Combined treatment of sodium ferulate, n-butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke.

The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n-butylidenephthalide (BP) and adipose-derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin-5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal-regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. 18 F-2-deoxy-glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain-blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin-5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke.

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ß-amyloid (Aß) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aß clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aß clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3ß pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg-1·d-1, ig) for 100 days. Furthermore, NTZ administration decreased Aß level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

Small molecule IVQ, as a prodrug of gluconeogenesis inhibitor QVO, efficiently ameliorates glucose homeostasis in type 2 diabetic mice.

Gluconeogenesis is a major source of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), thus targeting gluconeogenesis to suppress glucose production is a promising strategy for anti-T2DM drug discovery. In our preliminary in vitro studies, we found that a small-molecule (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (QVO) inhibited the hepatic glucose production (HGP) in primary hepatocytes. We further revealed that QVO suppressed hepatic gluconeogenesis involving calmodulin-dependent protein kinase kinase ß- and liver kinase B1-adenosine monophosphate-activated protein kinase (AMPK) pathways as well as AMPK-independent mitochondrial function-related signaling pathway. To evaluate QVO's anti-T2DM activity in vivo, which was impeded by the complicated synthesis route of QVO with a low yield, we designed and synthesized 4-[2-(1H-indol-3-yl)vinyl]quinoline (IVQ) as a prodrug with easier synthesis route and higher yield. IVQ did not inhibit the HGP in primary hepatocytes in vitro. Pharmacokinetic studies demonstrated that IVQ was quickly converted to QVO in mice and rats following administration. In both db/db and ob/ob mice, oral administration of IVQ hydrochloride (IVQ-HCl) (23 and 46 mg/kg every day, for 5 weeks) ameliorated hyperglycemia, and suppressed hepatic gluconeogenesis and activated AMPK signaling pathway in the liver tissues. Furthermore, IVQ caused neither cardiovascular system dysfunction nor genotoxicity. The good druggability of IVQ has highlighted its potential in the treatment of T2DM and the prodrug design for anti-T2DM drug development.

The effects of Chinese proprietary medicine and vaccination on patients with COVID-19: a retrospective study in Macao.

BACKGROUND: COVID-19 is continuing to ravage globally and has resulted in a huge health and financial burden. Chinese proprietary medicines, such as Lianhua Qingwen (LHQW) and Huoxiang Zhengqi (HXZQ) capsules, have been recommended for non-high-risk patients with COVID-19 in China. Based on this, we described the baseline information, using status of LHQW and HXZQ capsules and inoculation history of quarantined patients in the second half of 2022 in Macao. Additionally, we analyzed the underlying association among medicines administration, vaccination and COVID-19 indices, in order to explore novel clues for the regular control and prevention of local epidemic situation in the future. METHODS: A total of 976 patients in Macao quarantine hotels from June to August 2022 were included in the present study, of which, 857 subjects were followed-up for prognosis evaluation. During quarantine, the baseline demographic information, including sex, age, BMI, occupation and personal habits were collected. Additionally, the inoculation history, medicine employment status and cycle threshold (Ct) values were also reported. We interviewed the patients for collection of their symptoms at the beginning and end of quarantine, as well as prognostic ones. Basic statistical description of baseline information, vaccination history and medication were displayed. Chi-squared test or with continuous correction test was employed for comparison of dichotomous data between two or multiple groups. Binary logistic regression was applied to reveal the correlation between potential risk factors and Ct values or prognosis symptoms. We also used Cox regression model to identify the effect of different types of vaccine products on Ct value altering rate. RESULTS: Patients who were female (52.0%), engaged in service industry (31.8%), from Macao native (65.8%), never took physical exercises (33.6%) and preferred irritated diet (59.5%) enjoyed more dominant proportions. Over 80% of participants were inoculated and 74.6% of them chose inactivated COVID-19 vaccine produced by China National Biotech Group (CNBG). Participants used LHQW capsules accounted for 92.1% and the duration of medicating lasted for one to two weeks. All of the reported symptoms were significantly ameliorated after quarantine and the duration of quarantine was concentrated on 21 days. People with different age, sex, occupation and region had different choices of HXZQ administration and vaccination. Additionally, middle dose (4-5 boxes) of LHQW capsules exhibited evidently negative association with positive Ct values (adjusted, - 0.037 ± 0.19, p = 0.04). Two doses of CNBG and one dose of mRNA vaccine had obvious protective effect on reducing Ct positive rate (p = 0.041). Meanwhile, symptoms after quarantine were significantly positive correlated with those in prognosis (adjusted, 1.38 ± 0.18, p < 0.0001). CONCLUSION: Our study found that the administration of LHQW capsules was beneficial for Ct value turning negative, meanwhile, certain mixed inoculation may be the promoting factor to reduce the positive rate of Ct value. These findings provide data basis for the Chinese proprietary medicine treatment and mixed vaccination applying for prevention and control of local COVID-19 epidemic in the future.

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. METHODS: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. RESULTS: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. CONCLUSION: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Silent information regulator 1 inhibition induces lipid metabolism disorders of hepatocytes and enhances hepatitis C virus replication.

AIM: Hepatic steatosis is an important histopathological feature of chronic hepatitis C virus (HCV) infection. Silent information regulator 1 (SIRT1) plays key role in regulation of hepatic lipid metabolism. We investigated the possible effect of HCV replication on lipid metabolism of hepatocytes and expression of SIRT1 using Huh-7.5 cells harboring HCV replicon. METHODS: The level of reactive oxygen species (ROS) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the value of nicotinamide adenine dinucleotide (NAD(+) )/NADH was detected. The level of triacylglycerol (TG), total cholesterol (TC) and fatty acid ß-oxidation rate was detected. The activity and expression levels of SIRT1 and expression of its downstream lipid-metabolism genes were measured. RESULTS: In replicon cells, the level of ROS and MDA increased, SOD activity and the value of NAD(+) /NADH decreased, then the activity and expression level of mRNA and protein of SIRT1 reduced. Inhibition of SIRT1 decreased phosphorylation of forkhead box O1 (FoxO1), which not only upregulated SREBP-1c, FAS, ACC, SREBP-2, HMGR and HMGS genes and increased fatty acid synthesis; but also downregulated PPAR-α and CPT1A genes and decreased fatty acid ß-oxidation. Interferon treatment restored aforementioned changes. SIRT1 activator improved lipid metabolism disorders by an increase in fatty acid ß-oxidation and a decrease in TG and TC synthesis and inhibited HCV replication. CONCLUSION: HCV replication decreasing NAD(+) /NADH ratio may downregulate the activity and the expression of SIRT1, then change the expression profile of lipid metabolism-related genes, thereby cause lipid metabolism disorders of hepatocytes and promote HCV replication. Treatment with SIRT1 activator ameliorates lipid metabolic disorders and inhibits HCV replication.

[Inhibition of silent information regulator-1 in hepatocytes induces lipid metabolism disorders and enhances hepatitis C virus replication].

OBJECTIVE: To investigate the role of the host-encoded silent information regulator 1 (SIRT1) on hepatocytes' lipid metabolism under conditions of hepatitis C virus (HCV) infection and assess its potential effects on virus replication in vitro. METHODS: The Huh-7.5 human hepatocyte cell line was used as the control group and Huh-7.5 cells stably expressing the HCV replicon (Huh7.5-HCV) were used as the experimental group. Effects of interferon (IFN) treatment and activation of SIRT1 by resveratrol were also observed. The mRNA and protein expression levels of SIRT1 were detected by real time (q)PCR and western blotting. Effects on SIRT1 protein activity were tested by measuring the levels of reactive oxygen species (ROS) and the nicotinamide adenine dinucleotide (NAD+)/beta-nicotinamide adenine dinucleotide, reduced (NADH) by flow cytometry and chromatometry, and the levels of triacylglycerol (TG), total cholesterol (TC), and fatty acid beta oxidation rate by enzymatic analysis and liquid scintillation counting. Effects on mRNA expression of SIRT1 downstream lipid-metabolism genes were measured by qPCR. RESULTS: The Huh7.5-HCV cells had a significantly higher level of ROS (3.8+/-0.5 vs. Huh-7.5: 1.0+/-0.2; t = 12.736, P less than 0.01) but significantly lower levels of NAD+/NADH (0.03+/-0.01 vs. 0.12+/-0.03; t = 6.971, P less than 0.01), SIRT1 activity (0.3+/-0.1 vs. 1.0+/-0.2, 0.9+/-0.2, F = 6.766, P less than 0.01), SIRT1 mRNA (0.4+/-0.1 vs. 1.0+/-0.3, 0.9+/-0.2, F = 5.864, P less than 0.01), and SIRT1 protein (0.3+/-0.1 vs. 0.8+/-0.2, 0.9+/-0.2, F = 5.419, P less than 0.01). The lower levels of SIRT1 in Huh7.5-HCV cells accompanied decreased phosphorylation of the forkhead box O1 (FoxO1), which not only up-regulated the downstream genes of SREBP-1c, FAS, ACC, SREBP-2, HMGR and HMGS (which increased fatty acid synthesis) but also down-regulated the downstream genes of PPAR and CPT1A genes (which decreased fatty acid beta oxidation). IFN treatment restored all of the aforementioned changes. Resveratrol-induced SIRT activation improved the perturbations in lipid metabolism pathways, as evidenced by an increase in fatty acid beta oxidation and a decrease in TG and TC synthesis, as well as inhibited HCV replication. CONCLUSION: HCV may decrease the NAD+/NADH ratio in hepatocytes, leading to a down-regulation of SIRT1 activity and expression and perturbing the downstream expression profile of lipid metabolism-related factors, ultimately causing lipid metabolism disorders and establishing a permissive intracellular environment for HCV replication.

Spatial and temporal dynamics of large natural lake areas and shoreline morphology in the Yellow River Basin.

Given their important roles in the regulation and storage functions for river flow and in the regional ecological environment and ecosystem services, natural lakes are essential for the ecological protection and high-quality development of the Yellow River Basin. We used the Landsat TM/OLI remote sensing data to analyze the area changes of Dongping Lake, Gyaring Lake, and Ngoring Lake, three representative large natural lakes in the Yellow River Basin from 1990 to 2020. We used the landscape ecology approach to study the morphological characteristics of lake shoreline and shoreland changes and the relationship between the landscape indices. The results showed that the main areas of Gyaring Lake and Ngoring Lake were mainly in the trend of expansion, while the main area of Dongping Lake significantly reduced during 1990-2000 and 2010-2020. The changes in the area of lake all occurred mainly near the lake inlet of the river. The shoreline morphology of Dongping Lake was more complex, with the fragmentation and aggregation of shoreland landscape significantly changed. The circularity ratio of Gyaring Lake gradually decreased with the expansion of the lake area, and the number of patches in its shoreland changed significantly. The fractal dimension index-mean of the shoreland of Ngoring Lake was relatively high, the complexity of its shoreline landscape was stronger, and the number of patches had increased significantly from 2000 to 2010. Meanwhile, there was a significant correlation between certain lake shoreline (shoreland) landscape indices. The changes in circularity ratio and shoreline development coefficient caused changes in the patch density of shoreland.

Glomus mosseae improved the adaptability of alfalfa (Medicago sativa L.) to the coexistence of cadmium-polluted soils and elevated air temperature.

The coexistence of heavy metal-polluted soils and global warming poses serious threats to plants. Many studies indicate that arbuscular mycorrhizal fungi (AMF) can enhance the resistance of plants to adverse environments such as heavy metals and high temperature. However, few studies are carried out to explore the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and elevated temperature (ET). Here, we investigated the regulation of Glomus mosseae on the adaptability of alfalfa (Medicago sativa L.) to the coexistence of cadmium (Cd)-polluted soils and ET. G. mosseae significantly enhanced total chlorophyll and carbon (C) content in the shoots by 15.6% and 3.0%, respectively, and Cd, nitrogen (N), and phosphorus (P) uptake by the roots by 63.3%, 28.9%, and 85.2%, respectively, under Cd + ET. G. mosseae significantly increased ascorbate peroxidase activity, peroxidase (POD) gene expression, and soluble proteins content in the shoots by 13.4%, 130.3%, and 33.8%, respectively, and significantly decreased ascorbic acid (AsA), phytochelatins (PCs), and malondialdehyde (MDA) contents by 7.4%, 23.2%, and 6.5%, respectively, under ET + Cd. Additionally, G. mosseae colonization led to significant increases in POD (13.0%) and catalase (46.5%) activities, Cu/Zn-superoxide dismutase gene expression (33.5%), and MDA (6.6%), glutathione (22.2%), AsA (10.3%), cysteine (101.0%), PCs (13.8%), soluble sugars (17.5%), and proteins (43.4%) contents in the roots and carotenoids (23.2%) under ET + Cd. Cadmium, C, N, G. mosseae colonization rate, and chlorophyll significantly influenced shoots defenses and Cd, C, N, P, G. mosseae colonization rate, and sulfur significantly affected root defenses. In conclusion, G. mosseae obviously improved the defense capacity of alfalfa under ET + Cd. The results could improve our understanding of the regulation of AMF on the adaptability of plants to the coexistence of heavy metals and global warming and phytoremediation of heavy metal-polluted sites under global warming scenarios.

Efficacy and factors influencing treatment with peginterferon alpha-2a and ribavirin in elderly patients with chronic hepatitis C.

BACKGROUND: In China, hepatitis C virus (HCV) infection is characterized by an increasing prevalence during aging. This study was undertaken to evaluate the efficacy of treatment with peginterferon alpha-2a and ribavirin in elderly chronic hepatitis C (CHC) patients and study the factors related to the sustained virologic response (SVR). METHODS: The medical records of 417 patients treated with peginterferon and ribavirin were retrospectively analyzed. These patients were divided into two groups according to age: patients aged ≥ 65 years (n=140) and patients aged <65 years (n=277). The rate of ribavirin reduction or discontinuation and virologic response rates of the two groups were compared. The factors influencing SVR were studied by multivariate analysis. RESULTS: Ribavirin reduction or discontinuation was more frequent in patients aged ≥ 65 years than patients aged <65 years (37.1%, 52/140 vs 20.2%, 56/277; X2=13.883, P<0.001). For genotype 1, patients aged ≥ 65 years had a higher relapse rate (50.0%, 42/84 vs 29.2%, 52/178; X2=10.718, P=0.001) and a lower SVR rate (40.0%, 42/105 vs 60.0%, 126/210; X2=11.250, P=0.001) than patients aged <65 years. There were no significant differences in virologic response rates between the two groups for patients with genotype 2. For genotype 1, in patients aged ≥ 65 years, the SVR rate of females was lower than that of males (28.6%, 12/42 vs 47.6%, 30/63; X2=8.150, P=0.004); in the high viral load group, patients aged ≥ 65 years had a lower SVR rate than patients aged <65 years (30.0%, 18/60 vs 54.8%, 69/126; X2=10.010, P=0.002). In multivariate logistic regression analysis, the independent factors associated with SVR in patients aged ≥ 65 years were sex (P=0.020), genotype (P=0.005), ribavirin reduction or discontinuation (P=0.009) and presence of rapid virologic response (RVR) (P=0.001). CONCLUSIONS: The rate of ribavirin reduction or discontinuation and relapse rate of patients aged ≥ 65 years with genotype 1 are high, and the SVR rate is low. Age has no impact on virologic responses rates for genotype 2. Among patients ≥ 65 years old, genotype 2 patients and genotype 1 patients with a low baseline viral load or achieving RVR or male may benefit from combination therapy.

[A study of the relationship between neutropenia and clinical infection risk during treatment with peginterferon alfa-2a and ribavirin for chronic hepatitis C].

OBJECTIVE: To investigate the correlation between neutropenia (ANC) incidence and infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. METHODS: A retrospective cohort study of 399 patients treated with peginterferon and ribavirin derived from database of Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University was conducted. The incidence of infections and their relation with ANC were investigated. Potential risk factors for infection were identified by multivariate analysis. RESULTS: During treatment, neutropenia (ANC < 1.50 × 10(9)/L) occurred in 251 patients. Among which, mild neutropenia [ANC: (> 0.75 - < 1.50) × 10(9)/L], moderate neutropenia [ANC: (0.50 - 0.75) × 10(9)/L] and severe neutropenia (ANC < 0.50 × 10(9)/L) occurred in 132 patients, 103 patients and 16 patients, respectively. A total of 80 infections (20.1%) occurred, among which, 14 infections were defined as severe. There was no significant difference in infection rate between patients with and without neutropenia (19.9%, 50/251 vs 20.3%, 50/251; χ(2) = 0.007, P = 0.933). There was no significant difference in infection rate between patients with and without peginterferon dose reduction (21.5%, 31/144 vs 19.2%, 49/255; χ(2) = 0.307, P = 0.580). In multivariate logistic regression analysis, the independent factors associated with infection were age (P = 0.021), diabetes (P = 0.004) and cirrhosis (P = 0.012). CONCLUSIONS: Infections during treatment with peginterferon alfa and ribavirin for chronic hepatitis C are irrelevant to neutropenia. The independent factors associated with infection are age, diabetes and cirrhosis.

Potential advantages of a combination of chinese medicine and bone marrow mesenchymal stem cell transplantation for removing blood stasis and stimulating neogenesis during ischemic stroke treatment.

Combined treatment of ischemic stroke with Chinese medicine and exogenous bone marrow mesenchymal stem cell (BMSC) transplantation may improve the removal of blood stasis and stimulation of neogenesis. Chinese medicines that remove blood stasis not only promote blood circulation but also calm the endopathic wind, remove heat, resolve phlegm, remove toxic substances and strengthen body resistance. The medicinal targeting effect of Chinese medicine can promote the homing of BMSCs, and the synergistic therapeutic effects of drugs can contribute to BMSC differentiation. As such, exogenous BMSC transplantation has potential advantages for neogenesis. Chinese medicines and exogenous BMSCs provide complementary functions for the removal of blood stasis and tion of Chinese medicine and transplantation of exogenous BMSCs may be particularly suited to ischemic stroke treatment.

Preclinical studies of licorice in ulcerative colitis: A systematic review with meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice, as a traditional Chinese herbal medicine, possessing the efficacies of invigorating spleen and replenishing qi, heat-clearing and detoxicating, phlegm-resolving and cough suppressant, relieving spasm and pain, and hamonizing actions of various medicines. AIM OF THE STUDY: The goal of this systematic review, which includes meta-analysis and network pharmacology in preclinical studies, is to investigate the multiple efficacies of licorice on ulcerative colitis (UC). MATERIALS AND METHODS: We searched several databases, e.g., Web of Science, Elsevier ScienceDirect and PubMed until Januanry 2022 for literature collection, and the Review Manager 5.3 was used to analyze the data. To synthesize the retrieved data, the fixed and random-effects models were utilized, respectively, and network pharmacology was applied to confirm the mechanisms. RESULTS: Based on the result of meta-analysis, it suggested that the treatments of licorice extract and its active compounds showed strong therpeutic effects, which not only reflected the declining histological score, a index of the colitis severity [SMD = -2.86, 95% CI (-3.65, -2.08); P < 0.00001], but also reversed colonic shortness [WMD = 1.67, 95% CI (1.16, 2.19); P < 0.00001] between experimental UC model and licorice-treatment groups. In addition, it suggested the significant reduction of TNF-α level [SMD = -2.70, 95% CI (-3.23, -2.16); P < 0.00001], which acted as a crucial role in inflammatory response. Furthermore, from the results of network pharmacology, it indicated that anti-inflammation, anti-oxidative stress, immunomodulatory effect and microbiota homeostasis were the predominant therapeutic mechanisms of licorice extract and its active compounds treating UC. CONCLUSION: This systematic review with meta-analysis and network pharmacology demonstrates an efficient role of licorice extract and its active compounds in preclinical studies of UC, which provides supporting evidence for clinical trial implementation. However, there exist some limitations, such as technique quality decificency, missed reports due to negative outcome, failure to calculate sample size, and the risk of bias.

[Spatio-temporal relationship between vegetation restoration and ecosystem services in the Loess Plateau of Northern Shaanxi, China]. / é™•åŒ—é»„åœŸé«˜åŽŸæ¤è¢«æ¢å¤ä¸Žç”Ÿæ€ç³»ç»ŸæœåŠ¡çš„æ—¶ç©ºå ³ç³».

As the core region of the "Grain to Green" Program, the Loess Plateau of Northern Shaanxi became an example with the most dramatic changes in earth surface pattern and vegetation cover. Evaluating the effectiveness of vegetation restoration is important for promoting regional ecological environment. In this study, the fractional vegetation coverage (FVC) was used as the index to analyze the changes in vegetation coverage in this area. Soil conservation service, carbon sequestration service, habitat quality, and water yield were used to characterize the regional ecosystem services (ESs). The effects of FVC on ESs were analyzed based on the bivariate spatial autocorrelation model. The trade-off synergies and spatio-temporal variations of different scales of those indices were discussed. The results showed that the FVC of the study area presented a fluctuating upward trend from 2000 to 2020, with the annual average value increasing from 31.7% to 47.1%. Carbon sequestration service and soil conservation service were increased, habitat quality was stable. Water yield increased firstly and then decreased, with an overall upward trend. The ESs changes were scale-dependent. There was an obvious synergistic relationship among ESs. There was a significant spatial dependence between FVC and ESs, with some differences in the degree of correlation. FVC had the strongest impact on soil conservation, followed by carbon sequestration service. However, the increase of vegetation coverage and water consumption of forest and grass led to the negative effect of water yield reduction. In gene-ral, FVC in the Loess Plateau of Northern Shaanxi had achieved remarkable success, and the ecological environment had been significantly improved.

[Evaluation of ecological environment and urban development quality in Xi'an City, China]. / 西安市生态环境及城市发展质量评估.

Sound ecological environment is an important foundation for promoting high-quality urban development, as it determines the level and quality of urban construction and human settlements. Taking Xi'an as the study area, we used remote sensing ecological index (RSEI) to evaluate the urban ecological environment. The evaluation index system of high-quality urban development was constructed and the entire-array-polygon was used to evaluate the urban development quality. The coupling coordination degree model was used to analyze the temporal variations of the coupling coordination degree of those two factors. The results showed that the urban ecological condition of Xi'an showed a pattern of high in the south and low in the north, and that the level of RSEI had an upward trend in 2010-2020. The RESI of the six inner districts of Xi'an decreased, but the RESI of the surrounding districts of Xi'an was stable or improved. The urban development quality of Xi'an was improved in 2010-2020, though the quality level was still at the low level. The improvement of the three major subsystems of urban development was uneven, and the increase range of three subsystems from largest to smallest was ranked as ecological subsystem > economic subsystem > social subsystem. The coupling coordination of the two kinds of index increased in 2010-2020, and the coordination level had been prompted from barely coordinated to primary.

[Spatial and temporal variations of ecosystem service synergy and trade-off in Qinling Mountains, China]. / 秦岭生态系统服务协同与权衡的时空异质性.

The Qinling Mountains are an important ecological function area in China. Exploring the trade-offs and synergies of ecosystem services is important for ecological protection and sustainable development in the Qinling Mountains. In this study, we analyzed the spatio-temporal variations of land uses in the Qinling Mountains in 2000, 2010 and 2020 based on remote sensing, meteorological, and soil texture data. The amounts of carbon sequestration, water yield, habitat quality, and soil conservation were calculated with CASA, InVEST and RUSLE models. The relationships between its spatially heterogeneous characteristics and various ecosystem services were analyzed. The results showed that, from 2000 to 2020, the area of arable land and grassland in the study area continued to decrease, the area of forest and building land increased, and the change of water body and unused land was not noticeable. Carbon sequestration was high in the east and low in the west, with an increasing trend. Water production continued to decrease, showing a tendency of higher on the south slope and lower on the north slope. Habitat quality increased steadily, while soil conservation increased and then decreased. Ecosystem services varied across land classes and across ecosystems in the same land class. In general, there was a synergistic relationship between carbon sequestration and soil conservation, habitat quality and soil conservation, carbon sequestration, and habitat quality. There was trade-off between carbon sequestration and water production, soil conservation and water production, habitat quality, and water production. There were significant differences in the relationship between service volumes under different conditions. The results could reduce the risk of trade-offs and maximize overall benefits, and provide a reference for promoting ecologically high-quality development and achieving a win-win situation for natural resource management and human well-being.

[Relationship between economy and ecology of Pearl River Delta Urban Agglomeration based on ecological footprint of net primary productivity]. / 基于生态足迹-å‡€åˆçº§ç”Ÿäº§åŠ›çš„ç ä¸‰è§’åŸŽå¸‚ç¾¤ç»æµŽä¸Žç”Ÿæ€çš„å ³ç³».

With the acceleration of regional economic integration, human activities have played an increasingly crucial role in regional sustainable development. In this study, MODIS remote sensing data and ecological footprint of net primary productivity (EF-NPP) were leveraged to calculate the equivalence factor and yield factor of the six major biologically productive land areas in the Pearl River Delta Urban Agglomeration. We analyzed the changes in per capita ecological footprint, per capita ecological carrying capacity, natural resource utilization efficiency and ecological moderate population from 2000 to 2020. Results showed that the per capita ecological footprint in the Pearl River Delta Urban Agglomeration continued to rise from 2000 to 2020. The ecological occupation of energy land was the highest. The ecological footprint was high in west, low in middle, and higher in northwest of the study area. The per capita ecological carrying capacity was relatively high in Zhaoqing and Jiangmen and low in Shenzhen, Dongguan, Foshan and Zhongshan. The gap between the ecological moderate population and the regional actual population widened over time, reaching 30.62 million in 2020. The regional actual population was much larger than the ecological moderate population, indicating huge population pressure. The natural resource utilization efficiency of the three main industries was high. The economic benefits created by the per capita ecological footprint increased by 36800 yuan·hm-2 during the research period, with an average annual growth rate of 1800 yuan·hm-2. The growth rate of the tertiary industry was the highest. Therefore, the results could provide reference for the study on natural resource utilization efficiency in medium and small-scale regions.

Severe tinnitus and migraine headache in a 37-year-old woman treated with trastuzumab for breast cancer: A case report.

BACKGROUND: Trastuzumab is a generally safe agent prescribed in the systemic treatment of breast cancer. Tinnitus is not a currently known adverse event related to trastuzumab. Here, we describe a rare case of severe tinnitus and a migraine headache induced by trastuzumab used for adjuvant therapy. CASE SUMMARY: A 37-year-old woman was diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer. After surgery, she was treated with four cycles of epirubicin and cyclophosphamide; she then received docetaxel and a loading dose of trastuzumab plus pertuzumab. Less than half an hour after trastuzumab infusion, the patient complained of severe tinnitus and left-sided migraine headache. Trastuzumab monotherapy was discontinued immediately, and symptoms disappeared after 10 min. Trastuzumab was readministered, and severe tinnitus and migraine headache recurred. Trastuzumab was stopped, and severe tinnitus diminished after 10 min. Pertuzumab and docetaxel therapy was then administered, and no adverse events were observed. Subsequent infusions of trastuzumab every three weeks did not show the same symptoms. CONCLUSION: Although trastuzumab is well-tolerated in most patients, we should pay attention to the risk of severe tinnitus and migraine.

Lamivudine treatment is associated with improved survival in fulminant hepatitis B.

OBJECTIVE: Fulminant hepatitis B is a clinical syndrome that results from massive necrosis of liver cells leading to the development of hepatic encephalopathy. The aim of this study was to evaluate the efficacy of lamivudine in patients with fulminant hepatitis B and study the prognostic factors. METHODS: A matched retrospective cohort study using data on fulminant hepatitis B patients derived from our hospital database was conducted. Forty patients receiving lamivudine treatment were selected into the lamivudine treatment group with another 40 without lamivudine treatment studied as control. They were matched for sex, age and HBeAg status with lamivudine treatment group. The mortality of patients in two groups was compared. The influential factors on the mortality were studied by Cox proportional hazards model. RESULTS: The mortality of patients in the lamivudine group (n=38) was significantly lower than that of the control group (n=39) (63.2 vs. 84.6%; χ(2) =4.609, P=0.032). For patients without systemic inflammatory response syndrome (SIRS), the mortality of patients in the lamivudine group (n=25) was significantly lower than that of the control group (n=26) (52.0 vs. 80.8%; χ(2) =4.747, P=0.029). In multivariate Cox proportional hazards analyses, for patients without SIRS, age (P=0.037), ratio of total to direct bilirubin (P=0.008), treatment method (P=0.005) and the decline of hepatitis B virus (HBV) DNA load during therapy (P=0.019) were independent predictors of prognosis. CONCLUSIONS: Treatment with lamivudine significantly decreases the mortality of fulminant hepatitis B patients without SIRS, and a rapid decline of HBV DNA load is one of the good predictors for the treatment outcome.

[Impact of age and sex on virologic responses of peginterferon alfa-2a and ribavirin treatment in chronic hepatitis C].

OBJECTIVE: To investigate the impact of age and sex on virologic responses rates to peginterferon alfa-2a and ribavirin treatment in patients with chronic hepatitis C. METHODS: The medical records of 449 chronic hepatitis C patients, treated with peginterferon and ribavirin in Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University, were retrospectively analyzed. These patients were divided into three groups according to age: patients < 40 years (n = 131), patients 40 - 50 years (n = 131) and patients > 50 years (n = 187). The virologic response rates, the incidences of side events, and the rates of patients receiving ≥ 80% of planned peginterferon alfa-2a or ribavirin dose were compared between male and female patients in the three groups. The influential factors on sustained virologic response (SVR) of patients were studied by multivariate analysis. RESULTS: For genotype 1, in patients < 40 years group, the SVR rate of female was significantly higher than that of male (75.0%, 30/40 vs 54.0%, 27/50; P < 0.05); in patients 40-50 years group, there was no significant difference in the SVR rate between male and female (51.0%, 25/49 vs 53.7%, 22/41; P > 0.05); in patients > 50 years group, the SVR rate of female was significantly lower than that of male (31.1%, 19/61 vs 50.7%, 34/67; P < 0.05). For genotype 2, there were no significant differences in virologic response rates between male and female in the three groups. The incidence of adverse events of patients aged < 40 years group, 40 - 50 years group, > 50 years group, were 51.1% (67/131), 51.1% (67/131), and 70.6% (132/187), respectively, and the incidence of adverse events of patients aged > 50 years was significantly higher than those of other groups (P < 0.001). For genotype 1, in patients > 50 years group, the rate of patients receiving ≥ 80% of planned ribavirin dose of female was significantly lower than that of male (42.6%, 26/61 vs 62.7%, 42/67; P < 0.05). In multivariate analysis, the independent factors associated with SVR of patients aged > 50 years were sex (P = 0.013), genotypes (P = 0.002), cirrhosis (P = 0.004), ≥ 80% of planned ribavirin dose (P = 0.008) and presence of rapid virologic response (RVR) (P = 0.001). CONCLUSIONS: For genotype 1 patients, in patients < 40 years group the SVR rate of female is higher than that of male; in patients 40 - 50 years group, male and female share similar SVR rates; in patients > 50 years group the SVR rate of female is lower than that of male. Age and sex has no impact on virologic responses rates for genotype 2 patients.