Identification of priority areas for territorial space ecological restoration in arid area of Northwest China: A case study of Zhangye City in Heihe River basin.

Determining priority areas for territorial ecological restoration in the arid region of Northwest China based on the holistic protection and systematic governance is an important measure to build solid national ecological security barrier and promote the construction of territorial ecological civilization. Taking Zhangye City, a typical arid area city in Northwest China, as an example, we constructed the research framework of "ecological network-ecological sensitivities-ecological degradation" from two aspects of internal defects and external threats of ecological networks by using circuit theory and assessment methods of ecological service function importance, ecological sensitivity, and ecological degradation. We then identified the priority areas of territorial ecological restoration in northwest arid region and put forward the restoration strategies. The results showed that the priority areas of ecological restoration in Zhangye City were concentrated in the artificial shelterbelt along rivers and the plain-desert-oasis transition zone with fragile ecology and strong human interference. The ecological network of the study area included 39 ecological sources and 99 ecological corridors, and the highly sensitive and degraded areas were 1595.40 and 6.65 km2. Based on the internal defects and external threats of the ecological network, we identified 31 ecological pinch points, 7 obstacle points, and 753.56 km2 ecological source areas in the territorial spatial ecological restoration priority area. These areas were related to the connectivity of the ecological network internally and the stability maintenance of the ecosystem outwards, and were the areas to restoration in the future. Following the concept of overall protection and system restoration of territorial space, we put forward the idea of territorial space restoration by integrating internal defects and external threats of ecological network, which could provide scientific decision-making basis for comprehensive ecosystem management and territorial optimization of Zhangye City.

Three-Year Point Prevalence Survey of Antimicrobial Use in a Chinese University Hospital.

To evaluate the prevalence and quality of antimicrobial prescriptions using a Global Point Prevalence Survey (PPS) tool and help identify targets for improvement of antimicrobial prescribing and inform the development of antimicrobial stewardship activities. Antimicrobial prescriptions for inpatients staying at a hospital overnight were surveyed on one weekday in October 2018, November 2019, and November 2020. Data including basic patient information, antimicrobial drugs, quality evaluation of antimicrobial drug prescription, and the risk factors of nosocomial infection were collected from doctor network workstation. Patient information was anonymized and entered in the PPS Web application by physicians. A total of 720 patients (median age, 62 years) were surveyed. Of them, 246 (34.2%) were prescribed antimicrobials on the survey days. Hospital-wide antimicrobial use had a significantly decreasing trend (P < 0.001). The most commonly prescribed antimicrobial drugs were third-generation cephalosporins (40.5%), followed by quinolones (21.8%) and second-generation cephalosporin (12.5%). In our study, cefoperazone/sulbactam, ceftazidime, and levofloxacin were the most commonly used antimicrobials. The most common indication for antimicrobial use was pneumonia or lower respiratory tract infection (159/321, 49.5%). Antimicrobial for surgical prophylaxis represented 16.2% of the total antibiotic doses. Of those, 67.3% were administered for more than 24 h. The rate of adherence to antibiotic guidelines was 61.4%. The indications for antimicrobials were not documented in 54.5% of the prescriptions. Stop/review date was documented for 36.8% of prescriptions. The PPS tool is useful in identifying targets to enhance the quality of antimicrobial prescriptions to improve the adherence rate in hospitals. This survey can be used as a control to assess the rational application quality of antimicrobial after regular application of antimicrobial intervention.

Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation.

BACKGROUND: The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations. AIMS: We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation. PATIENTS/METHODS: This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events. RESULTS: The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months. CONCLUSIONS: Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

Recalcitrant nodular scabies showing excellent response to tofacitinib: five case reports.

Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.

Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy.

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1ß, monocyte chemotactic protein-1 and tumor necrosis factor -α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the DNA sequence. In the past decade, epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels. The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated. The diabetic condition facilitates epigenetic changes and influences target gene expression. In this review, we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.

Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Screening and identification of immune-related genes for immunotherapy and prognostic assessment in colorectal cancer patients.

BACKGROUND: Increasing evidence indicates that the immune microenvironment plays a key role in the genesis and progression of colorectal cancer (CRC). This study aimed to establish an immune-related gene (IRG) signature and determine its clinical prognostic value in patients with CRC. METHODS: The RNA sequencing and associated clinical data of CRC were downloaded from The Cancer Genome Atlas (TCGA) database. We then screened for differentially expressed IRGs by intersecting with IRGs obtained from the Immunology Database and Analysis Portal. Functional enrichment analyses were carried out to determine the potential biological functions and pathways of the IRGs. We also explored the specific molecular mechanisms of the IRGs by constructing regulatory networks. Prognostic IRGs were obtained by LASSO regression analysis, and subsequently, gene models were constructed in the TCGA dataset to confirm the predictive capacity of these IRGs. Finally, we used the TIMER tool to assess the immune properties of prognostic IRGs and correlate them with immune cells. RESULTS: We identified 409 differentially expressed IRGs in patients with CRC. Kyoto Encyclopaedia of Genes and Genomes and Gene Ontology enrichment analyses suggested that these differentially expressed IRGs were significantly related to 102 cancer signalling pathways and various biological functions. Based on the prediction and interaction results, we obtained 59 TF-IRG, 48 miRNA-IRG, and 214 drug-IRG interaction networks for CRC. Four prognostic genes (POMC, TNFRSF19, FGF2, and SCG2) were developed by integrating 47 survival-related IRGs and 42 characteristic CRC genes. The results of gene model showed that patients in the low risk group had better survival outcomes compared to those in the high risk group. The expression of POMC, TNFRSF19, FGF2, and SCG2 was significantly correlated with immune cells. CONCLUSION: This study identified some valid IRGs, and these findings can provide strong evidence for precision immunotherapy in patients with CRC.

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion.

AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 µm vs 268.8±12.0 µm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment. CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

Auricular erythermalgia showing excellent response to itraconazole: a case report.

Erythermalgia, a rare painful disorder, is characterized by recurrent pain attacking, warmth, and erythema that mainly involves the distal extremities. Red ear syndrome shares similar clinical features of erythermalgia afflicting the external ear with unilateral/bilateral distribution. The treatments of both diseases are still difficult without controlled therapeutics available up to date. A 12-year-old boy was referred because of 3 years of recurrent attacking of painful erythema and warmth that involved the ears alone, the episodes occurred several times daily with duration of dozens of minutes to hours for each flare. The symptoms could be relieved by cold water and triggered by heat stimuli as well as exciting and movement, and showed mild response to gabapentin, celecoxib, and topical lidocaine compounds in combination, but moderate to blocking injection of botulinum toxin to nervus auricularis magnus. However, systemic itraconazole 200 mg daily resulted in an excellent response after 5-week treatment, leading to milder erythema, warmth and burning sensation, shorter duration, and fewer relapses. The treatment continued for 6 months and then itraconazole was decreased to 100 mg daily for another 6 months until it was stopped, with maintenance of good conditions. In 3 months of follow-up after the treatment ceased, the patient had only 7 to 8 attacks over 10 days presenting as tolerable erythema that lasted for less than 10 min and relieved spontaneously, with absence of warmth and no need of treatment. We considered the patient to be a variant of erythermalgia rather than a red ear syndrome. The results showed that erythermalgia might involve the ears alone and itraconazole might be a potential agent for its treatment.

Roles and perspectives of inflammatory factors in diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is the leading cause of blindness in the working-age population, in which diabetic macular edema(DME)is the most common reason resulting in the vision impairment. Studies showed that inflammation factors play an important role in the pathogenesis and development of DME. Chronic hyperglycemia activates several biochemical pathways, leading to retinal hypoxia, oxidative stress and chronic inflammation. Intraretinal inflammation-related cells, such as microglia, monocytes/macrophages, Müller cells and retinal pigment epithelial cells, become activated and release a large number of inflammation-related factors and mediators, including the complement system, vascular endothelial growth factor(VEGF), placental growth factor(PlGF), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6 and IL-8, etc., resulting in the breakdown of the blood-retinal barrier and neuronal degeneration. In addition, up-regulatethe expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)by retinal vascular endothelial cells increased the adhesion of leukocyte and leukostasis, further aggravating retinal hypoxia and breakdown of the blood-retinal barrier, leading to the increased retinal vascular leakage and macular edema. Therefore, early treatment with anti-VEGF and anti-inflammatory are pivotal for the treatment of DME. In this review, we will discuss the role of inflammation factors in the pathogenesis of DME and the research status of the targeted drugs targeting inflammation, so as to provide reference for the treatment of DME.

GSA-Human: Genome Sequence Archive for Human.

The Genome Sequence Archive for Human (GSA-Human) is a data repository specialized for human genetic related data derived from biomedical researches, and also supports the data collection and management of National Key Research and Development Projects. GSA-Human has a data security management strategy according to the national regulations of human genetic resources. It provides two different models of data access: Open-access and Controlled-access. Open-access data are universally and freely accessible for global researchers, while Controlled-access ensures that data are accessed only by authorized users with the permission of the Data Access Committee (DAC). Till July 2021, GSA-Human has housed more than 5.27 PB of data from 750 datasets.

Role of gambogenic acid in regulating PI3K/Akt/NF-kß signaling pathways in rat model of acute hepatotoxicity.

The purpose of this study is to investigate the protective effect of gambogenic acid (GA) in acetaminophen (APAP)-induced hepatotoxicity in rat models. GA (10 mg/kg) was administered intraperitoneal (i.p.) to rats for 7 consecutive days followed by APAP (500 mg/kg) single dose (i.p.) on the final day after GA administration. The levels of MDA, GSH, SOD, CAT, GPx, GST, ALP, AST, ALT, proinflammatory cytokines (TNF-α, IL-1ß, IL-6), apoptosis markers (caspase-3 and -9, Bax, Bcl-2), 4-hydroxynonenal (4-HNE), and prostaglandin E2 (PGE2) were evaluated. Results exhibited protective effects of GA by inhibiting inflammation, preventing oxidative stress and apoptosis in APAP-induced liver. Histopathological changes caused by APAP were attenuated, protein expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were upregulated, and nuclear factor-kappa ß (NF-kß) was downregulated by GA. In summary, GA significantly exerted anti-inflammatory and antiapoptotic effects against APAP-induced hepatotoxicity potentially through regulation of PI3K/Akt and NF-kß signaling pathways.

Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy?

AIM: To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy (DR). METHODS: Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin. The retinas were harvested at 1 to 24wk after diabetes onset. Hypoxia-treated mouse microglial cell line (BV2 cells) was employed as the in vitro model to mimic diabetic condition. The expressions of Iba-1, CD11b, ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction, Western blot and immunofluorescence both in vivo and in vitro. RESULTS: Compared with age-matched normal control, the number of microglia (Iba-1 positive immunostaining) in diabetic rat retinas was increased from 1 to 24wk of diabetes, which was most obvious at 12wk of diabetes. Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control; however, there was statistically significant between two groups only at 2wk after diabetes onset. The mRNA expression of Iba-1 was decreased significantly at 2 and 4wk of diabetic rat retinas, and remained unchanged at 8 and 12wk of diabetes. In BV2 cells, there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups; however, its mRNA level was decreased significantly under hypoxia. To further characterize microglial activation, F4/80, CD11b and inflammatory factors were detected both in vivo and in vitro. Compared with normal control, the expressions of F4/80 and CD11b as well as the inflammatory factors, such as ICAM-1, iNOS, COX2, IL-1ß and IL-6, were increased significantly both in vivo and in vitro. CONCLUSION: Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR. However, Iba-1 immunostaining, in combination with other markers like CD11b and ICAM-1, could be well reflect the activation of microglia. Thus, it is of great importance to explore other potential marker to evaluate the activation of microglia.

Scenario analysis of vehicular emission abatement procedures in Xi'an, China.

Vehicular emissions contribute significantly to air pollution, and the number of vehicles in use is continuing to rise. Policymakers thus need to formulate vehicular emission reduction policies to improve urban air-quality. This study used different vehicle control scenarios to predict the associated potential of mitigating carbon monoxide (CO), volatile organic compounds (VOCs), nitrogen oxide (NOx), particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5), and particulate matter with an aerodynamic diameter less than 10 µm (PM10) in Xi'an China, in 2020 and 2025. One business-as-usual scenario and six control scenarios were established, and vehicular emission inventory was developed according to each scenario. The results revealed that eliminating high-emission vehicles and optimizing after-treatment devices would effectively reduce vehicular emissions. In addition, increasing the number of alternative fuel vehicles, restraining vehicle use, and restraining the growth of the vehicle population would all have certain effects on CO and VOCs emissions, but the effects would not be significant for NOx, PM2.5, and PM10. The results also indicated that if all control measures were stringently applied together, emissions of CO, VOCs, NOx, PM2.5, and PM10 would be reduced by 51.66%, 51.58%, 30.19%,71.12%, and 71.81% in 2020, and 53.55%, 51.44%, 19.09%, 54.88%, and 55.51%, in 2025, respectively.

An online coronavirus analysis platform from the National Genomics Data Center.

Since the first reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic, spreading to more than 200 countries and regions worldwide. With continued research progress and virus detection, SARS-CoV-2 genomes and sequencing data have been reported and accumulated at an unprecedented rate. To meet the need for fast analysis of these genome sequences, the National Genomics Data Center (NGDC) of the China National Center for Bioinformation (CNCB) has established an online coronavirus analysis platform, which includes de novoassembly, BLAST alignment, genome annotation, variant identification, and variant annotation modules. The online analysis platform can be freely accessed at the 2019 Novel Coronavirus Resource (2019nCoVR) (https://bigd.big.ac.cn/ncov/online/tools).

iTRAQ-based proteomics analysis of aqueous humor in patients with dry age-related macular degeneration.

AIM: To preliminarily test proteomics in aqueous humor in patients with dry age-related macular degeneration (AMD) by using the proteomic technology. METHODS: Aqueous humor samples were collected from patients with or without dry AMD, who underwent cataract surgery. The aqueous samples were analyzed with isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) technology. The differential expressed proteins were analyzed with gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis. The data were partly validated by ELISA and Western blot. False discovery rate (FDR) was used for statistical analysis. RESULTS: A total of 244 proteins were detected, in which 38 proteins were up-regulated and 51 were down-regulated significantly in patients with dry AMD compared with that in control groups (FDR value <1.0%). Several proteins, e.g., protein S100-A8 (S10A8), dystroglycan (DAG1), Ig alpha-1 chain C region (IGHA1), carbonic anhydrase 3 (CAH3) and alpha-1-acid glycoprotein (A1AG1) were increased more than 5 times of that in control group. The bioinformatics analysis showed that dry AMD is closely associated with inflammation or immune reaction, oxidative stress, blood coagulation and remodeling of extracellular matrix. CONCLUSION: iTRAQ-based proteomic analysis of aqueous humor demonstrate the differential expressions of proteins between dry AMD and control groups, providing the clues to understand the mechanisms and possible treatments of dry AMD.