Tumor microenvironment(TME)is a complex cellular environment where tumor cells reside,along with various types of cells and extracellular components surrounding the tumor cells.Immune cells are key components of TME,including tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),lymphocytes,regulatory T cells(Tregs),natural killer cells(NK cells),dendritic cells(DCs),and many others.It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy,radiotherapy,targeted therapy,and immunotherapy,and a leading cause of treatment failure.Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME.Consequently,overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment.In recent years,with in-depth research into immune cells within TME,significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells.Furthermore,therapeutic strategies that target these immune cells,signaling pathways,or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment.This article reviews the research advancements regarding the roles of TAMs,MDSCs,Tregs,and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance.Additionally,we explore the relationship of tumor-associated neutrophils(TANs)and B regulatory cells(Bregs)with tumor drug resistance.It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

Objective To investigate the predictive value of serum lipoprotein-associated phospho-lipase A2(Lp-PLA2)for long-term prognosis of elderly patients with stable coronary heart dis-ease(CHD).Methods A retrospective trial was conducted on 198 patients with stable CHD ad-mitted to our hospital from January 2016 to December 2018.All of them were followed up for 5 years,and divided into adverse cardiovascular event group(n=42)and control group(n=156)according to whether adverse cardiovascular events occurred during follow-up.Clinical features and Lp-PLA2 level were compared between the two groups.The predictive value of Lp-PLA2 for adverse cardiovascular events was analyzed in elderly patients with stable CHD within 5 years.Re-sults The adverse cardiovascular event group had significantly older age(74.95±7.02 vs 70.17±6.30 years,P=0.000),larger proportions of diabetes(54.76％vs 27.56％,P=0.001),of coronary artery stenosis ≥75％(69.05％vs 47.44％,P=0.013)and of left ventricular ejection fraction(LVEF)＜50％(50.00％vs 28.21％,P=0.008),and higher Lp-PLA2 level(478.38±187.54 U/L vs 308.17±126.73 U/L,P=0.000)when compared with the control group.The AUC value of age and Lp-PLA2 was 0.683(95％CI:0.590--0.776,P＜0.001)and 0.763(95％CI:0.677--0.848,P=0.763),respectively,in predicting the long-term prognosis in elderly patients with stable CHD.Multivariate logistic regression analysis showed that age,diabetes,coronary artery stenosis ≥75％,LVEF＜50％and Lp-PLA2 were independent influencing factors for adverse cardiovascular events within 5 years in elderly patients with stable CHD(P＜0.05,P＜0.01).Con-clusion Increased Lp-PLA2 level is associated with adverse cardiovascular events within 5 years in patients with stable CHD.

【Objective】 To explore the distribution of polymorphisms of miR-208 genes rs8022522 and rs12894524 locus in Guangxi healthy population and compare the differences in the polymorphism distribution in different population. 【Methods】 SNPscan technology was used to detect genotypes of rs8022522 and rs12894524 from 297 healthy people in Guangxi, and the results were compared with other populations from Human genome Haplotype Map(HapMap) data. 【Results】 Three genotypes, namely, AA (2.7%), AG (24.2%) and GG (73.1%), in rs8022522 were found, with the allele frequencies of A and G being 14.8% and 85.2%. The genotypes of rs12894524 locus were TT (1.3%), TG (13.5%) and GG (85.2%), and the frequency of T and G allele was 8.1% and 91.9%, respectively. rs8022522 and rs12894524 locus genotypes and allele frequencies were significantly different from HapMap-CEU, HapMap- YRI and HapMap-TSI (P<0.05). Compared with HapMap-JPT and HapMap-CHB, there was no significant difference in genotype or allele frequency between the two sites (P>0.05). As for the blood lipid level among the three genotypes in rs8022522, the level of high density lipoprotein cholesterol (HDL-C) with GG genotype was significantly different from that in AG group (P<0.05). 【Conclusion】 The polymorphisms of rs8022522 and rs12894524 of miR-208 gene in Guangxi population are different from those in other regions to varying degrees. The polymorphism of rs8022522 locus is related to the level of HDL-C.

Laparoscopic hepatectomy has been routinely used in all tumor types of the liver, but for tumors in the Ⅵ, Ⅶ and Ⅷ segments of the liver (referred to as tumors in a special position of the liver in this paper), laparoscopic hepatectomy has some difficulties in aspect of vision and operation due to the deep anatomical position. In the process of continuous experience accumulation, hepatobiliary surgeons have explored different surgical positions, surgical methods and surgical paths to solve the encountered difficulties. For tumors located in a special position of the liver, conventional laparoscopy, change of surgical posture, thoracoscopic or combined laparoscopy and retroperitoneal laparoscopy are effective and feasible. All of them have their own advantages.

Objective:To analyze the distribution characteristics of peripheral retinopathy in Chinese patients with diabetic retinopathy (DR).Methods:A cross-sectional study. From January to December 2019, 265 cases of 388 eyes of DR patients diagnosed in the eye examination of Guangdong Provincial People's Hospital were included in the study. Among them, there were 211 eyes in 148 males and 177 eyes in 117 females; the average age was 58.4±12.3 years. Ultra-wide-angle fundus imaging (UWF) examination was performed by Daytona in Aalborg, UK. Use Photoshop to simulate the standard 7-azimuth (S7F) area, which was used as the central retinal area 1-7. The peripheral retinal areas 3-7 (P3-P7) were the adjacent peripheral retinal areas of the central retinal area 3-7, respectively. Divided DR into peripheral lesion predominant type (PPL) and central lesion predominant type (PCL). PPL was defined as at least one peripheral retinal area with more severe disease than its adjacent central area. χ 2 test was performed on the difference of PPL composition ratio in each retinal area of eyes with different DR stages. Results:Among 388 eyes, 200 eyes were PPL (51.5%, 200/388). Compared of PPL composition ratios of eyes with different stages of DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR were 32 (36.8%, 32/87), 89 (55.3%, 89/161)), 42 (51.9%, 42/81), 37 (62.6%, 37/59), the difference was statistically significant ( χ2=11.440, P=0.010). Comparison of the distribution of PPL in each retinal area in DR eyes: in 200 PPL eyes, areas 3, 4, 5, 6, and 7 have 87, 101, 78, 67, and 38 eyes, respectively. The distribution of PPL in each retinal area in DR eyes was compared, and the difference was statistically significant ( χ2=37.640, P<0.001). Conclusions:PPL accounts for 51.5% of the eyes with DR. The DR stage are more severe, the proportion of PPL is higher. The temporal retinal peripheral lesions are the most common.

Objective:Under different diagnostic scenarios, we tried to establish a tuberculosis dynamic model, to predict the incidence burden and to provide evidence for developing the prevention and control programs of tuberculosis.Methods:A systematic dynamic model was established to fit the annual incidence rates of tuberculosis data from the China CDC, between 2005 and 2018. Basic reproductive number ( R0) was calculated. Impact of different diagnostic scenarios on tuberculosis burden was explored by numerical changes in diagnosis-related parameters. Results:Results from the Chi-square test indicated that the model accuracy appeared as: χ2=1.102 ( P=1.000). Also, the computed result showed that R0=0.063<1, indicating that tuberculosis would gradually be disappearing in China. Approaches that including 'reducing the delayed diagnosis time’or 'improving the timely medical treatment’would end the fluctuations of the number of infectious and hospitalized patients and thus leading to continuous reduction in the number of these patients, in a long run. Conclusions:This model fitted well for the trend of tuberculosis incidence rates between 2005 and 2018. Reducing the delay time in diagnosis and improving the rate of timely medical treatment could effectively reduce the long-term burden of tuberculosis. Improvement of this model would be further explored.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candi-date high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/zt-pub/DCT.

OBJECTIVETo investigate the association of SNP of CD40 gene and its serum levels with ischemic stroke (IS).

METHODSA total of 202 IS patients from a hospital of Baise city were enrolled in case group from May 2013 to November 2014. At the same time, 109 healthy people who had physical check-ups in the outpatient department at the same hospital were enrolled in the control group. All participants were from Guangxi Zhuang Autonomous Region and unrelated to each other. 3 ml venous blood were collected on the premise of informed consent. The single nucleotide polymorphisms of CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A were analyzed using a Snapshot SNP genotyping assays, and the serum levels of CD40 were tested by ELISA. t-test was used to compare the serum levels of CD40 between the case and control group, and the genotypes at different locuses in case group; χ(2) test was used to compare the distribution differences of the CD40 gene locuses in different genotypes and allele between the case group and the control group; alleles was established as independent variables, the occurrence of the IS as dependent variable, and expressed relative risk with OR (95%CI) value.

RESULTSIn the case group, the frequency of CC, CT and TT genotypes in CD40 gene rs1883832 C/T were 21.78% (44/202), 49.51% (100/202) and 28.71% (58/202), respectively, and 33.17% (66/199), 48.74% (97/199), 18.09% (36/199) in the control group, respectively, the differences between the two groups was significant (χ(2)=9.57, P=0.008). The CD40 serum levels were (62.7 ± 24.5) pg/ml in the case group, which was higher than that in the control group (45.3 ± 17.2) pg/ml (t=8.97, P<0.001). The serum levels of TT and CT genotypes in CD40 gene were (65.9 ± 26.3) and (64.3 ± 25.9) pg/ml, respectively, and the differences were significant when comparing with CC genotype (t equaled 5.34 and 5.03, respectively, P<0.001). The risk of developing IS was 1.56 times higher in 1883832 T allele carriers than that in rs1883832 C allele carriers (OR=1.56, 95% CI: 1.18-2.06); Combined genotype analysis displayed that CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A polymorphisms showed strong linkage disequilibrium, the case group TCCA haplotype was tested to be associated with a significantly increased risk of IS as compared with that in the control group(OR=2.49; 95%CI: 1.13-5.48).

CONCLUSIONCD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were possibly associated with ischemic stroke, and the susceptibility gene for ischemic stroke may be rs1883832 T allele.

Alleles ; CD40 Antigens ; blood ; genetics ; Case-Control Studies ; Cell Differentiation ; China ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Stroke ; blood ; genetics

Objective To investigate the expression and clinical significance of P-selectin in colorectal cancer cells. Methods The protein expression of P-selectin was detected by immunohistochemistry in colorectal cancer tissues ( n=116) and corresponding non-tumor normal mucosa(n=57). The differences of P-selectin expression in colorectal cancer tissues, corre?sponding non-tumor normal mucosa and the clinical pathological significance were compared and analysed in two groups. Results The expression of P-selectin protein was found not only in vascular endothelial cells but also in colorectal cancer cells. The positive rate of P-selectin expression was apparently higher in colorectal cancer cells (77.6%, 90/116) than that in normal mucosa (17.5%, 10/57,χ2=56.49, P<0.05). However, there were no significance in positive rates of P-selectin in colorectal cancer cells between tumors with different diameters, different degrees of differentiation, different depths of infiltration and with or without lymph node metastasis (80.6%vs. 74.1%, 79.0%vs. 74.3%, 78.4%vs. 76.9%, 82.7%vs. 73.4%, P>0.05). Conclusion The high expression of P-seletin in colorectal cancer cells is an important characteristic of colorectal cancer.

AIM: To explore the effect of hydrogen sulfide on the senescence of human umbilical vein endothe -lial cells (HUVECs) induced by high glucose.METHODS: Senescence model was established by treating HUVECs with33 mmol/L glucose for 48 h.The parameters were detected to demonstrate the effect of hydrogen sulfide on senescence andthe mechanism involved was also investigated .RESULTS: In the cells treated with high glucose, the proliferation was attenuatedwith a higher number of senescence -associated β-galactosidase (SA-β-Gal) positive cells, and plasminogen activatorinhibitor 1 (PAI-1) protein expression, malondialdehyde (MDA) production and NF-κB p65 activity were increasedsignificantly, but the expression of superoxide dismutase 1 (SOD1) was decreased.However, the cell number and SOD1expression were increased, and the number of SA-β-Gal positive cells, PAI-1 protein expression, MDA production and theactivity of NF-κB p65 were decreased after sodium hydrosulfide (100 and 200 μmol/L) treatment.CONCLUSION: Exogenoushydrogen sulfide prevents HUVECs against high glucose -induced senescence by suppressing oxidative stress and NF -κB p65 activity.