiogenic factors of LS174T Cells., Methods: The non-cytotoxic concentration of docetaxel and the activity of gelatinase were determined with MTT and gelatin zymography respectively, the expression of VEGF(vascular endothelial growth factor), bFGF (basic fibroblast growth factor), MMP (matrix metalloproteinase) 2 and MMP 9 was investigated with RT-PCR and Western blot., Results: The maximum non-cytotoxic concentration of docetaxel on LS174T Cells was 1.0 ng/ml. Compared with the solvent control group, 0.1, 0.5, 1.0 ng/ml of docetaxel could downregulate the expression of VEGF, bFGF, MMP 2 and MMP 9 and suppress the activity of gelatinase., Conclusion: Our study suggests that the non-cytotoxic concentrations of docetaxel have strong antiangiogenic activity on LS174T Cells, which suggests docetaxel may be a promising antiangiogenic agent.

Purpose: To measure psychophysically the thresholds for motion detection in the nasal and temporal directions under monocular viewing conditions in monkeys reared under conditions of daily alternating monocular occlusion (AMO). The hypothesis was that motion perception would be asymmetric with more sensitivity for motion in the nasal direction., Methods: Three monkeys subjected to AMO (AMO monkeys) and three normal monkeys were studied. All were trained with operant conditioning techniques to discriminate coherent from random motion in a random dot display. The percentage of dots in the display that moved either left or right was varied. Thresholds for motion detection of nasally directed and temporally directed stimuli were measured to determine whether the motion perception of AMO monkeys was asymmetric, as predicted., Results: A two-factor analysis of variance revealed a statistically significant difference between treatment groups (normal versus AMO) and directions (nasal versus temporal) and a significant interaction. The interaction was due to a significant difference between nasal and temporal directions for the AMO group, but no significant difference for the normal group. Planned comparisons were performed based on each animal's best eye (eye most sensitive to nasal motion) and worst eye (eye least sensitive to temporal motion). No significant differences were found between the two groups in the best eyes' responses to the nasal direction, but the worst eyes' responses in the temporal direction were significantly poorer in the AMO group. A neural model that can account for these findings is based on a Hebbian teacher located in the nucleus of the optic tract that strengthens connections of a subpopulation of directionally selective cortical neurons., Conclusions: AMO rearing results in asymmetric motion perception. Thresholds for detecting nasally directed motion are normal, whereas thresholds for detecting temporally directed motion are deficient. These results demonstrate that motion-processing mechanisms in primates exhibit experience-dependent developmental neural plasticity. The locus of the neural plasticity could be a subpopulation of directionally selective neurons in the striate cortex (V1).

Through mechanical analysis, it is discovered that the twined structure decides the amplification coefficient of the catgut tension. Many troubles of production can be explained with this mechanics model, and it could be used as a reference for medical sutures. The paper gives an accurate calculating formula for catgut design and its direct tensile strength through improving mechanics model. It can raise the material strength from 10 to over 31% depending on its twined structure.

We used quantitative autoradiography to determine whether the development of glutamate receptors correlates with the plastic period for monocular deprivation in rat visual cortex. To study glutamate receptors, we incubated sections of rat visual cortex with tritiated (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801), tritiated kainate, and tritiated amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). [3H]MK-801 is a noncompetitive ligand for the N-methyl-D-aspartate (NMDA) receptor. [3H]kainate and [3H]AMPA are competitive ligands for non-NMDA receptors. To compare glutamate binding sites with a nonglutamate binding site, we studied [3H]muscimol, which binds to gamma-aminobutyric acid (GABA)A receptors. [3H]MK-801 binding was maximal at postnatal day 26 (P26) and decreased in adulthood. [3H]AMPA binding was maximal at P18. [3H]kainate binding and [3H]muscimol binding were not age dependent. Dark rearing partially prevented the age-dependent decrease in [3H]MK-801 binding but had no effect on [3H]kainate or [3H]AMPA binding. Dark rearing decreased muscimol binding in adult animals. These results suggest that NMDA receptors, but not other glutamate receptors or GABAA receptors, are likely to be critical for developmental plasticity in rat visual cortex.

Differential translation of messenger RNA (mRNA) with stable secondary structure in the 5' untranslated leader may contribute to the dramatic changes in protein synthetic patterns that occur during oogenesis and early development. Plasmids that contained the bacterial gene chloramphenicol acetyltransferase and which encoded mRNA with (hpCAT) or without (CAT) a stable hairpin secondary structure in the 5' noncoding region were transcribed in vitro, and the resulting mRNAs were injected into Xenopus oocytes, eggs, and early embryos. During early oogenesis, hpCAT mRNA was translated at less than 3 percent of the efficiency of CAT mRNA. The relative translational potential of hpCAT reached 100 percent in the newly fertilized egg and returned to approximately 3 percent after the midblastula transition.

Nanao county, Guangdong province is a high incidence area of carcinoma of esophagus and gastric cardia carcinoma. By retrospective investigation of data in the past 14 years (1970 to 1983), the annual average crude mortality of carcinoma of esophagus and gastric cardia carcinoma was found to be 88.65/100,000, the age adjusted mortality of Chinese population was 82.91/100,000 and that of the world population was 113.09/100,000. The mortality of the male was 100.65/100,000 and of the female was 67.24/100,000 with the ratio of 1.38:1. As regards the relationship between the age and mortality, the highest rate occurs from 50 to 74. A higher mortality was also observed in the population engaged in salt production and fishing. The mortality was higher in the lower elevation areas than in the elevated regions.