[Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy].

OBJECTIVE: To investigate the effect of Fuyu Decoction on ventricular remodeling and its association with AMPK/mTOR pathway-mediated autophagy in rats with heart failure. METHODS: Thirty male Wistar rat models of heart failure induced by ligation of the left anterior descending coronary artery were divided into model group, Fuyu Decoction treatment group, Fuyu Decoction treatment +AMPK agonist group (n=10), with another 10 rats receiving sham operation as the Sham group. After 8 weeks of drug intervention, the changes of ventricular function and ventricular remodeling indexs of the rats were assessed. TTC staining was used to detect the myocardial infarction area, and HE and Masson staining were used to observe the pathological changes in the myocardial tissue. Western blotting was performed to detect the protein expressions of p-AMPK, p-mTOR, LC3-II, Beclin1 and p62 in the myocardial tissue. RESULTS: Compared with the sham-operated rats, the rat models of heart failure showed significantly increased left ventricular end-diastolic volume (LVEDV), left ventricular endsystolic volume (LVESV), and left ventricular mass index (LVMI) (P < 0.01), reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and decreased spherical index (SI) were (P < 0.01). The rat models also showed increased myocardial infarction area, obvious myocardial pathologies and fibrosis, increased apoptosis rate of the cardiomyocytes, enhanced myocardial expressions of p-AMPK, LC3-II/LC3-I and Beclin1 (P < 0.01), and reduced expressions of p-mTOR and p62 (P < 0.01). Fuyu Decoction treatment significantly ameliorated these changes in the rat models (all P < 0.01), but its effects were obviously blocked by treatment with EX229. CONCLUSION: Fuyu Decoction can improve ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR signaling-mediated autophagy in the cardiomyocytes.

Fermented rape pollen powder can alleviate benign prostatic hyperplasia in rats by reducing hormone content and changing gut microbiota.

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.

[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Replenishment of urban landscape ponds with reclaimed water: Spatiotemporal variations of water quality and mechanism of algal inhibition with alum sludge.

Algal blooms caused by high concentrations of nutrients (especially phosphorus) limit the use of recycled water (RW) for replenishing landscape ponds in the context of global water scarcity. Previous studies have demonstrated that alum sludge is a low cost phosphorus sorption medium, which could potentially be applied in constructed wetlands and sewage treatment plants. However, whether alum sludge can be used for algae inhibition in reclaimed water urban landscape ponds (RWULPs) should be explored. In this study, phosphorus removal and algae inhibition by alum sludge were investigated in a RWULP in China. The results highlight that there is a serious risk of algal blooms in RWULPs. The algal density was found to be 1.58 × 105 cell·mL-1, which is 6.84 times higher than that of the surface water ponds. The algal blooms presented a Cyanophyta-Chlorophyta-Bacillariophyta-type, and the dominant algae species were Microcystis flos-aquae (Wittr.) Kirchner, Chlorella vulgaris, and Scenedesmus quadricauda. Moreover, the removal rate of phosphorus by alum sludge was as high as 98% and eventually leads to phosphorus stress, which has an important effect on algae growth and algae inhibition rate of 80%. In addition, the proportion of phosphorus and nitrogen in the adsorbed alum sludge increased by 3.12% and 0.32%, respectively, and Al3+ was reduced by only 2.18%. Alum sludge is a potential inhibitor of algae in RWULPs that does not negatively impact the environment. These results are of great importance in algal bloom control of RWULPs and may help alleviate the problem of urban water resource scarcity.

Salt stress decreases seedling growth and development but increases quercetin and kaempferol content in Apocynum venetum.

Apocynum venetum L. is a traditional Chinese medicinal herb with great potential to treat angiocardiopathy. Its major medicinal constituents are flavonoids. However, the natural habitats of A. venetum are typically affected by salt stress, which can modify both biomass and accumulation of medicinal compounds. In this study, the effects of salt stress on growth and development of A. venetum, accumulation of flavonoids and expression patterns of genes involved in flavonoid biosynthesis were evaluated. In general, the growth and development of seedlings (seedling height, root length, leaf length, leaf width and seed germination) were inhibited by salt stress. Unlike typical halophytes, there was no optimal NaCl concentration range that promoted growth and development, but seedlings had an elevated DW/FW ratio under salt stress (induced by irrigation with 50, 100, 200 or 400 mm NaCl). Furthermore, quercetin and kaempferol were significantly accumulated in A. venetum seedlings under salt stress, resulting in a balanced content and reduced FW. Moreover, the expression of AvCHS, AvCHI and AvF3GT was inhibited by salt stress; however, AvF3'H, AvF3H and AvFLS, which are involved in the flavonol synthesis pathway, were up-regulated under salt stress, consistent with a decrease in total flavonoids and an increase of flavonols (quercetin and kaempferol). In summary, cultivation of A. venetum in saline soils appeared to be feasible and improved the medicinal quality of A. venetum (quercetin and kaempferol accumulation under salt stress), thus this species can effectively utilize saline soil resources.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

[Preliminary efficacy analysis of Cheng's Giraffe reconstruction after proximal gastrectomy in adenocarcinoma of esophagogastric junction].

Objective: To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG). Methods: Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux. Result: All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9. Conclusion: Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.

Pedunculoside attenuates pathological phenotypes of fibroblast-like synoviocytes and protects against collagen-induced arthritis.

Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA.

Isolation of flavonoids from apple peel using novel graphene oxide cotton fiber.

A novel graphene oxide cotton fibre (GOF) was used to adsorb flavonoids from crude ethanol extracts derived from apple peels. Ultra-high pressure liquid chromatography-mass spectrometry was used to analyse polyphenol content, and the resulting data demonstrated that GOF-based flash chromatography can be used to efficiently separate polyphenols from sugars and can facilitate the removal of 95% of the sugar content. Flavonoids can be easily separated from phenolic acids. Chalcones and flavonols were eluted with 100% methanol and subsequently flavan-3-ols can be eluted with 0.04 M sodium hydroxide. The novel GOF has the potential to be used in the isolation of flavonoids.

Tea Polyphenols as Inhibitors of Furan Formed in the Maillard Model System and Canned Coffee Model.

In this article, the effects of sugars and amino acids on furan formation via the Maillard reaction in low-moisture model systems were investigated. Glucose and alanine are important furan precursors, and the effects of the heating temperature, heating time, and molar ratio of glucose to alanine on furan formation were studied in glucose/alanine model system by response surface methodology. The heating temperature greatly affected furan formation. The maximum furan concentration was obtained with a glucose-to-alanine molar ratio of 0.83:1.00, by heating at 151 °C for 41 min. Tea polyphenols effectively inhibited furan formation in the glucose/alanine model and a canned coffee model. A high inhibition rate of 42.4% ± 1.5% was obtained in the canned coffee model during sterilization procedure with addition of 84 mg (the mass fraction is 12.1%) of tea polyphenols (99%). However, the content of aromatic components in the canned coffee model was significantly reduced at the same time. This study provides evidence for a good furan inhibitor that can be used in food processing.

Effects of dietary supplementing tannic acid in the ration of beef cattle on rumen fermentation, methane emission, microbial flora and nutrient digestibility.

Four adult Simmental male cattle (376 ± 9.0 kg initial BW), fitted with permanent rumen cannulas, were used in a 4 × 4 Latin square design to investigate the effects of dietary supplementing tannic acid (TA) on rumen fermentation, methane (CH4 ) production, rumen microbes, nutrient digestibility and plasma biochemical parameters. Four levels of TA, that is 0, 6.5, 13.0 or 26.0 g/kg dry matter (DM), were added to the basal ration (composed of corn silage and concentrate mixture) as experimental treatments respectively. Each experimental period consisted of a 12-day adaptation phase followed by a 3-day sampling phase. The results showed that supplementing TA at 26.0 g/kg DM decreased the relative abundance of protozoa, methanogens and Ruminococcus albus to the total ruminal bacterial 16S rDNA in beef cattle (p < 0.05). The results also showed that supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) the CH4 production (l/kg DM intake) by 11.1%, 14.7% and 33.6% respectively. Supplementing TA at 13.0 or 26.0 g/kg DM decreased the ratio of acetate to propionate and ammonia nitrogen (NH3 -N) (p < 0.05) and tended to decrease the total volatile fatty acid (VFA) concentration of rumen fluid (p = 0.07). Supplementing TA at 26.0 g/kg DM decreased DM and organic matter (OM) digestibility (p < 0.05), supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) crude protein (CP) digestibility by 5.0%, 8.6% and 15.7%, respectively, and supplementing TA at 6.5, 13.0 or 26.0 g/kg DM increased (p < 0.05) the plasma total antioxidant capability. It was concluded that supplementing TA in the ration of beef cattle decreased the CH4 production and digestibility of CP of beef cattle. Supplementing TA could be an effective option to mitigate CH4 emission form cattle, further research is necessary to study the effects of TA on the performance of cattle.

Protective effects of curcumin against mercury-induced hepatic injuries in rats, involvement of oxidative stress antagonism, and Nrf2-ARE pathway activation.

Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl2) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl2 treatment (0.6, 1.2, and 2.4 mg kg-1 day-1), and curcumin pretreatment (100 mg kg-1 day-1) groups. Exposure of HgCl2 resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg-1 HgCl2 significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl2 treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl2-induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl2 hepatotoxicity through antagonizing liver oxidative stress.

Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma.

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib therapy. It is therefore critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified a long non-coding RNA referred to as lncRNA-SRLR (sorafenib resistance-associated lncRNA in RCC) that is upregulated in intrinsically sorafenib-resistant RCCs. lncRNA-SRLR knockdown sensitized nonresponsive RCC cells to sorafenib treatment, whereas the overexpression of lncRNA-SRLR conferred sorafenib resistance to responsive RCC cells. Mechanistically, lncRNA-SRLR directly binds to NF-κB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance. A STAT3 inhibitor and IL-6-receptor antagonist both restored the response to sorafenib treatment. Moreover, a clinical investigation demonstrated that high levels of lncRNA-SRLR correlated with poor responses to sorafenib therapy in RCC patients. Collectively, lncRNA-SRLR may serve as not only a predictive biomarker for inherent sorafenib resistance but also as a therapeutic target to enhance responses to sorafenib in RCC patients.

[The national anti-opium-smoking campaigns across the country in the Republican Period].

Anti-opium-smoking had been the key policy of successive central and local governments from the late Qing Dynasty to the Republican Period. Since the establishment of the Nanjing Provisional Government in January 1912, the Anti-opium-smoking campaign had culminated across the country. Under the support of the government, the "National Anti-Opium Association of China" and "Association of Chinese People Rejecting Opium" were established which made an important contribution to China's anti-opium-smoking campaign.Yunnan, Shaanxi, Heilongjiang, Zhejiang, Shanghai and other local governments also combined with local specific circumstances to make anti-opium-smaking policy for punishing severely the opium cultivation, trade and opium smoking, thus, the overrun of opium began to be brought under an overall control.

Effect of compound Maqin decoction on TGF-ß1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-ß1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-ß1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-ß1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-ß1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-ß1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Process of Bipolaris sorghicola invasion of host cells.

Target leaf spot is a sorghum leaf disease caused by Bipolaris sorghicola, a species of fungus with a global distribution. In this study, we investigated the process by which B. sorghicola invades cells of barley, onion, Arabidopsis thaliana species, and sorghum. The results showed that within 8 h of coming into contact with host cells, the hyphal ends of B. sorghicola expand and form a uniform infective penetration pegbolt-like structure; a primary infection mycelium can be formed inside host cells within 24 h after contact, which can infect closed cells after 48 h. A mycelium can grow within the gap between cells and form infective hyphae. The pathogen infection process was the same in different host cells. B. sorghicola can affect root cells through soil infection, indicating that it may also have characteristics of soil-borne pathogens.

The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil.

The study aimed to clarify clinical significance of hepatitis B virus (HBV) rtA181S mutation in Chinese HBV-infected patients. A total of 18 419 patients with chronic HBV infection from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of polymerase was screened by direct sequencing, and the results were verified by clonal sequencing. Replication-competent mutant and wild-type HBV genomic amplicons were constructed and transfected into the HepG2 cells and cultured in the presence or absence of serially diluted nucleos(t)ide analogues. Intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of the drug (EC(50)). The rtA181S was detected in 98 patients with 12 kinds of mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and 8.2% in rtA181S-positive patients, in contrast to 84.6% and 15.4% in rtA181S-negative patients (P < 0.01). All rtA181S-positive patients had received nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic breakthrough. Phenotypic analysis of patient-derived viral strains showed that rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and 66.2% of natural replication capacity of wild-type strain, and 3.7-fold, 9.8-fold, 7.9-fold and 5.6-fold increased EC(50) to adefovir dipivoxil (ADV). The rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and ADV susceptibility was restored after the mutation was eliminated through site-directed mutagenesis. Rescue therapy with entecavir or combination therapy was effective in rtA181S-related ADV-refractory patients. The rtA181S mutation confers moderate resistance to ADV. It could be induced by either lamivudine or ADV and contribute ADV treatment failure.

A randomized, triple-masked, active-controlled investigation of the relative effects of dose, concentration, and infusion rate for continuous popliteal-sciatic nerve blocks in volunteers.

BACKGROUND: It remains unknown whether local anaesthetic dose is the only factor influencing continuous popliteal-sciatic nerve block effects, or whether concentration, volume, or both exert an influence as well. METHODS: Bilateral sciatic catheters were inserted in volunteers (n=24). Catheters were randomly assigned to ropivacaine of either 0.1% (8 ml h(-1)) or 0.4% (2 ml h(-1)) for 6 h. The primary endpoint was the tolerance to transcutaneous electrical stimulation within the tibial nerve distribution at hour 6. Secondary endpoints included current tolerance at other time points and plantar flexion maximum voluntary isometric contraction (22 h total). RESULTS: At hour 6, tolerance to cutaneous stimulation for limbs receiving 0.1% ropivacaine was [mean (standard deviation)] 27.0 (20.2) vs26.9 (20.4) mA for limbs receiving 0.4% [estimated mean difference 0.2 mA; 90% confidence interval (CI) -8.2 to 8.5; P=0.02 and 0.03 for lower and upper boundaries, respectively]. Because the 90% CI fell within the prespecified tolerance ±10 mA, we conclude that the effect of the two concentration/volume combinations were equivalent. Similar negative findings were found for the secondary outcomes. CONCLUSIONS: For continuous popliteal-sciatic nerve blocks, we found no evidence that local anaesthetic concentration and volume influence block characteristics, suggesting that local anaesthetic dose (mass) is the primary determinant of perineural infusion effects in this anatomic location. These findings suggest that for ambulatory perineural local anaesthetic infusion-for which there is usually a finite local anaesthetic reservoir-decreasing the basal rate while increasing the local anaesthetic concentration may allow for increased infusion duration without compromising postoperative analgesia. CLINICAL TRIAL REGISTRATION: NCT01898689.