Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Objective: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. Methods: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan–Meier analyses and Cox proportional hazards regression analyses. Results: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27–2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47–3.85;p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan–Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Conclusion Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Objective: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. Methods: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan–Meier analyses and Cox proportional hazards regression analyses. Results: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27–2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47–3.85;p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan–Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Conclusion Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Objective: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. Methods: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan–Meier analyses and Cox proportional hazards regression analyses. Results: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27–2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47–3.85;p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan–Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Conclusion Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

【Objective】 To explore the geographical environment factors that may affect serum uric acid (UA) of healthy people and explore the change trend of UA reference value at the national scale. 【Methods】 The UA reference values of 607905 healthy people from 565 loci in China were collected, and the correlation between 25 geographical environment factors and UA reference values was analyzed by correlation analysis. CatBoost model was constructed and SHAP value interpretation model was applied to predict the UA reference values of healthy people in counties and cities in China, and the geographical distribution map of UA reference values of healthy people in China was drawn by using ordinary Kriging. 【Results】 A total of 20 indicators, namely, latitude, altitude, annual average temperature, annual average relative humidity, annual precipitation, air temperature annual range, annual average wind speed, percentage of surface soil silt, surface soil bulk density, surface soil gravel content, surface soil organic matter content, surface soil PH, surface soil (clay) cation exchange capacity, surface soil (silt) cation exchange capacity, surface soil base saturation, total surface soil exchange capacity, T-CaCO3, T-CaSO4, surface soil alkalinity, and surface soil salt showed their correlation with UA reference value of healthy people nationwide. The spatial distribution of UA reference values of healthy people across the country differed, manifested as the changing trend of higher in high altitude regions, higher in coastal regions than in inland regions, lower in the mid-eastern region, and higher in Southwest China at similar altitudes. 【Conclusion】 This study lays a foundation for further studies on the mechanism of different influencing factors on UA reference value. CatBoost model was established to provide the basis for establishing reference standards using UA reference values as prognostic factors for hyperuricemia and related chronic diseases in different regions.

【Objective】 This paper screened the factors that may influence the spatial differentiation of Neutrophil-to-lymphocyte ratio （NLR） reference values in healthy adults in China and explored the trend of NLR reference values in China. 【Methods】 For this research， we collected the NLR of 162 681 healthy adults from 62 cities in China. Spearman regression analysis was used to analyze the correlation between NLR and 25 geography secondary indexes. We extracted 9 indexes with significant correlation， built a random forest （RF） model， and predicted the country’s urban healthy adults’ NLR reference value. By using the disjunctive Kriging method， we obtained the geographical distribution of NLR reference value of healthy adults in China. 【Results】 The reference value of NLR of healthy adults in China was significantly correlated with the 9 secondary indexes， namely， altitude， sunshine duration， annual average temperature， annual average relative humidity， annual temperature range， annual average wind speed， content of organic matter in topsoil， cation exchange capacity in topsoil （clay）， and total amount of CaSO4 in soil. The geographical distribution of NLR values of healthy adults in China showed a trend of being higher in Southeast China and lower in Northwest China， higher in coastal areas and lower in inland areas. 【Conclusion】 This study lays a foundation for further research on the mechanism of different influencing factors on the reference value of NLR index. A random forest model composed of significant influencing factors has been established to provide the basis for formulating reference criteria for the prognostic factors of the novel coronavirus using NLR reference values in different regions.

ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang （HQGZWWT） in the treatment of diabetic peripheral neuropathy （DPN） in MKR mice via regulating endoplasmic reticulum （ER） stress. MethodThirty-two 8-week-old MKR mice （half were male and half were female） were fed with a high-fat diet for four weeks， and then 1% streptozotocin （STZ） was injected intraperitoneally for five days. After the blood glucose was stabilized， the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose （FBG） value ≥11.1 mmol·L^-1 were randomly divided into model group ， Huangqi Guizhi Wuwutang in original dosage group （30 g·kg^-1·d^-1）， Huangqi Guizhi Wuwutang in formula dosage group （6.25 g·kg^-1·d^-1）， and positive drug group （mecobalamin tablets， 0.17 mg·kg^-1·d^-1）. Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group， the change in FBG was tested， and hematoxylin and eosin （HE） staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition， the expression of c-Jun N-terminal kinase （JNK）， phosphorylated c-Jun N-terminal kinase （p-JNK） and inositol requiring enzyme 1α （IRE1α） proteins was determined by immunohistochemical test and Western blot （WB）. ResultCompared with the conditions in the normal group and blank group， the time of paw withdrawal， paw licking and tail flick in the model group was shortened （P<0.01）， and the conduction velocity of sciatic nerve was decreased （P<0.01）. Compared with the conditions in the model group， the behavioral and functional indicators were improved by HQGZWWT （P<0.05，P<0.01）. The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group （P<0.05）， while that was lowered by HQGZWWT compared with the condition in the model group （P<0.05）. However， there was no difference among the treatment groups. According to the WB， the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group （P<0.05，P<0.01）， while that was decreased by HQGZWWT compared with the condition in the model group （P<0.05，P<0.01）. No difference was observed between the HQGZWWTO and HQGZWWTF groups. ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve， which may be related to its delaying the ER stress response of sciatic nerve.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To under-stand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot,real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phospho-proteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloro-plasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of pho-tosystem (PS) Ⅱ, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.

Objective: To provide a scientific standard of left ventricular Tei index for healthy people from various region of China, and to lay a reliable foundation for the evaluation of left ventricular diastolic and systolic function. Methods: The correlation and principal component analysis were used to explore the left ventricular Tei index, which based on the data of 3 562 samples from 50 regions of China by means of literature retrieval. hTe nine geographical factors were longitude(X1), latitude(X2), altitude(X3), annual sunshine hours (X4), the annual average temperature (X5), annual average relative humidity (X6), annual precipitation (X7), annual temperature range (X8) and annual average wind speed (X9). ArcGIS sotfware was applied to calculate the spatial distribution regularities of letf ventricular Tei index. Results: hTere is a signiifcant correlation between the healthy people’s letf ventricular Tei index and geographical factors, and the correlationcoeffcients were 0.107 (r1), 0.301 (r2), 0.029 (r3), 0.277 (r4),?0.256(r5),?0.289(r6),?0.320(r7), 0.310 (r8) and 0.117 (r9), respectively. A linear equation between the Tei index and the geographical factor was obtained by regression analysis based on the three extracting principal components. hTe geographical distribution tendency chart for healthy people’s letf Tei index was iftted out by the ArcGIS spatial interpolation analysis. Conclusion: hTe geographical distribution for letf ventricular Tei index in China follows certain pattern. hTe reference value in North is higher than that in South, while the value in East is higher than that in West.

Objective To explore the influence of glucose-lowering rate on left ventricular function in patients with type 2 diabetes mellitus (T2DM). Methods One hundred and thirty-two cases of type 2 diabetes mellitus and 135 cases of type 2 diabetes mellitus with coronary heart disease (T2DM+CHD)received intensive glucose lowering therapy. Then, after measuring left ventricular ejection fraction (LVEF) and E/A ratio, the variation was analyzed. Results LVEF was significantly higher than that before intensive therapy in T2DMsubgroup with glucose-lowering rate less than 6 m mol · L-1 · d-1( P＜0.05 ). So was T2DM+CHD subgroup with glucose-lowering rate less than 4 mmol· L-1 · d-1 (P＜0.05). LVEF was significantly lower than that before intensive therapy in T2DM+CHD subgroup with glucose-lowering rate greater than 4 mmol · L-1 · d-1( P＜0. 05 ),while by the end of following up for 3 months, LVEF stepped up and no significant difference was observed between subgroups ( P ＞ 0. 05 ). The E/A ratio stepped up in both subgroups after intensive therapy ( P ＜ 0. 05 ).Conclusions For T2DM patients with coronary heart disease, excessively fast glucose-lowering rate may impair left ventricular function. Long-term good control of blood glucose restores the impaired left ventricular function causes by excessively fast glucose-lowering rate. After intensive therapy, left ventricular diastolic function finally improves in both subgroups regardless of the glucose-lowering rate and coronary heart disease.