Comparing the effectiveness and safety of Sorafenib plus TACE with Apatinib plus TACE for treating patients with unresectable hepatocellular carcinoma: a multicentre propensity score matching study.

OBJECTIVE: Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC. METHODS: The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors. RESULTS: A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005). CONCLUSION: TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.

[Effect of hysteretic acupuncture on joint function and related cytokines in articular fluid in patients with knee osteoarthritis].

OBJECTIVE: To observe the difference of therapeutic effect between hysteretic acupuncture and Celecoxib capsules for knee osteoarthritis(KOA), and to investigate their effects on levels of interleukin 6(IL-6) and tumor necrosis factor α(TNF-α) in articular fluid. METHODS: Seventy-two patients with KOA were randomly divided into hysteretic acupuncture and me-dication groups, with 36 cases in each group. The patients of the hysteretic acupuncture group received hysteretic acupuncture stimulation at Dubi (ST35), Neixiyan (EX-LE4), Zusanli (ST36), Yanglingquan (GB34), Yinlingquan (SP9), Xuehai (SP10), Liangqiu (ST34) and Heding (EX-LE2) as the main acupoints for 30 min once daily. The patients of the medication group received oral administration of Celecoxib capsules(200 mg) once daily. Both of the two groups were treated with 14 days as a course of treatment, with a 2-day rest between each course of treatment, and the treatments were conducted for 2 courses. The visual analogue scale(VAS) score of pain, Lequesne index score, IL-6 and TNF-α level in joint fluid and the change of traditional Chinese medicine(TCM) syndrome score were observed before and after treatment. RESULTS: Compared with pre-treatment, the VAS score, Lequesne index score, IL-6 and TNF-α level, and total TCM syndrome score decreased significantly after treatment in both of the two groups (P<0.05). Hysteretic acupuncture was more effective in reducing VAS score, Lequesne index score, IL-6 and TNF-α level than Celecoxib capsules (P<0.05), and there was no significant difference in total TCM syndrome score and total effective rate between the two groups(P>0.05). No adverse events occurred in both groups during the treatment. CONCLUSION: Hysteretic acupuncture can effectively relieve pain symptoms and improve joint function in KOA patients. Its effect is comparable to that of oral administration of Celecoxib capsules.

An Indole Alkaloid Extracted from Evodia rutaecarpa Inhibits Colonic Motility of Rats In Vitro.

Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 µM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents (I Ca,L) in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak I Ca,L in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I-V) relationship of L-type calcium channels was modified by Evo, while the peak of the I-V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak I Ca,L. The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.

[Composition and Distribution of Biodegradable Compounds in the Macrophyte Dominated Zone of Lake Taihu].

In shallow eutrophic lakes, benthic bioclastic deposits accumulate abundant organic carbon derived from macrophyte detritus. Taking the typical macrophyte-dominated Xukou Bay as the study area, field investigations were performed using sediment cores to evaluate benthic phytodetritus accumulation. Specifically, nutrient contents, TOC/TN ratios, pigmentation, and biodegradable compounds were measured as descriptive parameters. The results show that the benthic bioclastic deposit had accumulated abundant pigments, nutrients, and biodegradable compounds derived from macrophytes detritus. These were mainly localized in the top 15 cm of sediments. Nitrogen loading in the sediments was significantly higher than phosphorous loading, with a distinct spatial difference; the total nitrogen content ranged from 127.2-2092.8 mg·kg-1 and total phosphorous content ranged from 222.1-528.4 mg·kg-1. Moreover, nitrogen loading (1033.6 mg·kg-1) in the vegetated zones were higher than in the unvegetated zones (325.2 mg·kg-1). In addition, carbohydrate (3.7 mg·g-1) was the dominant component of sedimentary bioclastic material, with lipids (2.8 mg·g-1) being the second most abundant of the biodegradable compounds. The major sources of nutrients and biodegradable compounds in the sediment were massive aggregates of macrophyte detritus. The pigment, nutrient, and biodegradable compound contents in the vegetated zones were significantly higher than in unvegetated zones (P<0.01). The benthic eutrophic state showed a trend from mesotrophic to eutrophic in Xukou Bay, which should be given more attention in the future management of freshwater lake ecosystems.

[Effect of Nutrient Loadings on the Regulation of Water Nitrogen and Phosphorus by Vallisneria natans and Its Photosynthetic Fluorescence Characteristics].

Submerged macrophytes are an important component of aquatic ecosystems. During the growing period, submerged macrophytes can absorb nitrogen and phosphorus nutrients to reduce pollution loadings. Shoots of submerged macrophytes can also promote the adhesion of suspended substances in water, reducing the turbidity. The release of nutrients in sediments can be suppressed by its root system, and the resuspension of sediments caused by disturbance of winds and waves can also be resisted. The role of submerged macrophytes in ecological restoration of eutrophic lakes has attracted widespread attention. In 1960, the submerged plants Vallisneria natans and Potamogeton malaianus had been the dominant species in East Taihu. However after 2002, Nymphoides peltatum, Elodea nattalii, P. malaianus, etc. have gradually taken over the dominant roles along with significant elevations of nitrogen and phosphorus levels. Nutrients in water are not the only key factors causing eutrophication of water bodies; the nutrient source for submerged plant growth affect both the purification efficiency and the photosynthetic characteristics of submerged macrophytes. Excessive nitrogen and phosphorus concentrations can inhibit the photosynthetic physiological activities of submerged macrophytes, affecting the succession of aquatic vegetation. In addition, under high nutrient conditions, the competition from periphytic algae and planktonic algae may also directly poison submerged macrophytes, leading to its degradation and disappearance. Systematic studies on the regulation and photosynthetic fluorescence response mechanism of submerged macrophytes to varied nutrient loadings are helpful in revealing their relationships. The seedlings of submerged macrophyte V. natans were transplanted in a laboratory mesocosm to study the effect of nutrient loadings on its regulation of water nitrogen and phosphorus. Three nitrogen and phosphorus loadings from low, medium, and high levels derived from nitrate, ammonium, and phosphate were setup as the aquatic medium for the plant growth. Twelve harvests were carried out to determine the evolution of nutrient removal performance of V. natans. Its photosynthetic fluorescence characteristics were measured by a pulse-amplitude modulated fluorometer (Diving-PAM). Results showed that the nitrogen and phosphorus adsorption abilities of V. natans were gradually enhanced with the increase of nutrient concentrations in the range of TN ≤ 12 mg·L-1 and TP ≤ 1.0 mg·L-1. In the treatment of high nutrient concentrations (TN=12 mg·L-1 and TP=1.0 mg·L-1), the removal rates of nitrogen and phosphorus reached more than 95%. V. natans preferentially absorbed ammonium nitrogen when its concentration was high. The medium nutrient concentrations (TN:8-12 mg·L-1 and TP:0.6-1.0 mg·L-1) did not significantly affect the Fv/Fm ratio of leaves. However, the low nutrient concentrations (TN=3 mg·L-1 and TP=0.3 mg·L-1) could improve the Fv/Fm ratio of leaves and were beneficial for the growth of V. natans. The inhibition of photosynthetic activity and light tolerance were enhanced with the increase in nutrient concentrations. The photosynthetic activity of V. natans gradually recovered with no significant changes in the capacity for light harvesting, when the nutrient concentrations gradually decreased in the water. Our results indicate that the high nitrogen and phosphorus loadings indeed hamper the photosynthetic capacity, which may subsequently restrain the maintenance of the dominance of V. natans in the submerged macrophyte communities.

A modeling understanding on the phosphorous removal performances of A2O and reversed A2O processes in a full-scale wastewater treatment plant.

Reversed A2O process (anoxic-anaerobic-aerobic) and conventional A2O process (anaerobic-anoxic-aerobic) are widely used in many wastewater treatment plants (WWTPs) in Asia. However, at present, there are still no consistent results to figure out which process has better total phosphorous (TP) removal performance and the mechanism for this difference was not clear yet. In this study, the treatment performances of both processes were compared in the same full-scale WWTP and the TP removal dynamics was analyzed by a modeling method. The treatment performance of full-scale WWTP showed the TP removal efficiency of the reversed A2O process was more efficient than in the conventional A2O process. The modeling results further reveal that the TP removal depends highly on the concentration and composition of influent COD. It had more efficient TP removal than the conventional A2O process only under conditions of sufficient influent COD and high fermentation products content. This study may lay a foundation for appropriate selection and optimization of treatment processes to suit practical wastewater properties.

[Characteristics of Organic Phosphorus Fractions in the Sediments of the Black Water Aggregation in Lake Taihu].

Potential release of phosphorus in lake sediments depends largely on the fractions and distribution of organic phosphorus. MaoDu was chosen as the research area in the west of Lake Taihu. The chemical forms of the surface sediments were investigated by the Ivannoff extraction methods. The results showed that the main organic phosphorus form of sediments at different sampling places was humic acid-OP. It accounted for 35% of the total organic phosphorus. Horizontal distribution: Total organic phosphorus content from the shore to the middle of total showed a trend of rising after decline; vertical distribution: Total organic phosphorus content was the lowest in 2-6 cm and the highest in 4-8 cm. Various phosphorus content followed the order of humic acid-OP > residual-OP > HCl-OP > fulvic acid-OP; the relative content of NaHCO3-OP in the total organic phosphorus content showed a trend of rising followed by reduction and then rising again from the shore to the middle, cyanobacteria residue deposition increased the content of NaHCO3-OP in sediment. Contents of NaHCO3-OP and humic acid-OP both first reduced, then increased and finally reduced in the vertical distribution, the content of NaHCO3-OP was the lowest in 4-6 cm and humic acid-OP was the highest in 4-8 cm. HCl-OP and fulvic-OP decreased with increasing depth in the vertical distribution. The content of residual-OP showed stable tendency in the vertical direction and was about 45 µg·g-1. Labile OP and pH, DO, the depth of water were significantly negatively correlated, OM and NaOH-Pi were significantly correlated with total organic phosphorus, labile OP, moderately labile OP and nonlabile OP. Three components of organic phosphorus had bio-availability and played an important role in lake eutrophication. The increase of the content of labile OP might promote the black water aggregation (BWA) in cyanobacteria accumulation.

[Community characteristics of crustacean zooplankton and its relationship with environmental factors in Suzhou Industrial Park, Jiangsu Province, China].

The monthly sampling data from June 2012 to May 2013 were used to study the composition and structure of the crustacean zooplankton community in the lakes and rivers of Suzhou Industrial Park. The variations in density and biomass of the crustacean zooplankton and their relationship with the environment factors were investigated. The results showed that a total of 42 species of crustacean zooplankton were found, including 24 species of cladocerans which belonged to 6 families and 12 genera, and 18 copepods which belonged to 7 families and 13 genera. The dominant species were Diaphanosoma brachyurum, Bosmina longirostris, Sinocalanus dorrii and Cyclops vicinus in all seasons of the year both in the rivers and the lakes. The density and biomass of the crustacean zooplankton in summer and autumn were higher than that in winter and spring, and there were two peaks in summer and autumn respectively both in the lakes and the rivers. The average density and biomass of cladocerans in the rivers were significantly higher than that in the lakes. There was no significant difference in the average density of Copepods between the rivers and the lakes, but the biomass in the rivers was higher than that in the lakes significantly. There were significant differences in dissolved oxygen, pH, Secchi depth, total dissolved solids, salinity, total phosphorus, total nitrogen and ammonium nitrogen between the lakes and the rivers. Redundancy analysis showed that the distribution of most of crustacean zooplankton was positively correlated with water temperature, the salinity, COD(Mn) and total phosphorus concentrations and only the distribution of the species belonging to genus Daphnia and Scapholeberis was positively correlated with O2 concentration, pH, and Secchi depth in both the rivers and the lakes in Suzhou Industrial Park.

[Coupling Effects of Decomposed Potamogeton crispus and Growing Ceratophyllum demersum on Water Quality and Plant Growth].

In order to study the coupling effects of decomposed Potamogeton crispus (P. crispus) and growing Ceratophyllum demersum (C. demersum) on water quality and the effects of different decomposed biomass on plant growth, the simulating experiments for seasonal changes of submerged macrophytes were conducted. The results indicated that the nutrient concentrations in water remained at a relatively low level with different decomposed biomass and they remained stable after 29 days of the experiment. The concentrations of total dissolved nitrogen (DTN), total nitrogen (TN), total phosphorous (TP), total dissolved phosphorous (DTP), organic carbon (TOC) and chlorophyll-a (Chl-a) were lower than 0. 514, 0. 559, 0. 080, 0. 014, 13. 94 and 26. 546 mg . L-1, respectively. The obvious improving effects on water quality were observed under coupling condition of decomposition and growth, especially when the treatment of decomposed P. crispus was 20 g, and the removal efficiency of TN, DTN, TP, DTP, TOC and Chl-a reached 89. 67% , 52. 51%, 94. 99%, 55. 59% and 98. 55%, respectively. Compared with the physiology of C. demersum in the early stage, the contents of total chlorophyll, soluble protein and malondialdehyde all increased under different decomposed biomass conditions, which suggested that the nutrient released from decomposed P. crispus promoted the growth of C. demersum. The coupling effects between P. crispus decomposition and C. demersum growth showed better improving effect on water quality and growth of C. demersum with treatment of 20 g decomposed P. crispus.

[Design space approach to optimize first ethanol precipitation process of Dangshen].

Design space approach is applied in this study to enhance the robustness of first ethanol precipitation process of Codonopsis Radix (Dangshen) by optimizing parameters. Total flavonoid recovery, dry matter removal, and pigment removal were defined as the process critical quality attributes (CQAs). Plackett-Burman designed experiments were carried out to find the critical process parameters (CPPs). Dry matter content of concentrated extract (DMCE), mass ratio of ethanol to concentrated extract (E/C ratio) and concentration of ethanol (CEA) were identified as the CPPs. Box-Behnken designed experiments were performed to establish the quantitative models between CPPs and CQAs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of Dangshen can be guaranteed by operating within the design space parameters. Recommended normal operation space are as follows: dry matter content of concentrated extract of 45.0% - 48.0%, E/C ratio of 2.48-2.80 g x g(-1), and the concentration of ethanol of 92.0% - 92.7%.

[Temporal and spatial variation of water nutrient level after exogenous nutrient input].

In order to study the spatial and temporal variations of nitrogen (N) and phosphorous (P) nutrition in artificial wetlands after a single exogenous nutrient input, 6 mosaic communities of 7 plant species were set up in a cement channel in the greenhouse. After the addition of N and P nutritional solutions, the concentrations of dissolved total nitrogen (DTN), dissolved total phosphorous (DTP), ammonia nitrogen (NH4(+)-N), nitrate nitrogen (NO3(-) -N) and nitrite nitrogen (NO2(-) -N) in the surface, middle, and bottom layers of the bulk water were determined regularly within 22 days. The results show that: (1) the water depth and measuring date have significant effects on nutritional contents while the type of plant communities have no such an influence; (2) the diffusion of nutrient from surface to the middle water layers is relatively slow, which costs 6 days under the current experimental condition; (3) in the bottom water layer, nutritional concentrations had no significant changes except for NO2-N, thus the exogenous nutrient input mainly affects the nutrient contents of surface and middle-level bulk water; (4) DTP and NH4(+) -N contents gradually decline to similar levels that before the nutritional input event until the end of experimental period, though DTN and NO3(-) -N content decrease much more slowly; (5) the fact that NO2(-) -N contents rise in water layers of all depths demonstrates that nitrification and denitrification in the process of N circulation are enhanced. It is concluded that exogenous nutrient inputs not only harm aquatic ecosystems but also directly threat human health.

[Effects on phosphorus fraction distribution in sediment by roots of Vallisneria natans].

The present study explored phosphorus fractions in sediments with the growth of Vallisneria natans. Sediment samples in different layers were collected at 20, 50 and 80 d, and vertical change of several phosphorus fractions were measured in the samples. The root distributions and biomass of the V. natans were measured. Our results showed that roots were distributed between 0 and 14 cm in the experimental device. The average number of roots and average root length were 58 and 5.86 cm. After 80 days growth, the percentage of V. natans root biomass were 45.99%, 32.75%, 16.03% and 5.23% in the sediment with depths of 0-3, 4-6, 7-10 and 11-14 cm. Total phosphorus (TP) content, phosphorus extracted by NaOH (NaOH-P), and organic phosphorus (OP) levels remarkably decreased (P < 0.05) in the area with a high concentration of tape grass roots. The content of phosphorus extracted by HCl (HCl-P), and inorganic phosphorus (IP), showed no significant difference (P > 0.05). The results suggest that V. natans root affects the migration and transformation of phosphorus species in the sediment.

[Influence of submerged macrophytes on phosphorus transference between sediment and overlying water in the growth period].

In order to study the process of phosphorus transfer between sediment and overlying water, Hydrilla verticillata and Vallisneria natans were cultured in spring, Potamogeton crispus was cultured in winter. Changes of environmental factors and phosphorus concentrations in water and sediment were investigated. The results indicated that: submerged macrophytes could reduce all phosphorus fractions in the overlying water. Phosphorus concentrations in overlying water maintained in a relative low level in the growth period of submerged macrophytes. The concentrations of total phosphorus (TP) in overlying water of H. verticillata, V. natans and P. crispus were 0.03-0.05, 0.04-0.12, 0.02-0.11 mg x L(-1), respectively. All phosphorus fractions in sediment were reduced. The maximum value between submerged macrophyte and control of H. verticillata, V. natans and P. crispus were 35.34, 60.67 and 25.92 mg x kg(-1), respectively. Dissolved oxygen (DO), redox potential (Eh) and pH in overlying water increased (DO 10.0-14.0 mg x L(-1), Eh 185-240 mV, pH 8.0-11.0) in the submerged macrophytes groups. Submerged macrophytes increased Eh( -140 - -23 mV) and maintained pH(7.2-8.0) in neutral range. The results indicated that submerged macrophytes affected phosphorus transferring between sediment and overlying water through increasing DO, Eh and pH in overlying water, and Eh in sediment.

[Preliminary exploring of hyperspectral remote sensing experiment for nitrogen and phosphorus in water].

The content of nitrogen and phosphorus in the waters is an important index to measure water quality, and the technique of remote sensing plays a large role in monitoring the change in environment. The reflectance spectra of nitrogen and phosphorus with different concentrations were measured to discover their special features under pure water condition in the laboratory by hyperspectral remote sensing technique. The result shows that nitrogen has reflectance peaks at 404 and 477 nm, and phosphorus at 350 nm, and these reflectance peaks have a good correlation with their concentrations, then a quantitative retrieval model was deduced for nitrogen and phosphorus based on that. These results will lay an important basis for further monitoring nitrogen and phosphorus by remote sensing technique in the big inland lakes, reservoirs and rivers.

[Effects of cutting on photosynthesis and purification efficiencies on nitrogen and phosphorus of the Lolium multiflorum].

Effects of different cutting intensities on the growth, photosynthesis and the purification efficiencies on nitrogen and phosphorus of the Lolium multiflorum by hydroponics experiment method were studied. The results were shown as followings: 1) Cutting could promote regeneration capacity of the Lolium mutiflorum, and sprout regeneration rate in C2 (stubble = 5 cm) achieved 2.78 cm x d(-1) after being cut 5 to 13 d, which was significantly more than zero-cutting (0.88 cm x d(-1)). The height, standing-biomass, productivity of cutting groups were significantly more than zero-cutting. Their compensation capacities were raised with the increase of cutting intensity, and the sprout height, total biomass of the serious cutting groups were 40.6-44.0 cm, 31.6-37.2 g, which indicates that the serious cutting is good for the biomass cumulation of the Lolium multiflorum. 2) Different cutting intensities have obvious effects on the chlorophyll contents of Lolium multiflorum: the chla and chla/chlb in C2 were about 1.85 mg x g(-1), 3.18, which was highest in treating groups, while they were lowest in zero-cutting. 3) The fluorescence chorophyll parameters had a significant changes in the different cutting intensities. With increasing cutting intensity, the values of phi PS II and ETR were significant increased: the phi PS II and ETR in C2 were about 1.13 and 1.09 times of those in zero-cutting, indicating cutting could improve the photosynthetic capacity of Lolium multiflorum. 4) The purification efficiencies on TN, NH4+ -N, TP and COD had a significant increase with the cutting intensities increase, and the purification rate on TN, NH4+ -N, TP and COD of C2 was 1.07,1.20, 1.05,1.44 times more than zero-cutting respectively. 5) About 2-5 cm of stubble was the best cutting height of Lolium multiflorum, which can applied a technical references for ecological bed management.