Distinct Function of Estrogen Receptors in the Rodent Anterior Cingulate Cortex in Pain-related Aversion.

BACKGROUND: Brain-derived estrogen is implicated in pain-related aversion; however, which estrogen receptors mediate this effect remains unclear. This study hypothesized that the different estrogen receptors in the rostral anterior cingulate cortex play distinct roles in pain-related aversion. METHODS: Formalin-induced conditioned place avoidance and place escape/avoidance paradigms were used to evaluate pain-related aversion in rodents. Immunohistochemistry and Western blotting were used to detect estrogen receptor expression. Patch-clamp recordings were used to examine N-methyl-D-aspartate-mediated excitatory postsynaptic currents in rostral anterior cingulate cortex slices. RESULTS: The administration of the estrogen receptor-ß antagonist 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP) or the G protein-coupled estrogen receptor-1 antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15) but not the estrogen receptor-α antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) into the rostral anterior cingulate cortex blocked pain-related aversion in rats (avoidance score, mean ± SD: 1,3-bis [4-hydroxyphenyl]-4-methyl-5-(4-[2-piperidinylethoxy] phenol)-1H-pyrazole dihydrochloride (MPP): 47.0 ± 18.9%, 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP): -7.4 ± 20.6%, and [3aS*,4R*,9bR*]-4-[6-bromo-1,3-benzodioxol-5-yl]-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15): -4.6 ± 17.0% vs. vehicle: 46.5 ± 12.2%; n = 7 to 9; P < 0.0001). Consistently, estrogen receptor-ß knockdown but not estrogen receptor-α knockdown by short-hairpin RNA also inhibited pain-related aversion in mice (avoidance score, mean ± SD: estrogen receptor-α-short-hairpin RNA: 26.0 ± 7.1% and estrogen receptor-ß-short-hairpin RNA: 6.3 ± 13.4% vs. control short-hairpin RNA: 29.1 ± 9.1%; n = 7 to 10; P < 0.0001). Furthermore, the direct administration of the estrogen receptor-ß agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) or the G protein-coupled estrogen receptor-1 agonist (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1) into the rostral anterior cingulate cortex resulted in conditioned place avoidance (avoidance score, mean ± SD: 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN): 35.3 ± 9.5% and (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1): 43.5 ± 22.8% vs. vehicle: 0.3 ± 14.9%; n = 8; P < 0.0001) but did not affect mechanical or thermal sensitivity. The activation of the estrogen receptor-ß/protein kinase A or G protein-coupled estrogen receptor-1/protein kinase B pathway elicited the long-term potentiation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. CONCLUSIONS: These findings indicate that estrogen receptor-ß and G protein-coupled estrogen receptor-1 but not estrogen receptor-α in the rostral anterior cingulate cortex contribute to pain-related aversion by modulating N-methyl-D-aspartate receptor-mediated excitatory synaptic transmission.

Recurrent multiple neurofibromatosis type 1 of the right lower limb.

Neurofibromatosis type 1 is an autosomal dominant inherited disease, which is characterized by the presence of multiple neurofibromas. We encountered a case in which a sporadic dispersed neurofibroma recurred locally on numerous occasions extending over 16 years. The patient developed multiple masses with a focus of neurofibroma on the right lower limb, which were excised. The patient was initially diagnosed with inflammatory changes via computed tomography and magnetic resonance imaging; however, subsequently, pathological and immunohistochemical examinations revealed an intraneural neurofibroma. The patient underwent a comprehensive and complete local resection several times. After a continuous postoperative follow-up strategy, the patient recovered well. This report describes a case of primary manifestations of multiple and recurrent neurofibromas. We aim to emphasize the possibility of a unique, recurrent, non-healing neurofibroma and review the diagnostic techniques utilized to reach a definitive diagnosis. Early and complete surgical resection is an effective method to treat and prevent this type of neurofibroma.

Balsam-pear-like rutile/anatase core/shell titania nanorod arrays for photoelectrochemical water splitting.

In this work, a solution combustion followed by dissolution in hydrogen peroxide is adopted to achieve a precursor for decorating anatase TiO2 nanosheets along single-crystalline rutile TiO2 nanorods, which achieves balsam-pear-like core/shell nanorod arrays with enhanced photoelectrochemical water splitting. The enhanced photoelectrochemical performance is attributed to the novel nanoarchitecture, which can simultaneously offer a high surface area, enhanced light-harvesting, a rutile/anatase junction for charge carrier separation and a conductive pathway for charge carrier collection. The photoanode design can also give hints to other functional materials.

Colorectal cancer's burden attributable to a diet high in processed meat in the Belt and Road Initiative countries.

BACKGROUND: Colorectal cancer (CRC) plays a significant role in morbidity, mortality, and economic cost in the Belt and Road Initiative ("B and R") countries. In addition, these countries have a substantial consumption of processed meat. However, the burden and trend of CRC in relation to the consumption of a diet high in processed meat (DHPM-CRC) in these "B and R" countries remain unknown. AIM: To analyze the burden and trend of DHPM-CRC in the "B and R" countries from 1990 to 2019. METHODS: We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC. Numbers and age-standardized rates (ASRs) of deaths along with the disability-adjusted life years (DALYs) were determined among the "B and R" countries in 1990 and 2019. Using joinpoint regression analysis, the average annual percent change (AAPC) was used to analyze the temporal trends of age-standardized DALYs rate (ASDALR) from 1990 to 2019 and in the final decade (2010-2019). RESULTS: We found geographical differences in the burden of DHPM-CRC among "B and R" countries, with the three highest-ranking countries being the Russian Federation, China, and Ukraine in 1990, and China, the Russian Federation, and Poland in 2019. The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019 (all P < 0.05). The absolute number of deaths and DALYs in DHPM-CRC were 3151.15 [95% uncertainty interval (UI) 665.74-5696.64] and 83249.31 (95%UI 15628.64-151956.31) in China in 2019. However, the number of deaths (2627.57-2528.51) and DALYs (65867.39-55378.65) for DHPM-CRC in the Russian Federation has declined. The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam, Southeast Asia, with an AAPC value of 3.90% [95% confidence interval (CI): 3.63%-4.16%], whereas the fastest decline was observed in Kyrgyzstan, Central Asia, with an AAPC value of -2.05% (95% CI: -2.37% to -1.73%). A substantial upward trend in ASR of mortality, years lived with disability, years of life lost, and DALYs from DHPM-CRC changes in 1990-2019 and the final decade (2010-2019) for most Maritime Silk Route members in East Asia, South Asia, Southeast Asia, North Africa, and the Middle East, as well as Central Europe, while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly (all P < 0.05). The ASDALR for DHPM-CRC increased more in males than in females (all P < 0.05). For those aged 50-74 years, the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend, except for 20 members, including 7 members in Central Asia, Maldives, and 12 high or high-middle social development index (SDI) members in other regions (all P < 0.05). CONCLUSION: The burden of DHPM-CRC varies substantially across "B and R" countries and threatens public health. Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in "B and R" countries via extensive collaboration.

[Synergistic apoptotic effect of the combination of diosgenin and TRAIL on non-small-cell lung cancer cell line A549 evaluated with the Chou-Talalay method].

This study is to investigate the apoptotic induction effect of the combination of diosgenin and TNF-related apoptosis-inducing ligand (TRAIL) on non-small-cell lung cancer cell line A549 by using the Chou-Talalay method, and observe the mechanism of the combination. The apoptotic effect of diosgenin or TRAIL alone and their combination on A549 and normal cell line 293T proliferation was measured by MTT assay. Chou-Talalay method was used to evaluate the combination effect. Apoptosis was examined by Hoechst 33342 staining and flow cytometry assay. Western blotting detects the expression of apoptosis-associated proteins. Diosgenin or TRAIL alone can inhibit proliferation ofA549 in a concentration-dependent manner. According to the Chou-Talalay method, when f(a) = 0.1, CI > 1, when f(a) > 0.1, CI < 1. Combined with TRAIL, the IC50 of diosgenin decreases from 21.864 to 14.810 micromol x L(-1) (P < 0.05) on A549 cells. But for 293T cells, IC50 of diosgenin does not change significantly. As with Hoechst 33342 staining and flow cytometry assay, the apoptosis ratios also increased in the combination group. At protein expression level, combination-treated group displays increased Caspase-8, Caspase-9, Bid, Caspase-3 activation and PARP cleavage, significantly decreased Bcl-2 and increased Bax expression, and MAPK pathways were activated. The combination of diosgenin and TRAIL has synergistic effect on A549 cells.

Titanium oxide-based optoelectronic synapses with visual memory synergistically adjusted by internal emotions and ambient illumination.

Brain-inspired neuromorphic computing has become one of the critical technologies to overcome the bottleneck of von Neumann architecture. It is a vital step to construct a brain-like neuromorphic computing system at the hardware level by utilizing artificial synaptic devices. Compared with electronic synaptic devices, optoelectronic synaptic devices have the advantages of low power consumption, low crosstalk, and high bandwidth. Artificial optoelectronic synapses, analogous to retinal structure, can directly respond to and process light signal information to mimic the neuromorphic visual system. As high-level nerve impulses, both generated and regulated, emotions affect the strength and persistence of memory. Ambient illumination can provide visual perception to distinguish the size, color, and other characteristics of objects as well as affect the nonvisual functions of individuals, such as emotional states, thereby affecting learning and memory function. Herein, an artificial optoelectronic synapse composed of ITO/TiO2-x /p-Si was proposed. A variety of biologically dependent synaptic plasticity relating to learning and memory, including short-term synaptic plasticity, long-term synaptic plasticity, and learning-forgetting-relearning multifunctional advanced synaptic activity, was successfully simulated. A 3 × 3 artificial optoelectronic synapse array based on 9 devices was constructed to mimic the functions of visual learning and memory affected by internal emotion and ambient illumination. The proposed artificial optoelectronic synapse will exhibit great potential in visual and image information perception and memory.

[Soil-crop Distribution and Health Risk Assessment of Organochlorine Pesticides on Typical Agricultural Land in Southern Leizhou Peninsula].

The residual content of organochlorine pesticides (OCPs) in soil and crops of typical agricultural land in the southern Leizhou peninsula were determined using gas chromatography-mass spectrometry (GC-MS). Additionally, the bioconcentration factors of organochlorine pesticides in eight crops were investigated, and the human health risk was evaluated. The results indicated that 10 types of OCPs were detected to varying degrees; HCHs and heptachlor were the main OCPs in the study area, with the residual contents of 23.83-111.51 ng·g-1 and 11.01-25.97 ng·g-1 in soil and 7.54-61.28 ng·g-1 and 3.96-30.97 ng·g-1 in crops, respectively. A small number of soil and crop samples were found to exceed the standard. The ratio of α-HCH/γ-HCH was less than 1 in 87.50% of the soil samples, and ß-HCH/α-HCH was larger than 1. This indicates that the HCHs were probably derived from the recent use of lindane and historical residual pollution, whereas the heptachlor was mainly derived from underground insect pests and the application of termite control agents. The enrichment ability of OCPs was significantly different among different crops. The bioaccumulation capacity of vegetables was higher than that of fruit. Furthermore, bulb vegetables (leeks) were significantly stronger than other vegetables. A human health risk assessment of OCPs showed that OCP-combined pollution would not cause significant health risks to the population in the study area. However, the maximum value of HI in some crop samples was greater than 1, indicating that there were still potential risks, which should not be ignored.

Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia.

Recently programmed death-ligand 1 (PD-L1) receptor PD-1 was found in dorsal root ganglion (DRG) neurons, and PD-L1 activates PD-1 to inhibit inflammatory and neuropathic pain by modulating neuronal excitability. However, the downstream signaling of PD-1 in sensory neurons remains unclear. Here, we show that PD-L1 activated Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1) to downregulate transient receptor potential vanilloid 1 (TRPV1) in DRG neurons and inhibit bone cancer pain in mice. Local injection of PD-L1 produced analgesia. PD-1 in DRG neurons colocalized with TRPV1 and SHP-1. PD-L1 induced the phosphorylation of SHP-1 in DRG TRPV1 neurons and inhibited TRPV1 currents. Loss of TRPV1 in mice abolished bone cancer-induced thermal hyperalgesia and PD-L1 analgesia. Conditioned deletion of SHP-1 in NaV1.8+ neurons aggravated bone cancer pain and diminished the inhibition of PD-L1 on TRPV1 currents and pain. Together, our findings suggest that PD-L1/PD-1 signaling suppresses bone cancer pain via inhibition of TRPV1 activity. Our results also suggest that SHP-1 in sensory neurons is an endogenous pain inhibitor and delays the development of bone cancer pain via suppressing TRPV1 function.

Enhancement of antitumor properties of TRAIL by targeted delivery to the tumor neovasculature.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent with tumor-selective apoptotic activity. TRAIL plays a role in the innate and adaptive immune response and autoimmune disease and may also be involved in hepatic cell death and inflammation. For these reasons, chronic exposure to TRAIL may have deleterious side effects in patients as a cancer therapeutic. In this study, we have improved the antitumor activity of TRAIL by targeted delivery to the tumor vasculature, leading to dramatic enhancement of its therapeutic properties. TRAIL was fused to the ACDCRGDCFC peptide (named RGD-L-TRAIL), a ligand of alpha(V)beta(3) and alpha(V)beta(5) integrins. Biological activity was evaluated in vitro and antitumor efficacy was investigated in vivo as a single agent and in combination with irinotecan hydrochloride (CPT-11). The fusion protein RGD-L-TRAIL, but not TRAIL or RGE-L-TRAIL, specifically bound to microvascular endothelial cells in a dose-dependent manner and showed enhanced apoptosis-inducing activity (caspase-3 and caspase-8 activation) in alpha(V)beta(3) and alpha(V)beta(5) integrin-positive cancer cells. In addition, RGD-L-TRAIL was more effective in suppressing tumor growth of COLO-205 tumor-bearing mice than an equivalent dose of TRAIL. The antitumor effect of RGD-L-TRAIL was further enhanced by combination with CPT-11 in both TRAIL-sensitive COLO-205 and TRAIL-resistive HT-29 tumor xenograft models. Our findings suggest that the novel fusion protein RGD-L-TRAIL can directly target tumor endothelial cells as well as alpha(V)beta(3) and alpha(V)beta(5) integrin-positive tumor cells. The tumor-targeted delivery of TRAIL derivatives, such as RGD-L-TRAIL, may prove to be a promising lead candidate for cancer therapy.

A univariate ternary logic and three-valued multiplier implemented in a nano-columnar crystalline zinc oxide memristor.

Memristors, which feature small sizes, fast speeds, low power, CMOS compatibility and nonvolatile modulation of device resistance, are promising candidates for next-generation data storage and in-memory computing paradigms. Compared to the binary logics enabled by memristor devices, ternary logics with larger information-carrying capacity can provide higher computation efficiency with simple operation schemes, reduced circuit complexity and smaller chip areas. In this study, we report the fabrication of memristor devices based on nano-columnar crystalline ZnO thin films; they show symmetric and reliable multi-level resistive switching characteristics over three hundred cycles, which benefits the implementation of univariate ternary logic operations. Experimental results demonstrate that a three-valued logic complete set can be realized by the univariate operations of the present ZnO memristor device, and a ternary multiplier unit circuit is designed for potential applications. The present methodology can be beneficial for constructing future high-performance computation architectures.

Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

CRA(Crosolic Acid) isolated from Actinidia valvata Dunn.Radix induces apoptosis of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF-κB pathway.

A natural ursolic compound, 2α,3ß-dihydroxy-urs-12-en-28-oic acid (corosolic acid, CRA) was isolated from the root of Actinidia valvata Dunn. (A. valvata Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to investigate the anticancer effect of CRA in human gastric cancer cell line BGC823 cells and the underlying apoptotic mechanism of CRA was examined in BGC823 cell lines. The results showed that CRA significantly suppressed the viability of BGC823 cells in a concentration- and time-dependent manner. CRA also significantly increased the sub G1 population by cell cycle analysis in a concentration dependent manner. Exposure to CRA decreased p65, bcl-2, Fas, smac mRNA and protein expression, and increased IκBα, bax, survivin mRNA and protein expression. Results of immunofluorescence staining and EMSA further indicated CRA induced apoptosis by inhibiting nuclear translocation of nuclear factor NF-κB subunit p65. Consistently overall, our findings suggest that CRA induces apoptosis via inhibition of NF-κB (p65) expression level and activation of IκBα in BGC cells as a potent anticancer candidate for gastric cancer treatment.

Repeated Multiple Neurofibromatosis Type 1 in the Right Lower Limb: A Case Report.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease characterized by the presence of multiple neurofibromas. We encountered a unique case of NF1 that manifested as a recurrent soft tissue neurofibroma in the right lower limb that developed over a period of 16 years. The patient presented with a painless mass that was initially diagnosed as inflammatory changes via computed tomography and magnetic resonance imaging. However, the condition was subsequently diagnosed as an intraneural neurofibroma via pathological and immunohistochemical examination, which showed a focal to patchy lymphocytic chronic inflammatory infiltrate and several non-encapsulated masses with clear boundaries that were easily distinguishable from the adjacent neurofibroma. The mass relapsed three times over 3 years since it was discovered, for which the patient underwent comprehensive and complete local resection several times. Postoperative continuous follow-up confirmed that the patient recovered well. Early and complete surgical resection is an effective method for treating and preventing recurrent neurofibromas. However, because of the importance of pathologic examination in the diagnosis of such cases, this uncommon entity might be underreported in patients with NF1.

FU Wen-bin's experience in treatment of depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder / 中国针灸

Based on the thinking of integrative and holistic acupuncture and moxibustion, FU Wen -bin proposes to treat depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder. In clinical practice, the treatment pattern of "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" is applied, acupuncture, refined moxibustion, intradermal needle and other therapies are comprehensively adopted, acupoints on the heart meridian, pericardium meridian and gallbladder meridian are selected or back-shu points and front-mu points of the heart, gallbladder and pericardium are matched, and the acupoints on the conception vessel and governor vessel and with the functions of tonifying kidney and regulating qi are added to calm the heart and tranquilize the mind, so as the symptoms of depression and obsessive-compulsive can be effectively relieved.

Application to immunoassays of the fusion protein between protein ZZ and enhanced green fluorescent protein.

Enhanced green fluorescent protein (EGFP) from Aequorea victoria was fused to the C terminal region of protein ZZ, an artificial synthetic IgG Fc fragment binding protein derived from tandem repeats of the B domain of protein A. The ZZ-EGFP fusion protein was expressed in Escherichia coli with a His(6) tag and purified in high yield by one-step Ni(2+) chelating affinity chromatography. It was then used in the immunoblot analysis of GST and TNFalpha as well as in immunofluorescent assays of 293T cells transfected with IRF3, an interferon regulatory factor which localized in cytoplasm without virus infection. The fusion protein also performed effectively in FACS analysis of surface integrin beta3 subunit on 293 T cells. The chimeric protein bound various antibodies from different animal sources, directed against a variety of proteins. Thus, ZZ-EGFP showed broad promise in potential immunological applications.

[Pollution Characteristics and Ecological Risk Assessment of Organochlorine Pesticides in Water Source Areas of Guangdong and Guangxi].

The concentrations of 16 organochlorine pesticides (OCPs) in 7 water samples collected from different sites of water source areas of Guangdong and Guangxi were detected by SPE-GC-MS, and then the pollution characteristics were analyzed. This study established species sensitivity distribution(SSD) curves with BurrⅢ distribution model. In the meantime, HC5 values were calculated by BurrliOZ software, which were used to evaluate the toxicity effects of OCPs towards aquatic organisms. Finally, margin of safety concentration values were calculated to assess the ecological risk. The results showed that the concentration of OCPs varied from 6.64 to 34.19 ng·L-1, with a mean value of 16.76 ng·L-1, while HCHs and DDTs contributed a lot. HCHs were predominately originated from lindane, which is a component in household insecticide, while DDTs were from dicofol contamination or historical residues. Vertebrates could stand severer toxicity in comparison with invertebrates. α-endosulfan showed a greater toxicity towards aquatic plants and microorganisms than others, while p, p'-DDT turned out to be the most hazardous pollutant to vertebrates and invertebrates among the 16 OCPs studied. Generally speaking, OCPs in study areas didn't show conspicuous ecological risks towards aquatic organisms, DDTs and α-endosulfan, however, are still worth paying close attention due to their high potential risks.

Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model.

The growth of tumor is angiogenesis-dependent and it often contains hypoxia and necrotic areas. Salmonella VNP20009 could target and replicate in hypoxia and necrotic areas within tumor and induce antitumor effect. Angiogenesis inhibitor endostatin could reduce tumor angiogenesis and inhibit its growth. However, in the phase I trials of VNP20009 and endostatin at the maximum-tolerated dose, no antitumor effects for bacteria therapy and minor therapeutic effects for endostatin treatment were seen. The ineffectiveness of these agents in clinical trials suggests that the combination of these agents with synergic modalities might be necessary. Here we described antitumor effects mediated by the combination of VNP20009 with recombinant human endostatin in B16F10 murine melanoma model with the aim to exploit tumor-targeting of bacteria and anti-angiogenesis strategy to enhance therapeutic efficacy. Combination therapy of these agents significantly enhanced antitumor effects by inducing greater tumor growth inhibition, more severe tumor tissue necrosis as well as less blood vessel density than those induced by either of treatments. The findings suggest that the combination of tumor-targeting bacteria with angiogenesis inhibitor might be of value for the treatment of solid tumors.

2ß, 3ß, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) isolated from Actinidia chinensis Radix inhibits NCI-H460 cell proliferation by decreasing NF-κB expression.

A natural ursolic compound, 2ß, 3ß, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidia chinensis Planch (A. chinensis Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to investigate the anticancer effect of TUA in non-small cell lung cancer cells (NSCLCCs) and the underlying apoptotic mechanism of TUA was examined in NCI-H460 cell lines. Cell proliferation, apoptosis and cell cycle were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of transcription factor NF-κB was determined by EMSA method. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The effect of TUA on NF-κB mRNA expression in NCI-H460 cells was detected by RT-PCR. TUA significantly suppressed the viability of NCI-H460 cells. Also, TUA significantly increased the sub G1 population by cell cycle analysis and in a concentration dependent manner in NCI-H460 cells. Such an effect was accompanied by p65 (NF-κB subunit) inactivation by an inhibition of IκBα phosphorylation, and by inhibition of p65 mRNA expressions. Consistently Overall, our findings suggest that TUA induces apoptosis via inhibition of NF-κB (p65) expression level and activation of IκBα in NCI-H460 cells as a potent anticancer candidate for lung cancer treatment.

The comparison of robot-assisted laparoscopic and open pyelolithotomy in the management of nonstaghorn renal calculi larger than 2 cm / 复旦学报（医学版）

Objective To investigate the feasibility and safety of robot-assisted laparoscopic pyelolithotomy (RALPL) as the surgical management for nonstaghorn renal calculi larger than 2 cm. Methods Among the patients admitted to our hospital for nonstaghorn renal calculi larger than 2 cm between Jun. ,2013 and Jun. ,2017, a retrospective analysis was performed on the treatment outcome of patients undergoing RALPL (48 cases) and open pyelolithotomy (OPL) (44 cases). The initial stone-free rate, mean operating time, hemoglobin drop, off-bed activity time and hospital stay were compared between two groups. Results Compared with OPL group, RALPL group had a higher initial stone-free rate (91. 66% vs. 70.45%, P < 0.05), and had significant lesser hemoglobin drop, shorter operating time, off-bed activity time and hospital stay. There was no ClavienⅡ or above complications in RALPL group, but there were 2 cases of ClavienⅡcomplications in OPL group. Conclusions Transperitoneal approach RALPL has a better visual angle to observe renal pelvis and calyces, and can ensure a higher initial stone-free rate under the conditions of low intrarenal pelvic pressure and leaving renal parenchyma and vessels intact. RALPL is a minimally invasive, effective and safe treatment, and is an alternative indication for renal calculi larger than 2 cm (including renal pelvis stones with accompanying renal calyceal stones).

The Application of the Technique in the Protection of PCI / 昆明医科大学学报

Objective To explore the treatment of percutaneous coronary intervention (PCI), and to comparatively study on the protection of side support by using the active and passive expansion technique.Method 78 patients with coronary artery disease were protected by using balloon technique, there were two groups: the active expansion group (n=41) and the side support balloon (n=37), the TIMI classification、myocardial perfusion rating (MBG), TIMI myocardial perfusion rating (TMP) and the incidence of marginal vascular interlayer were observed and analyzed. Results After the main support was put in, the proportion of patients with side branches of TIMI、 MBG and TMP was at level 3 and the proportion of patients with active balloon expansion was 93％, the margin expansion group was 84％, the difference was not statistically significant (P＞0.05); the incidence of intersecting vascular interlayer in active dilatation group was 24％, the margin expansion group was 8％, and there were statistical differences (P＜0.05). Conclusions Using the technique of holding balloon to protect the side branches, both the active expansion of the side support balloon and the expansion of the side support balloon can significantly reduce the risk of the main stent placement in the posterior branch of the blood vessel, however the incidence of side branch vascular interlayer was lower.