Microscopic and spectroscopic analysis of atmospheric iron-containing single particles in Lhasa, Tibet.

The Tibetan Plateau, known as the "Third Pole", is currently in a state of perturbation caused by intensified human activity. In this study, 56 samples were obtained at the five sampling sites in typical area of Lhasa city and their physical and chemical properties were investigated by TEM/EDS, STXM, and NEXAFS spectroscopy. After careful examination of 3387 single particles, the results showed that Fe should be one of the most frequent metal elements. The Fe-containing single particles in irregular shape and micrometer size was about 7.8% and might be mainly from local sources. Meanwhile, the Fe was located on the subsurface of single particles and might be existed in the form of iron oxide. Interestingly, the core-shell structure of iron-containing particles were about 38.8% and might be present as single-, dual- or triple-core shell structure and multi-core shell structure with the Fe/Si ratios of 17.5, 10.5, 2.9 and 1.2, respectively. Meanwhile, iron and manganese were found to coexist with identical distributions in the single particles, which might induce a synergistic effect between iron and manganese in catalytic oxidation. Finally, the solid spherical structure of Fe-containing particles without an external layer were about 53.4%. The elements of Fe and Mn were co-existed, and might be presented as iron oxide-manganese oxide-silica composite. Moreover, the ferrous and ferric forms of iron might be co-existed. Such information can be valuable in expanding our understanding of Fe-containing particles in the Tibetan Plateau atmosphere.

[Research progress on chemical constituents and pharmacological effects of Ajania plants].

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

[Exploration and practice on construction of Tibetan medicine prescription information database and knowledge discovery].

This study aimed to explore the underlying framework and data characteristics of Tibetan prescription information. The information on Tibetan medicine prescriptions was collected based on 11 Tibetan medicine classics, such as Four Medical Canons(Si Bu Yi Dian). The optimal classification method was used to summarize the information structure of Tibetan medicine prescriptions and sort out the key problems and solutions in data collection, standardization, translation, and analysis. A total of 11 316 prescriptions were collected, involving 139 011 entries and 63 567 pieces of efficacy information of drugs in prescriptions. The information on Tibe-tan medicine prescriptions could be summarized into a "seven-in-one" framework of "serial number-source-name-composition-efficacy-appendix-remarks" and 18 expansion layers, which contained all information related to the inheritance, processing, origin, dosage, semantics, etc. of prescriptions. Based on the framework, this study proposed a "historical timeline" method for mining the origin of prescription inheritance, a "one body and five layers" method for formulating prescription drug specifications, a "link-split-link" method for constructing efficacy information, and an advanced algorithm suitable for the research of Tibetan prescription knowledge discovery. Tibetan medicine prescriptions have obvious characteristics and advantages under the guidance of the theories of "three factors", "five sources", and "Ro-nus-zhu-rjes" of Tibetan medicine. Based on the characteristics of Tibetan medicine prescriptions, this study proposed a multi-level and multi-attribute underlying data architecture, providing new methods and models for the construction of Tibetan medicine prescription information database and knowledge discovery and improving the consistency and interoperability of Tibetan medicine prescription information with standards at all levels, which is expected to realize the "ancient and modern connection-cleaning up the source-data sharing", so as to promote the informatization and modernization research path of Tibetan medicine prescriptions.

[Investigation and clarification of traditional measuring units of Tibetan medicine].

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.

[Analysis of the principles of Tibetan medicine processing].

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.

Sensible Functional Linear Discriminant Analysis Effectively Discriminates Enhanced Raman Spectra of Mycobacterium Species.

Tuberculosis caused by Mycobacterium tuberculosis complex (MTBC) is one of the major infectious diseases in the world. Identification of MTBC and differential diagnosis of nontuberculous mycobacteria (NTM) species impose challenges because of their taxonomic similarity. This study describes a differential diagnosis method using the surface-enhanced Raman scattering (SERS) measurement of molecules released by Mycobacterium species. Conventional principal component analysis and linear discriminant analysis methods successfully separated the acquired spectrum of MTBC from those of NTM species but failed to distinguish between the spectra of different NTM species. A novel sensible functional linear discriminant analysis (SLDA), projecting the averaged spectrum of a bacterial specie to the subspace orthogonal to the within-species random variation, thereby eliminating its influence in applying linear discriminant analysis, was employed to effectively discriminate not only MTBC but also species of NTM. The successful demonstration of this SERS-SLDA method opens up new opportunities for the rapid differentiation of Mycobacterium species.

A non-linear ensemble model-based surgical risk calculator for mixed data from multiple surgical fields.

BACKGROUND: The misestimation of surgical risk is a serious threat to the lives of patients when implementing surgical risk calculator. Improving the accuracy of postoperative risk prediction has received much attention and many methods have been proposed to cope with this problem in the past decades. However, those linear approaches are inable to capture the non-linear interactions between risk factors, which have been proved to play an important role in the complex physiology of the human body, and thus may attenuate the performance of surgical risk calculators. METHODS: In this paper, we presented a new surgical risk calculator based on a non-linear ensemble algorithm named Gradient Boosting Decision Tree (GBDT) model, and explored the corresponding pipeline to support it. In order to improve the practicability of our approach, we designed three different modes to deal with different data situations. Meanwhile, considering that one of the obstacles to clinical acceptance of surgical risk calculators was that the model was too complex to be used in practice, we reduced the number of input risk factors according to the importance of them in GBDT. In addition, we also built some baseline models and similar models to compare with our approach. RESULTS: The data we used was three-year clinical data from Surgical Outcome Monitoring and Improvement Program (SOMIP) launched by the Hospital Authority of Hong Kong. In all experiments our approach shows excellent performance, among which the best result of area under curve (AUC), Hosmer-Lemeshow test ([Formula: see text]) and brier score (BS) can reach 0.902, 7.398 and 0.047 respectively. After feature reduction, the best result of AUC, [Formula: see text] and BS of our approach can still be maintained at 0.894, 7.638 and 0.060, respectively. In addition, we also performed multiple groups of comparative experiments. The results show that our approach has a stable advantage in each evaluation indicator. CONCLUSIONS: The experimental results demonstrate that NL-SRC can not only improve the accuracy of predicting the surgical risk of patients, but also effectively capture important risk factors and their interactions. Meanwhile, it also has excellent performance on the mixed data from multiple surgical fields.

[Multimodal Analgesia of Enhanced Recovery after Surgery Management in Lobectomy by Video-assisted Thoracoscopic Surgery].

Video-assisted thoracoscopic surgery(VATS)has become the main method of lobectomy.Multimodal analgesia is one of the core contents of enhanced recovery after surgery(ERAS)management in VATS lobectomy,which aims to control perioperative pain,reduce stress response,and achieve rapid recovery after surgery.In recent years,multimodal analgesia has developed rapidly,emphasizing the comprehensive implementation of a variety of analgesic methods and the synergistic application of analgesics with different mechanisms.This article reviews the new progress in the implementation of multimodal analgesia in VATS lobectomy and addresses the current problems and challenges,aiming to help develop more effective and practical analgesic strategies of ERAS.

Therapeutic Erythrocytapheresis Is Effective in Treating High Altitude Polycythemia on the Qinghai-Tibet Plateau.

INTRODUCTION: High altitude polycythemia (HAPC) is a common chronic disease at high altitudes. It is characterized by excessive erythrocytosis (≥190 g·L-1 in females or ≥210 g·L-1 in males). HAPC severely jeopardizes the health status of plateau dwellers. The Qinghai-Tibet plateau, with an elevation above 4000 m, is the highest plateau in the world. Both Han and Tibetan populations residing there face the threat of HAPC. Therapeutic erythrocytapheresis (TE) was introduced to Tibet as an alternative to phlebotomy in 2015. METHODS: In this study, we retrospectively analyzed 155 patients with HAPC treated with TE in Tibet. Routine blood testing values before and after TE were compared to evaluate treatment efficacy. The efficiency rate, defined as the rate of increase in red blood cell depletion attained by TE compared with 450 mL whole blood phlebotomy, was calculated using whole blood volume and hematocrit before and after treatment and used to identify patients who maintained a normal hemoglobin level in the year after the TE procedure. RESULTS: On average, TE reduced red blood cell levels by 1.5×1012·L-1, hemoglobin concentration by 52 g·L-1, and hematocrit by 14% (P<0.001 for each). Patients who underwent TE with an efficiency rate ≥1.9 were more likely to maintain a normal hemoglobin level in the following year than those who underwent TE with an efficiency rate <1.9 (90 vs 28%, P<0.01). CONCLUSIONS: TE is a feasible therapeutic method to treat HAPC on the Qinghai-Tibet plateau. The efficiency rate is a useful tool to predict the expected interval between TE procedures.

[Study on mechanism of Tibetan medicine Zuomua Decoction in treatment of hypertension based on network pharmacology and molecular docking technology].

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.

Hyperascyrins L - N, rare methylated polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum ascyron.

Seven natural compounds, including new compounds hyperascyrins L-N (1-3) and four known compounds (4-7), were acquired from the aerial parts of Hypericum ascyron, that were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). The structures of these compounds were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data. The neuroprotective activities and hepatoprotective activity of these compounds (10 µM) were evaluated. Compounds 1, 2 and 3 exhibited neuroprotection activity. Compounds 1 and 3 show hepatoprotective activity.

[Study on regularity of Tibetan medicine in treatment of gZav-Grib disease (apoplexy sequelae) based on HIS clinical medical records].

This research is launched to look for the medication rules and characteristics of Tibetan medicine in the treatment of gZav-Grib( apoplexy sequelae). HIS records of gZav-Grib patients were selected from the Tibetan Hospital of Tibet Autonomous Region and Tibetan Hospital of the city of Naqu. SPSS Modeler,Gephi and other data mining and visualization software were used to study the actual law of drug use in the treatment of gZav-Grib in Tibetan medicine. Finally,479 cases of gZav-Grib patients in Tibetan medicine were included. Their average age is 63 and average hospital stay was 32 days. In total,82 Tibetan medicine prescriptions were used for treating gZav-Grib. The frequency in the front is Twenty-flavor Chenxiang Pills( 338 times),Ruyi Zhenbao Pills( 322 times),and Seventy-flavor Zhenzhu Pills( 315 times). According to the regularity of Tebitan medicine,they were applied in different time periods including the early morning,morning,noon,and evening,for example,in the early morning: Seventy-flavor Zhenzhu Pills,morning: Ruyi Zhenbao Pills,noon: Eighteen-flavor Dujuan Pills,evening: Twenty-flavor Chenxiang Pills. In the clinical joint,18 groups were found in the 10% support and 70% confidence. There are two prescriptions confidence more than 80% which nature focus on Gan,Ruan,Xi,Liang,Dun,Han,Wen. gZav-Grib of Tibetan medicine can be divided into two types: r Lung-Grib type and k Hrag-Grib type,in which the medicine of r Lung-Grib type takes Seventy-flavor Zhenzhu Pills as the core prescription,while the medicine of k Hrag-Grib type takes Ruyi Zhenbao Pills as the core prescription. It is found that the treatment of gZav-Grib by Tibetan medicine is mainly dominated by the treatment idea about " Therapeutic r Lung and blood,Consideration of venous diseases". Treatment functions is promoting the circulation of Qi,clearing blood heat and getting rid of bad blood,achieving the purpose of treating both principal secondary aspect of gZav-Grib. The research methods based on the HIS can't only optimize the Tibetan treating gZav-Grib sequela treatment plan and rule of medication,but also provide the scientific basis for Tibetan medicine treat gZav-Grib.

[Content determination of four diester diterpenoid alkaloids in leaves of Aconitum kusnezoffii by HPLC].

This present study is to develop an HPLC method for simultaneous determination of four diester diterpenoid alkaloids, beiwutine, mesaconitine, hypaconitine and aconitine in the leaves of Aconitum kusnezoffii, so as to provide evidence of the quality control of this herb. The four constituents were measured on a Waters XBridge CC18 column(4.6 mmχ250 mm, 5 µm). The mobile phase was acetonitrile-40 mmol·L⁻¹ ammonium acetate solution(adjusted pH to 10.5 with ammonia solution)(33:67) with isocratic elution at a flow rate of 1.0 mL·min⁻¹; the detection wavelength was 235 nm; the column temperature was 30 °C, and the injection volume was 10 µL. Next, this contents of the four diester diterpenoid alkaloids in 12 samples were 0.025 5-0.088 5, 0.039 1-0.071 5, 0.026 6-0.081 0 and 0.008 12-0.031 2 mg·g⁻¹, respectively. Next, this method has been successfully applied to the analysis of A. kusnezoffii folium in different harvest periods. The contents of the four alkaloids decreased primarily, and then increased with the postponing of harvest. The established method is proved to be accurate and sensitive for the determination of alkaloids in A. kusnezoffii folium, and may be useful for the quality improvement of this herbal medicine. Moreover, these results indicated the scientific significance for the toxicity and the suitable harvest time of this herb.

[Dog Fecal Contamination by Echinococcus in Cuomei County of Tibet in 2015].

Objective: To understand dog fecal contamination by Echinococcus in Lhoka Prefecture of Tibet and provide basis for development of prevention and control strategies. Methods: Survey spots were sampled around the Zhegu Village of Zhegu Town in Cuomei County of Tibet using the mechanical sampling method in May, 2015. The positions of spots, amount of dog feces, types of camps, pastures, terrains, vegetations and land cover, as well as information concerning the existence of household garbage, were recorded. The linear distance from survey spot to the center of the village was calculated. Dog feces were sampled in survey spot and examined the copro-antigen for Echinococcus contamination by ELISA. The distribution characteristics of fecal contamination were analyzed by chi-square test, Fisher's exact test, Kruskal-Wallis test and Nemenyi test. Results: Seventy-nine survey spots were selected for sampling. A total of 226 feces samples were obtained in 37 of the spots. ELISA results showed that the copro-antigen positive rate was 23.9%（54/226）, the averaged density of feces and the averaged density of positive feces were 0.317 9/100 m2 and 0.075 9/100 m2, with a maximum of 2.555 6/100 m2 and 0.555 6/100 m2 respectively. The density of feces and the density of positive feces were both higher in summer camps（0.601 9/100 m2 and 0.157 4/100 m2 respectively） than in non-camps（0.170 2/100 m2 and 0.033 1/100 m2）（χ2=18.248 4，P<0.01；χ2=15.274 3，P<0.01）. In addition, the density of feces and the density of positive feces were both higher in survey spots with household garbage（0.679 0/100 m2, 0.177 0/100 m2） than in those without household garbage （0.130 3/100 m2 and 0.023 5/100 m2）（χ2=34.634 7，P<0.01；χ2=26.109 1，P<0.01）; as well as higher in survey spots ≥10 km from the center of the village（0.403 7/100 m2, 0.107 4/100 m2） than in those <10 km（0.265 3/100 m2, 0.056 7/100 m2）（χ2=4.432 7，P<0.05；χ2=4.045 5，P<0.05）. Conclusion: The Cuomei County of Tibet is facing a serious situation of dog fecal contamination by Echinococcus. Summer camps, areas with household garbage, and districts with a ≥10 km linear distance from the village center may provide reference for determining the regions for hydatidosis prevention and control.

Sparse linear modeling of next-generation mRNA sequencing (RNA-Seq) data for isoform discovery and abundance estimation.

Since the inception of next-generation mRNA sequencing (RNA-Seq) technology, various attempts have been made to utilize RNA-Seq data in assembling full-length mRNA isoforms de novo and estimating abundance of isoforms. However, for genes with more than a few exons, the problem tends to be challenging and often involves identifiability issues in statistical modeling. We have developed a statistical method called "sparse linear modeling of RNA-Seq data for isoform discovery and abundance estimation" (SLIDE) that takes exon boundaries and RNA-Seq data as input to discern the set of mRNA isoforms that are most likely to present in an RNA-Seq sample. SLIDE is based on a linear model with a design matrix that models the sampling probability of RNA-Seq reads from different mRNA isoforms. To tackle the model unidentifiability issue, SLIDE uses a modified Lasso procedure for parameter estimation. Compared with deterministic isoform assembly algorithms (e.g., Cufflinks), SLIDE considers the stochastic aspects of RNA-Seq reads in exons from different isoforms and thus has increased power in detecting more novel isoforms. Another advantage of SLIDE is its flexibility of incorporating other transcriptomic data such as RACE, CAGE, and EST into its model to further increase isoform discovery accuracy. SLIDE can also work downstream of other RNA-Seq assembly algorithms to integrate newly discovered genes and exons. Besides isoform discovery, SLIDE sequentially uses the same linear model to estimate the abundance of discovered isoforms. Simulation and real data studies show that SLIDE performs as well as or better than major competitors in both isoform discovery and abundance estimation. The SLIDE software package is available at https://sites.google.com/site/jingyijli/SLIDE.zip.

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation.

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

Characteristics of Vernal Keratoconjunctivitis in Lhasa: A Single-Center, Observational Study.

The incidence of vernal keratoconjunctivitis (VKC) varies across different ethnicities and regions. To investigate the clinical features of VKC in Tibet, a single-center case series of VKC was retrospectively reviewed from a general hospital in Lhasa over one year. General data and typical manifestations were recorded. Horner-Trantas dots, limbal neovascularization, pseudogerontoxon and upper palpebral conjunctival papilla were seen in most of these patients. Patients with signs such as limbal pannus (t = 2.18, P < 0.05), pseudogerontoxon (t = 2.61, P < 0.05), and Horner-Trantas dots (t = 2.33, P < 0.05) appeared to have longer disease courses, while patients with upper palpebral conjunctival lesions had earlier onset times (t = 2.12, P < 0.05). The clinical signs of VKC on the Tibetan Plateau are more obvious, and the ocular surface is commonly and severely involved.

USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/ß-catenin.

BACKGROUND: USPs are a family of enzymes that regulate protein degradation, and their dysregulation has been implicated in the development and progression of cancer. AIMS: This study aimed to determine whether ubiquitin-specific proteases 3 (USP3) could be a potential target for therapy in hepatocellular carcinoma (HCC), particularly in resistant HCC. This study systematically investigated the role of USP3 in HCC, with a focus on chemo-resistant HCC cells. METHODS: The level of USP3 from clinical samples was measured using an ELISA assay. Cell proliferation, apoptosis, migration, and anchorage-independent colony formation assays were performed. Transfection was performed to knock down USP3 expression and measure ß-catenin activity, and real-time PCR was used to measure levels of MYC and CYCLIN D1 genes. RESULTS: USP3 protein was upregulated in HCC tissues, but its upregulation was not associated with clinicopathology. USP3 knockdown had a similar inhibitory effect on growth in both sensitive and resistant HCC cells, did not affect migration, and induced apoptosis in sensitive but not resistant HCC cells. Furthermore, USP3 knockdown was more effective in suppressing anchorage-independent colony formation in chemoresistant HCC cells compared to their chemo-sensitive counterparts. Pearson correlation coefficient analysis revealed a strong positive correlation between USP3 and CTNNB1, and consistently, USP3 knockdown reduced the levels and activities of ß-catenin in HCC cells. Using a Wnt activator (lithium) in rescue studies significantly reversed the inhibitory effects of USP3 knockdown. CONCLUSION: The findings suggest that inhibiting USP3 is an effective strategy against cancer stem cells and chemo-resistant HCC cells.

Sichen Formula Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Blocking the TLR4 Signaling Pathways.

Purpose: Sichen (SC) formula is a classic prescription of Tibetan medicine. Due to its potential anti-inflammatory effect, the SC formula has been clinically used to treat respiratory diseases for many years in the Chinese Tibet region. The present study aimed to investigate the anti-inflammatory effect of SC and explore the underlying mechanisms. Methods: SC formula was characterized by HPLC analysis. The acute lung injury (ALI) mouse model was induced by direct intratracheal lipopolysaccharide (LPS) instillation, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Meanwhile, RAW264.7 macrophages were stimulated by LPS. The contents of inflammatory mediators in the culture medium were determined by ELISA. Protein levels were determined by immunohistochemical staining or Western blotting. Nuclear localization of NF-κB, AP-1, and IRF3 was performed using immunofluorescence and Western blotting. Results: In the LPS-induced ALI mouse model, SC treatment suppressed the secretion of inflammatory mediators (TNF-α, IL-6, IL-1ß, MCP-1, MIP-1α, and RANTES) in BALF. SC treatment hindered the recruitment of macrophages. SC treatment also inhibited the expression of CD68, p-p65, and TLR4 in the lung tissue. In the LPS-exposed RAW264.7 cells, the cell viability was not changed up to 400 µg/mL of SC. SC concentration-dependently suppressed the production of nitric oxide, prostaglandin E2, TNF-α, IL-6, MCP-1, MIP-1α, and RANTES in LPS-challenged RAW264.7 cells. The expression levels of iNOS, COX-2, p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/ß, p-IκB, p-p65, p-c-Jun, and p-IRF3 were decreased after SC treatment. Moreover, the nuclear translocation of p65, c-Jun, and IRF3 was also blocked by SC treatment. Conclusion: SC treatment inhibited the inflammatory responses in LPS-induced ALI mouse model/RAW264.7 macrophages. The underlying mechanism of this action may be closely associated with the suppression of TLR4 signaling pathways. These research findings provide further pharmacological justifications for the medicinal use of SC in the management of respiratory diseases.

Prevalence, self-awareness, treatment, and control of hypertension in Lhasa, Tibet.

To investigate the prevalence, self-awareness, and treatment of hypertension in Lhasa, Tibet, a total of 1370 native Tibetan aged ≥18 years were selected, using stratified proportional sampling. The study showed that the prevalence of hypertension was 51.2%, significantly higher in men (56.0%) than in women (48.0%) (P = .004). The hypertension prevalence increased with increasing age (77.8% in 60-74 y and 82.5% in ≥75 y groups) and was higher in urban, suburban, or agricultural area than in pastoral area (P < .001). The self-awareness, treatment, and control rate of hypertension were 63.5%, 24.3% and 7.7%, respectively. In multivariable regression analysis, age, urban residence, amount of daily intake of fat and oil, and body mass index <18.5 kg/m(2) were independently associated with hypertension. In conclusion, hypertension was highly prevalent among native Tibetan people in Lhasa, and the rates of self-awareness, treatment, and control of hypertension were low.