Synthesis and QSAR study of novel α-methylene-γ-butyrolactone derivatives as antifungal agents.

Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC50) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC50=22.91, 18.89µM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R2=0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC50=18.89µM (against B. cinerea.) but low cytotoxicity with IC50=35.4µM (against HepG2 cell line) and IC50=68.8µM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency.

Genome-wide Identification and analysis of the stress-resistance function of the TPS (Trehalose-6-Phosphate Synthase) gene family in cotton.

BACKGROUND: Trehalose (a-D-glucopyranosyl a-D-glucopyranoside) is a nonreducing disaccharide and is widely distributed in bacteria, fungi, algae, plants and invertebrates. In the study, the identification of trehalose-6-phosphate synthase (TPS) genes stress-related in cotton, and the genetic structure analysis and molecular evolution analysis of TPSs were conducted with bioinformatics methods, which could lay a foundation for further research of TPS functions in cotton. RESULTS: The genome information of Gossypium raimondii (group D), G. arboreum L. (group A), and G. hirsutum L. (group AD) was used in the study. Fifty-three TPSs were identified comprising 15 genes in group D, 14 in group A, and 24 in group AD. Bioinformatics methods were used to analyze the genetic structure and molecular evolution of TPSs. Real-time PCR analysis was performed to investigate the expression patterns of gene family members. All TPS family members in cotton can be divided into two subfamilies: Class I and Class II. The similarity of the TPS sequence is high within the same species and close within their family relatives. The genetic structures of two TPS subfamily members are different, with more introns and a more complicated gene structure in Class I. There is a TPS domain(Glyco transf_20) at the N-terminal in all TPS family members and a TPP domain(Trehalose_PPase) at the C-terminal in all except GrTPS6, GhTPS4, and GhTPS9. All Class II members contain a UDP-forming domain. The responses to environmental stresses showed that stresses could induce the expression of TPSs but the expression patterns vary with different stresses. CONCLUSIONS: The distribution of TPSs varies with different species but is relatively uniform on chromosomes. Genetic structure varies with different gene members, and expression levels vary with different stresses and exhibit tissue specificity. The upregulated genes in upland cotton TM-1 is significantly more than that in G. raimondii and G. arboreum L. Shixiya 1.

Serum cystatin C and indices of lung function in elderly Chinese men with chronic obstructive pulmonary disease.

OBJECTIVE: The aim of this cross-sectional case-control study was to determine the relationship between serum cystatin C (sCysC) levels and lung function in elderly male patients with chronic obstructive pulmonary disease (COPD). METHODS: This study included 251 Chinese men (age ≥ 65 years) who were divided into COPD (n = 129) and non-COPD (n = 122) groups. Participants underwent lung function and laboratory testing, including measurement of sCysC levels. Relationships between sCysC concentration and indices of lung function were assessed by multiple regression analysis. RESULTS: Participants in the COPD group displayed higher sCysC concentrations (P = 0.041) and lower lung function (P < 0.001) compared to participants in the non-COPD group. Multiple linear regression analyses revealed that the reciprocal of the sCysC concentration (1/sCysC) was positively associated with the predicted forced expiratory volume in 1 s in all subjects (ß = 0.156, P = 0.009). The findings indicate that high sCysC levels were directly associated with decreased lung function in elderly Chinese men with COPD. CONCLUSIONS: High sCysC concentration may be a potential indicator of impaired lung function, and its application may improve the diagnosis and assessment of COPD severity in elderly male patients.

Synthesis, antifungal activities and qualitative structure activity relationship of carabrone hydrazone derivatives as potential antifungal agents.

Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents.

Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome. / ç”µé’ˆå¹²é¢„å¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ æµ·é©¬ç»„ç»‡è›‹ç™½è´¨ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.

[Research progress on the effect mechanism of acupuncture-moxibustion for pressure injuries].

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.

[Analgesic mechanism of acupuncture on neuropathic pain].

The research progress of acupuncture analgesia in recent years is analyzed to summarize the analgesic mechanism of acupuncture on neuropathic pain. The analgesic mechanism of acupuncture on neuropathic pain is discussed from peripheral level and central level, including peripheral sensitization and immune inflammatory response, changes of ion channel, central sensitization, regulation of cell signal pathway, activation of spinal glial cells, etc. It is suggested that the focus of future research should include conducting in-vitro studies with the help of multi-omics technology to detect the changes of metabolic substances and signal pathway molecules in patients with neuropathic pain before and after acupuncture to further clarify the mechanism of acupuncture analgesia.

The relationship between chronic obstructive pulmonary disease and non-small cell lung cancer in the elderly.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and NSCLC often coexist and have poor prognoses, but studies investigating the impact of COPD on NSCLC have reported inconsistent findings. The objective of this study was to compare survival between NSCLC patients with and without COPD. METHODS: Medical records were retrospectively collected from 301 elderly patients pathologically diagnosed with NSCLC from the Chinese PLA General Hospital. Ultimately, a total of 200 patients were enrolled in the analysis. The survival rates between the COPD-NSCLC and non-COPD NSCLC were assessed using log-rank and Cox proportional hazard regression analyses. RESULTS: A total of 117 COPD-NSCLC and 93 non-COPD NSCLC patients were enrolled in the analysis. The median overall survival times were 108.5 months in the non-COPD group and 45.0 months in the COPD group (HR: 2.05; 95% CI, 1.36-2.97, P = 0.0004). After 118 patients underwent propensity score matching, the median overall survival times were 100.6 months in the non-COPD group and 51.9 months in the COPD group (HR: 1.59; 95% CI, 1.096-2.64, P = 0.0459). The multivariate analysis showed that presence of COPD (HR 1.619, P = 0.030), old age (HR 1.007, P < 00001), an advanced disease stage (stage Ⅲ HR 5.513, P < 0.0001; stage Ⅳ HR 11.743, P < 0.0001), the squamous cell carcinoma histological subtype (HR 3.106, P < 0.0001), the presence of a cough (HR 2.463, P = 0.001) a higher serum carcinoembryonic antigen level (HR 1.001, P = 0.023) and higher NRL (HR 2.615, P = 0.007) were independent factors that were significantly associated with poorer survival. CONCLUSION: A diagnosis of COPD had significant poorer survival outcomes in NSCLC than that of patients without COPD in this elderly population.

In vivo effects of Pain Relieving Plaster on closed soft tissue injury in rabbit ears.

BACKGROUND: Soft tissue injury imposes major public health burdens worldwide. The positive effect of China's Tibetan medicine and the Lamiophlomis rotata-based herbal Pain Relieving Plaster (PRP) on healing closed soft tissue injury (CSTI) has been reported. The herbs contained in Plaster are also referred as 'blood-activating and stasis-dispelling' in herbal medicine. The formula of the plaster contains four China's Tibetan medical herbs, including Lamiophlomis rotata, Oxytropis falcate Bunge, Curcuma longa Linn, and Myricaria bracteata. Two of these herbs (Lamiophlomis rotate; Curcuma longa Linn) are commonly used in different formulae of Chinese medicine. The objective of this study is to use an interdisciplinary approach to test the hypothesis that the formula and its components influence the process of CSTI. METHODS: In vivo models have been established in 30 rabbit ear pinnae and studied for: (1) blood flow velocity (BFV) which was affected by pressure of 21.2 kg/cm2 for 30 second over the local rabbit ear tissue; (2) edema formation of the closed soft tissue injury; (3) in vivo local temperature change. RESULTS: The results of in vivo studies indicated that CSTI significantly increased the velocity of blood flow and increased edema formation within the control group. The PRP extracts for 5 hours significantly slowed down the BFV of CSTI in rabbit ears, markedly decreased the elevated edema level from the 3rd to the 5th day. CONCLUSION: The ingredients contained in the formula have positive effects in healing CSTI and further study is worth exploring.

Primary splenic angiosarcoma with liver metastasis: A case report and literature review.

Primary splenic angiosarcoma (PSA) is an unusual and highly malignant vascular tumour with a high rate of metastatic. Moreover, the research on prognosis of the disease is poor. The epidemiology, etiology, clinical diagnosis and treatment of the disease remain challenging, because case reports of the disease are few in number. In accordance with other malignant tumors, PSA is very aggressive, and the majority of patients in which this disease is found are at an advanced stage. Almost all patients die within 12 mo of diagnosis irrespective of treatment. We report here a woman who had complained of upper bellyache and anorexia for 10 d. Magnetic resonance imaging showed enlargement of the spleen with multiple heterogeneous masses in the lower pole of the spleen. A hand-assisted laparoscopic splenectomy was performed which allowed histopathologic diagnosis. The patient was diagnosed with PSA and liver metastasis, and succumbed to the disease 35 d after surgery. The literature was finished combined with the clinical features, diagnosis and management of PSA.

[Factors of influence on quality evaluation of adhesive property on cataplasma].

OBJECTIVE: To provide experimental proof for establishing a standard quality evaluation method of adhesive property on Cataplasma by studying the factors of effect on evaluation of adhesive quality on Cataplasma. METHOD: With 180 degrees peel off test, tensile shear and adhesive force test, the influence caused by the square of samples, texture of fabric base and the moisture loss was tested with multifunctional material tester and first stickiness tester. RESULT: The peel off strength of 40 mm wide sample is 26% lower than that of the 20 mm wide sample (P < 0.05), and tensile shear strength had no significant difference. The peel off strength of transverse fabric base was higher than that of lengthways fabric base (P < 0.01). The tensile shear strength of transverse fabric base was lower than that of lengthways fabric base (P < 0.05). The sample with 35% moisture lost had a maximum tensile shear strength and the sample which lost 30% moisture lost had a maximum peel off strength; The sample which lost 20% moisture lost had a maximum first adhesive force. CONCLUSION: The square of samples, the texture of fabric base and the moisture loss of samples can all affect the evaluation of adhesive quality on Cataplasma.

[Effects of tension relaxation by small needle knife on muscle tension and nerve endings after compression of gracilis muscle in rats].

OBJECTIVE: To determine the effect of tension relaxation by small needle knife on the muscle tension and morphology changes of nerve terminals when sustained pressure was applied to muscular tissue. METHODS: Rat gracilis muscles were exposed to pressure in vivo at 70 kPa for 2 hours. Sixty rats were divided into three groups: normal, control and experiment group respectively. In all rats except the six normal ones, the lower legs were considered as the control group, and the right left as experiment group. At day 1, 2 and 3, 9 rats from the two groups were randomly selected and sacrificed in order to determine the muscle tension change. At the same time, muscle histology and morphology changes of nerve terminals were observed. RESULTS: Abnormal tension increased in muscles under compression of 70 kPa. At the 1st and 2nd days, there were no significant differences between the two groups. Compared with control group, the tension was lower in experiment group, and there was statistically significant difference (P < 0.01) between the two groups. Exposure of striated muscle tissue to intensive and prolonged compression may pathologically alter its microstructure. Histological evaluation showed that this stiffening accompanied extensive necrotic damage. The changes could not be found in the nerve terminals. CONCLUSION: Deep muscle tissue that undergoes prolonged compression may significantly increase its stiffness during acute injury. Tension relaxation applied by small needle knife can effectively reduce the mechanical load which is harmful to the whole tissue.

[Effects of small needle knife on the substance P in the dorsal root ganglion and spinal cord of rats].

OBJECTIVE: To study the mechanism of synthesis of substance P (SP) in the dorsal root ganglion (DRG) and the release of it in the dorsal horn of the spinal cord of rats after compression of skeletal muscle, and to observe the influence of small needle knife. METHODS: Sustained pressure of 70 kPa was applied to rats, muscular tissues for 2 hours. The rats were divided into three groups: normal, control and experiment group respectively. In all rats except the six normal ones, the lower legs were compressed once one day. The left leg was considered as the control group, the right left was experiment group, which were divided into the 1st day, the 2nd day and the 3rd day within the two groups. Experiment group was treated with small needle knife after the muscular tissue was compressed. After completing the stimulation, the DRG related to the muscle and part of spinal cord were removed for the qualification of SP-like immunoreactivity using immunohistochemistry. The dark brown stains on the DRG and on the REXed laminae I and II in the dorsal horn of the spinal cord were counted by Image-Pro Plus software. RESULTS: SP-like immunoreactivity in the side treated by the small needle knife was enhanced comparing with the counterpart in DRG in normal group (P < 0.01). The integrated optical density of SP like immunoreactivity of the DRG in the experiment group were significantly reduced compared with the control group (P < 0.05). However, the release of SP from spinal cord in experiment group was lower than that in the control group at the 1st day and the 3rd day (P < 0.01), with the opposite result of the 2nd day. CONCLUSION: Based on the fact that SP is a nociceptive neurotransmitter, the present study suggests that tension relaxation by small needle knife reduces expression of SP in the DRG, and shows no effects on the release of SP from the spinal cord in short-term (3 days).

[The influence of rotary manipulation on the internal pressure of cervical nucleus pulposus].

OBJECTIVE: To measure the pressure changes inside the cervical nucleus pulposus in fresh human cervical specimen by imitating different rotary manipulations. METHODS: The load of 100 N was applied for 5 second on the six fresh male cervical samples by using material test system, which imitated the human head weigh and the strength of cervical extensor muscle. After that, traction, rotation and pulling on the samples were performed in different sequence under the force of 150, 200, 300 N respectively. Three states were included in adding the load state A: samples were loaded with traction and then rotation to the biggest angle, pulling backward for 15 degrees; state B: samples were loaded with rotary stress to the biggest angle and then loaded with traction, pulling backward for 15 degrees; state C: samples were loaded simultaneously with traction and rotary stress to the biggest angle, pulling backward for 15 degrees. The internal pressure of cervical nucleus pulposus at segment of C(3,4), C(4,5), C(5,6), and C7 was measurred by micro-pressure sensors for state A, B, C and for the imitation of head weight and the strength of cervical extensor muscle. RESULTS: The pressure inside the cervical nucleus pulposus at segments C(5,6), C(6,7) was higher than that at segments C(3,4) and C(4,5) (P < 0.05) by loading stress with 100 N for 5 seconds. The internal pressure of the nucleus pulposus decreased with the increase of traction (P < 0.05), and increased when traction and rotary force were loaded. State A, the value of increased pressure within the nucleus pulposus became smaller and smaller while increasing of the traction force loaded (P < 0.05). State B, the increase of internal pressure in nucleus pulposus became obvious as loading pressure increased (P < 0.05). State C, the internal pressure in nucleus pulposus was not increased obviously (P > 0.05). There was a transitional pressure raise inside all cervical nucleus pulposus when pulling added after different sepuence traction and rotary strength was applied, however, the internal pressure of state A was significantly higher than that of state B or C (P < 0.05). There was also a transitional pressure raise inside all cervical nucleus pulposus when pulling added in different strength (P < 0.05),the internal pressure by pulling with 150 N was obviously higher than that with 200 N and 300 N (P < 0.05). CONCLUSION: The order of rotation first and traction second should be avoided when practice of rotary manupuplation in case protrusion of the nucleus pulposus. Meanwhile, proper traction should be applied along with rotary manipulation in order to increase its safety.

[Randomized control clinical study on third lumbar transverse process syndrome treated by knife needle].

OBJECTIVE: To evaluate the therapeutic effects of knife needle on third lumbar transverse process syndrome. METHODS: From 2007.3 to 2007.12, patients were divided into treatment group and control group according to the random digits table, 34 and 35 patients respectively. Patients in both groups were separately treated for 3 weeks, with knife needle in treatment group and electroacupuncture in control group. In treatment group, 12 patients were male and 22 patients were female, the average age was (42.33 +/- 7.86) years. In control group, 16 patients were male and 19 patients were female, the average age was (44.73 +/- 10.34) years. The changes of biomechanics, local tension and tenderness index were observed and recorded respectively before and after the therapy, and the results obtained from two groups were then compared with each other. The JOA score was used to evaluate the clinical effect. RESULTS: Sixty patients finished the clinical observation. The treatment efficacy was evaluated according to the JOA score in 60 cases. The soft tissue tension in treatment group was lower than that in the control group (P=0.00004). Excellent result was found in 18 cases, good in 9 cases, fair in 3 cases and poor in 0 case. CONCLUSION: Tension relaxation by needle knife can effectively improve the clinical symptoms and signs of third lumbar transverse process syndrome.

[Application of ultrasonic microscopy in biomechanical properties measurement of cancellous bone].

OBJECTIVE: Ultrasound scanning can provide the information of acoustic impedance through the ultrasonic reflection theory. This study tries to introduce the application of the ultrasonic technique in predicting biomechanical properties of cancellous bone. METHODS: The rat femoral head embedded in plexiglass was used as the bone specimens for ultrasound scanning and the gray scale images scanned by ultrasound microscope were collected and analyzed. RESULTS: The value of acoustic impedance was calculated by analyzing the gray scale image. CONCLUSION: The application of ultrasonic microscopy can show more value about the microstructure of biomechanical properties of bone tissue.